Psoriasis

NEW ORLEANS – All but one Janus kinase (JAK) inhibitor with dermatologic indications carries a boxed warning that lists multiple risks for drugs in this class, including the risk of major adverse cardiac events (MACE), even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.  

Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream. 
 

Basis of boxed warnings

In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m².

After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.

In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.

Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
 

Evidence of difference in dermatology

There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.

For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.

When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.

Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.

“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.

Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.  

Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”

“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
 

Risk-benefit considerations in dermatology

This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.

Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.

“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”

George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.

“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.

“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”

Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.

Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.

A version of this article originally appeared on Medscape.com.

NEW ORLEANS – All but one Janus kinase (JAK) inhibitor with dermatologic indications carries a boxed warning that lists multiple risks for drugs in this class, including the risk of major adverse cardiac events (MACE), even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.  

Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream. 
 

Basis of boxed warnings

In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m².

After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.

In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.

Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
 

Evidence of difference in dermatology

There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.

For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.

When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.

Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.

“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.

Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.  

Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”

“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
 

Risk-benefit considerations in dermatology

This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.

Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.

“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”

George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.

“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.

“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”

Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.

Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.

A version of this article originally appeared on Medscape.com.

NEW ORLEANS – All but one Janus kinase (JAK) inhibitor with dermatologic indications carries a boxed warning that lists multiple risks for drugs in this class, including the risk of major adverse cardiac events (MACE), even though the basis for all the risks is a rheumatoid arthritis study, according to a critical review at the annual meeting of the American Academy of Dermatology.  

Given the fact that the postmarketing RA study was specifically enriched with high-risk patients by requiring an age at enrollment of at least 50 years and the presence of at least one cardiovascular risk factor, the extrapolation of these risks to dermatologic indications is “not necessarily data-driven,” said Brett A. King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn.

The recently approved deucravacitinib is the only JAK inhibitor that has so far been exempt from these warnings. Instead, based on the ORAL Surveillance study, published in the New England Journal of Medicine, the Food and Drug Administration requires a boxed warning in nearly identical language for all the other JAK inhibitors. Relative to tofacitinib, the JAK inhibitor tested in ORAL Surveillance, many of these drugs differ by JAK selectivity and other characteristics that are likely relevant to risk of adverse events, Dr. King said. The same language has even been applied to topical ruxolitinib cream. 
 

Basis of boxed warnings

In ORAL Surveillance, about 4,300 high-risk patients with RA were randomized to one of two doses of tofacitinib (5 mg or 10 mg) twice daily or a tumor necrosis factor (TNF) inhibitor. All patients in the trial were taking methotrexate, and almost 60% were taking concomitant corticosteroids. The average body mass index of the study population was about 30 kg/m².

After a median 4 years of follow-up (about 5,000 patient-years), the incidence of many of the adverse events tracked in the study were higher in the tofacitinib groups, including serious infections, MACE, thromboembolic events, and cancer. Dr. King did not challenge the importance of these data, but he questioned whether they are reasonably extrapolated to dermatologic indications, particularly as many of those treated are younger than those common to an RA population.

In fact, despite a study enriched for a higher risk of many events tracked, most adverse events were only slightly elevated, Dr. King pointed out. For example, the incidence of MACE over the 4 years of follow-up was 3.4% among those taking any dose of tofacitinib versus 2.5% of those randomized to TNF inhibitor. Rates of cancer were 4.2% versus 2.9%, respectively. There were also absolute increases in the number of serious infections and thromboembolic events for tofacitinib relative to TNF inhibitor.

Dr. King acknowledged that the numbers in ORAL Surveillance associated tofacitinib with a higher risk of serious events than TNF inhibitor in patients with RA, but he believes that “JAK inhibitor safety is almost certainly not the same in dermatology as it is in rheumatology patients.”
 

Evidence of difference in dermatology

There is some evidence to back this up. Dr. King cited a recently published study in RMD Open that evaluated the safety profile of the JAK inhibitor upadacitinib in nearly 7,000 patients over 15,000 patient-years of follow-up. Drug safety data were evaluated with up to 5.5 years of follow-up from 12 clinical trials of the four diseases for which upadacitinib is now indicated. Three were rheumatologic (RA, psoriatic arthritis, and ankylosing spondylitis), and the fourth was atopic dermatitis (AD). Fourteen outcomes, including numerous types of infection, MACE, hepatic complications, and malignancy, were compared with methotrexate and the TNF inhibitor adalimumab.

For the RA diseases, upadacitinib was associated with a greater risk than comparators for several outcomes, including serious infections. But in AD, there was a smaller increased risk of adverse outcomes for the JAK inhibitor relative to comparators.

When evaluated by risk of adverse events across indications, for MACE, the exposure-adjusted event rates for upadacitinib were less than 0.1 in patients treated for AD over the observation period versus 0.3 and 0.4 for RA and psoriatic arthritis, respectively. Similarly, for venous thromboembolism, the rates for upadacitinib were again less than 0.1 in patients with AD versus 0.4 and 0.2 in RA and psoriatic arthritis, respectively.

Referring back to the postmarketing study, Dr. King emphasized that it is essential to consider how the boxed warning for JAK inhibitors was generated before applying them to dermatologic indications.

“Is a 30-year-old patient with a dermatologic disorder possibly at the same risk as the patients in the study from which we got the boxed warning? The answer is simply no,” he said.

Like the tofacitinib data in the ORAL Surveillance study, the upadacitinib clinical trial data are not necessarily relevant to other JAK inhibitors. In fact, Dr. King pointed out that the safety profiles of the available JAK inhibitors are not identical, an observation that is consistent with differences in JAK inhibitor selectivity that has implications for off-target events.  

Dr. King does not dismiss the potential risks outlined in the current regulatory cautions about the use of JAK inhibitors, but he believes that dermatologists should be cognizant of “where the black box warning comes from.”

“We need to think carefully about the risk-to-benefit ratio in older patients or patients with risk factors, such as obesity and diabetes,” he said. But the safety profile of JAK inhibitors “is almost certainly better” than the profile suggested in boxed warnings applied to JAK inhibitors for dermatologic indications, he advised.
 

Risk-benefit considerations in dermatology

This position was supported by numerous other experts when asked for their perspectives. “I fully agree,” said Emma Guttman-Yassky, MD, PhD, system chair of dermatology and immunology, Icahn School of Medicine, Mount Sinai, New York.

Like Dr. King, Dr. Guttman-Yassky did not dismiss the potential risks of JAK inhibitors when treating dermatologic diseases.

“While JAK inhibitors need monitoring as advised, adopting a boxed warning from an RA study for patients who are older [is problematic],” she commented. A study with the nonselective tofacitinib in this population “cannot be compared to more selective inhibitors in a much younger population, such as those treated [for] alopecia areata or atopic dermatitis.”

George Z. Han, MD, PhD, an associate professor of dermatology, Zucker School of Medicine, Hofstra, Northwell Medical Center, New Hyde Park, New York, also agreed but added some caveats.

“The comments about the ORAL Surveillance study are salient,” he said in an interview. “This kind of data should not directly be extrapolated to other patient types or to other medications.” However, one of Dr. Han’s most important caveats involves long-term use.

“JAK inhibitors are still relatively narrow-therapeutic-window drugs that in a dose-dependent fashion could lead to negative effects, including thromboembolic events, abnormalities in red blood cells, white blood cells, platelets, and lipids,” he said. While doses used in dermatology “are generally below the level of any major concern,” Dr. Han cautioned that “we lack definitive data” on long-term use, and this is important for understanding “any potential small risk of rare events, such as malignancy or thromboembolism.”

Saakshi Khattri, MD, a colleague of Dr. Guttman-Yassky at Mount Sinai, said the risks of JAK inhibitors should not be underestimated, but she also agreed that risk “needs to be delivered in the right context.” Dr. Khattri, who is board certified in both dermatology and rheumatology, noted the safety profiles of available JAK inhibitors differ and that extrapolating safety from an RA study to dermatologic indications does not make sense. “Different diseases, different age groups,” she said.

Dr. King has reported financial relationships with more than 15 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 20 pharmaceutical companies, including companies that make JAK inhibitors. Dr. Han reports financial relationships with Amgen, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, PellePharm, Pfizer, and UCB. Dr. Khattri has reported financial relationships with AbbVie, Arcutis, Bristol-Myers Squibb, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB.

A version of this article originally appeared on Medscape.com.

Given the characteristic clinical presentation, the most likely diagnosis is psoriasis.

Dr. Lawrence Eichenfield

Psoriasis is a chronic immune-mediated disease that is characterized by well-demarcated thick scaly plaques on face, scalp, and intertriginous skin. Psoriasis is more common in adults than children, but the incidence of psoriasis in children has increased over time.¹ Clinical presentation of psoriasis includes erythematous hyperkeratotic plaques, usually sharply demarcated. Pediatric patients may have multiple small papules and plaques less than 1 cm in size – “drop-size” – known as guttate lesions. Scalp and facial involvement are common in children. Chronic, inflamed plaques with coarse scale can involve ears, elbows, knees, and umbilicus, and nail changes can include pits, ridges, hyperkeratosis, and onycholysis or “oil spots.” While the diagnosis is clinical, biopsy can sometimes be useful to distinguish psoriasis from other papulosquamous conditions. Psoriasis in children is associated with obesity, higher rates of cardiovascular disease over a lifetime, as well as arthritis and mental health disorders.²
 

What’s the differential diagnosis?

The differential diagnosis for psoriasis can include papulosquamous diseases such as nummular eczema, pityriasis rosea, and pityriasis rubra pilaris. Tinea corporis may also be considered.

Nummular eczema, also known as “discoid eczema” is characterized by multiple pruritic, coin-shaped, eczematous lesions that may be actively oozing. The term “nummular” is derived from the Latin for “coin,” as lesions are distinct and annular. It is commonly associated with atopic dermatitis, and may be seen with contact dermatitis as well. Oozing, lichenification, hyperpigmentation and limited extent of skin coverage can help distinguish nummular dermatitis from psoriasis.

Pityriasis rosea is a common self-limited disease that is characterized by the appearance of acute, oval, papulosquamous patches on the trunk and proximal areas of the extremities. It usually begins with a characteristic “herald” patch, a single round or oval, sharply demarcated, pink lesion on the chest, neck, or back. Pityriasis rosea and guttate psoriasis may show similar clinical findings but the latter lacks a herald patch and is often preceded by streptococcal throat infection.

Pityriasis rubra pilaris is a rarer inflammatory disease characterized by follicular, hyperkeratotic papules, thick orange waxy palms (palmoplantar keratoderma), and erythroderma. It can also cause hair loss, nail changes, and itching. The rash shows areas with no involvement, “islands of sparing,” which is a signature characteristic of pityriasis rubra pilaris. Skin biopsies are an important diagnostic tool for pityriasis rubra pilaris. In the case of circumscribed pityriasis rubra pilaris, it may look similar to psoriasis, but it can be differentiated in that it is often accompanied by characteristic follicular papules and involvement of the palms, which are more waxy and orange in color.

When evaluating annular scaly patches, it is always important to consider tinea corporis. Tinea corporis will commonly have an annular border of scale with relative clearing in the center of lesions. In addition, when topical corticosteroids are used for prolonged periods, skin fungal infections can develop into “tinea incognito,” with paradoxical worsening since the immune response is suppressed and the fungal infection worsens.

Our patient had been previously treated with topical corticosteroids (medium to high strength) and topical calcineurin inhibitors without significant improvement. Other topical therapies for psoriasis include vitamin analogues, tazarotene, and newer therapies such as topical roflumilast (a phosphodiesterase-4 inhibitor approved for psoriasis in children over 12 years of age).^3,4 In addition, as the indications for biological agents have been expanded, there are various options for treating psoriasis in children and adolescents when more active treatment is needed. Systemic therapies for more severe disease include traditional systemic immunosuppressives (for example, methotrexate, cyclosporine) and biologic agents. The four biologic agents currently approved for children are etanercept, ustekinumab, ixekizumab, and secukinumab. Our patient was treated with ustekinumab, which is an injectable biologic agent that blocks interleukin-12/23, with good response to date.
 

Dr. Al-Nabti is a clinical fellow in the division of pediatric and adolescent dermatology; Dr. Choi is a visiting research physician in the division of pediatric and adolescent dermatology; and Dr. Eichenfield is vice-chair of the department of dermatology and professor of dermatology and pediatrics, all at the University of California, San Diego, and Rady Children’s Hospital, San Diego. They have no relevant disclosures.

References

1. Tollefson MM et al. J Am Acad Dermatol. 2010;62(6):979-87.

2. Menter A et al. J Am Acad Dermatol. 2020;82(1):161-201.

3. Mark G et al. JAMA. 2022;328(11):1073-84.

4. Eichenfield LF et al. Pediatr Dermatol. 2018;35(2):170-81.

Given the characteristic clinical presentation, the most likely diagnosis is psoriasis.

Dr. Lawrence Eichenfield

Psoriasis is a chronic immune-mediated disease that is characterized by well-demarcated thick scaly plaques on face, scalp, and intertriginous skin. Psoriasis is more common in adults than children, but the incidence of psoriasis in children has increased over time.¹ Clinical presentation of psoriasis includes erythematous hyperkeratotic plaques, usually sharply demarcated. Pediatric patients may have multiple small papules and plaques less than 1 cm in size – “drop-size” – known as guttate lesions. Scalp and facial involvement are common in children. Chronic, inflamed plaques with coarse scale can involve ears, elbows, knees, and umbilicus, and nail changes can include pits, ridges, hyperkeratosis, and onycholysis or “oil spots.” While the diagnosis is clinical, biopsy can sometimes be useful to distinguish psoriasis from other papulosquamous conditions. Psoriasis in children is associated with obesity, higher rates of cardiovascular disease over a lifetime, as well as arthritis and mental health disorders.²
 

What’s the differential diagnosis?

The differential diagnosis for psoriasis can include papulosquamous diseases such as nummular eczema, pityriasis rosea, and pityriasis rubra pilaris. Tinea corporis may also be considered.

Nummular eczema, also known as “discoid eczema” is characterized by multiple pruritic, coin-shaped, eczematous lesions that may be actively oozing. The term “nummular” is derived from the Latin for “coin,” as lesions are distinct and annular. It is commonly associated with atopic dermatitis, and may be seen with contact dermatitis as well. Oozing, lichenification, hyperpigmentation and limited extent of skin coverage can help distinguish nummular dermatitis from psoriasis.

Pityriasis rosea is a common self-limited disease that is characterized by the appearance of acute, oval, papulosquamous patches on the trunk and proximal areas of the extremities. It usually begins with a characteristic “herald” patch, a single round or oval, sharply demarcated, pink lesion on the chest, neck, or back. Pityriasis rosea and guttate psoriasis may show similar clinical findings but the latter lacks a herald patch and is often preceded by streptococcal throat infection.

Pityriasis rubra pilaris is a rarer inflammatory disease characterized by follicular, hyperkeratotic papules, thick orange waxy palms (palmoplantar keratoderma), and erythroderma. It can also cause hair loss, nail changes, and itching. The rash shows areas with no involvement, “islands of sparing,” which is a signature characteristic of pityriasis rubra pilaris. Skin biopsies are an important diagnostic tool for pityriasis rubra pilaris. In the case of circumscribed pityriasis rubra pilaris, it may look similar to psoriasis, but it can be differentiated in that it is often accompanied by characteristic follicular papules and involvement of the palms, which are more waxy and orange in color.

When evaluating annular scaly patches, it is always important to consider tinea corporis. Tinea corporis will commonly have an annular border of scale with relative clearing in the center of lesions. In addition, when topical corticosteroids are used for prolonged periods, skin fungal infections can develop into “tinea incognito,” with paradoxical worsening since the immune response is suppressed and the fungal infection worsens.

Our patient had been previously treated with topical corticosteroids (medium to high strength) and topical calcineurin inhibitors without significant improvement. Other topical therapies for psoriasis include vitamin analogues, tazarotene, and newer therapies such as topical roflumilast (a phosphodiesterase-4 inhibitor approved for psoriasis in children over 12 years of age).^3,4 In addition, as the indications for biological agents have been expanded, there are various options for treating psoriasis in children and adolescents when more active treatment is needed. Systemic therapies for more severe disease include traditional systemic immunosuppressives (for example, methotrexate, cyclosporine) and biologic agents. The four biologic agents currently approved for children are etanercept, ustekinumab, ixekizumab, and secukinumab. Our patient was treated with ustekinumab, which is an injectable biologic agent that blocks interleukin-12/23, with good response to date.
 

Dr. Al-Nabti is a clinical fellow in the division of pediatric and adolescent dermatology; Dr. Choi is a visiting research physician in the division of pediatric and adolescent dermatology; and Dr. Eichenfield is vice-chair of the department of dermatology and professor of dermatology and pediatrics, all at the University of California, San Diego, and Rady Children’s Hospital, San Diego. They have no relevant disclosures.

References

1. Tollefson MM et al. J Am Acad Dermatol. 2010;62(6):979-87.

2. Menter A et al. J Am Acad Dermatol. 2020;82(1):161-201.

3. Mark G et al. JAMA. 2022;328(11):1073-84.

4. Eichenfield LF et al. Pediatr Dermatol. 2018;35(2):170-81.

Given the characteristic clinical presentation, the most likely diagnosis is psoriasis.

Dr. Lawrence Eichenfield

Psoriasis is a chronic immune-mediated disease that is characterized by well-demarcated thick scaly plaques on face, scalp, and intertriginous skin. Psoriasis is more common in adults than children, but the incidence of psoriasis in children has increased over time.¹ Clinical presentation of psoriasis includes erythematous hyperkeratotic plaques, usually sharply demarcated. Pediatric patients may have multiple small papules and plaques less than 1 cm in size – “drop-size” – known as guttate lesions. Scalp and facial involvement are common in children. Chronic, inflamed plaques with coarse scale can involve ears, elbows, knees, and umbilicus, and nail changes can include pits, ridges, hyperkeratosis, and onycholysis or “oil spots.” While the diagnosis is clinical, biopsy can sometimes be useful to distinguish psoriasis from other papulosquamous conditions. Psoriasis in children is associated with obesity, higher rates of cardiovascular disease over a lifetime, as well as arthritis and mental health disorders.²
 

What’s the differential diagnosis?

The differential diagnosis for psoriasis can include papulosquamous diseases such as nummular eczema, pityriasis rosea, and pityriasis rubra pilaris. Tinea corporis may also be considered.

Nummular eczema, also known as “discoid eczema” is characterized by multiple pruritic, coin-shaped, eczematous lesions that may be actively oozing. The term “nummular” is derived from the Latin for “coin,” as lesions are distinct and annular. It is commonly associated with atopic dermatitis, and may be seen with contact dermatitis as well. Oozing, lichenification, hyperpigmentation and limited extent of skin coverage can help distinguish nummular dermatitis from psoriasis.

Pityriasis rosea is a common self-limited disease that is characterized by the appearance of acute, oval, papulosquamous patches on the trunk and proximal areas of the extremities. It usually begins with a characteristic “herald” patch, a single round or oval, sharply demarcated, pink lesion on the chest, neck, or back. Pityriasis rosea and guttate psoriasis may show similar clinical findings but the latter lacks a herald patch and is often preceded by streptococcal throat infection.

Pityriasis rubra pilaris is a rarer inflammatory disease characterized by follicular, hyperkeratotic papules, thick orange waxy palms (palmoplantar keratoderma), and erythroderma. It can also cause hair loss, nail changes, and itching. The rash shows areas with no involvement, “islands of sparing,” which is a signature characteristic of pityriasis rubra pilaris. Skin biopsies are an important diagnostic tool for pityriasis rubra pilaris. In the case of circumscribed pityriasis rubra pilaris, it may look similar to psoriasis, but it can be differentiated in that it is often accompanied by characteristic follicular papules and involvement of the palms, which are more waxy and orange in color.

When evaluating annular scaly patches, it is always important to consider tinea corporis. Tinea corporis will commonly have an annular border of scale with relative clearing in the center of lesions. In addition, when topical corticosteroids are used for prolonged periods, skin fungal infections can develop into “tinea incognito,” with paradoxical worsening since the immune response is suppressed and the fungal infection worsens.

Our patient had been previously treated with topical corticosteroids (medium to high strength) and topical calcineurin inhibitors without significant improvement. Other topical therapies for psoriasis include vitamin analogues, tazarotene, and newer therapies such as topical roflumilast (a phosphodiesterase-4 inhibitor approved for psoriasis in children over 12 years of age).^3,4 In addition, as the indications for biological agents have been expanded, there are various options for treating psoriasis in children and adolescents when more active treatment is needed. Systemic therapies for more severe disease include traditional systemic immunosuppressives (for example, methotrexate, cyclosporine) and biologic agents. The four biologic agents currently approved for children are etanercept, ustekinumab, ixekizumab, and secukinumab. Our patient was treated with ustekinumab, which is an injectable biologic agent that blocks interleukin-12/23, with good response to date.
 

Dr. Al-Nabti is a clinical fellow in the division of pediatric and adolescent dermatology; Dr. Choi is a visiting research physician in the division of pediatric and adolescent dermatology; and Dr. Eichenfield is vice-chair of the department of dermatology and professor of dermatology and pediatrics, all at the University of California, San Diego, and Rady Children’s Hospital, San Diego. They have no relevant disclosures.

References

1. Tollefson MM et al. J Am Acad Dermatol. 2010;62(6):979-87.

2. Menter A et al. J Am Acad Dermatol. 2020;82(1):161-201.

3. Mark G et al. JAMA. 2022;328(11):1073-84.

4. Eichenfield LF et al. Pediatr Dermatol. 2018;35(2):170-81.

Patients with psoriasis treated with interleukin-12/23 inhibitors or IL-23 inhibitors were less likely to develop inflammatory arthritis, compared with those treated with tumor necrosis factor (TNF) inhibitors, according to findings from a large retrospective study.

While previous retrospective cohort studies have found biologic therapies for psoriasis can reduce the risk of developing psoriatic arthritis when compared with other treatments such as phototherapy and oral nonbiologic disease-modifying antirheumatic drugs, this analysis is the first to compare classes of biologics, Shikha Singla, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues wrote in The Lancet Rheumatology.

In the analysis, researchers used the TriNetX database, which contains deidentified data from electronic medical health records from health care organizations across the United States. The study included adults diagnosed with psoriasis who were newly prescribed a biologic approved by the Food and Drug Administration for the treatment of psoriasis. Biologics were defined by drug class: anti-TNF, anti-IL-17, anti-IL-23, and anti–IL-12/23. Any patient with a diagnosis of psoriatic arthritis or other inflammatory arthritis prior to receiving a biologic prescription or within 2 weeks of receiving the prescription were excluded.

The researchers identified 15,501 eligible patients diagnosed with psoriasis during Jan. 1, 2014, to June 1, 2022, with an average follow-up time of 2.4 years. The researchers chose to start the study period in 2014 because the first non–anti-TNF drug for psoriatic arthritis was approved by the FDA in 2013 – the anti–IL-12/23 drug ustekinumab. During the study period, 976 patients developed inflammatory arthritis and were diagnosed on average 528 days after their biologic prescription.

In a multivariable analysis, the researchers found that patients prescribed IL-23 inhibitors (guselkumab [Tremfya], risankizumab [Skyrizi], tildrakizumab [Ilumya]) were nearly 60% less likely (adjusted hazard ratio, 0.41; 95% confidence interval, 0.17–0.95) to develop inflammatory arthritis than were patients taking TNF inhibitors (infliximab [Remicade], adalimumab [Humira], etanercept [Enbrel], golimumab [Simponi], certolizumab pegol [Cimzia]). The risk of developing arthritis was 42% lower (aHR, 0.58; 95% CI, 0.43-0.76) with the IL-12/23 inhibitor ustekinumab (Stelara), but there was no difference in outcomes among patients taking with IL-17 inhibitors (secukinumab [Cosentyx], ixekizumab [Taltz], or brodalumab [Siliq]), compared with TNF inhibitors. For the IL-12/23 inhibitor ustekinumab, all sensitivity analyses did not change this association. For IL-23 inhibitors, the results persisted when excluding patients who developed arthritis within 3 or 6 months after first biologic prescription and when using a higher diagnostic threshold for incident arthritis.

“There is a lot of interest in understanding if treatment of psoriasis will prevent onset of psoriatic arthritis,” said Joel M. Gelfand, MD, MSCE, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, who was asked to comment on the results.

“To date, the literature is inconclusive with some studies suggesting biologics reduce risk of PsA, whereas others suggest biologic use is associated with an increased risk of PsA,” he said. “The current study is unique in that it compares biologic classes to one another and suggests that IL-12/23 and IL-23 biologics are associated with a reduced risk of PsA compared to psoriasis patients treated with TNF inhibitors and no difference was found between TNF inhibitors and IL-17 inhibitors.”

While the study posed an interesting research question, “I wouldn’t use these results to actually change treatment patterns,” Alexis R. Ogdie-Beatty, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia, said in an interview. She coauthored a commentary on the analysis. Dr. Gelfand also emphasized that this bias may have influenced the results and that these findings “should not impact clinical practice at this time.”

Although the analyses were strong, Dr. Ogdie-Beatty noted, there are inherent biases in this type of observational data that cannot be overcome. For example, if a patient comes into a dermatologist’s office with psoriasis and also has joint pain, the dermatologist may suspect that a patient could also have psoriatic arthritis and would be more likely to choose a drug that will work well for both of these conditions.

“The drugs that are known to work best for psoriatic arthritis are the TNF inhibitors and the IL-17 inhibitors,” she said. So, while the analysis found these medications were associated with higher incidence of PsA, the dermatologist was possibly treating presumptive arthritis and the patient had yet to be referred to a rheumatologist to confirm the diagnosis.

The researchers noted that they attempted to mitigate these issues by requiring that patients have at least 1 year of follow-up before receiving biologic prescription “to capture only the patients with no previous codes for any type of arthritis,” as well as conducting six sensitivity analyses.

The authors, and Dr. Ogdie-Beatty and Dr. Gelfand agreed that more research is necessary to confirm these findings. A large randomized trial may be “prohibitively expensive,” the authors noted, but pooled analyses from previous clinical trials may help with this issue. “We identified 14 published randomized trials that did head-to-head comparisons of different biologic classes with regard to effect on psoriasis, and these trials collectively contained data on more than 13,000 patients. Pooled analyses of these data could confirm the findings of the present study and would be adequately powered.”

But that approach also has limitations, as psoriatic arthritis was not assessed an outcome in these studies, Dr. Ogdie-Beatty noted. Randomizing patients who are already at a higher risk of developing PsA to different biologics could be one approach to address these questions without needing such a large patient population.

The study was conducted without outside funding or industry involvement. Dr. Singla reported no relevant financial relationships with industry, but several coauthors reported financial relationships with pharmaceutical companies that market biologics for psoriasis and psoriatic arthritis. Dr. Ogdie-Beatty reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB. Dr. Gelfand reported financial relationships with Abbvie, Amgen, BMS, Boehringer Ingelheim, FIDE, Lilly, Leo, Janssen Biologics, Novartis, Pfizer, and UCB. Dr. Gelfand is a deputy editor for the Journal of Investigative Dermatology.

This article was updated 3/15/23.

Patients with psoriasis treated with interleukin-12/23 inhibitors or IL-23 inhibitors were less likely to develop inflammatory arthritis, compared with those treated with tumor necrosis factor (TNF) inhibitors, according to findings from a large retrospective study.

While previous retrospective cohort studies have found biologic therapies for psoriasis can reduce the risk of developing psoriatic arthritis when compared with other treatments such as phototherapy and oral nonbiologic disease-modifying antirheumatic drugs, this analysis is the first to compare classes of biologics, Shikha Singla, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues wrote in The Lancet Rheumatology.

In the analysis, researchers used the TriNetX database, which contains deidentified data from electronic medical health records from health care organizations across the United States. The study included adults diagnosed with psoriasis who were newly prescribed a biologic approved by the Food and Drug Administration for the treatment of psoriasis. Biologics were defined by drug class: anti-TNF, anti-IL-17, anti-IL-23, and anti–IL-12/23. Any patient with a diagnosis of psoriatic arthritis or other inflammatory arthritis prior to receiving a biologic prescription or within 2 weeks of receiving the prescription were excluded.

The researchers identified 15,501 eligible patients diagnosed with psoriasis during Jan. 1, 2014, to June 1, 2022, with an average follow-up time of 2.4 years. The researchers chose to start the study period in 2014 because the first non–anti-TNF drug for psoriatic arthritis was approved by the FDA in 2013 – the anti–IL-12/23 drug ustekinumab. During the study period, 976 patients developed inflammatory arthritis and were diagnosed on average 528 days after their biologic prescription.

In a multivariable analysis, the researchers found that patients prescribed IL-23 inhibitors (guselkumab [Tremfya], risankizumab [Skyrizi], tildrakizumab [Ilumya]) were nearly 60% less likely (adjusted hazard ratio, 0.41; 95% confidence interval, 0.17–0.95) to develop inflammatory arthritis than were patients taking TNF inhibitors (infliximab [Remicade], adalimumab [Humira], etanercept [Enbrel], golimumab [Simponi], certolizumab pegol [Cimzia]). The risk of developing arthritis was 42% lower (aHR, 0.58; 95% CI, 0.43-0.76) with the IL-12/23 inhibitor ustekinumab (Stelara), but there was no difference in outcomes among patients taking with IL-17 inhibitors (secukinumab [Cosentyx], ixekizumab [Taltz], or brodalumab [Siliq]), compared with TNF inhibitors. For the IL-12/23 inhibitor ustekinumab, all sensitivity analyses did not change this association. For IL-23 inhibitors, the results persisted when excluding patients who developed arthritis within 3 or 6 months after first biologic prescription and when using a higher diagnostic threshold for incident arthritis.

“There is a lot of interest in understanding if treatment of psoriasis will prevent onset of psoriatic arthritis,” said Joel M. Gelfand, MD, MSCE, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, who was asked to comment on the results.

“To date, the literature is inconclusive with some studies suggesting biologics reduce risk of PsA, whereas others suggest biologic use is associated with an increased risk of PsA,” he said. “The current study is unique in that it compares biologic classes to one another and suggests that IL-12/23 and IL-23 biologics are associated with a reduced risk of PsA compared to psoriasis patients treated with TNF inhibitors and no difference was found between TNF inhibitors and IL-17 inhibitors.”

While the study posed an interesting research question, “I wouldn’t use these results to actually change treatment patterns,” Alexis R. Ogdie-Beatty, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia, said in an interview. She coauthored a commentary on the analysis. Dr. Gelfand also emphasized that this bias may have influenced the results and that these findings “should not impact clinical practice at this time.”

Although the analyses were strong, Dr. Ogdie-Beatty noted, there are inherent biases in this type of observational data that cannot be overcome. For example, if a patient comes into a dermatologist’s office with psoriasis and also has joint pain, the dermatologist may suspect that a patient could also have psoriatic arthritis and would be more likely to choose a drug that will work well for both of these conditions.

“The drugs that are known to work best for psoriatic arthritis are the TNF inhibitors and the IL-17 inhibitors,” she said. So, while the analysis found these medications were associated with higher incidence of PsA, the dermatologist was possibly treating presumptive arthritis and the patient had yet to be referred to a rheumatologist to confirm the diagnosis.

The researchers noted that they attempted to mitigate these issues by requiring that patients have at least 1 year of follow-up before receiving biologic prescription “to capture only the patients with no previous codes for any type of arthritis,” as well as conducting six sensitivity analyses.

The authors, and Dr. Ogdie-Beatty and Dr. Gelfand agreed that more research is necessary to confirm these findings. A large randomized trial may be “prohibitively expensive,” the authors noted, but pooled analyses from previous clinical trials may help with this issue. “We identified 14 published randomized trials that did head-to-head comparisons of different biologic classes with regard to effect on psoriasis, and these trials collectively contained data on more than 13,000 patients. Pooled analyses of these data could confirm the findings of the present study and would be adequately powered.”

But that approach also has limitations, as psoriatic arthritis was not assessed an outcome in these studies, Dr. Ogdie-Beatty noted. Randomizing patients who are already at a higher risk of developing PsA to different biologics could be one approach to address these questions without needing such a large patient population.

The study was conducted without outside funding or industry involvement. Dr. Singla reported no relevant financial relationships with industry, but several coauthors reported financial relationships with pharmaceutical companies that market biologics for psoriasis and psoriatic arthritis. Dr. Ogdie-Beatty reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB. Dr. Gelfand reported financial relationships with Abbvie, Amgen, BMS, Boehringer Ingelheim, FIDE, Lilly, Leo, Janssen Biologics, Novartis, Pfizer, and UCB. Dr. Gelfand is a deputy editor for the Journal of Investigative Dermatology.

This article was updated 3/15/23.

Patients with psoriasis treated with interleukin-12/23 inhibitors or IL-23 inhibitors were less likely to develop inflammatory arthritis, compared with those treated with tumor necrosis factor (TNF) inhibitors, according to findings from a large retrospective study.

While previous retrospective cohort studies have found biologic therapies for psoriasis can reduce the risk of developing psoriatic arthritis when compared with other treatments such as phototherapy and oral nonbiologic disease-modifying antirheumatic drugs, this analysis is the first to compare classes of biologics, Shikha Singla, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues wrote in The Lancet Rheumatology.

In the analysis, researchers used the TriNetX database, which contains deidentified data from electronic medical health records from health care organizations across the United States. The study included adults diagnosed with psoriasis who were newly prescribed a biologic approved by the Food and Drug Administration for the treatment of psoriasis. Biologics were defined by drug class: anti-TNF, anti-IL-17, anti-IL-23, and anti–IL-12/23. Any patient with a diagnosis of psoriatic arthritis or other inflammatory arthritis prior to receiving a biologic prescription or within 2 weeks of receiving the prescription were excluded.

The researchers identified 15,501 eligible patients diagnosed with psoriasis during Jan. 1, 2014, to June 1, 2022, with an average follow-up time of 2.4 years. The researchers chose to start the study period in 2014 because the first non–anti-TNF drug for psoriatic arthritis was approved by the FDA in 2013 – the anti–IL-12/23 drug ustekinumab. During the study period, 976 patients developed inflammatory arthritis and were diagnosed on average 528 days after their biologic prescription.

In a multivariable analysis, the researchers found that patients prescribed IL-23 inhibitors (guselkumab [Tremfya], risankizumab [Skyrizi], tildrakizumab [Ilumya]) were nearly 60% less likely (adjusted hazard ratio, 0.41; 95% confidence interval, 0.17–0.95) to develop inflammatory arthritis than were patients taking TNF inhibitors (infliximab [Remicade], adalimumab [Humira], etanercept [Enbrel], golimumab [Simponi], certolizumab pegol [Cimzia]). The risk of developing arthritis was 42% lower (aHR, 0.58; 95% CI, 0.43-0.76) with the IL-12/23 inhibitor ustekinumab (Stelara), but there was no difference in outcomes among patients taking with IL-17 inhibitors (secukinumab [Cosentyx], ixekizumab [Taltz], or brodalumab [Siliq]), compared with TNF inhibitors. For the IL-12/23 inhibitor ustekinumab, all sensitivity analyses did not change this association. For IL-23 inhibitors, the results persisted when excluding patients who developed arthritis within 3 or 6 months after first biologic prescription and when using a higher diagnostic threshold for incident arthritis.

“There is a lot of interest in understanding if treatment of psoriasis will prevent onset of psoriatic arthritis,” said Joel M. Gelfand, MD, MSCE, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, who was asked to comment on the results.

“To date, the literature is inconclusive with some studies suggesting biologics reduce risk of PsA, whereas others suggest biologic use is associated with an increased risk of PsA,” he said. “The current study is unique in that it compares biologic classes to one another and suggests that IL-12/23 and IL-23 biologics are associated with a reduced risk of PsA compared to psoriasis patients treated with TNF inhibitors and no difference was found between TNF inhibitors and IL-17 inhibitors.”

While the study posed an interesting research question, “I wouldn’t use these results to actually change treatment patterns,” Alexis R. Ogdie-Beatty, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia, said in an interview. She coauthored a commentary on the analysis. Dr. Gelfand also emphasized that this bias may have influenced the results and that these findings “should not impact clinical practice at this time.”

Although the analyses were strong, Dr. Ogdie-Beatty noted, there are inherent biases in this type of observational data that cannot be overcome. For example, if a patient comes into a dermatologist’s office with psoriasis and also has joint pain, the dermatologist may suspect that a patient could also have psoriatic arthritis and would be more likely to choose a drug that will work well for both of these conditions.

“The drugs that are known to work best for psoriatic arthritis are the TNF inhibitors and the IL-17 inhibitors,” she said. So, while the analysis found these medications were associated with higher incidence of PsA, the dermatologist was possibly treating presumptive arthritis and the patient had yet to be referred to a rheumatologist to confirm the diagnosis.

The researchers noted that they attempted to mitigate these issues by requiring that patients have at least 1 year of follow-up before receiving biologic prescription “to capture only the patients with no previous codes for any type of arthritis,” as well as conducting six sensitivity analyses.

The authors, and Dr. Ogdie-Beatty and Dr. Gelfand agreed that more research is necessary to confirm these findings. A large randomized trial may be “prohibitively expensive,” the authors noted, but pooled analyses from previous clinical trials may help with this issue. “We identified 14 published randomized trials that did head-to-head comparisons of different biologic classes with regard to effect on psoriasis, and these trials collectively contained data on more than 13,000 patients. Pooled analyses of these data could confirm the findings of the present study and would be adequately powered.”

But that approach also has limitations, as psoriatic arthritis was not assessed an outcome in these studies, Dr. Ogdie-Beatty noted. Randomizing patients who are already at a higher risk of developing PsA to different biologics could be one approach to address these questions without needing such a large patient population.

The study was conducted without outside funding or industry involvement. Dr. Singla reported no relevant financial relationships with industry, but several coauthors reported financial relationships with pharmaceutical companies that market biologics for psoriasis and psoriatic arthritis. Dr. Ogdie-Beatty reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB. Dr. Gelfand reported financial relationships with Abbvie, Amgen, BMS, Boehringer Ingelheim, FIDE, Lilly, Leo, Janssen Biologics, Novartis, Pfizer, and UCB. Dr. Gelfand is a deputy editor for the Journal of Investigative Dermatology.

This article was updated 3/15/23.

Sleep deprivation can increase emotional distress and mood disorders; reduce quality of life; and lead to cognitive, memory, and performance deficits.¹ Military service predisposes members to disordered sleep due to the rigors of deployments and field training, such as long shifts, shift changes, stressful work environments, and time zone changes. Evidence shows that sleep deprivation is associated with cardiovascular disease, gastrointestinal disease, and some cancers.² We explore multiple mechanisms by which sleep deprivation may affect the skin. We also review the potential impacts of sleep deprivation on specific topics in dermatology, including atopic dermatitis (AD), psoriasis, alopecia areata, physical attractiveness, wound healing, and skin cancer.

Sleep and Military Service

Approximately 35.2% of Americans experience short sleep duration, which the Centers for Disease Control and Prevention defines as sleeping fewer than 7 hours per 24-hour period.³ Short sleep duration is even more common among individuals working in protective services and the military (50.4%).⁴ United States military service members experience multiple contributors to disordered sleep, including combat operations, shift work, psychiatric disorders such as posttraumatic stress disorder, and traumatic brain injury.⁵ Bramoweth and Germain⁶ described the case of a 27-year-old man who served 2 combat tours as an infantryman in Afghanistan, during which time he routinely remained awake for more than 24 hours at a time due to night missions and extended operations. Even when he was not directly involved in combat operations, he was rarely able to keep a regular sleep schedule.⁶ Service members returning from deployment also report decreased sleep. In one study (N=2717), 43% of respondents reported short sleep duration (<7 hours of sleep per night) and 29% reported very short sleep duration (<6 hours of sleep per night).⁷ Even stateside, service members experience acute sleep deprivation during training.⁸

Sleep and Skin

The idea that skin conditions can affect quality of sleep is not controversial. Pruritus, pain, and emotional distress associated with different dermatologic conditions have all been implicated in adversely affecting sleep.⁹ Given the effects of sleep deprivation on other organ systems, it also can affect the skin. Possible mechanisms of action include negative effects of sleep deprivation on the hypothalamic-pituitary-adrenal (HPA) axis, cutaneous barrier function, and immune function. First, the HPA axis activity follows a circadian rhythm.¹⁰ Activation outside of the bounds of this normal rhythm can have adverse effects on sleep. Alternatively, sleep deprivation and decreased sleep quality can negatively affect the HPA axis.¹⁰ These changes can adversely affect cutaneous barrier and immune function.¹¹ Cutaneous barrier function is vitally important in the context of inflammatory dermatologic conditions. Transepidermal water loss, a measurement used to estimate cutaneous barrier function, is increased by sleep deprivation.¹² Finally, the cutaneous immune system is an important component of inflammatory dermatologic conditions, cancer immune surveillance, and wound healing, and it also is negatively impacted by sleep deprivation.¹³ This framework of sleep deprivation affecting the HPA axis, cutaneous barrier function, and cutaneous immune function will help to guide the following discussion on the effects of decreased sleep on specific dermatologic conditions.

Atopic Dermatitis—Individuals with AD are at higher odds of having insomnia, fatigue, and overall poorer health status, including more sick days and increased visits to a physician.¹⁴ Additionally, it is possible that the relationship between AD and sleep is not unidirectional. Chang and Chiang¹⁵ discussed the possibility of sleep disturbances contributing to AD flares and listed 3 possible mechanisms by which sleep disturbance could potentially flare AD: exacerbation of the itch-scratch cycle; changes in the immune system, including a possible shift to helper T cell (T_H2) dominance; and worsening of chronic stress in patients with AD. These changes may lead to a vicious cycle of impaired sleep and AD exacerbations. It may be helpful to view sleep impairment and AD as comorbid conditions requiring co-management for optimal outcomes. This perspective has military relevance because even without considering sleep deprivation, deployment and field conditions are known to increase the risk for AD flares.¹⁶

Psoriasis—Psoriasis also may have a bidirectional relationship with sleep. A study utilizing data from the Nurses’ Health Study showed that working a night shift increased the risk for psoriasis.¹⁷ Importantly, this connection is associative and not causative. It is possible that other factors in those who worked night shifts such as probable decreased UV exposure or reported increased body mass index played a role. Studies using psoriasis mice models have shown increased inflammation with sleep deprivation.¹⁸ Another possible connection is the effect of sleep deprivation on the gut microbiome. Sleep dysfunction is associated with altered gut bacteria ratios, and similar gut bacteria ratios were found in patients with psoriasis, which may indicate an association between sleep deprivation and psoriasis disease progression.¹⁹ There also is an increased association of obstructive sleep apnea in patients with psoriasis compared to the general population.²⁰ Fortunately, the rate of consultations for psoriasis in deployed soldiers in the last several conflicts has been quite low, making up only 2.1% of diagnosed dermatologic conditions,²¹ which is because service members with moderate to severe psoriasis likely will not be deployed.

Alopecia Areata—Alopecia areata also may be associated with sleep deprivation. A large retrospective cohort study looking at the risk for alopecia in patients with sleep disorders showed that a sleep disorder was an independent risk factor for alopecia areata.²² The impact of sleep on the HPA axis portrays a possible mechanism for the negative effects of sleep deprivation on the immune system. Interestingly, in this study, the association was strongest for the 0- to 24-year-old age group. According to the 2020 demographics profile of the military community, 45% of active-duty personnel are 25 years or younger.²³ Fortunately, although alopecia areata can be a distressing condition, it should not have much effect on military readiness, as most individuals with this diagnosis are still deployable.

Physical Appearance—Studies where raters evaluate photographs of sleep-deprived and well-rested individuals have shown that sleep-deprived individuals are more likely to be perceived as looking sad and/or having hanging eyelids, red and/or swollen eyes, wrinkles around the eyes, dark circles around the eyes, pale skin, and/or droopy corners of the mouth.²⁴ Additionally, raters indicated that they perceived the sleep-deprived individuals as less attractive, less healthy, and more sleepy and were less inclined to socialize with them.²⁵ Interestingly, attempts to objectively quantify the differences between the 2 groups have been less clear.^26,27 Although the research is not yet definitive, it is feasible to assume that sleep deprivation is recognizable, and negative perceptions may be manifested about the sleep-deprived individual’s appearance. This can have substantial social implications given the perception that individuals who are viewed as more attractive also tend to be perceived as more competent.²⁸ In the context of the military, this concept becomes highly relevant when promotions are considered. For some noncommissioned officer promotions in the US Army, the soldier will present in person before a board of superiors who will “determine their potential to serve at the recommended rank.” Army doctrine instructs the board members to “consider the Soldier’s overall personal appearance, bearing, self-confidence, oral expression and conversational skills, and attitude when determining each Soldier’s potential.”²⁹ In this context, a sleep-deprived soldier would be at a very real disadvantage for a promotion based on their appearance, even if the other cognitive effects of sleep deprivation are not considered.

Final Thoughts

Although more research is needed, there is evidence that sleep deprivation can negatively affect the skin. Randomized controlled trials looking at groups of individuals with specific dermatologic conditions with a very short sleep duration group (<6 hours of sleep per night), short sleep duration group (<7 hours of sleep per night), and a well-rested group (>7 hours of sleep per night) could be very helpful in this endeavor. Possible mechanisms include the HPA axis, immune system, and skin barrier function that are associated with sleep deprivation. Specific dermatologic conditions that may be affected by sleep deprivation include AD, psoriasis, alopecia areata, physical appearance, wound healing, and skin cancer. The impact of sleep deprivation on dermatologic conditions is particularly relevant to the military, as service members are at an increased risk for short sleep duration. It is possible that improving sleep may lead to better disease control for many dermatologic conditions.

Sleep deprivation can increase emotional distress and mood disorders; reduce quality of life; and lead to cognitive, memory, and performance deficits.¹ Military service predisposes members to disordered sleep due to the rigors of deployments and field training, such as long shifts, shift changes, stressful work environments, and time zone changes. Evidence shows that sleep deprivation is associated with cardiovascular disease, gastrointestinal disease, and some cancers.² We explore multiple mechanisms by which sleep deprivation may affect the skin. We also review the potential impacts of sleep deprivation on specific topics in dermatology, including atopic dermatitis (AD), psoriasis, alopecia areata, physical attractiveness, wound healing, and skin cancer.

Sleep and Military Service

Approximately 35.2% of Americans experience short sleep duration, which the Centers for Disease Control and Prevention defines as sleeping fewer than 7 hours per 24-hour period.³ Short sleep duration is even more common among individuals working in protective services and the military (50.4%).⁴ United States military service members experience multiple contributors to disordered sleep, including combat operations, shift work, psychiatric disorders such as posttraumatic stress disorder, and traumatic brain injury.⁵ Bramoweth and Germain⁶ described the case of a 27-year-old man who served 2 combat tours as an infantryman in Afghanistan, during which time he routinely remained awake for more than 24 hours at a time due to night missions and extended operations. Even when he was not directly involved in combat operations, he was rarely able to keep a regular sleep schedule.⁶ Service members returning from deployment also report decreased sleep. In one study (N=2717), 43% of respondents reported short sleep duration (<7 hours of sleep per night) and 29% reported very short sleep duration (<6 hours of sleep per night).⁷ Even stateside, service members experience acute sleep deprivation during training.⁸

Sleep and Skin

The idea that skin conditions can affect quality of sleep is not controversial. Pruritus, pain, and emotional distress associated with different dermatologic conditions have all been implicated in adversely affecting sleep.⁹ Given the effects of sleep deprivation on other organ systems, it also can affect the skin. Possible mechanisms of action include negative effects of sleep deprivation on the hypothalamic-pituitary-adrenal (HPA) axis, cutaneous barrier function, and immune function. First, the HPA axis activity follows a circadian rhythm.¹⁰ Activation outside of the bounds of this normal rhythm can have adverse effects on sleep. Alternatively, sleep deprivation and decreased sleep quality can negatively affect the HPA axis.¹⁰ These changes can adversely affect cutaneous barrier and immune function.¹¹ Cutaneous barrier function is vitally important in the context of inflammatory dermatologic conditions. Transepidermal water loss, a measurement used to estimate cutaneous barrier function, is increased by sleep deprivation.¹² Finally, the cutaneous immune system is an important component of inflammatory dermatologic conditions, cancer immune surveillance, and wound healing, and it also is negatively impacted by sleep deprivation.¹³ This framework of sleep deprivation affecting the HPA axis, cutaneous barrier function, and cutaneous immune function will help to guide the following discussion on the effects of decreased sleep on specific dermatologic conditions.

Atopic Dermatitis—Individuals with AD are at higher odds of having insomnia, fatigue, and overall poorer health status, including more sick days and increased visits to a physician.¹⁴ Additionally, it is possible that the relationship between AD and sleep is not unidirectional. Chang and Chiang¹⁵ discussed the possibility of sleep disturbances contributing to AD flares and listed 3 possible mechanisms by which sleep disturbance could potentially flare AD: exacerbation of the itch-scratch cycle; changes in the immune system, including a possible shift to helper T cell (T_H2) dominance; and worsening of chronic stress in patients with AD. These changes may lead to a vicious cycle of impaired sleep and AD exacerbations. It may be helpful to view sleep impairment and AD as comorbid conditions requiring co-management for optimal outcomes. This perspective has military relevance because even without considering sleep deprivation, deployment and field conditions are known to increase the risk for AD flares.¹⁶

Psoriasis—Psoriasis also may have a bidirectional relationship with sleep. A study utilizing data from the Nurses’ Health Study showed that working a night shift increased the risk for psoriasis.¹⁷ Importantly, this connection is associative and not causative. It is possible that other factors in those who worked night shifts such as probable decreased UV exposure or reported increased body mass index played a role. Studies using psoriasis mice models have shown increased inflammation with sleep deprivation.¹⁸ Another possible connection is the effect of sleep deprivation on the gut microbiome. Sleep dysfunction is associated with altered gut bacteria ratios, and similar gut bacteria ratios were found in patients with psoriasis, which may indicate an association between sleep deprivation and psoriasis disease progression.¹⁹ There also is an increased association of obstructive sleep apnea in patients with psoriasis compared to the general population.²⁰ Fortunately, the rate of consultations for psoriasis in deployed soldiers in the last several conflicts has been quite low, making up only 2.1% of diagnosed dermatologic conditions,²¹ which is because service members with moderate to severe psoriasis likely will not be deployed.

Alopecia Areata—Alopecia areata also may be associated with sleep deprivation. A large retrospective cohort study looking at the risk for alopecia in patients with sleep disorders showed that a sleep disorder was an independent risk factor for alopecia areata.²² The impact of sleep on the HPA axis portrays a possible mechanism for the negative effects of sleep deprivation on the immune system. Interestingly, in this study, the association was strongest for the 0- to 24-year-old age group. According to the 2020 demographics profile of the military community, 45% of active-duty personnel are 25 years or younger.²³ Fortunately, although alopecia areata can be a distressing condition, it should not have much effect on military readiness, as most individuals with this diagnosis are still deployable.

Physical Appearance—Studies where raters evaluate photographs of sleep-deprived and well-rested individuals have shown that sleep-deprived individuals are more likely to be perceived as looking sad and/or having hanging eyelids, red and/or swollen eyes, wrinkles around the eyes, dark circles around the eyes, pale skin, and/or droopy corners of the mouth.²⁴ Additionally, raters indicated that they perceived the sleep-deprived individuals as less attractive, less healthy, and more sleepy and were less inclined to socialize with them.²⁵ Interestingly, attempts to objectively quantify the differences between the 2 groups have been less clear.^26,27 Although the research is not yet definitive, it is feasible to assume that sleep deprivation is recognizable, and negative perceptions may be manifested about the sleep-deprived individual’s appearance. This can have substantial social implications given the perception that individuals who are viewed as more attractive also tend to be perceived as more competent.²⁸ In the context of the military, this concept becomes highly relevant when promotions are considered. For some noncommissioned officer promotions in the US Army, the soldier will present in person before a board of superiors who will “determine their potential to serve at the recommended rank.” Army doctrine instructs the board members to “consider the Soldier’s overall personal appearance, bearing, self-confidence, oral expression and conversational skills, and attitude when determining each Soldier’s potential.”²⁹ In this context, a sleep-deprived soldier would be at a very real disadvantage for a promotion based on their appearance, even if the other cognitive effects of sleep deprivation are not considered.

Final Thoughts

Although more research is needed, there is evidence that sleep deprivation can negatively affect the skin. Randomized controlled trials looking at groups of individuals with specific dermatologic conditions with a very short sleep duration group (<6 hours of sleep per night), short sleep duration group (<7 hours of sleep per night), and a well-rested group (>7 hours of sleep per night) could be very helpful in this endeavor. Possible mechanisms include the HPA axis, immune system, and skin barrier function that are associated with sleep deprivation. Specific dermatologic conditions that may be affected by sleep deprivation include AD, psoriasis, alopecia areata, physical appearance, wound healing, and skin cancer. The impact of sleep deprivation on dermatologic conditions is particularly relevant to the military, as service members are at an increased risk for short sleep duration. It is possible that improving sleep may lead to better disease control for many dermatologic conditions.

Sleep deprivation can increase emotional distress and mood disorders; reduce quality of life; and lead to cognitive, memory, and performance deficits.¹ Military service predisposes members to disordered sleep due to the rigors of deployments and field training, such as long shifts, shift changes, stressful work environments, and time zone changes. Evidence shows that sleep deprivation is associated with cardiovascular disease, gastrointestinal disease, and some cancers.² We explore multiple mechanisms by which sleep deprivation may affect the skin. We also review the potential impacts of sleep deprivation on specific topics in dermatology, including atopic dermatitis (AD), psoriasis, alopecia areata, physical attractiveness, wound healing, and skin cancer.

Sleep and Military Service

Approximately 35.2% of Americans experience short sleep duration, which the Centers for Disease Control and Prevention defines as sleeping fewer than 7 hours per 24-hour period.³ Short sleep duration is even more common among individuals working in protective services and the military (50.4%).⁴ United States military service members experience multiple contributors to disordered sleep, including combat operations, shift work, psychiatric disorders such as posttraumatic stress disorder, and traumatic brain injury.⁵ Bramoweth and Germain⁶ described the case of a 27-year-old man who served 2 combat tours as an infantryman in Afghanistan, during which time he routinely remained awake for more than 24 hours at a time due to night missions and extended operations. Even when he was not directly involved in combat operations, he was rarely able to keep a regular sleep schedule.⁶ Service members returning from deployment also report decreased sleep. In one study (N=2717), 43% of respondents reported short sleep duration (<7 hours of sleep per night) and 29% reported very short sleep duration (<6 hours of sleep per night).⁷ Even stateside, service members experience acute sleep deprivation during training.⁸

Sleep and Skin

The idea that skin conditions can affect quality of sleep is not controversial. Pruritus, pain, and emotional distress associated with different dermatologic conditions have all been implicated in adversely affecting sleep.⁹ Given the effects of sleep deprivation on other organ systems, it also can affect the skin. Possible mechanisms of action include negative effects of sleep deprivation on the hypothalamic-pituitary-adrenal (HPA) axis, cutaneous barrier function, and immune function. First, the HPA axis activity follows a circadian rhythm.¹⁰ Activation outside of the bounds of this normal rhythm can have adverse effects on sleep. Alternatively, sleep deprivation and decreased sleep quality can negatively affect the HPA axis.¹⁰ These changes can adversely affect cutaneous barrier and immune function.¹¹ Cutaneous barrier function is vitally important in the context of inflammatory dermatologic conditions. Transepidermal water loss, a measurement used to estimate cutaneous barrier function, is increased by sleep deprivation.¹² Finally, the cutaneous immune system is an important component of inflammatory dermatologic conditions, cancer immune surveillance, and wound healing, and it also is negatively impacted by sleep deprivation.¹³ This framework of sleep deprivation affecting the HPA axis, cutaneous barrier function, and cutaneous immune function will help to guide the following discussion on the effects of decreased sleep on specific dermatologic conditions.

Atopic Dermatitis—Individuals with AD are at higher odds of having insomnia, fatigue, and overall poorer health status, including more sick days and increased visits to a physician.¹⁴ Additionally, it is possible that the relationship between AD and sleep is not unidirectional. Chang and Chiang¹⁵ discussed the possibility of sleep disturbances contributing to AD flares and listed 3 possible mechanisms by which sleep disturbance could potentially flare AD: exacerbation of the itch-scratch cycle; changes in the immune system, including a possible shift to helper T cell (T_H2) dominance; and worsening of chronic stress in patients with AD. These changes may lead to a vicious cycle of impaired sleep and AD exacerbations. It may be helpful to view sleep impairment and AD as comorbid conditions requiring co-management for optimal outcomes. This perspective has military relevance because even without considering sleep deprivation, deployment and field conditions are known to increase the risk for AD flares.¹⁶

Psoriasis—Psoriasis also may have a bidirectional relationship with sleep. A study utilizing data from the Nurses’ Health Study showed that working a night shift increased the risk for psoriasis.¹⁷ Importantly, this connection is associative and not causative. It is possible that other factors in those who worked night shifts such as probable decreased UV exposure or reported increased body mass index played a role. Studies using psoriasis mice models have shown increased inflammation with sleep deprivation.¹⁸ Another possible connection is the effect of sleep deprivation on the gut microbiome. Sleep dysfunction is associated with altered gut bacteria ratios, and similar gut bacteria ratios were found in patients with psoriasis, which may indicate an association between sleep deprivation and psoriasis disease progression.¹⁹ There also is an increased association of obstructive sleep apnea in patients with psoriasis compared to the general population.²⁰ Fortunately, the rate of consultations for psoriasis in deployed soldiers in the last several conflicts has been quite low, making up only 2.1% of diagnosed dermatologic conditions,²¹ which is because service members with moderate to severe psoriasis likely will not be deployed.

Alopecia Areata—Alopecia areata also may be associated with sleep deprivation. A large retrospective cohort study looking at the risk for alopecia in patients with sleep disorders showed that a sleep disorder was an independent risk factor for alopecia areata.²² The impact of sleep on the HPA axis portrays a possible mechanism for the negative effects of sleep deprivation on the immune system. Interestingly, in this study, the association was strongest for the 0- to 24-year-old age group. According to the 2020 demographics profile of the military community, 45% of active-duty personnel are 25 years or younger.²³ Fortunately, although alopecia areata can be a distressing condition, it should not have much effect on military readiness, as most individuals with this diagnosis are still deployable.

Physical Appearance—Studies where raters evaluate photographs of sleep-deprived and well-rested individuals have shown that sleep-deprived individuals are more likely to be perceived as looking sad and/or having hanging eyelids, red and/or swollen eyes, wrinkles around the eyes, dark circles around the eyes, pale skin, and/or droopy corners of the mouth.²⁴ Additionally, raters indicated that they perceived the sleep-deprived individuals as less attractive, less healthy, and more sleepy and were less inclined to socialize with them.²⁵ Interestingly, attempts to objectively quantify the differences between the 2 groups have been less clear.^26,27 Although the research is not yet definitive, it is feasible to assume that sleep deprivation is recognizable, and negative perceptions may be manifested about the sleep-deprived individual’s appearance. This can have substantial social implications given the perception that individuals who are viewed as more attractive also tend to be perceived as more competent.²⁸ In the context of the military, this concept becomes highly relevant when promotions are considered. For some noncommissioned officer promotions in the US Army, the soldier will present in person before a board of superiors who will “determine their potential to serve at the recommended rank.” Army doctrine instructs the board members to “consider the Soldier’s overall personal appearance, bearing, self-confidence, oral expression and conversational skills, and attitude when determining each Soldier’s potential.”²⁹ In this context, a sleep-deprived soldier would be at a very real disadvantage for a promotion based on their appearance, even if the other cognitive effects of sleep deprivation are not considered.

Final Thoughts

Although more research is needed, there is evidence that sleep deprivation can negatively affect the skin. Randomized controlled trials looking at groups of individuals with specific dermatologic conditions with a very short sleep duration group (<6 hours of sleep per night), short sleep duration group (<7 hours of sleep per night), and a well-rested group (>7 hours of sleep per night) could be very helpful in this endeavor. Possible mechanisms include the HPA axis, immune system, and skin barrier function that are associated with sleep deprivation. Specific dermatologic conditions that may be affected by sleep deprivation include AD, psoriasis, alopecia areata, physical appearance, wound healing, and skin cancer. The impact of sleep deprivation on dermatologic conditions is particularly relevant to the military, as service members are at an increased risk for short sleep duration. It is possible that improving sleep may lead to better disease control for many dermatologic conditions.

The often-delayed diagnosis of isolated nail psoriasis (NP), along with the possibility of a “reciprocal relationship” with psoriatic arthritis, “should serve as an impetus for dermatologists to improve their diagnostic accuracy,” investigators said in a research letter.

Diagnosis of isolated NP was delayed by almost 3 years among the 87 cases recorded and “arthritis was most often diagnosed concurrently with NP,” at a major nail referral center between Jan. 1, 2001, and Dec. 21, 2022, Michelle J. Chang of Drexel University, Philadelphia, and associates reported.

In what the authors say is, “the largest study documenting clinical and histologic features in patients with isolated NP,” the two most common clinical features were onycholysis and nail plate pitting, seen in 79% and 70% of cases, respectively. No other single feature had a prevalence higher than 28%.

The most frequent clinical dyad was onycholysis and pitting in 66% of patients, followed by onycholysis/nail thickening in 33% and onycholysis/splinter hemorrhage in 32%. The most common histologic features were parakeratosis in 79% and neutrophil infiltration in 48%, the investigators said.

Psoriatic arthritis (PsA), a focus of the study, occurred in 10 (11%) of the 87 individuals with isolated NP. Considering this finding, and “the close proximity between the nail apparatus and joint, we hypothesize a reciprocal relationship, with nail unit inflammation precipitating PsA,” Ms. Chang and associates wrote.

Senior author, Shari Lipner, MD, PhD, of the department of dermatology, Weill Cornell Medicine, New York, is a consultant for Ortho-Dermatologics, Hoth Therapeutics, and BelleTorus. Ms. Chang and the two other investigators had no conflicts of interest to declare.

 

The often-delayed diagnosis of isolated nail psoriasis (NP), along with the possibility of a “reciprocal relationship” with psoriatic arthritis, “should serve as an impetus for dermatologists to improve their diagnostic accuracy,” investigators said in a research letter.

Diagnosis of isolated NP was delayed by almost 3 years among the 87 cases recorded and “arthritis was most often diagnosed concurrently with NP,” at a major nail referral center between Jan. 1, 2001, and Dec. 21, 2022, Michelle J. Chang of Drexel University, Philadelphia, and associates reported.

In what the authors say is, “the largest study documenting clinical and histologic features in patients with isolated NP,” the two most common clinical features were onycholysis and nail plate pitting, seen in 79% and 70% of cases, respectively. No other single feature had a prevalence higher than 28%.

The most frequent clinical dyad was onycholysis and pitting in 66% of patients, followed by onycholysis/nail thickening in 33% and onycholysis/splinter hemorrhage in 32%. The most common histologic features were parakeratosis in 79% and neutrophil infiltration in 48%, the investigators said.

Psoriatic arthritis (PsA), a focus of the study, occurred in 10 (11%) of the 87 individuals with isolated NP. Considering this finding, and “the close proximity between the nail apparatus and joint, we hypothesize a reciprocal relationship, with nail unit inflammation precipitating PsA,” Ms. Chang and associates wrote.

Senior author, Shari Lipner, MD, PhD, of the department of dermatology, Weill Cornell Medicine, New York, is a consultant for Ortho-Dermatologics, Hoth Therapeutics, and BelleTorus. Ms. Chang and the two other investigators had no conflicts of interest to declare.

 

The often-delayed diagnosis of isolated nail psoriasis (NP), along with the possibility of a “reciprocal relationship” with psoriatic arthritis, “should serve as an impetus for dermatologists to improve their diagnostic accuracy,” investigators said in a research letter.

Diagnosis of isolated NP was delayed by almost 3 years among the 87 cases recorded and “arthritis was most often diagnosed concurrently with NP,” at a major nail referral center between Jan. 1, 2001, and Dec. 21, 2022, Michelle J. Chang of Drexel University, Philadelphia, and associates reported.

In what the authors say is, “the largest study documenting clinical and histologic features in patients with isolated NP,” the two most common clinical features were onycholysis and nail plate pitting, seen in 79% and 70% of cases, respectively. No other single feature had a prevalence higher than 28%.

The most frequent clinical dyad was onycholysis and pitting in 66% of patients, followed by onycholysis/nail thickening in 33% and onycholysis/splinter hemorrhage in 32%. The most common histologic features were parakeratosis in 79% and neutrophil infiltration in 48%, the investigators said.

Psoriatic arthritis (PsA), a focus of the study, occurred in 10 (11%) of the 87 individuals with isolated NP. Considering this finding, and “the close proximity between the nail apparatus and joint, we hypothesize a reciprocal relationship, with nail unit inflammation precipitating PsA,” Ms. Chang and associates wrote.

Senior author, Shari Lipner, MD, PhD, of the department of dermatology, Weill Cornell Medicine, New York, is a consultant for Ortho-Dermatologics, Hoth Therapeutics, and BelleTorus. Ms. Chang and the two other investigators had no conflicts of interest to declare.

 

HONOLULU – In the clinical experience of April W. Armstrong, MD, MPH, topical therapies typically don’t work well for nail psoriasis, so she sometimes resorts to intralesional injections combined with systemic therapy.

One might think of intralesional injections “as a torture method from the medieval days,” she said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!, but intramatricial corticosteroid injections have been performed for many years as a treatment for nail psoriasis, typically with triamcinolone acetonide.

Doug Brunk/MDedge News

According to Dr. Armstrong, professor of dermatology and associate dean of clinical research at the University of Southern California, Los Angeles, nail matrix psoriasis can present as pitting, leukonychia, red macules in the lunula, crumbling, or trachyonychia. Nail bed psoriasis can present as splinter hemorrhages and onycholysis, hyperkeratosis and splinter hemorrhages, salmon patch or oil spot dyschromia, or onycholysis and salmon patch dyschromia.

In a German cross-sectional study of patients with psoriasis, nails were one of the body sites that have the greatest impact on quality of life – especially those in younger age groups.

While topical treatments are generally considered first for limited disease involving special areas such as the nails, systemic therapy is warranted in patients with moderate-to-severe involvement of specific sites or in those refractory to topical therapy, Dr. Armstrong said.

In 2018, Indian researchers published results from an open-label study of 17 patients, with nail psoriasis, comparing three treatments . Patients were assigned to three groups of 30 nails each and treated with intramatricial injections of triamcinolone acetonide (10 mg/mL), methotrexate (25 mg/mL), and cyclosporine (50 mg/mL), respectively. Each nail was treated with two injections at 6-week intervals and graded at 24 weeks using the Nail Psoriasis Severity Index (NAPSI). In the triamcinolone acetonide and methotrexate groups, 50% of treated nails showed a greater than 75% improvement at 24 weeks, compared with 33% of those in the cyclosporine group. The most side effects occurred in the nails treated with cyclosporine.

When Dr. Armstrong performs intramatricial injections, she uses triamcinolone acetonide at 10 mg/mL. However, she said, “my favorite way of treating severe nail psoriasis is with biologics.”

In an early study of patients with moderate to severe psoriasis treated with the tumor necrosis factor blocker adalimumab 80 mg subcutaneously at week 0, followed by 40 mg subcutaneously every other week from weeks 1 to 15, a post hoc analysis on the effects on nail psoriasis showed a 10-point decrease in the median NAPSI score through week 16 – from 21 to 11 .

In VOYAGE 2, which compared the interleukin-23 blocker guselkumab and adalimumab in patients with moderate to severe psoriasis, the mean percent improvement from baseline in the NAPSI score was similar in patients treated with adalimumab or guselkumab at week 16 (39.6% vs. 46.9%, respectively) and at week 24 (55% vs. 53.7%).

In another study of patients with nail psoriasis, researchers evaluated the efficacy of the IL-17A antagonist secukinumab 150 mg, 300 mg, or placebo at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter for 2.5 years. At 2.5 years, the mean reduction in NAPSI score was 63.6% in the secukinumab 150 mg group and 73.3% in the secukinumab 300 mg group.

“I do have to tell my patients what to expect, because the nails grow out slowly, but over time we do see this increase in efficacy,” Dr. Armstrong said.

Studies of another IL-17A antagonist, ixekizumab, have yielded positive results as well, she noted. In 2021, Taiwanese researchers published a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. They drew from 39 studies involving 15,673 patients with nail psoriasis and found that the oral Janus kinase inhibitor tofacitinib and ixekizumab had the best efficacy for treating nail psoriasis in 10-16 weeks and 24-26 weeks, respectively.

“They found that overall, the biologics have a good effect on nail psoriasis and that the treatment effects are overall quite similar,” Dr. Armstrong said.

Dr. Armstrong disclosed that she is a consultant or adviser for numerous pharmaceutical companies. She has also received research funding from Bristol-Myers Squibb, Dermavant, Dermira, Leo, Lilly, Pfizer, and UCB Pharma.

HONOLULU – In the clinical experience of April W. Armstrong, MD, MPH, topical therapies typically don’t work well for nail psoriasis, so she sometimes resorts to intralesional injections combined with systemic therapy.

One might think of intralesional injections “as a torture method from the medieval days,” she said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!, but intramatricial corticosteroid injections have been performed for many years as a treatment for nail psoriasis, typically with triamcinolone acetonide.

Doug Brunk/MDedge News

According to Dr. Armstrong, professor of dermatology and associate dean of clinical research at the University of Southern California, Los Angeles, nail matrix psoriasis can present as pitting, leukonychia, red macules in the lunula, crumbling, or trachyonychia. Nail bed psoriasis can present as splinter hemorrhages and onycholysis, hyperkeratosis and splinter hemorrhages, salmon patch or oil spot dyschromia, or onycholysis and salmon patch dyschromia.

In a German cross-sectional study of patients with psoriasis, nails were one of the body sites that have the greatest impact on quality of life – especially those in younger age groups.

While topical treatments are generally considered first for limited disease involving special areas such as the nails, systemic therapy is warranted in patients with moderate-to-severe involvement of specific sites or in those refractory to topical therapy, Dr. Armstrong said.

In 2018, Indian researchers published results from an open-label study of 17 patients, with nail psoriasis, comparing three treatments . Patients were assigned to three groups of 30 nails each and treated with intramatricial injections of triamcinolone acetonide (10 mg/mL), methotrexate (25 mg/mL), and cyclosporine (50 mg/mL), respectively. Each nail was treated with two injections at 6-week intervals and graded at 24 weeks using the Nail Psoriasis Severity Index (NAPSI). In the triamcinolone acetonide and methotrexate groups, 50% of treated nails showed a greater than 75% improvement at 24 weeks, compared with 33% of those in the cyclosporine group. The most side effects occurred in the nails treated with cyclosporine.

When Dr. Armstrong performs intramatricial injections, she uses triamcinolone acetonide at 10 mg/mL. However, she said, “my favorite way of treating severe nail psoriasis is with biologics.”

In an early study of patients with moderate to severe psoriasis treated with the tumor necrosis factor blocker adalimumab 80 mg subcutaneously at week 0, followed by 40 mg subcutaneously every other week from weeks 1 to 15, a post hoc analysis on the effects on nail psoriasis showed a 10-point decrease in the median NAPSI score through week 16 – from 21 to 11 .

In VOYAGE 2, which compared the interleukin-23 blocker guselkumab and adalimumab in patients with moderate to severe psoriasis, the mean percent improvement from baseline in the NAPSI score was similar in patients treated with adalimumab or guselkumab at week 16 (39.6% vs. 46.9%, respectively) and at week 24 (55% vs. 53.7%).

In another study of patients with nail psoriasis, researchers evaluated the efficacy of the IL-17A antagonist secukinumab 150 mg, 300 mg, or placebo at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter for 2.5 years. At 2.5 years, the mean reduction in NAPSI score was 63.6% in the secukinumab 150 mg group and 73.3% in the secukinumab 300 mg group.

“I do have to tell my patients what to expect, because the nails grow out slowly, but over time we do see this increase in efficacy,” Dr. Armstrong said.

Studies of another IL-17A antagonist, ixekizumab, have yielded positive results as well, she noted. In 2021, Taiwanese researchers published a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. They drew from 39 studies involving 15,673 patients with nail psoriasis and found that the oral Janus kinase inhibitor tofacitinib and ixekizumab had the best efficacy for treating nail psoriasis in 10-16 weeks and 24-26 weeks, respectively.

“They found that overall, the biologics have a good effect on nail psoriasis and that the treatment effects are overall quite similar,” Dr. Armstrong said.

Dr. Armstrong disclosed that she is a consultant or adviser for numerous pharmaceutical companies. She has also received research funding from Bristol-Myers Squibb, Dermavant, Dermira, Leo, Lilly, Pfizer, and UCB Pharma.

HONOLULU – In the clinical experience of April W. Armstrong, MD, MPH, topical therapies typically don’t work well for nail psoriasis, so she sometimes resorts to intralesional injections combined with systemic therapy.

One might think of intralesional injections “as a torture method from the medieval days,” she said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!, but intramatricial corticosteroid injections have been performed for many years as a treatment for nail psoriasis, typically with triamcinolone acetonide.

Doug Brunk/MDedge News

According to Dr. Armstrong, professor of dermatology and associate dean of clinical research at the University of Southern California, Los Angeles, nail matrix psoriasis can present as pitting, leukonychia, red macules in the lunula, crumbling, or trachyonychia. Nail bed psoriasis can present as splinter hemorrhages and onycholysis, hyperkeratosis and splinter hemorrhages, salmon patch or oil spot dyschromia, or onycholysis and salmon patch dyschromia.

In a German cross-sectional study of patients with psoriasis, nails were one of the body sites that have the greatest impact on quality of life – especially those in younger age groups.

While topical treatments are generally considered first for limited disease involving special areas such as the nails, systemic therapy is warranted in patients with moderate-to-severe involvement of specific sites or in those refractory to topical therapy, Dr. Armstrong said.

In 2018, Indian researchers published results from an open-label study of 17 patients, with nail psoriasis, comparing three treatments . Patients were assigned to three groups of 30 nails each and treated with intramatricial injections of triamcinolone acetonide (10 mg/mL), methotrexate (25 mg/mL), and cyclosporine (50 mg/mL), respectively. Each nail was treated with two injections at 6-week intervals and graded at 24 weeks using the Nail Psoriasis Severity Index (NAPSI). In the triamcinolone acetonide and methotrexate groups, 50% of treated nails showed a greater than 75% improvement at 24 weeks, compared with 33% of those in the cyclosporine group. The most side effects occurred in the nails treated with cyclosporine.

When Dr. Armstrong performs intramatricial injections, she uses triamcinolone acetonide at 10 mg/mL. However, she said, “my favorite way of treating severe nail psoriasis is with biologics.”

In an early study of patients with moderate to severe psoriasis treated with the tumor necrosis factor blocker adalimumab 80 mg subcutaneously at week 0, followed by 40 mg subcutaneously every other week from weeks 1 to 15, a post hoc analysis on the effects on nail psoriasis showed a 10-point decrease in the median NAPSI score through week 16 – from 21 to 11 .

In VOYAGE 2, which compared the interleukin-23 blocker guselkumab and adalimumab in patients with moderate to severe psoriasis, the mean percent improvement from baseline in the NAPSI score was similar in patients treated with adalimumab or guselkumab at week 16 (39.6% vs. 46.9%, respectively) and at week 24 (55% vs. 53.7%).

In another study of patients with nail psoriasis, researchers evaluated the efficacy of the IL-17A antagonist secukinumab 150 mg, 300 mg, or placebo at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter for 2.5 years. At 2.5 years, the mean reduction in NAPSI score was 63.6% in the secukinumab 150 mg group and 73.3% in the secukinumab 300 mg group.

“I do have to tell my patients what to expect, because the nails grow out slowly, but over time we do see this increase in efficacy,” Dr. Armstrong said.

Studies of another IL-17A antagonist, ixekizumab, have yielded positive results as well, she noted. In 2021, Taiwanese researchers published a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. They drew from 39 studies involving 15,673 patients with nail psoriasis and found that the oral Janus kinase inhibitor tofacitinib and ixekizumab had the best efficacy for treating nail psoriasis in 10-16 weeks and 24-26 weeks, respectively.

“They found that overall, the biologics have a good effect on nail psoriasis and that the treatment effects are overall quite similar,” Dr. Armstrong said.

Dr. Armstrong disclosed that she is a consultant or adviser for numerous pharmaceutical companies. She has also received research funding from Bristol-Myers Squibb, Dermavant, Dermira, Leo, Lilly, Pfizer, and UCB Pharma.

While most providers think that biosimilars will positively impact care, few feel that the economic benefits of biosimilars to date are enough to motivate switching.

Fuse/Thinkstock

In a new survey of over 350 dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, clinicians shared their opinions on the rapidly evolving landscape of biosimilars, detailing top concerns about prescribing these medications and how they presently use biosimilars in clinical practice. Across all specialties, providers said they would be most likely to prescribe biosimilars to new patients or if a patient’s health plan mandated the switch. Most providers listed concerns about biosimilar efficacy and lack of economic benefit as the main barriers to adoption of biosimilars in clinical practice.

Cardinal Health, a health care services company based in Dublin, Ohio, conducted the surveys from July through October 2022.
 

Rheumatologists want cost-savings for patients

2023 is gearing up to be a big year for biosimilars for inflammatory diseases, with at least eight adalimumab biosimilars entering the market in the United States. Amjevita, manufactured by Amgen, was the first to become commercially available on Jan. 31. Out of 103 surveyed rheumatologists, 62% said they were very comfortable prescribing biosimilars to patients, and 32% said they were somewhat comfortable. Providers said they would be most likely to prescribe a biosimilar to new patients (40%) or if biosimilars were mandated by a patient’s health plan (41%). Nearly one-third (31%) of rheumatologists said that a discount of 21%-30% from a reference product would be necessary to consider switching a patient to a biosimilar.

There are several reasons why a rheumatologist might be wary of switching patients to biosimilars, said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “Rheumatologists will always express concern about changing medications that work well for their patients. It is not ideal to ‘force switch’ to a different product, even if it is almost identical,” he told this news organization in an email. “Also, we must remember that a patient on a biologic has failed traditional medications, which speaks to the struggle a patient must endure to get their disease under control. Fail-first situations can cause a rheumatologist to be initially resistant or hesitant to any changes.”

The top concerns among rheumatologists about prescribing biosimilars were medication efficacy (36%), lack of economic benefit (24%), and evaluating when to prescribe a biosimilar versus a reference product (17%). For adalimumab biosimilars, rheumatologists said that interchangeability – a regulatory designation where a biosimilar can be automatically substituted for its reference product at the pharmacy – and citrate-free formulation were the most important product attributes. Sixty-four percent of providers also noted that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

“There needs to be a true reduction in price, to change providers’ opinions on the economic benefits of biosimilars – in the system generally and for the patient,” Dr. Snow said. “Things will get there eventually, but it is not there yet, based on the list prices we see for some biosimilars.”
 

Gastroenterologists emphasize patient education

Gastroenterology is another specialty to be affected by the influx of adalimumab biosimilars. Out of 72 surveyed gastroenterologists, 86% said they were very comfortable prescribing biosimilars. About half (49%) said they would be most likely to prescribe a biosimilar to patients with health plans mandating a biosimilar. More than 60% of surveyed gastroenterologists said that biosimilars would positively impact care; providers were divided on the current economic benefits of biosimilars, with 36% saying that the current discounts on biosimilars versus reference products were not favorable enough to motivate switching, and 35% stating that they were. A total of 40% of surveyed providers said that savings of 21%-30%, compared with savings of a reference product, would motivate them to switch patients to a biosimilar, with all other clinical factors being equal.

Gastroenterologists said that, along with the efficacy and cost savings of biosimilars, providing patient education (18%) was a top concern when prescribing biosimilars. Eighty-four percent of respondents said that educating patients about biosimilars as safe and effective treatment options was at least somewhat important. Nearly all participants (99%) cited device ease-of-use as at least somewhat important when considering prescribing adalimumab biosimilars, in addition to interchangeability (97%) and citrate-free formulation (93%).

“Despite general acceptance of biosimilars, there remains some uncertainty regarding their place in the current gastroenterology landscape,” wrote Vivek Kaul, MD, a professor of medicine at the University of Rochester (N.Y.) Medical Center, in the report. “This is likely because only half of the survey respondents believed that biosimilars will positively impact gastroenterology care, further highlighting the ongoing need for real-world data and incorporation of biosimilar use and interchangeability into clinical guidelines.”

Few dermatologists currently prescribe biosimilars

Eight out of ten dermatologists reported being at least somewhat comfortable prescribing biosimilars to patients, though fewer than 20% said they had prescribed a biosimilar in the past year. This indicates limited adoption of infliximab biosimilars, which were the only biosimilars with a dermatologic indication available in 2022, Alex Gross, MD, a dermatologist in Cumming, Ga., noted in his featured commentary in the report. Just 15% of respondents disagreed that biosimilars would have a positive impact on care, and 41% said they were excited about new biosimilars becoming available.

About half (47%) of dermatologists thought the economic benefits of biosimilars were not strong enough to motivate switching patients from reference products. Twenty-nine percent of respondents said that discounts of 21%-30% from a reference product would motivate them to switch patients to a biosimilar, with all other clinical factors being equal, while 20% said they were not likely to prescribe a biosimilar regardless of savings.

Dermatologists may be concerned that these cost savings may not be passed onto patients, said Alison Ehrlich, MD, a dermatologist in Washington, in an email to this news organization. Patient out-of-pocket cost savings would need to be “both significant and transparent” to begin to change providers’ minds, she noted.

Biosimilar efficacy was a top concern for 48% of dermatologists, while 13% said their main concern around prescribing biosimilars was lack of payer adoption. At least 95% of providers said that device ease-of-use and interchangeability were the most important attributes when considering adalimumab biosimilars. Nearly two-thirds (65%) reported that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

If both patients and providers are informed on biosimilar use and there are cost benefits, dermatologists’ opinions may become more favorable toward biosimilars, but that will take time, Dr. Ehrlich said. “We are very early in the game for biosimilar use in dermatology,” she added.
 

Ophthalmologists remain wary

Biosimilars have been relatively new to ophthalmology, with the first ranibizumab biosimilar becoming commercially available in July 2022. In the survey, 64 retina specialists were asked different questions than participants from other specialties to gauge ophthalmologists› familiarity with the biosimilars approval process and their overall comfort prescribing these medications. The primary concerns with prescribing biosimilars among respondents was payer coverage (52%), being uncomfortable with biosimilars from a clinical standpoint (48%), and administrative barriers (45%), such as prior authorization. Despite this lack of comfort with biosimilars, two-thirds of participants thought the U.S. Food and Drug Administration approval process for these medications was sufficient to evaluate their efficacy and safety. Still, fewer than half (48%) of providers said they do or would prescribe biosimilars.

George Williams, MD, a spokesperson for the American Academy of Ophthalmology, noted that the FDA approval process for biosimilars was not as rigorous as for the respective reference product, and fewer patients are followed over a shorter time period. “Since anti–[vascular endothelial growth factor (VEGF)] therapy for indications such as neovascular age-related macular degeneration continues indefinitely over years, ophthalmologists may have concerns about the long-term efficacy and safety when applied to larger real-world populations. Ophthalmologists are well aware of safety issues with VEGF inhibitors arising after FDA approval,” he told this news organization in an email.

When asked about the likelihood of using either aflibercept or ranibizumab biosimilars in their clinical practice once commercially available, 70% of ophthalmologists said they would be at least somewhat likely to prescribe aflibercept biosimilars, and 64% said they would be at least somewhat likely to prescribe ranibizumab biosimilars. About half of respondents said they would not likely switch a currently stable patient on either aflibercept or ranibizumab to the corresponding biosimilar. More than half of ophthalmologists (56%) said they would prescribe a biosimilar only if it had an interchangeability designation.

Out of all four specialties, ophthalmologists more frequently reported that higher discounts from a reference product would be necessary to consider switching a patient to a biosimilar. Currently, many ophthalmologists are comfortable with the off-label use of bevacizumab (Avastin) for treating wet age-related macular degeneration, which also offers more cost savings than any currently available biosimilar on the market, Dr. Williams said.

While the limited number of respondents makes it difficult to draw concrete conclusions, Dr. Williams emphasized that the AAO supported the use of biosimilars. “We believe that with clinical experience ophthalmic biosimilars will become useful therapeutic agents,” he noted.

A version of this article first appeared on Medscape.com.

While most providers think that biosimilars will positively impact care, few feel that the economic benefits of biosimilars to date are enough to motivate switching.

Fuse/Thinkstock

In a new survey of over 350 dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, clinicians shared their opinions on the rapidly evolving landscape of biosimilars, detailing top concerns about prescribing these medications and how they presently use biosimilars in clinical practice. Across all specialties, providers said they would be most likely to prescribe biosimilars to new patients or if a patient’s health plan mandated the switch. Most providers listed concerns about biosimilar efficacy and lack of economic benefit as the main barriers to adoption of biosimilars in clinical practice.

Cardinal Health, a health care services company based in Dublin, Ohio, conducted the surveys from July through October 2022.
 

Rheumatologists want cost-savings for patients

2023 is gearing up to be a big year for biosimilars for inflammatory diseases, with at least eight adalimumab biosimilars entering the market in the United States. Amjevita, manufactured by Amgen, was the first to become commercially available on Jan. 31. Out of 103 surveyed rheumatologists, 62% said they were very comfortable prescribing biosimilars to patients, and 32% said they were somewhat comfortable. Providers said they would be most likely to prescribe a biosimilar to new patients (40%) or if biosimilars were mandated by a patient’s health plan (41%). Nearly one-third (31%) of rheumatologists said that a discount of 21%-30% from a reference product would be necessary to consider switching a patient to a biosimilar.

There are several reasons why a rheumatologist might be wary of switching patients to biosimilars, said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “Rheumatologists will always express concern about changing medications that work well for their patients. It is not ideal to ‘force switch’ to a different product, even if it is almost identical,” he told this news organization in an email. “Also, we must remember that a patient on a biologic has failed traditional medications, which speaks to the struggle a patient must endure to get their disease under control. Fail-first situations can cause a rheumatologist to be initially resistant or hesitant to any changes.”

The top concerns among rheumatologists about prescribing biosimilars were medication efficacy (36%), lack of economic benefit (24%), and evaluating when to prescribe a biosimilar versus a reference product (17%). For adalimumab biosimilars, rheumatologists said that interchangeability – a regulatory designation where a biosimilar can be automatically substituted for its reference product at the pharmacy – and citrate-free formulation were the most important product attributes. Sixty-four percent of providers also noted that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

“There needs to be a true reduction in price, to change providers’ opinions on the economic benefits of biosimilars – in the system generally and for the patient,” Dr. Snow said. “Things will get there eventually, but it is not there yet, based on the list prices we see for some biosimilars.”
 

Gastroenterologists emphasize patient education

Gastroenterology is another specialty to be affected by the influx of adalimumab biosimilars. Out of 72 surveyed gastroenterologists, 86% said they were very comfortable prescribing biosimilars. About half (49%) said they would be most likely to prescribe a biosimilar to patients with health plans mandating a biosimilar. More than 60% of surveyed gastroenterologists said that biosimilars would positively impact care; providers were divided on the current economic benefits of biosimilars, with 36% saying that the current discounts on biosimilars versus reference products were not favorable enough to motivate switching, and 35% stating that they were. A total of 40% of surveyed providers said that savings of 21%-30%, compared with savings of a reference product, would motivate them to switch patients to a biosimilar, with all other clinical factors being equal.

Gastroenterologists said that, along with the efficacy and cost savings of biosimilars, providing patient education (18%) was a top concern when prescribing biosimilars. Eighty-four percent of respondents said that educating patients about biosimilars as safe and effective treatment options was at least somewhat important. Nearly all participants (99%) cited device ease-of-use as at least somewhat important when considering prescribing adalimumab biosimilars, in addition to interchangeability (97%) and citrate-free formulation (93%).

“Despite general acceptance of biosimilars, there remains some uncertainty regarding their place in the current gastroenterology landscape,” wrote Vivek Kaul, MD, a professor of medicine at the University of Rochester (N.Y.) Medical Center, in the report. “This is likely because only half of the survey respondents believed that biosimilars will positively impact gastroenterology care, further highlighting the ongoing need for real-world data and incorporation of biosimilar use and interchangeability into clinical guidelines.”

Few dermatologists currently prescribe biosimilars

Eight out of ten dermatologists reported being at least somewhat comfortable prescribing biosimilars to patients, though fewer than 20% said they had prescribed a biosimilar in the past year. This indicates limited adoption of infliximab biosimilars, which were the only biosimilars with a dermatologic indication available in 2022, Alex Gross, MD, a dermatologist in Cumming, Ga., noted in his featured commentary in the report. Just 15% of respondents disagreed that biosimilars would have a positive impact on care, and 41% said they were excited about new biosimilars becoming available.

About half (47%) of dermatologists thought the economic benefits of biosimilars were not strong enough to motivate switching patients from reference products. Twenty-nine percent of respondents said that discounts of 21%-30% from a reference product would motivate them to switch patients to a biosimilar, with all other clinical factors being equal, while 20% said they were not likely to prescribe a biosimilar regardless of savings.

Dermatologists may be concerned that these cost savings may not be passed onto patients, said Alison Ehrlich, MD, a dermatologist in Washington, in an email to this news organization. Patient out-of-pocket cost savings would need to be “both significant and transparent” to begin to change providers’ minds, she noted.

Biosimilar efficacy was a top concern for 48% of dermatologists, while 13% said their main concern around prescribing biosimilars was lack of payer adoption. At least 95% of providers said that device ease-of-use and interchangeability were the most important attributes when considering adalimumab biosimilars. Nearly two-thirds (65%) reported that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

If both patients and providers are informed on biosimilar use and there are cost benefits, dermatologists’ opinions may become more favorable toward biosimilars, but that will take time, Dr. Ehrlich said. “We are very early in the game for biosimilar use in dermatology,” she added.
 

Ophthalmologists remain wary

Biosimilars have been relatively new to ophthalmology, with the first ranibizumab biosimilar becoming commercially available in July 2022. In the survey, 64 retina specialists were asked different questions than participants from other specialties to gauge ophthalmologists› familiarity with the biosimilars approval process and their overall comfort prescribing these medications. The primary concerns with prescribing biosimilars among respondents was payer coverage (52%), being uncomfortable with biosimilars from a clinical standpoint (48%), and administrative barriers (45%), such as prior authorization. Despite this lack of comfort with biosimilars, two-thirds of participants thought the U.S. Food and Drug Administration approval process for these medications was sufficient to evaluate their efficacy and safety. Still, fewer than half (48%) of providers said they do or would prescribe biosimilars.

George Williams, MD, a spokesperson for the American Academy of Ophthalmology, noted that the FDA approval process for biosimilars was not as rigorous as for the respective reference product, and fewer patients are followed over a shorter time period. “Since anti–[vascular endothelial growth factor (VEGF)] therapy for indications such as neovascular age-related macular degeneration continues indefinitely over years, ophthalmologists may have concerns about the long-term efficacy and safety when applied to larger real-world populations. Ophthalmologists are well aware of safety issues with VEGF inhibitors arising after FDA approval,” he told this news organization in an email.

When asked about the likelihood of using either aflibercept or ranibizumab biosimilars in their clinical practice once commercially available, 70% of ophthalmologists said they would be at least somewhat likely to prescribe aflibercept biosimilars, and 64% said they would be at least somewhat likely to prescribe ranibizumab biosimilars. About half of respondents said they would not likely switch a currently stable patient on either aflibercept or ranibizumab to the corresponding biosimilar. More than half of ophthalmologists (56%) said they would prescribe a biosimilar only if it had an interchangeability designation.

Out of all four specialties, ophthalmologists more frequently reported that higher discounts from a reference product would be necessary to consider switching a patient to a biosimilar. Currently, many ophthalmologists are comfortable with the off-label use of bevacizumab (Avastin) for treating wet age-related macular degeneration, which also offers more cost savings than any currently available biosimilar on the market, Dr. Williams said.

While the limited number of respondents makes it difficult to draw concrete conclusions, Dr. Williams emphasized that the AAO supported the use of biosimilars. “We believe that with clinical experience ophthalmic biosimilars will become useful therapeutic agents,” he noted.

A version of this article first appeared on Medscape.com.

While most providers think that biosimilars will positively impact care, few feel that the economic benefits of biosimilars to date are enough to motivate switching.

Fuse/Thinkstock

In a new survey of over 350 dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, clinicians shared their opinions on the rapidly evolving landscape of biosimilars, detailing top concerns about prescribing these medications and how they presently use biosimilars in clinical practice. Across all specialties, providers said they would be most likely to prescribe biosimilars to new patients or if a patient’s health plan mandated the switch. Most providers listed concerns about biosimilar efficacy and lack of economic benefit as the main barriers to adoption of biosimilars in clinical practice.

Cardinal Health, a health care services company based in Dublin, Ohio, conducted the surveys from July through October 2022.
 

Rheumatologists want cost-savings for patients

2023 is gearing up to be a big year for biosimilars for inflammatory diseases, with at least eight adalimumab biosimilars entering the market in the United States. Amjevita, manufactured by Amgen, was the first to become commercially available on Jan. 31. Out of 103 surveyed rheumatologists, 62% said they were very comfortable prescribing biosimilars to patients, and 32% said they were somewhat comfortable. Providers said they would be most likely to prescribe a biosimilar to new patients (40%) or if biosimilars were mandated by a patient’s health plan (41%). Nearly one-third (31%) of rheumatologists said that a discount of 21%-30% from a reference product would be necessary to consider switching a patient to a biosimilar.

There are several reasons why a rheumatologist might be wary of switching patients to biosimilars, said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “Rheumatologists will always express concern about changing medications that work well for their patients. It is not ideal to ‘force switch’ to a different product, even if it is almost identical,” he told this news organization in an email. “Also, we must remember that a patient on a biologic has failed traditional medications, which speaks to the struggle a patient must endure to get their disease under control. Fail-first situations can cause a rheumatologist to be initially resistant or hesitant to any changes.”

The top concerns among rheumatologists about prescribing biosimilars were medication efficacy (36%), lack of economic benefit (24%), and evaluating when to prescribe a biosimilar versus a reference product (17%). For adalimumab biosimilars, rheumatologists said that interchangeability – a regulatory designation where a biosimilar can be automatically substituted for its reference product at the pharmacy – and citrate-free formulation were the most important product attributes. Sixty-four percent of providers also noted that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

“There needs to be a true reduction in price, to change providers’ opinions on the economic benefits of biosimilars – in the system generally and for the patient,” Dr. Snow said. “Things will get there eventually, but it is not there yet, based on the list prices we see for some biosimilars.”
 

Gastroenterologists emphasize patient education

Gastroenterology is another specialty to be affected by the influx of adalimumab biosimilars. Out of 72 surveyed gastroenterologists, 86% said they were very comfortable prescribing biosimilars. About half (49%) said they would be most likely to prescribe a biosimilar to patients with health plans mandating a biosimilar. More than 60% of surveyed gastroenterologists said that biosimilars would positively impact care; providers were divided on the current economic benefits of biosimilars, with 36% saying that the current discounts on biosimilars versus reference products were not favorable enough to motivate switching, and 35% stating that they were. A total of 40% of surveyed providers said that savings of 21%-30%, compared with savings of a reference product, would motivate them to switch patients to a biosimilar, with all other clinical factors being equal.

Gastroenterologists said that, along with the efficacy and cost savings of biosimilars, providing patient education (18%) was a top concern when prescribing biosimilars. Eighty-four percent of respondents said that educating patients about biosimilars as safe and effective treatment options was at least somewhat important. Nearly all participants (99%) cited device ease-of-use as at least somewhat important when considering prescribing adalimumab biosimilars, in addition to interchangeability (97%) and citrate-free formulation (93%).

“Despite general acceptance of biosimilars, there remains some uncertainty regarding their place in the current gastroenterology landscape,” wrote Vivek Kaul, MD, a professor of medicine at the University of Rochester (N.Y.) Medical Center, in the report. “This is likely because only half of the survey respondents believed that biosimilars will positively impact gastroenterology care, further highlighting the ongoing need for real-world data and incorporation of biosimilar use and interchangeability into clinical guidelines.”

Few dermatologists currently prescribe biosimilars

Eight out of ten dermatologists reported being at least somewhat comfortable prescribing biosimilars to patients, though fewer than 20% said they had prescribed a biosimilar in the past year. This indicates limited adoption of infliximab biosimilars, which were the only biosimilars with a dermatologic indication available in 2022, Alex Gross, MD, a dermatologist in Cumming, Ga., noted in his featured commentary in the report. Just 15% of respondents disagreed that biosimilars would have a positive impact on care, and 41% said they were excited about new biosimilars becoming available.

About half (47%) of dermatologists thought the economic benefits of biosimilars were not strong enough to motivate switching patients from reference products. Twenty-nine percent of respondents said that discounts of 21%-30% from a reference product would motivate them to switch patients to a biosimilar, with all other clinical factors being equal, while 20% said they were not likely to prescribe a biosimilar regardless of savings.

Dermatologists may be concerned that these cost savings may not be passed onto patients, said Alison Ehrlich, MD, a dermatologist in Washington, in an email to this news organization. Patient out-of-pocket cost savings would need to be “both significant and transparent” to begin to change providers’ minds, she noted.

Biosimilar efficacy was a top concern for 48% of dermatologists, while 13% said their main concern around prescribing biosimilars was lack of payer adoption. At least 95% of providers said that device ease-of-use and interchangeability were the most important attributes when considering adalimumab biosimilars. Nearly two-thirds (65%) reported that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

If both patients and providers are informed on biosimilar use and there are cost benefits, dermatologists’ opinions may become more favorable toward biosimilars, but that will take time, Dr. Ehrlich said. “We are very early in the game for biosimilar use in dermatology,” she added.
 

Ophthalmologists remain wary

Biosimilars have been relatively new to ophthalmology, with the first ranibizumab biosimilar becoming commercially available in July 2022. In the survey, 64 retina specialists were asked different questions than participants from other specialties to gauge ophthalmologists› familiarity with the biosimilars approval process and their overall comfort prescribing these medications. The primary concerns with prescribing biosimilars among respondents was payer coverage (52%), being uncomfortable with biosimilars from a clinical standpoint (48%), and administrative barriers (45%), such as prior authorization. Despite this lack of comfort with biosimilars, two-thirds of participants thought the U.S. Food and Drug Administration approval process for these medications was sufficient to evaluate their efficacy and safety. Still, fewer than half (48%) of providers said they do or would prescribe biosimilars.

George Williams, MD, a spokesperson for the American Academy of Ophthalmology, noted that the FDA approval process for biosimilars was not as rigorous as for the respective reference product, and fewer patients are followed over a shorter time period. “Since anti–[vascular endothelial growth factor (VEGF)] therapy for indications such as neovascular age-related macular degeneration continues indefinitely over years, ophthalmologists may have concerns about the long-term efficacy and safety when applied to larger real-world populations. Ophthalmologists are well aware of safety issues with VEGF inhibitors arising after FDA approval,” he told this news organization in an email.

When asked about the likelihood of using either aflibercept or ranibizumab biosimilars in their clinical practice once commercially available, 70% of ophthalmologists said they would be at least somewhat likely to prescribe aflibercept biosimilars, and 64% said they would be at least somewhat likely to prescribe ranibizumab biosimilars. About half of respondents said they would not likely switch a currently stable patient on either aflibercept or ranibizumab to the corresponding biosimilar. More than half of ophthalmologists (56%) said they would prescribe a biosimilar only if it had an interchangeability designation.

Out of all four specialties, ophthalmologists more frequently reported that higher discounts from a reference product would be necessary to consider switching a patient to a biosimilar. Currently, many ophthalmologists are comfortable with the off-label use of bevacizumab (Avastin) for treating wet age-related macular degeneration, which also offers more cost savings than any currently available biosimilar on the market, Dr. Williams said.

While the limited number of respondents makes it difficult to draw concrete conclusions, Dr. Williams emphasized that the AAO supported the use of biosimilars. “We believe that with clinical experience ophthalmic biosimilars will become useful therapeutic agents,” he noted.

A version of this article first appeared on Medscape.com.

Gastroenterologists in 2023 will have more tools in their arsenal to treat patients with Crohn’s disease or ulcerative colitis. As many as 8-10 adalimumab biosimilars are anticipated to come on the market this year, giving mainstay drug Humira some vigorous competition.

Three scenarios will drive adalimumab biosimilar initiation: Insurance preference for the initial treatment of a newly diagnosed condition, a change in a patient’s insurance plan, or an insurance-mandated switch, said Edward C. Oldfield IV, MD, assistant professor at Eastern Virginia Medical School’s division of gastroenterology in Norfolk.

Even with more drugs to choose from, some gastroenterologists may be hesitant to make a switch. “Outside of these scenarios, I would encourage patients to remain on their current biologic so long as cost and accessibility remain stable,” said Dr. Oldfield.

Many factors will contribute to the success of biosimilars. Will physicians be prescribing them? How are biosimilars placed on formularies and will they be given preferred status?  How will manufacturers price their biosimilars? “We have to wait and see to get the answers to these questions,” said Steven Newmark, JD, MPA, chief legal officer and director of policy, Global Healthy Living Foundation/CreakyJoints, a nonprofit advocacy organization based in New York.

Prescribing biosimilars is no different than prescribing originator biologics, so providers should know how to use them, said Mr. Newmark. “Most important will be the availability of patient-friendly resources that providers can share with their patients to provide education about and confidence in using biosimilars,” he added.

Overall, biosimilars are a good thing, said Dr. Oldfield. “In the long run they should bring down costs and increase access to medications for our patients.”

Others are skeptical that the adalimumab biosimilars will save patients much money.

Biosimilar laws were created to lower costs. However, if a patient with insurance pays only $5 a month out of pocket for Humira – a drug that normally costs $7,000 without coverage – it’s unlikely they would want to switch unless there’s comparable savings from the biosimilar, said Stephen B. Hanauer, MD, medical director of the Digestive Health Center and professor of medicine at Northwestern Medicine, Northwestern University, Evanston, Ill.

Like generics, Humira biosimilars may face some initial backlash, said Dr. Hanauer.
 

2023 broadens scope of adalimumab treatments

The American Gastroenterological Association describes a biosimilar as something that’s “highly similar to, but not an exact copy of, a biologic reference product already approved” by the Food and Drug Administration. Congress under the 2010 Affordable Care Act created a special, abbreviated pathway to approval for biosimilars.

AbbVie’s Humira, the global revenue for which exceeded $20 billion in 2021, has long dominated the U.S. market on injectable treatments for autoimmune diseases. The popular drug faces some competition in 2023, however, following a series of legal settlements that allowed AbbVie competitors to release their own adalimumab biosimilars.

“So far, we haven’t seen biosimilars live up to their potential in the U.S. in the inflammatory space,” said Mr. Newmark. This may change, however. Previously, biosimilars have required infusion, which demanded more time, commitment, and travel from patients. “The new set of forthcoming Humira biosimilars are injectables, an administration method preferred by patients,” he said.

The FDA will approve a biosimilar if it determines that the biological product is highly similar to the reference product, and that there are no clinically meaningful differences between the biological and reference product in terms of the safety, purity, and potency of the product. 

The agency to date has approved 8 adalimumab biosimilars. These include: Idacio (adalimumab-aacf, Fresenius Kabi); Amjevita (adalimumab-atto, Amgen); Hadlima (adalimumab-bwwd, Organon); Cyltezo (adalimumab-adbm, Boehringer Ingelheim); Yusimry (adalimumab-aqvh from Coherus BioSciences); Hulio (adalimumab-fkjp; Mylan/Fujifilm Kyowa Kirin Biologics); Hyrimoz (adalimumab-adaz, Sandoz), and Abrilada (adalimumab-afzb, Pfizer).

“While FDA doesn’t formally track when products come to market, we know based on published reports that application holders for many of the currently FDA-approved biosimilars plan to market this year, starting with Amjevita being the first adalimumab biosimilar launched” in January, said Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars at the agency.

At press time, two other companies (Celltrion and Alvotech/Teva) were awaiting FDA approval for their adalimumab biosimilar drugs.

Among the eight approved drugs, Cyltezo is the only one that has a designation for interchangeability with Humira.

An interchangeable biosimilar may be substituted at the pharmacy without the intervention of the prescriber – much like generics are substituted, depending on state laws, said Dr. Yim. “However, in terms of safety and effectiveness, FDA’s standards for approval mean that biosimilar or interchangeable biosimilar products can be used in place of the reference product they were compared to.”

FDA-approved biosimilars undergo a rigorous evaluation for safety, effectiveness, and quality for their approved conditions of use, she continued. “Therefore, patients and health care providers can rely on a biosimilar to be as safe and effective for its approved uses as the original biological product.”
 

Remicade as a yard stick

Gastroenterologists dealt with this situation once before, when Remicade (infliximab) biosimilars came on the market in 2016, noted Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic.

Remicade and Humira are both tumor necrosis factor inhibitors with the same mechanism of action and many of the same indications. “We already had that experience with Remicade and biosimilar switch 2 or 3 years ago. Now we’re talking about Humira,” said Dr. Regueiro.

Most GI doctors have prescribed one of the more common infliximab biosimilars (Inflectra or Renflexis), noted Dr. Oldfield.

Cardinal Health, which recently surveyed 300 gastroenterologists, rheumatologists, and dermatologists about adalimumab biosimilars, found that gastroenterologists had the highest comfort level in prescribing them. Their top concern, however, was changing a patient from adalimumab to an adalimumab biosimilar.

For most patients, Dr. Oldfield sees the Humira reference biologic and biosimilar as equivalent.

However, he said he would change a patient’s drug only if there were a good reason or if his hand was forced by insurance. He would not make the change for a patient who recently began induction with the reference biologic or a patient with highly active clinical disease.

“While there is limited data to support this, I would also have some qualms about changing a patient from reference biologic to a biosimilar if they previously had immune-mediated pharmacokinetic failure due to antibody development with a biologic and were currently doing well on their new biologic,” he said.

Those with a new ulcerative colitis or Crohn’s diagnosis who are initiating a biologic for the first time might consider a biosimilar. If a patient is transitioning from a reference biologic to a biosimilar, “I would want to make that change during a time of stable remission and with the recognition that the switch is not a temporary switch, but a long-term switch,” he continued.

A paper that reviewed 23 observational studies of adalimumab and other biosimilars found that switching biosimilars was safe and effective. But if possible, patients should minimize the number of switches until more robust long-term data are available, added Dr. Oldfield.

If a patient is apprehensive about switching to a new therapy, “one may need to be cognizant of the ‘nocebo’ effect in which there is an unexplained or unfavorable therapeutic effect after switching,” he said.

Other gastroenterologists voiced similar reservations about switching. “I won’t use an adalimumab biosimilar unless the patient requests it, the insurance requires it, or there is a cost advantage for the patient such that they prefer it,” said Doug Wolf, MD, an Atlanta gastroenterologist.

“There is no medical treatment advantage to a biosimilar, especially if switching from Humira,” added Dr. Wolf.

Insurance will guide treatment

Once a drug is approved for use by the FDA, that drug will be available in all 50 states. “Different private insurance formularies, as well as state Medicaid formularies, might affect the actual ability of patients to receive such drugs,” said Mr. Newmark.

Patients should consult with their providers and insurance companies to see what therapies are available, he advised.

Dr. Hanauer anticipates some headaches arising for patients and doctors alike when negotiating for a specific drug.

Cyltezo may be the only biosimilar interchangeable with Humira, but the third-party pharmacy benefit manager (PBM) could negotiate for one of the noninterchangeable ones. “On a yearly basis they could switch their preference,” said Dr. Hanauer.

In the Cardinal Health survey, more than 60% of respondents said they would feel comfortable prescribing an adalimumab biosimilar only with an interchangeability designation.

A PBM may offer a patient Cyltezo if it’s cheaper than Humira. If the patient insists on staying on Humira, then they’ll have to pay more for that drug on their payer’s formulary, said Dr. Hanauer. In a worst-case scenario, a physician may have to appeal on a patient’s behalf to get Humira if the insurer offers only the biosimilar.

Taking that step to appeal is a major hassle for the physician, and leads to extra back door costs as well, said Dr. Hanauer.

Humira manufacturer AbbVie, in turn, may offer discounts and rebates to the PBMs to put Humira on their formulary. “That’s the AbbVie negotiating power. It’s not that the cost is going to be that much different. It’s going to be that there are rebates and discounts that are going to make the cost different,” he added.

As a community physician, Dr. Oldfield has specific concerns about accessibility.

The ever-increasing burden of insurance documentation and prior authorization means it can take weeks or months to get these medications approved. “The addition of new biosimilars is a welcome entrance if it can get patients the medications they need when they need it,” he said.

When it comes to prescribing biologics, many physicians rely on ancillary staff for assistance. It’s a team effort to sift through all the paperwork, observed Dr. Oldfield.

“While many community GI practices have specialized staff to deal with prior authorizations, they are still a far cry from the IBD [inflammatory bowel disease] academic centers where there are often pharmacists, nursing specialists, and home-monitoring programs to check in on patients,” he explained.

Landscape on cost is uncertain

At present, little is known about the cost of the biosimilars and impact on future drug pricing, said Dr. Oldfield.

At least for Medicare, Humira biosimilars will be considered Medicare Part D drugs if used for a medically accepted indication, said a spokesperson for the Centers for Medicare and Medicaid Services.

Part D sponsors (pharmacy and therapeutic committees) “will make the determination as to whether Amjevita and other products will be added to their formularies,” said the spokesperson.

Patients never saw a significant cost savings with Remicade biosimilars. “I imagine the same would be true with biosimilars for Humira,” said Dr. Regueiro. Patients may see greater access to these drugs, however, because the insurance plan or the pharmacy plan will make them more readily available, he added.

The hope is that, as biosimilars are introduced, the price of the originator biologic will go down, said Mr. Newmark. “Therefore, we can expect Humira to be offered at a lower price as it faces competition. Where it will sit in comparison to the forthcoming biosimilars will depend on how much biosimilar companies drop their price and how much pressure will be on PBMs and insurers to cover the lowest list price drug,” he said.

AbbVie did not respond to several requests for comment.

Charitable patient assistance programs for biosimilars or biologics can help offset the price of copayments, Mr. Newmark offered.

Ideally, insurers will offer designated biosimilars at a reduced or even no out-of-pocket expense on their formularies. This should lead to a decreased administrative burden for approval with streamlined (or even removal) of prior authorizations for certain medications, said Dr. Oldfield.

Without insurance or medication assistance programs, the cost of biosimilars is prohibitively expensive, he added.

“Biosimilars have higher research, development, and manufacturing costs than what people conventionally think of [for] a generic medication.”

Educating, advising patients

Dr. Oldfield advised that gastroenterologists refer to biologics by the generic name rather than branded name when initiating therapy unless there is a very specific reason not to. “This approach should make the process more streamlined and less subjected to quick denials for brand-only requests as biosimilars start to assume a larger market share,” he said.

Uptake of the Humira biosimilars also will depend on proper education of physicians and patients and their comfort level with the biosimilars, said Dr. Regueiro. Cleveland Clinic uses a team approach to educate on this topic, relying on pharmacists, clinicians, and nurses to explain that there’s no real difference between the reference drug and its biosimilars, based on efficacy and safety data.

Physicians can also direct patients to patient-friendly resources, said Mr. Newmark. “By starting the conversation early, it ensures that when/if the time comes that your patient is switched to or chooses a biosimilar they will feel more confident because they have the knowledge to make decisions about their care.”

The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars , is a free resource for patients, he added.

It’s important that doctors also understand these products so they can explain to their patients what to expect, said the FDA’s Dr. Yim. The FDA provides educational materials on its website, including a comprehensive curriculum toolkit.

Dr. Hanauer has served as a consultant for AbbVie, Amgen, American College of Gastroenterology, GlaxoSmithKline, American Gastroenterological Association, Pfizer, and a host of other companies . Dr. Regueiro has served on advisory boards and as a consultant for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET Pharma Solutions,Trellis, and Boehringer Ingelheim Pharmaceuticals. Dr. Wolf, Dr. Yim, Dr. Oldfield, and Mr. Newmark have no financial conflicts of interest.

Gastroenterologists in 2023 will have more tools in their arsenal to treat patients with Crohn’s disease or ulcerative colitis. As many as 8-10 adalimumab biosimilars are anticipated to come on the market this year, giving mainstay drug Humira some vigorous competition.

Three scenarios will drive adalimumab biosimilar initiation: Insurance preference for the initial treatment of a newly diagnosed condition, a change in a patient’s insurance plan, or an insurance-mandated switch, said Edward C. Oldfield IV, MD, assistant professor at Eastern Virginia Medical School’s division of gastroenterology in Norfolk.

Even with more drugs to choose from, some gastroenterologists may be hesitant to make a switch. “Outside of these scenarios, I would encourage patients to remain on their current biologic so long as cost and accessibility remain stable,” said Dr. Oldfield.

Many factors will contribute to the success of biosimilars. Will physicians be prescribing them? How are biosimilars placed on formularies and will they be given preferred status?  How will manufacturers price their biosimilars? “We have to wait and see to get the answers to these questions,” said Steven Newmark, JD, MPA, chief legal officer and director of policy, Global Healthy Living Foundation/CreakyJoints, a nonprofit advocacy organization based in New York.

Prescribing biosimilars is no different than prescribing originator biologics, so providers should know how to use them, said Mr. Newmark. “Most important will be the availability of patient-friendly resources that providers can share with their patients to provide education about and confidence in using biosimilars,” he added.

Overall, biosimilars are a good thing, said Dr. Oldfield. “In the long run they should bring down costs and increase access to medications for our patients.”

Others are skeptical that the adalimumab biosimilars will save patients much money.

Biosimilar laws were created to lower costs. However, if a patient with insurance pays only $5 a month out of pocket for Humira – a drug that normally costs $7,000 without coverage – it’s unlikely they would want to switch unless there’s comparable savings from the biosimilar, said Stephen B. Hanauer, MD, medical director of the Digestive Health Center and professor of medicine at Northwestern Medicine, Northwestern University, Evanston, Ill.

Like generics, Humira biosimilars may face some initial backlash, said Dr. Hanauer.
 

2023 broadens scope of adalimumab treatments

The American Gastroenterological Association describes a biosimilar as something that’s “highly similar to, but not an exact copy of, a biologic reference product already approved” by the Food and Drug Administration. Congress under the 2010 Affordable Care Act created a special, abbreviated pathway to approval for biosimilars.

AbbVie’s Humira, the global revenue for which exceeded $20 billion in 2021, has long dominated the U.S. market on injectable treatments for autoimmune diseases. The popular drug faces some competition in 2023, however, following a series of legal settlements that allowed AbbVie competitors to release their own adalimumab biosimilars.

“So far, we haven’t seen biosimilars live up to their potential in the U.S. in the inflammatory space,” said Mr. Newmark. This may change, however. Previously, biosimilars have required infusion, which demanded more time, commitment, and travel from patients. “The new set of forthcoming Humira biosimilars are injectables, an administration method preferred by patients,” he said.

The FDA will approve a biosimilar if it determines that the biological product is highly similar to the reference product, and that there are no clinically meaningful differences between the biological and reference product in terms of the safety, purity, and potency of the product. 

The agency to date has approved 8 adalimumab biosimilars. These include: Idacio (adalimumab-aacf, Fresenius Kabi); Amjevita (adalimumab-atto, Amgen); Hadlima (adalimumab-bwwd, Organon); Cyltezo (adalimumab-adbm, Boehringer Ingelheim); Yusimry (adalimumab-aqvh from Coherus BioSciences); Hulio (adalimumab-fkjp; Mylan/Fujifilm Kyowa Kirin Biologics); Hyrimoz (adalimumab-adaz, Sandoz), and Abrilada (adalimumab-afzb, Pfizer).

“While FDA doesn’t formally track when products come to market, we know based on published reports that application holders for many of the currently FDA-approved biosimilars plan to market this year, starting with Amjevita being the first adalimumab biosimilar launched” in January, said Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars at the agency.

At press time, two other companies (Celltrion and Alvotech/Teva) were awaiting FDA approval for their adalimumab biosimilar drugs.

Among the eight approved drugs, Cyltezo is the only one that has a designation for interchangeability with Humira.

An interchangeable biosimilar may be substituted at the pharmacy without the intervention of the prescriber – much like generics are substituted, depending on state laws, said Dr. Yim. “However, in terms of safety and effectiveness, FDA’s standards for approval mean that biosimilar or interchangeable biosimilar products can be used in place of the reference product they were compared to.”

FDA-approved biosimilars undergo a rigorous evaluation for safety, effectiveness, and quality for their approved conditions of use, she continued. “Therefore, patients and health care providers can rely on a biosimilar to be as safe and effective for its approved uses as the original biological product.”
 

Remicade as a yard stick

Gastroenterologists dealt with this situation once before, when Remicade (infliximab) biosimilars came on the market in 2016, noted Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic.

Remicade and Humira are both tumor necrosis factor inhibitors with the same mechanism of action and many of the same indications. “We already had that experience with Remicade and biosimilar switch 2 or 3 years ago. Now we’re talking about Humira,” said Dr. Regueiro.

Most GI doctors have prescribed one of the more common infliximab biosimilars (Inflectra or Renflexis), noted Dr. Oldfield.

Cardinal Health, which recently surveyed 300 gastroenterologists, rheumatologists, and dermatologists about adalimumab biosimilars, found that gastroenterologists had the highest comfort level in prescribing them. Their top concern, however, was changing a patient from adalimumab to an adalimumab biosimilar.

For most patients, Dr. Oldfield sees the Humira reference biologic and biosimilar as equivalent.

However, he said he would change a patient’s drug only if there were a good reason or if his hand was forced by insurance. He would not make the change for a patient who recently began induction with the reference biologic or a patient with highly active clinical disease.

“While there is limited data to support this, I would also have some qualms about changing a patient from reference biologic to a biosimilar if they previously had immune-mediated pharmacokinetic failure due to antibody development with a biologic and were currently doing well on their new biologic,” he said.

Those with a new ulcerative colitis or Crohn’s diagnosis who are initiating a biologic for the first time might consider a biosimilar. If a patient is transitioning from a reference biologic to a biosimilar, “I would want to make that change during a time of stable remission and with the recognition that the switch is not a temporary switch, but a long-term switch,” he continued.

A paper that reviewed 23 observational studies of adalimumab and other biosimilars found that switching biosimilars was safe and effective. But if possible, patients should minimize the number of switches until more robust long-term data are available, added Dr. Oldfield.

If a patient is apprehensive about switching to a new therapy, “one may need to be cognizant of the ‘nocebo’ effect in which there is an unexplained or unfavorable therapeutic effect after switching,” he said.

Other gastroenterologists voiced similar reservations about switching. “I won’t use an adalimumab biosimilar unless the patient requests it, the insurance requires it, or there is a cost advantage for the patient such that they prefer it,” said Doug Wolf, MD, an Atlanta gastroenterologist.

“There is no medical treatment advantage to a biosimilar, especially if switching from Humira,” added Dr. Wolf.

Insurance will guide treatment

Once a drug is approved for use by the FDA, that drug will be available in all 50 states. “Different private insurance formularies, as well as state Medicaid formularies, might affect the actual ability of patients to receive such drugs,” said Mr. Newmark.

Patients should consult with their providers and insurance companies to see what therapies are available, he advised.

Dr. Hanauer anticipates some headaches arising for patients and doctors alike when negotiating for a specific drug.

Cyltezo may be the only biosimilar interchangeable with Humira, but the third-party pharmacy benefit manager (PBM) could negotiate for one of the noninterchangeable ones. “On a yearly basis they could switch their preference,” said Dr. Hanauer.

In the Cardinal Health survey, more than 60% of respondents said they would feel comfortable prescribing an adalimumab biosimilar only with an interchangeability designation.

A PBM may offer a patient Cyltezo if it’s cheaper than Humira. If the patient insists on staying on Humira, then they’ll have to pay more for that drug on their payer’s formulary, said Dr. Hanauer. In a worst-case scenario, a physician may have to appeal on a patient’s behalf to get Humira if the insurer offers only the biosimilar.

Taking that step to appeal is a major hassle for the physician, and leads to extra back door costs as well, said Dr. Hanauer.

Humira manufacturer AbbVie, in turn, may offer discounts and rebates to the PBMs to put Humira on their formulary. “That’s the AbbVie negotiating power. It’s not that the cost is going to be that much different. It’s going to be that there are rebates and discounts that are going to make the cost different,” he added.

As a community physician, Dr. Oldfield has specific concerns about accessibility.

The ever-increasing burden of insurance documentation and prior authorization means it can take weeks or months to get these medications approved. “The addition of new biosimilars is a welcome entrance if it can get patients the medications they need when they need it,” he said.

When it comes to prescribing biologics, many physicians rely on ancillary staff for assistance. It’s a team effort to sift through all the paperwork, observed Dr. Oldfield.

“While many community GI practices have specialized staff to deal with prior authorizations, they are still a far cry from the IBD [inflammatory bowel disease] academic centers where there are often pharmacists, nursing specialists, and home-monitoring programs to check in on patients,” he explained.

Landscape on cost is uncertain

At present, little is known about the cost of the biosimilars and impact on future drug pricing, said Dr. Oldfield.

At least for Medicare, Humira biosimilars will be considered Medicare Part D drugs if used for a medically accepted indication, said a spokesperson for the Centers for Medicare and Medicaid Services.

Part D sponsors (pharmacy and therapeutic committees) “will make the determination as to whether Amjevita and other products will be added to their formularies,” said the spokesperson.

Patients never saw a significant cost savings with Remicade biosimilars. “I imagine the same would be true with biosimilars for Humira,” said Dr. Regueiro. Patients may see greater access to these drugs, however, because the insurance plan or the pharmacy plan will make them more readily available, he added.

The hope is that, as biosimilars are introduced, the price of the originator biologic will go down, said Mr. Newmark. “Therefore, we can expect Humira to be offered at a lower price as it faces competition. Where it will sit in comparison to the forthcoming biosimilars will depend on how much biosimilar companies drop their price and how much pressure will be on PBMs and insurers to cover the lowest list price drug,” he said.

AbbVie did not respond to several requests for comment.

Charitable patient assistance programs for biosimilars or biologics can help offset the price of copayments, Mr. Newmark offered.

Ideally, insurers will offer designated biosimilars at a reduced or even no out-of-pocket expense on their formularies. This should lead to a decreased administrative burden for approval with streamlined (or even removal) of prior authorizations for certain medications, said Dr. Oldfield.

Without insurance or medication assistance programs, the cost of biosimilars is prohibitively expensive, he added.

“Biosimilars have higher research, development, and manufacturing costs than what people conventionally think of [for] a generic medication.”

Educating, advising patients

Dr. Oldfield advised that gastroenterologists refer to biologics by the generic name rather than branded name when initiating therapy unless there is a very specific reason not to. “This approach should make the process more streamlined and less subjected to quick denials for brand-only requests as biosimilars start to assume a larger market share,” he said.

Uptake of the Humira biosimilars also will depend on proper education of physicians and patients and their comfort level with the biosimilars, said Dr. Regueiro. Cleveland Clinic uses a team approach to educate on this topic, relying on pharmacists, clinicians, and nurses to explain that there’s no real difference between the reference drug and its biosimilars, based on efficacy and safety data.

Physicians can also direct patients to patient-friendly resources, said Mr. Newmark. “By starting the conversation early, it ensures that when/if the time comes that your patient is switched to or chooses a biosimilar they will feel more confident because they have the knowledge to make decisions about their care.”

The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars , is a free resource for patients, he added.

It’s important that doctors also understand these products so they can explain to their patients what to expect, said the FDA’s Dr. Yim. The FDA provides educational materials on its website, including a comprehensive curriculum toolkit.

Dr. Hanauer has served as a consultant for AbbVie, Amgen, American College of Gastroenterology, GlaxoSmithKline, American Gastroenterological Association, Pfizer, and a host of other companies . Dr. Regueiro has served on advisory boards and as a consultant for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET Pharma Solutions,Trellis, and Boehringer Ingelheim Pharmaceuticals. Dr. Wolf, Dr. Yim, Dr. Oldfield, and Mr. Newmark have no financial conflicts of interest.

Gastroenterologists in 2023 will have more tools in their arsenal to treat patients with Crohn’s disease or ulcerative colitis. As many as 8-10 adalimumab biosimilars are anticipated to come on the market this year, giving mainstay drug Humira some vigorous competition.

Three scenarios will drive adalimumab biosimilar initiation: Insurance preference for the initial treatment of a newly diagnosed condition, a change in a patient’s insurance plan, or an insurance-mandated switch, said Edward C. Oldfield IV, MD, assistant professor at Eastern Virginia Medical School’s division of gastroenterology in Norfolk.

Even with more drugs to choose from, some gastroenterologists may be hesitant to make a switch. “Outside of these scenarios, I would encourage patients to remain on their current biologic so long as cost and accessibility remain stable,” said Dr. Oldfield.

Many factors will contribute to the success of biosimilars. Will physicians be prescribing them? How are biosimilars placed on formularies and will they be given preferred status?  How will manufacturers price their biosimilars? “We have to wait and see to get the answers to these questions,” said Steven Newmark, JD, MPA, chief legal officer and director of policy, Global Healthy Living Foundation/CreakyJoints, a nonprofit advocacy organization based in New York.

Prescribing biosimilars is no different than prescribing originator biologics, so providers should know how to use them, said Mr. Newmark. “Most important will be the availability of patient-friendly resources that providers can share with their patients to provide education about and confidence in using biosimilars,” he added.

Overall, biosimilars are a good thing, said Dr. Oldfield. “In the long run they should bring down costs and increase access to medications for our patients.”

Others are skeptical that the adalimumab biosimilars will save patients much money.

Biosimilar laws were created to lower costs. However, if a patient with insurance pays only $5 a month out of pocket for Humira – a drug that normally costs $7,000 without coverage – it’s unlikely they would want to switch unless there’s comparable savings from the biosimilar, said Stephen B. Hanauer, MD, medical director of the Digestive Health Center and professor of medicine at Northwestern Medicine, Northwestern University, Evanston, Ill.

Like generics, Humira biosimilars may face some initial backlash, said Dr. Hanauer.
 

2023 broadens scope of adalimumab treatments

The American Gastroenterological Association describes a biosimilar as something that’s “highly similar to, but not an exact copy of, a biologic reference product already approved” by the Food and Drug Administration. Congress under the 2010 Affordable Care Act created a special, abbreviated pathway to approval for biosimilars.

AbbVie’s Humira, the global revenue for which exceeded $20 billion in 2021, has long dominated the U.S. market on injectable treatments for autoimmune diseases. The popular drug faces some competition in 2023, however, following a series of legal settlements that allowed AbbVie competitors to release their own adalimumab biosimilars.

“So far, we haven’t seen biosimilars live up to their potential in the U.S. in the inflammatory space,” said Mr. Newmark. This may change, however. Previously, biosimilars have required infusion, which demanded more time, commitment, and travel from patients. “The new set of forthcoming Humira biosimilars are injectables, an administration method preferred by patients,” he said.

The FDA will approve a biosimilar if it determines that the biological product is highly similar to the reference product, and that there are no clinically meaningful differences between the biological and reference product in terms of the safety, purity, and potency of the product. 

The agency to date has approved 8 adalimumab biosimilars. These include: Idacio (adalimumab-aacf, Fresenius Kabi); Amjevita (adalimumab-atto, Amgen); Hadlima (adalimumab-bwwd, Organon); Cyltezo (adalimumab-adbm, Boehringer Ingelheim); Yusimry (adalimumab-aqvh from Coherus BioSciences); Hulio (adalimumab-fkjp; Mylan/Fujifilm Kyowa Kirin Biologics); Hyrimoz (adalimumab-adaz, Sandoz), and Abrilada (adalimumab-afzb, Pfizer).

“While FDA doesn’t formally track when products come to market, we know based on published reports that application holders for many of the currently FDA-approved biosimilars plan to market this year, starting with Amjevita being the first adalimumab biosimilar launched” in January, said Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars at the agency.

At press time, two other companies (Celltrion and Alvotech/Teva) were awaiting FDA approval for their adalimumab biosimilar drugs.

Among the eight approved drugs, Cyltezo is the only one that has a designation for interchangeability with Humira.

An interchangeable biosimilar may be substituted at the pharmacy without the intervention of the prescriber – much like generics are substituted, depending on state laws, said Dr. Yim. “However, in terms of safety and effectiveness, FDA’s standards for approval mean that biosimilar or interchangeable biosimilar products can be used in place of the reference product they were compared to.”

FDA-approved biosimilars undergo a rigorous evaluation for safety, effectiveness, and quality for their approved conditions of use, she continued. “Therefore, patients and health care providers can rely on a biosimilar to be as safe and effective for its approved uses as the original biological product.”
 

Remicade as a yard stick

Gastroenterologists dealt with this situation once before, when Remicade (infliximab) biosimilars came on the market in 2016, noted Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic.

Remicade and Humira are both tumor necrosis factor inhibitors with the same mechanism of action and many of the same indications. “We already had that experience with Remicade and biosimilar switch 2 or 3 years ago. Now we’re talking about Humira,” said Dr. Regueiro.

Most GI doctors have prescribed one of the more common infliximab biosimilars (Inflectra or Renflexis), noted Dr. Oldfield.

Cardinal Health, which recently surveyed 300 gastroenterologists, rheumatologists, and dermatologists about adalimumab biosimilars, found that gastroenterologists had the highest comfort level in prescribing them. Their top concern, however, was changing a patient from adalimumab to an adalimumab biosimilar.

For most patients, Dr. Oldfield sees the Humira reference biologic and biosimilar as equivalent.

However, he said he would change a patient’s drug only if there were a good reason or if his hand was forced by insurance. He would not make the change for a patient who recently began induction with the reference biologic or a patient with highly active clinical disease.

“While there is limited data to support this, I would also have some qualms about changing a patient from reference biologic to a biosimilar if they previously had immune-mediated pharmacokinetic failure due to antibody development with a biologic and were currently doing well on their new biologic,” he said.

Those with a new ulcerative colitis or Crohn’s diagnosis who are initiating a biologic for the first time might consider a biosimilar. If a patient is transitioning from a reference biologic to a biosimilar, “I would want to make that change during a time of stable remission and with the recognition that the switch is not a temporary switch, but a long-term switch,” he continued.

A paper that reviewed 23 observational studies of adalimumab and other biosimilars found that switching biosimilars was safe and effective. But if possible, patients should minimize the number of switches until more robust long-term data are available, added Dr. Oldfield.

If a patient is apprehensive about switching to a new therapy, “one may need to be cognizant of the ‘nocebo’ effect in which there is an unexplained or unfavorable therapeutic effect after switching,” he said.

Other gastroenterologists voiced similar reservations about switching. “I won’t use an adalimumab biosimilar unless the patient requests it, the insurance requires it, or there is a cost advantage for the patient such that they prefer it,” said Doug Wolf, MD, an Atlanta gastroenterologist.

“There is no medical treatment advantage to a biosimilar, especially if switching from Humira,” added Dr. Wolf.

Insurance will guide treatment

Once a drug is approved for use by the FDA, that drug will be available in all 50 states. “Different private insurance formularies, as well as state Medicaid formularies, might affect the actual ability of patients to receive such drugs,” said Mr. Newmark.

Patients should consult with their providers and insurance companies to see what therapies are available, he advised.

Dr. Hanauer anticipates some headaches arising for patients and doctors alike when negotiating for a specific drug.

Cyltezo may be the only biosimilar interchangeable with Humira, but the third-party pharmacy benefit manager (PBM) could negotiate for one of the noninterchangeable ones. “On a yearly basis they could switch their preference,” said Dr. Hanauer.

In the Cardinal Health survey, more than 60% of respondents said they would feel comfortable prescribing an adalimumab biosimilar only with an interchangeability designation.

A PBM may offer a patient Cyltezo if it’s cheaper than Humira. If the patient insists on staying on Humira, then they’ll have to pay more for that drug on their payer’s formulary, said Dr. Hanauer. In a worst-case scenario, a physician may have to appeal on a patient’s behalf to get Humira if the insurer offers only the biosimilar.

Taking that step to appeal is a major hassle for the physician, and leads to extra back door costs as well, said Dr. Hanauer.

Humira manufacturer AbbVie, in turn, may offer discounts and rebates to the PBMs to put Humira on their formulary. “That’s the AbbVie negotiating power. It’s not that the cost is going to be that much different. It’s going to be that there are rebates and discounts that are going to make the cost different,” he added.

As a community physician, Dr. Oldfield has specific concerns about accessibility.

The ever-increasing burden of insurance documentation and prior authorization means it can take weeks or months to get these medications approved. “The addition of new biosimilars is a welcome entrance if it can get patients the medications they need when they need it,” he said.

When it comes to prescribing biologics, many physicians rely on ancillary staff for assistance. It’s a team effort to sift through all the paperwork, observed Dr. Oldfield.

“While many community GI practices have specialized staff to deal with prior authorizations, they are still a far cry from the IBD [inflammatory bowel disease] academic centers where there are often pharmacists, nursing specialists, and home-monitoring programs to check in on patients,” he explained.

Landscape on cost is uncertain

At present, little is known about the cost of the biosimilars and impact on future drug pricing, said Dr. Oldfield.

At least for Medicare, Humira biosimilars will be considered Medicare Part D drugs if used for a medically accepted indication, said a spokesperson for the Centers for Medicare and Medicaid Services.

Part D sponsors (pharmacy and therapeutic committees) “will make the determination as to whether Amjevita and other products will be added to their formularies,” said the spokesperson.

Patients never saw a significant cost savings with Remicade biosimilars. “I imagine the same would be true with biosimilars for Humira,” said Dr. Regueiro. Patients may see greater access to these drugs, however, because the insurance plan or the pharmacy plan will make them more readily available, he added.

The hope is that, as biosimilars are introduced, the price of the originator biologic will go down, said Mr. Newmark. “Therefore, we can expect Humira to be offered at a lower price as it faces competition. Where it will sit in comparison to the forthcoming biosimilars will depend on how much biosimilar companies drop their price and how much pressure will be on PBMs and insurers to cover the lowest list price drug,” he said.

AbbVie did not respond to several requests for comment.

Charitable patient assistance programs for biosimilars or biologics can help offset the price of copayments, Mr. Newmark offered.

Ideally, insurers will offer designated biosimilars at a reduced or even no out-of-pocket expense on their formularies. This should lead to a decreased administrative burden for approval with streamlined (or even removal) of prior authorizations for certain medications, said Dr. Oldfield.

Without insurance or medication assistance programs, the cost of biosimilars is prohibitively expensive, he added.

“Biosimilars have higher research, development, and manufacturing costs than what people conventionally think of [for] a generic medication.”

Educating, advising patients

Dr. Oldfield advised that gastroenterologists refer to biologics by the generic name rather than branded name when initiating therapy unless there is a very specific reason not to. “This approach should make the process more streamlined and less subjected to quick denials for brand-only requests as biosimilars start to assume a larger market share,” he said.

Uptake of the Humira biosimilars also will depend on proper education of physicians and patients and their comfort level with the biosimilars, said Dr. Regueiro. Cleveland Clinic uses a team approach to educate on this topic, relying on pharmacists, clinicians, and nurses to explain that there’s no real difference between the reference drug and its biosimilars, based on efficacy and safety data.

Physicians can also direct patients to patient-friendly resources, said Mr. Newmark. “By starting the conversation early, it ensures that when/if the time comes that your patient is switched to or chooses a biosimilar they will feel more confident because they have the knowledge to make decisions about their care.”

The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars , is a free resource for patients, he added.

It’s important that doctors also understand these products so they can explain to their patients what to expect, said the FDA’s Dr. Yim. The FDA provides educational materials on its website, including a comprehensive curriculum toolkit.

Dr. Hanauer has served as a consultant for AbbVie, Amgen, American College of Gastroenterology, GlaxoSmithKline, American Gastroenterological Association, Pfizer, and a host of other companies . Dr. Regueiro has served on advisory boards and as a consultant for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET Pharma Solutions,Trellis, and Boehringer Ingelheim Pharmaceuticals. Dr. Wolf, Dr. Yim, Dr. Oldfield, and Mr. Newmark have no financial conflicts of interest.

HONOLULU – During office visits with Andrew Blauvelt, MD, MBA, many patients well controlled on biologic therapy for their moderate to severe psoriasis often ask him when their scheduled injections can stop.

The most common question he hears is, “ ‘Why do I have to keep doing this? I’ve been clear for 2 or 3 years,’ ” Dr. Blauvelt, president of Oregon Medical Research Center, Portland, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “We have terrific drugs for psoriasis, but how can we do better?”

According to Dr. Blauvelt, there are at least six future strategies to treat psoriasis, induce remission, and/or cure the disease:

Development of oral biologics. At least two companies are developing a peptide-type small molecule that blocks interleukin (IL)-17 or IL-23 signaling, but would be given as a pill, he said. Another concept in the works is a robotic pill for drug delivery. The pill, which is being developed by Rani Therapeutics, protects the biotherapeutic drug payload from digestion in the GI tract and auto-injects it into the wall of the small intestine, according to a report of two studies that demonstrated the safety and tolerability of the robotic pill in healthy humans.

Doug Brunk/MDedge News

In an animal study, the same researchers showed that delivering monoclonal antibodies with the robotic pill achieved bioavailability on par with that obtained by standard subcutaneous injections.

Identifying “super responders” who require less frequent dosing of medication. “There’s data to suggest that we can kind of back off treatment in these patients,” Dr. Blauvelt said.

Hitting treatment hard and early. “There’s a concept in medicine of hitting disease hard and hitting it early, before the disease can establish itself and cause damage,” he said.

Targeting tissue resident memory T cells. In psoriasis, the idea is that if you treat earlier, when patients are just diagnosed, “perhaps you might be able to decrease resident memory T cells that set up shop in the skin and are responsible for disease recurrences,” Dr. Blauvelt said. “Research has shown that IL-23 blockers decrease tissue resident memory T cells, and IL-17 blockers don’t. This could explain why we see long remissions in this class of drug because we’re getting at these resident memory T cells and knocking them down,” he explained. “Our hypothesis is that hitting hard and early in the treatment course with high-dose IL-23 blockade may be an effective strategy to induce long-term remissions and possible cure, what we call ‘knock-out therapy.’ ”

In a pilot study of 20 patients, Dr. Blauvelt and colleagues are evaluating whether higher initial doses of the IL-23 antagonist risankizumab (300 mg and 600 mg, 2 times and 4 times the standard initial doses for plaque psoriasis) can more effectively target resident memory T cells. “This involves dosing at weeks 0, 4, and 16, then stopping and measuring resident T cells in the tissue to see how long we can induce psoriasis remissions,” Dr. Blauvelt said.

“I have no data to share, but I think we have the potential for unprecedented PASI-100 numbers with no added safety concerns, and the potential to break away from established regular dosing patterns,” such as the possibility of yearly dosing, the possibility of long-term remissions, and the possibility of cure in some patients, he noted.

Inducing tolerance. This refers to efforts aimed at increasing regulatory T cells, which are natural T cells that calm inflammation. He described it as “revving up our natural anti-inflammatory T cells to help balance the immune system.”

Gene editing. This involves using CRISPR gene editing technology to cut genes as a way to cure disease. “What if we cut the IL-23 receptor?” Dr. Blauvelt asked. “You would get rid of that whole signaling pathway. Would the patient be fine?”

In an interview a the meeting, Linda Stein Gold, MD, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit, said that Dr. Blauvelt “has a very exciting view” of the future of psoriasis treatments. “I think that some of it will come true; we’ll have to see which,” Dr. Stein Gold said. “The idea that we might be able to change the trajectory of disease by being aggressive upfront, and possibly modify the course, is exciting. That would be a wonderful new treatment approach.”

Dr. Blauvelt disclosed ties with AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Arena, ASLAN Pharma, Athenex, Bluefin, Boehringer Ingelheim, Bristol Myers Squibb, Cara, Dermavant, EcoR1, Escient, Evelo, Evommune, Forte, Galderma, Highlightll, Incyte, Innovent Bio, Janssen, Landos, Leo, Lilly, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi-Genzyme, Spherix, Sun Pharmaceuticals Industries, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor.

Dr. Stein Gold disclosed ties with Almirall, Cutera, Dermata, Galderma, Novartis, Ortho Dermatologics, and Sun Pharmaceutical Industries, Ltd.

Medscape and this news organization are owned by the same parent company.

HONOLULU – During office visits with Andrew Blauvelt, MD, MBA, many patients well controlled on biologic therapy for their moderate to severe psoriasis often ask him when their scheduled injections can stop.

The most common question he hears is, “ ‘Why do I have to keep doing this? I’ve been clear for 2 or 3 years,’ ” Dr. Blauvelt, president of Oregon Medical Research Center, Portland, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “We have terrific drugs for psoriasis, but how can we do better?”

According to Dr. Blauvelt, there are at least six future strategies to treat psoriasis, induce remission, and/or cure the disease:

Development of oral biologics. At least two companies are developing a peptide-type small molecule that blocks interleukin (IL)-17 or IL-23 signaling, but would be given as a pill, he said. Another concept in the works is a robotic pill for drug delivery. The pill, which is being developed by Rani Therapeutics, protects the biotherapeutic drug payload from digestion in the GI tract and auto-injects it into the wall of the small intestine, according to a report of two studies that demonstrated the safety and tolerability of the robotic pill in healthy humans.

Doug Brunk/MDedge News

In an animal study, the same researchers showed that delivering monoclonal antibodies with the robotic pill achieved bioavailability on par with that obtained by standard subcutaneous injections.

Identifying “super responders” who require less frequent dosing of medication. “There’s data to suggest that we can kind of back off treatment in these patients,” Dr. Blauvelt said.

Hitting treatment hard and early. “There’s a concept in medicine of hitting disease hard and hitting it early, before the disease can establish itself and cause damage,” he said.

Targeting tissue resident memory T cells. In psoriasis, the idea is that if you treat earlier, when patients are just diagnosed, “perhaps you might be able to decrease resident memory T cells that set up shop in the skin and are responsible for disease recurrences,” Dr. Blauvelt said. “Research has shown that IL-23 blockers decrease tissue resident memory T cells, and IL-17 blockers don’t. This could explain why we see long remissions in this class of drug because we’re getting at these resident memory T cells and knocking them down,” he explained. “Our hypothesis is that hitting hard and early in the treatment course with high-dose IL-23 blockade may be an effective strategy to induce long-term remissions and possible cure, what we call ‘knock-out therapy.’ ”

In a pilot study of 20 patients, Dr. Blauvelt and colleagues are evaluating whether higher initial doses of the IL-23 antagonist risankizumab (300 mg and 600 mg, 2 times and 4 times the standard initial doses for plaque psoriasis) can more effectively target resident memory T cells. “This involves dosing at weeks 0, 4, and 16, then stopping and measuring resident T cells in the tissue to see how long we can induce psoriasis remissions,” Dr. Blauvelt said.

“I have no data to share, but I think we have the potential for unprecedented PASI-100 numbers with no added safety concerns, and the potential to break away from established regular dosing patterns,” such as the possibility of yearly dosing, the possibility of long-term remissions, and the possibility of cure in some patients, he noted.

Inducing tolerance. This refers to efforts aimed at increasing regulatory T cells, which are natural T cells that calm inflammation. He described it as “revving up our natural anti-inflammatory T cells to help balance the immune system.”

Gene editing. This involves using CRISPR gene editing technology to cut genes as a way to cure disease. “What if we cut the IL-23 receptor?” Dr. Blauvelt asked. “You would get rid of that whole signaling pathway. Would the patient be fine?”

In an interview a the meeting, Linda Stein Gold, MD, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit, said that Dr. Blauvelt “has a very exciting view” of the future of psoriasis treatments. “I think that some of it will come true; we’ll have to see which,” Dr. Stein Gold said. “The idea that we might be able to change the trajectory of disease by being aggressive upfront, and possibly modify the course, is exciting. That would be a wonderful new treatment approach.”

Dr. Blauvelt disclosed ties with AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Arena, ASLAN Pharma, Athenex, Bluefin, Boehringer Ingelheim, Bristol Myers Squibb, Cara, Dermavant, EcoR1, Escient, Evelo, Evommune, Forte, Galderma, Highlightll, Incyte, Innovent Bio, Janssen, Landos, Leo, Lilly, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi-Genzyme, Spherix, Sun Pharmaceuticals Industries, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor.

Dr. Stein Gold disclosed ties with Almirall, Cutera, Dermata, Galderma, Novartis, Ortho Dermatologics, and Sun Pharmaceutical Industries, Ltd.

Medscape and this news organization are owned by the same parent company.

HONOLULU – During office visits with Andrew Blauvelt, MD, MBA, many patients well controlled on biologic therapy for their moderate to severe psoriasis often ask him when their scheduled injections can stop.

The most common question he hears is, “ ‘Why do I have to keep doing this? I’ve been clear for 2 or 3 years,’ ” Dr. Blauvelt, president of Oregon Medical Research Center, Portland, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! “We have terrific drugs for psoriasis, but how can we do better?”

According to Dr. Blauvelt, there are at least six future strategies to treat psoriasis, induce remission, and/or cure the disease:

Development of oral biologics. At least two companies are developing a peptide-type small molecule that blocks interleukin (IL)-17 or IL-23 signaling, but would be given as a pill, he said. Another concept in the works is a robotic pill for drug delivery. The pill, which is being developed by Rani Therapeutics, protects the biotherapeutic drug payload from digestion in the GI tract and auto-injects it into the wall of the small intestine, according to a report of two studies that demonstrated the safety and tolerability of the robotic pill in healthy humans.

Doug Brunk/MDedge News

In an animal study, the same researchers showed that delivering monoclonal antibodies with the robotic pill achieved bioavailability on par with that obtained by standard subcutaneous injections.

Identifying “super responders” who require less frequent dosing of medication. “There’s data to suggest that we can kind of back off treatment in these patients,” Dr. Blauvelt said.

Hitting treatment hard and early. “There’s a concept in medicine of hitting disease hard and hitting it early, before the disease can establish itself and cause damage,” he said.

Targeting tissue resident memory T cells. In psoriasis, the idea is that if you treat earlier, when patients are just diagnosed, “perhaps you might be able to decrease resident memory T cells that set up shop in the skin and are responsible for disease recurrences,” Dr. Blauvelt said. “Research has shown that IL-23 blockers decrease tissue resident memory T cells, and IL-17 blockers don’t. This could explain why we see long remissions in this class of drug because we’re getting at these resident memory T cells and knocking them down,” he explained. “Our hypothesis is that hitting hard and early in the treatment course with high-dose IL-23 blockade may be an effective strategy to induce long-term remissions and possible cure, what we call ‘knock-out therapy.’ ”

In a pilot study of 20 patients, Dr. Blauvelt and colleagues are evaluating whether higher initial doses of the IL-23 antagonist risankizumab (300 mg and 600 mg, 2 times and 4 times the standard initial doses for plaque psoriasis) can more effectively target resident memory T cells. “This involves dosing at weeks 0, 4, and 16, then stopping and measuring resident T cells in the tissue to see how long we can induce psoriasis remissions,” Dr. Blauvelt said.

“I have no data to share, but I think we have the potential for unprecedented PASI-100 numbers with no added safety concerns, and the potential to break away from established regular dosing patterns,” such as the possibility of yearly dosing, the possibility of long-term remissions, and the possibility of cure in some patients, he noted.

Inducing tolerance. This refers to efforts aimed at increasing regulatory T cells, which are natural T cells that calm inflammation. He described it as “revving up our natural anti-inflammatory T cells to help balance the immune system.”

Gene editing. This involves using CRISPR gene editing technology to cut genes as a way to cure disease. “What if we cut the IL-23 receptor?” Dr. Blauvelt asked. “You would get rid of that whole signaling pathway. Would the patient be fine?”

In an interview a the meeting, Linda Stein Gold, MD, director of clinical research and division head of dermatology at the Henry Ford Health System, Detroit, said that Dr. Blauvelt “has a very exciting view” of the future of psoriasis treatments. “I think that some of it will come true; we’ll have to see which,” Dr. Stein Gold said. “The idea that we might be able to change the trajectory of disease by being aggressive upfront, and possibly modify the course, is exciting. That would be a wonderful new treatment approach.”

Dr. Blauvelt disclosed ties with AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Arcutis, Arena, ASLAN Pharma, Athenex, Bluefin, Boehringer Ingelheim, Bristol Myers Squibb, Cara, Dermavant, EcoR1, Escient, Evelo, Evommune, Forte, Galderma, Highlightll, Incyte, Innovent Bio, Janssen, Landos, Leo, Lilly, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi-Genzyme, Spherix, Sun Pharmaceuticals Industries, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor.

Dr. Stein Gold disclosed ties with Almirall, Cutera, Dermata, Galderma, Novartis, Ortho Dermatologics, and Sun Pharmaceutical Industries, Ltd.

Medscape and this news organization are owned by the same parent company.

A new tool for predicting which patients with psoriasis will develop psoriatic arthritis (PsA) is showing promise for such clinical applications as early treatment in those at risk or trials to prevent PsA, according to a summary of progress at the annual meeting of the Canadian Rheumatology Association.

Based on current levels of sensitivity and specificity, psoriasis “can be predicted with reasonable accuracy,” reported Lihi Eder, MD, PhD, director of research in the rheumatology division at the University of Toronto.

The predictive method, called PRESTO (Prediction of Psoriatic Arthritis Tool), is based on variables readily available in clinical practice, according to Dr. Eder. Once values are assigned to the risk factors, the risk of PsA over a 1-year or 5-year time frame can be estimated with a calculator.

She called PRESTO the “first clinical tool for predicting PsA among psoriasis patients.”

The work on this tool began in 2006 when the International Psoriasis and Arthritis Research Team (IPART) initiated a prospectively collected cohort of psoriasis patients. To be enrolled, patients had to be free of signs and symptoms of arthritis upon examination by a rheumatologist. They were then invited to return annually for follow-up that again included screening for joint involvement by a rheumatologist.

At baseline and at follow-up evaluations, 13 predictors were evaluated. These involved psoriasis characteristics, such as nail pitting; symptoms, such as stiffness; comorbidities, such as additional inflammatory diseases; and laboratory values, such as upregulated markers of inflammation.

Symptoms and signs used to predict PsA

Dr. Eder and her colleagues applied regression models to select an optimal combination of variables weighted for predictive value. Variables offering predictive value included higher PASI (Psoriasis Area and Severity Index), greater fatigue score as measured by FACIT (Functional Assessment of Chronic Illness Therapy) score, greater morning stiffness, and greater pain.

When applied to 635 patients in the IPART cohort, in which there were 51 incident PsA cases over 1 year and 75 incident cases over 5 years, the area under the curve (AUC) for PRESTO at the cutoffs studied was 72% for the 1-year time window and 75% for the 5-year time window.

These levels are associated with adequate accuracy, according to Dr. Eder, who explained that “an AUC greater than 70% is considered reasonable” for clinical applicability.

Moreover, the cutoffs can be adjusted for the specific purpose of the predictive tool. For example, to screen patients for risk, lower cutoffs could be employed to increase sensitivity. In order to select patients for a clinical trial to prevent PsA, higher cutoffs could be employed to increase specificity.

But sensitivities and specificities move in opposite directions when cutoffs are adjusted. Showing data from the 5-year prediction model, Dr. Eder reported that specificities climbed from about 58% to 97% as cutoffs were increased. The sensitivities with these adjustments fell from 79% to 14%.

In general, Dr. Eder said there was “excellent calibration” for the cutoffs employed when they compared the predicted and observed rates of PsA according to quintile of predictive probability. The differences were particularly minor over a 1-year time period. Over the 5-year period, observed rates were somewhat higher than predicted in the fourth and fifth quintile, but, again, this discrepancy could be modified for specific applications with cutoff adjustments.

Validation studies are planned

Even though psoriasis patients in IPART represents one of the largest cohorts of prospectively collected psoriasis patients, Dr. Eder acknowledged that the sample size would be considered “moderate” for developing a predictive model. However, the fact that the data were collected prospectively using standardized methodology strengthens the findings and provides the basis for the next step.

“Validation studies are planned with external cohorts,” said Dr. Eder, who indicated that a viable tool for identifying psoriasis patients at risk for PsA is likely. Even if it is not employed routinely in its current form at the level of individual patient care, she predicted that it will have value at a research level for understanding the relationship of psoriasis to PsA.

Christopher T. Ritchlin, MD, a professor and researcher at the University of Rochester (N.Y.), agreed that PRESTO has important potential as a clinical tool. Dr. Ritchlin has been involved in the development of PRESTO but was not involved in the presentation made at the CRA annual meeting.

“The PRESTO tool has the ability to predict the 2- and 5-year risk of developing psoriatic arthritis, which is an important advance if confirmed,” he said in an interview. He pointed out that approximately 25%-30% who develop psoriasis will go on to develop PsA but until now there has been no way to identify them.

“This tool may provide a pathway to early intervention,” he said.

Dr. Eder has financial relationships with AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB. Dr. Ritchlin has financial relationships with many of the same companies.

A new tool for predicting which patients with psoriasis will develop psoriatic arthritis (PsA) is showing promise for such clinical applications as early treatment in those at risk or trials to prevent PsA, according to a summary of progress at the annual meeting of the Canadian Rheumatology Association.

Based on current levels of sensitivity and specificity, psoriasis “can be predicted with reasonable accuracy,” reported Lihi Eder, MD, PhD, director of research in the rheumatology division at the University of Toronto.

The predictive method, called PRESTO (Prediction of Psoriatic Arthritis Tool), is based on variables readily available in clinical practice, according to Dr. Eder. Once values are assigned to the risk factors, the risk of PsA over a 1-year or 5-year time frame can be estimated with a calculator.

She called PRESTO the “first clinical tool for predicting PsA among psoriasis patients.”

The work on this tool began in 2006 when the International Psoriasis and Arthritis Research Team (IPART) initiated a prospectively collected cohort of psoriasis patients. To be enrolled, patients had to be free of signs and symptoms of arthritis upon examination by a rheumatologist. They were then invited to return annually for follow-up that again included screening for joint involvement by a rheumatologist.

At baseline and at follow-up evaluations, 13 predictors were evaluated. These involved psoriasis characteristics, such as nail pitting; symptoms, such as stiffness; comorbidities, such as additional inflammatory diseases; and laboratory values, such as upregulated markers of inflammation.

Symptoms and signs used to predict PsA

Dr. Eder and her colleagues applied regression models to select an optimal combination of variables weighted for predictive value. Variables offering predictive value included higher PASI (Psoriasis Area and Severity Index), greater fatigue score as measured by FACIT (Functional Assessment of Chronic Illness Therapy) score, greater morning stiffness, and greater pain.

When applied to 635 patients in the IPART cohort, in which there were 51 incident PsA cases over 1 year and 75 incident cases over 5 years, the area under the curve (AUC) for PRESTO at the cutoffs studied was 72% for the 1-year time window and 75% for the 5-year time window.

These levels are associated with adequate accuracy, according to Dr. Eder, who explained that “an AUC greater than 70% is considered reasonable” for clinical applicability.

Moreover, the cutoffs can be adjusted for the specific purpose of the predictive tool. For example, to screen patients for risk, lower cutoffs could be employed to increase sensitivity. In order to select patients for a clinical trial to prevent PsA, higher cutoffs could be employed to increase specificity.

But sensitivities and specificities move in opposite directions when cutoffs are adjusted. Showing data from the 5-year prediction model, Dr. Eder reported that specificities climbed from about 58% to 97% as cutoffs were increased. The sensitivities with these adjustments fell from 79% to 14%.

In general, Dr. Eder said there was “excellent calibration” for the cutoffs employed when they compared the predicted and observed rates of PsA according to quintile of predictive probability. The differences were particularly minor over a 1-year time period. Over the 5-year period, observed rates were somewhat higher than predicted in the fourth and fifth quintile, but, again, this discrepancy could be modified for specific applications with cutoff adjustments.

Validation studies are planned

Even though psoriasis patients in IPART represents one of the largest cohorts of prospectively collected psoriasis patients, Dr. Eder acknowledged that the sample size would be considered “moderate” for developing a predictive model. However, the fact that the data were collected prospectively using standardized methodology strengthens the findings and provides the basis for the next step.

“Validation studies are planned with external cohorts,” said Dr. Eder, who indicated that a viable tool for identifying psoriasis patients at risk for PsA is likely. Even if it is not employed routinely in its current form at the level of individual patient care, she predicted that it will have value at a research level for understanding the relationship of psoriasis to PsA.

Christopher T. Ritchlin, MD, a professor and researcher at the University of Rochester (N.Y.), agreed that PRESTO has important potential as a clinical tool. Dr. Ritchlin has been involved in the development of PRESTO but was not involved in the presentation made at the CRA annual meeting.

“The PRESTO tool has the ability to predict the 2- and 5-year risk of developing psoriatic arthritis, which is an important advance if confirmed,” he said in an interview. He pointed out that approximately 25%-30% who develop psoriasis will go on to develop PsA but until now there has been no way to identify them.

“This tool may provide a pathway to early intervention,” he said.

Dr. Eder has financial relationships with AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB. Dr. Ritchlin has financial relationships with many of the same companies.

A new tool for predicting which patients with psoriasis will develop psoriatic arthritis (PsA) is showing promise for such clinical applications as early treatment in those at risk or trials to prevent PsA, according to a summary of progress at the annual meeting of the Canadian Rheumatology Association.

Based on current levels of sensitivity and specificity, psoriasis “can be predicted with reasonable accuracy,” reported Lihi Eder, MD, PhD, director of research in the rheumatology division at the University of Toronto.

The predictive method, called PRESTO (Prediction of Psoriatic Arthritis Tool), is based on variables readily available in clinical practice, according to Dr. Eder. Once values are assigned to the risk factors, the risk of PsA over a 1-year or 5-year time frame can be estimated with a calculator.

She called PRESTO the “first clinical tool for predicting PsA among psoriasis patients.”

The work on this tool began in 2006 when the International Psoriasis and Arthritis Research Team (IPART) initiated a prospectively collected cohort of psoriasis patients. To be enrolled, patients had to be free of signs and symptoms of arthritis upon examination by a rheumatologist. They were then invited to return annually for follow-up that again included screening for joint involvement by a rheumatologist.

At baseline and at follow-up evaluations, 13 predictors were evaluated. These involved psoriasis characteristics, such as nail pitting; symptoms, such as stiffness; comorbidities, such as additional inflammatory diseases; and laboratory values, such as upregulated markers of inflammation.

Symptoms and signs used to predict PsA

Dr. Eder and her colleagues applied regression models to select an optimal combination of variables weighted for predictive value. Variables offering predictive value included higher PASI (Psoriasis Area and Severity Index), greater fatigue score as measured by FACIT (Functional Assessment of Chronic Illness Therapy) score, greater morning stiffness, and greater pain.

When applied to 635 patients in the IPART cohort, in which there were 51 incident PsA cases over 1 year and 75 incident cases over 5 years, the area under the curve (AUC) for PRESTO at the cutoffs studied was 72% for the 1-year time window and 75% for the 5-year time window.

These levels are associated with adequate accuracy, according to Dr. Eder, who explained that “an AUC greater than 70% is considered reasonable” for clinical applicability.

Moreover, the cutoffs can be adjusted for the specific purpose of the predictive tool. For example, to screen patients for risk, lower cutoffs could be employed to increase sensitivity. In order to select patients for a clinical trial to prevent PsA, higher cutoffs could be employed to increase specificity.

But sensitivities and specificities move in opposite directions when cutoffs are adjusted. Showing data from the 5-year prediction model, Dr. Eder reported that specificities climbed from about 58% to 97% as cutoffs were increased. The sensitivities with these adjustments fell from 79% to 14%.

In general, Dr. Eder said there was “excellent calibration” for the cutoffs employed when they compared the predicted and observed rates of PsA according to quintile of predictive probability. The differences were particularly minor over a 1-year time period. Over the 5-year period, observed rates were somewhat higher than predicted in the fourth and fifth quintile, but, again, this discrepancy could be modified for specific applications with cutoff adjustments.

Validation studies are planned

Even though psoriasis patients in IPART represents one of the largest cohorts of prospectively collected psoriasis patients, Dr. Eder acknowledged that the sample size would be considered “moderate” for developing a predictive model. However, the fact that the data were collected prospectively using standardized methodology strengthens the findings and provides the basis for the next step.

“Validation studies are planned with external cohorts,” said Dr. Eder, who indicated that a viable tool for identifying psoriasis patients at risk for PsA is likely. Even if it is not employed routinely in its current form at the level of individual patient care, she predicted that it will have value at a research level for understanding the relationship of psoriasis to PsA.

Christopher T. Ritchlin, MD, a professor and researcher at the University of Rochester (N.Y.), agreed that PRESTO has important potential as a clinical tool. Dr. Ritchlin has been involved in the development of PRESTO but was not involved in the presentation made at the CRA annual meeting.

“The PRESTO tool has the ability to predict the 2- and 5-year risk of developing psoriatic arthritis, which is an important advance if confirmed,” he said in an interview. He pointed out that approximately 25%-30% who develop psoriasis will go on to develop PsA but until now there has been no way to identify them.

“This tool may provide a pathway to early intervention,” he said.

Dr. Eder has financial relationships with AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB. Dr. Ritchlin has financial relationships with many of the same companies.