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Deucravacitinib offers biologic-like psoriasis efficacy in oral form
and a range of other chronic inflammatory diseases, Bruce E. Strober, MD, PhD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
Deucravacitinib solely blocks tyrosine kinase 2 (TYK2) signaling without touching Janus kinase (JAK) 1, 2, or 3. In so doing, it inhibits several cytokines important for inflammation: interleukin-12, IL-13, and interferon-alpha and -beta. Yet it doesn’t affect the numerous pathways mediated by JAKs 1-3, many of which relate to growth and development of cell lineages, including production of erythropoietin, thrombopoietin, granulocyte-macrophage colony-stimulating factor, prolactin, growth hormone, and leptin. These deucravacitinib characteristics should translate into fewer off-target side effects than with oral JAK inhibitors.
“The promise of TYK2 inhibition that’s brought to you by deucravacitinib is there will be no laboratory monitoring and the effects will be narrow in blocking inflammation,” said Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and in private practice in Cromwell, Conn.
He highlighted the positive results of a randomized, phase 2, dose-ranging study conducted in 267 patients with moderate or severe plaque psoriasis. Participants had an average baseline Psoriasis Area and Severity Index (PASI) score of 19, with a Dermatology Life Quality Index score of about 12. At the top dose of 12 mg once daily, 75% of patients achieved a PASI 75 response at week 12, and 44% reached a PASI 90, as did 69% and 44%, respectively, who were on deucravacitinib at 3 mg twice daily. Those are collective efficacy numbers similar to adalimumab (Humira) or ustekinumab (Stelara).
Deucravacitinib may provide efficacy “like one of our second-tier biological therapies, yet it will be oral,” Dr. Strober commented.
Importantly, no laboratory abnormalities were detected in this trial. Only mild side effects were documented, most prominently acne, which occurred in dose-dependent fashion in 2% of patients on 3 mg of deucravacitinib twice daily and 4% at 12 mg once daily.
“The treatment of the acne that is elicited by this drug is yet to be fully described, but I’m sure we’ll learn the best approaches, given that acne is in our wheel house,” the dermatologist added.
Bristol-Myers Squibb has announced positive results from the pivotal phase 3 POETYK PSO-1 trial. Deucravacitinib at 6 mg once daily met both of its coprimary efficacy endpoints in the study, which included 666 patients with moderate to severe psoriasis. The TYK 2 inhibitor demonstrated superiority to both placebo and oral apremilast (Otezla) at week 16. The company said the safety profile was consistent with the phase 2 results, and that the full details of the phase 3 trial will be presented next year at a major medical meeting.
In addition, positive phase 2 results were reported for deucravacitinib in the treatment of psoriatic arthritis in a randomized trial presented at the fall 2020 meeting of the American College of Rheumatology. Deucravacitinib is also under study for lupus and inflammatory bowel disease.
Dr. Strober, an active clinical trialist, reported serving as a consultant to more than two dozen pharmaceutical companies, including Bristol-Myers Squibb.
MedscapeLive and this news organization are owned by the same parent company.
and a range of other chronic inflammatory diseases, Bruce E. Strober, MD, PhD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
Deucravacitinib solely blocks tyrosine kinase 2 (TYK2) signaling without touching Janus kinase (JAK) 1, 2, or 3. In so doing, it inhibits several cytokines important for inflammation: interleukin-12, IL-13, and interferon-alpha and -beta. Yet it doesn’t affect the numerous pathways mediated by JAKs 1-3, many of which relate to growth and development of cell lineages, including production of erythropoietin, thrombopoietin, granulocyte-macrophage colony-stimulating factor, prolactin, growth hormone, and leptin. These deucravacitinib characteristics should translate into fewer off-target side effects than with oral JAK inhibitors.
“The promise of TYK2 inhibition that’s brought to you by deucravacitinib is there will be no laboratory monitoring and the effects will be narrow in blocking inflammation,” said Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and in private practice in Cromwell, Conn.
He highlighted the positive results of a randomized, phase 2, dose-ranging study conducted in 267 patients with moderate or severe plaque psoriasis. Participants had an average baseline Psoriasis Area and Severity Index (PASI) score of 19, with a Dermatology Life Quality Index score of about 12. At the top dose of 12 mg once daily, 75% of patients achieved a PASI 75 response at week 12, and 44% reached a PASI 90, as did 69% and 44%, respectively, who were on deucravacitinib at 3 mg twice daily. Those are collective efficacy numbers similar to adalimumab (Humira) or ustekinumab (Stelara).
Deucravacitinib may provide efficacy “like one of our second-tier biological therapies, yet it will be oral,” Dr. Strober commented.
Importantly, no laboratory abnormalities were detected in this trial. Only mild side effects were documented, most prominently acne, which occurred in dose-dependent fashion in 2% of patients on 3 mg of deucravacitinib twice daily and 4% at 12 mg once daily.
“The treatment of the acne that is elicited by this drug is yet to be fully described, but I’m sure we’ll learn the best approaches, given that acne is in our wheel house,” the dermatologist added.
Bristol-Myers Squibb has announced positive results from the pivotal phase 3 POETYK PSO-1 trial. Deucravacitinib at 6 mg once daily met both of its coprimary efficacy endpoints in the study, which included 666 patients with moderate to severe psoriasis. The TYK 2 inhibitor demonstrated superiority to both placebo and oral apremilast (Otezla) at week 16. The company said the safety profile was consistent with the phase 2 results, and that the full details of the phase 3 trial will be presented next year at a major medical meeting.
In addition, positive phase 2 results were reported for deucravacitinib in the treatment of psoriatic arthritis in a randomized trial presented at the fall 2020 meeting of the American College of Rheumatology. Deucravacitinib is also under study for lupus and inflammatory bowel disease.
Dr. Strober, an active clinical trialist, reported serving as a consultant to more than two dozen pharmaceutical companies, including Bristol-Myers Squibb.
MedscapeLive and this news organization are owned by the same parent company.
and a range of other chronic inflammatory diseases, Bruce E. Strober, MD, PhD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
Deucravacitinib solely blocks tyrosine kinase 2 (TYK2) signaling without touching Janus kinase (JAK) 1, 2, or 3. In so doing, it inhibits several cytokines important for inflammation: interleukin-12, IL-13, and interferon-alpha and -beta. Yet it doesn’t affect the numerous pathways mediated by JAKs 1-3, many of which relate to growth and development of cell lineages, including production of erythropoietin, thrombopoietin, granulocyte-macrophage colony-stimulating factor, prolactin, growth hormone, and leptin. These deucravacitinib characteristics should translate into fewer off-target side effects than with oral JAK inhibitors.
“The promise of TYK2 inhibition that’s brought to you by deucravacitinib is there will be no laboratory monitoring and the effects will be narrow in blocking inflammation,” said Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and in private practice in Cromwell, Conn.
He highlighted the positive results of a randomized, phase 2, dose-ranging study conducted in 267 patients with moderate or severe plaque psoriasis. Participants had an average baseline Psoriasis Area and Severity Index (PASI) score of 19, with a Dermatology Life Quality Index score of about 12. At the top dose of 12 mg once daily, 75% of patients achieved a PASI 75 response at week 12, and 44% reached a PASI 90, as did 69% and 44%, respectively, who were on deucravacitinib at 3 mg twice daily. Those are collective efficacy numbers similar to adalimumab (Humira) or ustekinumab (Stelara).
Deucravacitinib may provide efficacy “like one of our second-tier biological therapies, yet it will be oral,” Dr. Strober commented.
Importantly, no laboratory abnormalities were detected in this trial. Only mild side effects were documented, most prominently acne, which occurred in dose-dependent fashion in 2% of patients on 3 mg of deucravacitinib twice daily and 4% at 12 mg once daily.
“The treatment of the acne that is elicited by this drug is yet to be fully described, but I’m sure we’ll learn the best approaches, given that acne is in our wheel house,” the dermatologist added.
Bristol-Myers Squibb has announced positive results from the pivotal phase 3 POETYK PSO-1 trial. Deucravacitinib at 6 mg once daily met both of its coprimary efficacy endpoints in the study, which included 666 patients with moderate to severe psoriasis. The TYK 2 inhibitor demonstrated superiority to both placebo and oral apremilast (Otezla) at week 16. The company said the safety profile was consistent with the phase 2 results, and that the full details of the phase 3 trial will be presented next year at a major medical meeting.
In addition, positive phase 2 results were reported for deucravacitinib in the treatment of psoriatic arthritis in a randomized trial presented at the fall 2020 meeting of the American College of Rheumatology. Deucravacitinib is also under study for lupus and inflammatory bowel disease.
Dr. Strober, an active clinical trialist, reported serving as a consultant to more than two dozen pharmaceutical companies, including Bristol-Myers Squibb.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
Home phototherapy never looked better, expert says
Kenneth B. Gordon, MD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
“In my practice, I’m using more and more home UVB, and there are a number of reasons for that. It’s more convenient and easier for the patient, as it’s getting more difficult for patients to give up time from work to come to the office. And I might add that, in this time of COVID-19, people don’t want to come to the office. It’s generally less expensive for patients because of copays, which increase the cost of UVB. And believe it or not, I believe it’s easier for the clinician as well. I write a prescription, the patient gets a number of treatments, and I don’t lose any sleep because I think it’s very difficult for patients to get into trouble with narrow-band UVB at home,” explained Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“There’s all sorts of insurance company silliness in getting this paid for, but if you do get it paid for, I think it’s a really effective way to treat psoriasis,” the dermatologist added.
A Dutch multicenter randomized trial demonstrated that home UVB phototherapy for psoriasis was equally safe and effective as outpatient UVB phototherapy, and with greater patient satisfaction.
Surveys show most dermatologists consider phototherapy their preferred treatment for patients with extensive psoriasis because its side effect profile is so benign, compared with that of systemic therapies, be they biologic agents or older drugs such as methotrexate or acitretin. Phototherapy is particularly popular for use in women of childbearing potential, since it’s a nonsystemic therapy.
And speaking of side effects, Dr. Gordon declared, “The risks of narrow-band UVB are sometimes, I believe, exaggerated.” Indeed, he considers the No. 1 side effect of office-based phototherapy to be the loss of productive time.
“Simply put, phototherapy in the office is very easy for me. I write a prescription, the tech takes care of it, and if there’s a problem I’m handy to see the patient. But for the patient, it’s very difficult. Whereas it might take only a few minutes to get the treatment in-office, it takes a lot of time to get to the office, and many patients don’t have transportation. So I think the loss of productive time with phototherapy has to be considered a side effect,” Dr. Gordon said.
Turning to the therapy’s other side effects, he said that although there is some degree of photoaging associated with narrow-band UVB – which is far and away the most commonly used form of phototherapy in the United States – it’s nothing close to the photoaging caused by PUVA.
“I don’t believe that PUVA, with all the destruction of the skin that you see with it, is a significant part of our treatment modalities today,” Dr. Gordon said.
Sunburn is a risk with narrow-band UVB, especially if the dose is ramped up too quickly. Reactivation of herpes simplex virus infection is a frequent problem, and one patients find especially concerning when it manifests as eruptions of cold sores on the face.
The side effect of narrow-band UVB of greatest interest to most patients and physicians is skin cancer. “This is an extremely controversial area,” the dermatologist observed.
Unlike with PUVA, there has never been a convincing study to show that narrow-band UVB is associated with significantly increased risks of keratinocyte carcinomas or melanoma. A large Scottish study found no significantly increased risk, but a modestly increased trend for more squamous cell carcinomas. How modest? The investigators calculated that it would require 50,000 psoriasis patients with a minimum of 100 narrow-band UVB treatments to be followed for 5 years in order to demonstrate a twofold increased risk of the malignancy.
“In other words, it takes an incredible number of patients to be able to see a difference in a skin cancer that we can relatively easily treat. That’s why when I see patients, I don’t emphasize the risk of skin cancer,” Dr. Gordon said.
Similarly reassuring was a Swedish study, which showed the skin cancer rate in UVB-treated psoriasis patients was no different than in the general population.
Guideline recommendations regarding UVB phototherapy and skin cancer risk are all over the map. French guidelines advise a maximum of 230 narrow-band UVB treatments. British guidelines recommend reducing narrow-band UVB exposure to skin areas with significant sun exposure. American guidelines leave the topic untouched, Dr. Gordon noted.
He reported having no financial conflicts of interest regarding his presentation, as neither he, the Medical College of Wisconsin, or its department of dermatology receive any payment for phototherapy services he prescribes. Those payments go to the hospital system where he works. MedscapeLive and this news organization are owned by the same parent company.
Kenneth B. Gordon, MD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
“In my practice, I’m using more and more home UVB, and there are a number of reasons for that. It’s more convenient and easier for the patient, as it’s getting more difficult for patients to give up time from work to come to the office. And I might add that, in this time of COVID-19, people don’t want to come to the office. It’s generally less expensive for patients because of copays, which increase the cost of UVB. And believe it or not, I believe it’s easier for the clinician as well. I write a prescription, the patient gets a number of treatments, and I don’t lose any sleep because I think it’s very difficult for patients to get into trouble with narrow-band UVB at home,” explained Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“There’s all sorts of insurance company silliness in getting this paid for, but if you do get it paid for, I think it’s a really effective way to treat psoriasis,” the dermatologist added.
A Dutch multicenter randomized trial demonstrated that home UVB phototherapy for psoriasis was equally safe and effective as outpatient UVB phototherapy, and with greater patient satisfaction.
Surveys show most dermatologists consider phototherapy their preferred treatment for patients with extensive psoriasis because its side effect profile is so benign, compared with that of systemic therapies, be they biologic agents or older drugs such as methotrexate or acitretin. Phototherapy is particularly popular for use in women of childbearing potential, since it’s a nonsystemic therapy.
And speaking of side effects, Dr. Gordon declared, “The risks of narrow-band UVB are sometimes, I believe, exaggerated.” Indeed, he considers the No. 1 side effect of office-based phototherapy to be the loss of productive time.
“Simply put, phototherapy in the office is very easy for me. I write a prescription, the tech takes care of it, and if there’s a problem I’m handy to see the patient. But for the patient, it’s very difficult. Whereas it might take only a few minutes to get the treatment in-office, it takes a lot of time to get to the office, and many patients don’t have transportation. So I think the loss of productive time with phototherapy has to be considered a side effect,” Dr. Gordon said.
Turning to the therapy’s other side effects, he said that although there is some degree of photoaging associated with narrow-band UVB – which is far and away the most commonly used form of phototherapy in the United States – it’s nothing close to the photoaging caused by PUVA.
“I don’t believe that PUVA, with all the destruction of the skin that you see with it, is a significant part of our treatment modalities today,” Dr. Gordon said.
Sunburn is a risk with narrow-band UVB, especially if the dose is ramped up too quickly. Reactivation of herpes simplex virus infection is a frequent problem, and one patients find especially concerning when it manifests as eruptions of cold sores on the face.
The side effect of narrow-band UVB of greatest interest to most patients and physicians is skin cancer. “This is an extremely controversial area,” the dermatologist observed.
Unlike with PUVA, there has never been a convincing study to show that narrow-band UVB is associated with significantly increased risks of keratinocyte carcinomas or melanoma. A large Scottish study found no significantly increased risk, but a modestly increased trend for more squamous cell carcinomas. How modest? The investigators calculated that it would require 50,000 psoriasis patients with a minimum of 100 narrow-band UVB treatments to be followed for 5 years in order to demonstrate a twofold increased risk of the malignancy.
“In other words, it takes an incredible number of patients to be able to see a difference in a skin cancer that we can relatively easily treat. That’s why when I see patients, I don’t emphasize the risk of skin cancer,” Dr. Gordon said.
Similarly reassuring was a Swedish study, which showed the skin cancer rate in UVB-treated psoriasis patients was no different than in the general population.
Guideline recommendations regarding UVB phototherapy and skin cancer risk are all over the map. French guidelines advise a maximum of 230 narrow-band UVB treatments. British guidelines recommend reducing narrow-band UVB exposure to skin areas with significant sun exposure. American guidelines leave the topic untouched, Dr. Gordon noted.
He reported having no financial conflicts of interest regarding his presentation, as neither he, the Medical College of Wisconsin, or its department of dermatology receive any payment for phototherapy services he prescribes. Those payments go to the hospital system where he works. MedscapeLive and this news organization are owned by the same parent company.
Kenneth B. Gordon, MD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
“In my practice, I’m using more and more home UVB, and there are a number of reasons for that. It’s more convenient and easier for the patient, as it’s getting more difficult for patients to give up time from work to come to the office. And I might add that, in this time of COVID-19, people don’t want to come to the office. It’s generally less expensive for patients because of copays, which increase the cost of UVB. And believe it or not, I believe it’s easier for the clinician as well. I write a prescription, the patient gets a number of treatments, and I don’t lose any sleep because I think it’s very difficult for patients to get into trouble with narrow-band UVB at home,” explained Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“There’s all sorts of insurance company silliness in getting this paid for, but if you do get it paid for, I think it’s a really effective way to treat psoriasis,” the dermatologist added.
A Dutch multicenter randomized trial demonstrated that home UVB phototherapy for psoriasis was equally safe and effective as outpatient UVB phototherapy, and with greater patient satisfaction.
Surveys show most dermatologists consider phototherapy their preferred treatment for patients with extensive psoriasis because its side effect profile is so benign, compared with that of systemic therapies, be they biologic agents or older drugs such as methotrexate or acitretin. Phototherapy is particularly popular for use in women of childbearing potential, since it’s a nonsystemic therapy.
And speaking of side effects, Dr. Gordon declared, “The risks of narrow-band UVB are sometimes, I believe, exaggerated.” Indeed, he considers the No. 1 side effect of office-based phototherapy to be the loss of productive time.
“Simply put, phototherapy in the office is very easy for me. I write a prescription, the tech takes care of it, and if there’s a problem I’m handy to see the patient. But for the patient, it’s very difficult. Whereas it might take only a few minutes to get the treatment in-office, it takes a lot of time to get to the office, and many patients don’t have transportation. So I think the loss of productive time with phototherapy has to be considered a side effect,” Dr. Gordon said.
Turning to the therapy’s other side effects, he said that although there is some degree of photoaging associated with narrow-band UVB – which is far and away the most commonly used form of phototherapy in the United States – it’s nothing close to the photoaging caused by PUVA.
“I don’t believe that PUVA, with all the destruction of the skin that you see with it, is a significant part of our treatment modalities today,” Dr. Gordon said.
Sunburn is a risk with narrow-band UVB, especially if the dose is ramped up too quickly. Reactivation of herpes simplex virus infection is a frequent problem, and one patients find especially concerning when it manifests as eruptions of cold sores on the face.
The side effect of narrow-band UVB of greatest interest to most patients and physicians is skin cancer. “This is an extremely controversial area,” the dermatologist observed.
Unlike with PUVA, there has never been a convincing study to show that narrow-band UVB is associated with significantly increased risks of keratinocyte carcinomas or melanoma. A large Scottish study found no significantly increased risk, but a modestly increased trend for more squamous cell carcinomas. How modest? The investigators calculated that it would require 50,000 psoriasis patients with a minimum of 100 narrow-band UVB treatments to be followed for 5 years in order to demonstrate a twofold increased risk of the malignancy.
“In other words, it takes an incredible number of patients to be able to see a difference in a skin cancer that we can relatively easily treat. That’s why when I see patients, I don’t emphasize the risk of skin cancer,” Dr. Gordon said.
Similarly reassuring was a Swedish study, which showed the skin cancer rate in UVB-treated psoriasis patients was no different than in the general population.
Guideline recommendations regarding UVB phototherapy and skin cancer risk are all over the map. French guidelines advise a maximum of 230 narrow-band UVB treatments. British guidelines recommend reducing narrow-band UVB exposure to skin areas with significant sun exposure. American guidelines leave the topic untouched, Dr. Gordon noted.
He reported having no financial conflicts of interest regarding his presentation, as neither he, the Medical College of Wisconsin, or its department of dermatology receive any payment for phototherapy services he prescribes. Those payments go to the hospital system where he works. MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
COVID-19 vaccines: Safe for immunocompromised patients?
Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.
The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.
At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.
In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”
That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.
“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”
Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”
However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.
The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.
COVID-19 vaccines
Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.
But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.
In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.
The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.
“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”
Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.
It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.
According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.
As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?
Risk vs. benefit
Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.
“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”
The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”
That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”
Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”
So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.
“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
No waiting needed
Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.
“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”
However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”
Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.
The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.
He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.
Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”
He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”
Boosting efficacy
Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”
With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”
As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”
There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”
The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”
Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”
Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”
Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”
Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”
He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”
The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.
Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.
The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.
At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.
In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”
That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.
“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”
Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”
However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.
The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.
COVID-19 vaccines
Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.
But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.
In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.
The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.
“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”
Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.
It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.
According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.
As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?
Risk vs. benefit
Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.
“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”
The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”
That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”
Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”
So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.
“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
No waiting needed
Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.
“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”
However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”
Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.
The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.
He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.
Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”
He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”
Boosting efficacy
Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”
With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”
As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”
There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”
The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”
Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”
Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”
Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”
Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”
He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”
The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.
Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.
The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.
At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.
In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”
That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.
“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”
Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”
However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.
The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.
COVID-19 vaccines
Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.
But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.
In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.
The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.
“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”
Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.
It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.
According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.
As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?
Risk vs. benefit
Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.
“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”
The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”
That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”
Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”
So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.
“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
No waiting needed
Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.
“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”
However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”
Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.
The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.
He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.
Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”
He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”
Boosting efficacy
Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”
With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”
As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”
There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”
The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”
Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”
Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”
Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”
Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”
He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”
The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.
Diet and Skin: A Primer
Dermatologists frequently learn about skin conditions that are directly linked to diet. For example, we know that nutritional deficiencies can impact the hair, skin, and nails, and that celiac disease manifests with dermatitis herpetiformis of the skin. Patients commonly ask their dermatologists about the impact of diet on their skin. There are many outdated myths, but research on the subject is increasingly demonstrating important associations. Dermatologists must become familiar with the data on this topic so that we can provide informed counseling for our patients. This article reviews the current literature on associations between diet and 3 common cutaneous conditions—acne, psoriasis, and atopic dermatitis [AD]—and provides tips on how to best address our patients’ questions on this topic.
Acne
Studies increasingly support an association between a high glycemic diet (foods that lead to a spike in serum glucose) and acne; Bowe et al1 provided an excellent summary of the topic in 2010. This year, a large prospective cohort study of more than 24,000 participants demonstrated an association between adult acne and a diet high in milk, sugary beverages and foods, and fatty foods.2 In prospective cohort studies of more than 6000 adolescent girls and 4000 adolescent boys, Adebamowo et al3,4 demonstrated a correlation between skim milk consumption and acne. Whey protein supplementation also has been implicated in acne flares.5,6 The biological mechanism of the impact of high glycemic index foods and acne is believed to be mainly via activation of the insulinlike growth factor 1 (IGF-1) pathway, which promotes androgen synthesis and increases androgen bioavailability via decreased synthesis of sex hormone binding globulin.1,2 Insulinlike growth factor 1 also stimulates its downstream target, mammalian target of rapamycin (mTOR), leading to activation of antiapoptotic and proliferation signaling, ultimately resulting in oxidative stress and inflammation causing acne.2 Penso et al2 noted that patients with IGF-1 deficiency (Laron syndrome) never develop acne unless treated with exogenous IGF-1, further supporting its role in acne formation.7 There currently is a paucity of randomized controlled trials assessing the impact of diet on acne.
Psoriasis
The literature consistently shows that obesity is a predisposing factor for psoriasis. Additionally, weight gain may cause flares of existing psoriasis.8 Promotion of a healthy diet is an important factor in the management of obesity, alongside physical activity and, in some cases, medication and bariatric surgery.9 Patients with psoriasis who are overweight have been shown to experience improvement in their psoriasis after weight loss secondary to diet and exercise.8,10 The joint American Academy of Dermatology and National Psoriasis Foundation guidelines recommend that dermatologists advise patients to practice a healthy lifestyle including a healthy diet and communicate with a patient’s primary care provider so they can be appropriately evaluated and treated for comorbidities including metabolic syndrome, diabetes, and hyperlipidemia.11 In the NutriNet-Santé cohort study, investigators found an inverse correlation between psoriasis severity and adherence to a Mediterranean diet, which the authors conclude supports the hypothesis that this may slow the progression of psoriasis.12 In a single meta-analysis, it was reported that patients with psoriasis have a 3-fold increased risk for celiac disease compared to the general population.13 It remains unknown if these data are generalizable to the US population. Dermatologists should consider screening patients with psoriasis for celiac disease based on reported symptoms. When suspected, it is necessary to order appropriate serologies and consider referral to gastroenterology prior to recommending a gluten-free diet, as elimination of gluten prior to testing may lead to false-negative results.
Atopic Dermatitis
Patients and parents/guardians of children with AD often ask about the impact of diet on the condition. A small minority of patients may experience flares of AD due to ongoing, non–IgE-mediated allergen exposure.14 Diet as a trigger for flares should be suspected in children with persistent, moderate to severe AD. In these patients, allergen avoidance may lead to improvement but not resolution of AD. Allergens ordered from most common to least common are the following: eggs, milk, peanuts/tree nuts, shellfish, soy, and wheat.15 Additionally, it is important to note that children with AD are at higher risk for developing life-threatening, IgE-mediated food allergies compared to the general population (37% vs 6.8%).16,17 The LEAP (Learning Early about Peanut Allergy) study led to a paradigm shift in prevention of peanut allergies in high-risk children (ie, those with severe AD and/or egg allergy), providing data to support the idea that early introduction of allergenic foods such as peanuts may prevent severe allergies.18 Further studies are necessary to clarify the population in which allergen testing and recommendations on food avoidance are warranted vs early introduction.19
Conclusion
Early data support the relationship between diet and many common dermatologic conditions, including acne, psoriasis, and AD. Dermatologists should be familiar with the evidence supporting the relationship between diet and various skin conditions to best answer patients’ questions and counsel as appropriate. It is important for dermatologists to continue to stay up-to-date on the literature on this subject as new data emerge. Knowledge about the relationship between diet and skin allows dermatologists to not only support our patients’ skin health but their overall health as well.
- Bowe WP, Joshi SS, Shalita AR. Diet and acne. J Am Acad Dermatol. 2010;63:124-141.
- Penso L, Touvier M, Deschasaux M, et al. Association between adult acne and dietary behaviors: findings from the NutriNet-Santé prospective cohort study. JAMA Dermatol. 2020;156:854-862.
- Adebamowo CA, Spiegelman D, Berkey CS, et al. Milk consumption and acne in teenaged boys. J Am Acad Dermatol. 2008;58:787-793.
- Adebamowo CA, Spiegelman D, Berkey CS, et al. Milk consumption and acne in adolescent girls. Dermatol Online J. 2006;12:1.
- Silverberg NB. Whey protein precipitating moderate to severe acne flares in 5 teenaged athletes. Cutis. 2012;90:70-72.
- Cengiz FP, Cemil BC, Emiroglu N, et al. Acne located on the trunk, whey protein supplementation: is there any association? Health Promot Perspect. 2017;7:106-108.
- Ben-Amitai D, Laron Z. Effect of insulin-like growth factor-1 deficiency or administration on the occurrence of acne. J Eur Acad Dermatol Venereol. 2011;25:950-954.
- Jensen P, Skov L. Psoriasis and obesity [published online February 23, 2017]. Dermatology. 2016;232:633-639.
- Extreme obesity, and what you can do. American Heart Association website. https://www.heart.org/en/healthy-living/healthy-eating/losing-weight/extreme-obesity-and-what-you-can-do. Updated April 18, 2014. Accessed November 30, 2020.
- Naldi L, Conti A, Cazzaniga S, et al. Diet and physical exercise in psoriasis: a randomized controlled trial. Br J Dermatol. 2014;170:634-642.
- Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80:1073-1113.
- Phan C, Touvier M, Kesse-Guyot E, et al. Association between Mediterranean anti-inflammatory dietary profile and severity of psoriasis: results from the NutriNet-Santé cohort. JAMA Dermatol. 2018;154:1017-1024.
- Ungprasert P, Wijarnpreecha K, Kittanamongkolchai W. Psoriasis and risk of celiac disease: a systematic review and meta-analysis. Indian J Dermatol. 2017;62:41-46.
- Silverberg NB, Lee-Wong M, Yosipovitch G. Diet and atopic dermatitis. Cutis. 2016;97:227-232.
- Bieber T, Bussmann C. Atopic dermatitis. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. China: Elsevier Saunders; 2012:203-218.
- Eigenmann PA, Sicherer SH, Borkowski TA, et al. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics. 1998;101:E8.
- Age-adjusted percentages (with standard errors) of hay fever, respiratory allergies, food allergies, and skin allergies in the past 12 months for children under age 18 years, by selected characteristics: United States, 2016. CDC website. https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2016_SHS_Table_C-2.pdf. Accessed December 8, 2020.
- Du Toit G, Roberts G, Sayre PH, et al; LEAP study team. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803-813.
- Sugita K, Akdis CA. Recent developments and advances in atopic dermatitis and food allergy [published online October 22, 2019]. Allergol Int. 2020;69:204-214.
Dermatologists frequently learn about skin conditions that are directly linked to diet. For example, we know that nutritional deficiencies can impact the hair, skin, and nails, and that celiac disease manifests with dermatitis herpetiformis of the skin. Patients commonly ask their dermatologists about the impact of diet on their skin. There are many outdated myths, but research on the subject is increasingly demonstrating important associations. Dermatologists must become familiar with the data on this topic so that we can provide informed counseling for our patients. This article reviews the current literature on associations between diet and 3 common cutaneous conditions—acne, psoriasis, and atopic dermatitis [AD]—and provides tips on how to best address our patients’ questions on this topic.
Acne
Studies increasingly support an association between a high glycemic diet (foods that lead to a spike in serum glucose) and acne; Bowe et al1 provided an excellent summary of the topic in 2010. This year, a large prospective cohort study of more than 24,000 participants demonstrated an association between adult acne and a diet high in milk, sugary beverages and foods, and fatty foods.2 In prospective cohort studies of more than 6000 adolescent girls and 4000 adolescent boys, Adebamowo et al3,4 demonstrated a correlation between skim milk consumption and acne. Whey protein supplementation also has been implicated in acne flares.5,6 The biological mechanism of the impact of high glycemic index foods and acne is believed to be mainly via activation of the insulinlike growth factor 1 (IGF-1) pathway, which promotes androgen synthesis and increases androgen bioavailability via decreased synthesis of sex hormone binding globulin.1,2 Insulinlike growth factor 1 also stimulates its downstream target, mammalian target of rapamycin (mTOR), leading to activation of antiapoptotic and proliferation signaling, ultimately resulting in oxidative stress and inflammation causing acne.2 Penso et al2 noted that patients with IGF-1 deficiency (Laron syndrome) never develop acne unless treated with exogenous IGF-1, further supporting its role in acne formation.7 There currently is a paucity of randomized controlled trials assessing the impact of diet on acne.
Psoriasis
The literature consistently shows that obesity is a predisposing factor for psoriasis. Additionally, weight gain may cause flares of existing psoriasis.8 Promotion of a healthy diet is an important factor in the management of obesity, alongside physical activity and, in some cases, medication and bariatric surgery.9 Patients with psoriasis who are overweight have been shown to experience improvement in their psoriasis after weight loss secondary to diet and exercise.8,10 The joint American Academy of Dermatology and National Psoriasis Foundation guidelines recommend that dermatologists advise patients to practice a healthy lifestyle including a healthy diet and communicate with a patient’s primary care provider so they can be appropriately evaluated and treated for comorbidities including metabolic syndrome, diabetes, and hyperlipidemia.11 In the NutriNet-Santé cohort study, investigators found an inverse correlation between psoriasis severity and adherence to a Mediterranean diet, which the authors conclude supports the hypothesis that this may slow the progression of psoriasis.12 In a single meta-analysis, it was reported that patients with psoriasis have a 3-fold increased risk for celiac disease compared to the general population.13 It remains unknown if these data are generalizable to the US population. Dermatologists should consider screening patients with psoriasis for celiac disease based on reported symptoms. When suspected, it is necessary to order appropriate serologies and consider referral to gastroenterology prior to recommending a gluten-free diet, as elimination of gluten prior to testing may lead to false-negative results.
Atopic Dermatitis
Patients and parents/guardians of children with AD often ask about the impact of diet on the condition. A small minority of patients may experience flares of AD due to ongoing, non–IgE-mediated allergen exposure.14 Diet as a trigger for flares should be suspected in children with persistent, moderate to severe AD. In these patients, allergen avoidance may lead to improvement but not resolution of AD. Allergens ordered from most common to least common are the following: eggs, milk, peanuts/tree nuts, shellfish, soy, and wheat.15 Additionally, it is important to note that children with AD are at higher risk for developing life-threatening, IgE-mediated food allergies compared to the general population (37% vs 6.8%).16,17 The LEAP (Learning Early about Peanut Allergy) study led to a paradigm shift in prevention of peanut allergies in high-risk children (ie, those with severe AD and/or egg allergy), providing data to support the idea that early introduction of allergenic foods such as peanuts may prevent severe allergies.18 Further studies are necessary to clarify the population in which allergen testing and recommendations on food avoidance are warranted vs early introduction.19
Conclusion
Early data support the relationship between diet and many common dermatologic conditions, including acne, psoriasis, and AD. Dermatologists should be familiar with the evidence supporting the relationship between diet and various skin conditions to best answer patients’ questions and counsel as appropriate. It is important for dermatologists to continue to stay up-to-date on the literature on this subject as new data emerge. Knowledge about the relationship between diet and skin allows dermatologists to not only support our patients’ skin health but their overall health as well.
Dermatologists frequently learn about skin conditions that are directly linked to diet. For example, we know that nutritional deficiencies can impact the hair, skin, and nails, and that celiac disease manifests with dermatitis herpetiformis of the skin. Patients commonly ask their dermatologists about the impact of diet on their skin. There are many outdated myths, but research on the subject is increasingly demonstrating important associations. Dermatologists must become familiar with the data on this topic so that we can provide informed counseling for our patients. This article reviews the current literature on associations between diet and 3 common cutaneous conditions—acne, psoriasis, and atopic dermatitis [AD]—and provides tips on how to best address our patients’ questions on this topic.
Acne
Studies increasingly support an association between a high glycemic diet (foods that lead to a spike in serum glucose) and acne; Bowe et al1 provided an excellent summary of the topic in 2010. This year, a large prospective cohort study of more than 24,000 participants demonstrated an association between adult acne and a diet high in milk, sugary beverages and foods, and fatty foods.2 In prospective cohort studies of more than 6000 adolescent girls and 4000 adolescent boys, Adebamowo et al3,4 demonstrated a correlation between skim milk consumption and acne. Whey protein supplementation also has been implicated in acne flares.5,6 The biological mechanism of the impact of high glycemic index foods and acne is believed to be mainly via activation of the insulinlike growth factor 1 (IGF-1) pathway, which promotes androgen synthesis and increases androgen bioavailability via decreased synthesis of sex hormone binding globulin.1,2 Insulinlike growth factor 1 also stimulates its downstream target, mammalian target of rapamycin (mTOR), leading to activation of antiapoptotic and proliferation signaling, ultimately resulting in oxidative stress and inflammation causing acne.2 Penso et al2 noted that patients with IGF-1 deficiency (Laron syndrome) never develop acne unless treated with exogenous IGF-1, further supporting its role in acne formation.7 There currently is a paucity of randomized controlled trials assessing the impact of diet on acne.
Psoriasis
The literature consistently shows that obesity is a predisposing factor for psoriasis. Additionally, weight gain may cause flares of existing psoriasis.8 Promotion of a healthy diet is an important factor in the management of obesity, alongside physical activity and, in some cases, medication and bariatric surgery.9 Patients with psoriasis who are overweight have been shown to experience improvement in their psoriasis after weight loss secondary to diet and exercise.8,10 The joint American Academy of Dermatology and National Psoriasis Foundation guidelines recommend that dermatologists advise patients to practice a healthy lifestyle including a healthy diet and communicate with a patient’s primary care provider so they can be appropriately evaluated and treated for comorbidities including metabolic syndrome, diabetes, and hyperlipidemia.11 In the NutriNet-Santé cohort study, investigators found an inverse correlation between psoriasis severity and adherence to a Mediterranean diet, which the authors conclude supports the hypothesis that this may slow the progression of psoriasis.12 In a single meta-analysis, it was reported that patients with psoriasis have a 3-fold increased risk for celiac disease compared to the general population.13 It remains unknown if these data are generalizable to the US population. Dermatologists should consider screening patients with psoriasis for celiac disease based on reported symptoms. When suspected, it is necessary to order appropriate serologies and consider referral to gastroenterology prior to recommending a gluten-free diet, as elimination of gluten prior to testing may lead to false-negative results.
Atopic Dermatitis
Patients and parents/guardians of children with AD often ask about the impact of diet on the condition. A small minority of patients may experience flares of AD due to ongoing, non–IgE-mediated allergen exposure.14 Diet as a trigger for flares should be suspected in children with persistent, moderate to severe AD. In these patients, allergen avoidance may lead to improvement but not resolution of AD. Allergens ordered from most common to least common are the following: eggs, milk, peanuts/tree nuts, shellfish, soy, and wheat.15 Additionally, it is important to note that children with AD are at higher risk for developing life-threatening, IgE-mediated food allergies compared to the general population (37% vs 6.8%).16,17 The LEAP (Learning Early about Peanut Allergy) study led to a paradigm shift in prevention of peanut allergies in high-risk children (ie, those with severe AD and/or egg allergy), providing data to support the idea that early introduction of allergenic foods such as peanuts may prevent severe allergies.18 Further studies are necessary to clarify the population in which allergen testing and recommendations on food avoidance are warranted vs early introduction.19
Conclusion
Early data support the relationship between diet and many common dermatologic conditions, including acne, psoriasis, and AD. Dermatologists should be familiar with the evidence supporting the relationship between diet and various skin conditions to best answer patients’ questions and counsel as appropriate. It is important for dermatologists to continue to stay up-to-date on the literature on this subject as new data emerge. Knowledge about the relationship between diet and skin allows dermatologists to not only support our patients’ skin health but their overall health as well.
- Bowe WP, Joshi SS, Shalita AR. Diet and acne. J Am Acad Dermatol. 2010;63:124-141.
- Penso L, Touvier M, Deschasaux M, et al. Association between adult acne and dietary behaviors: findings from the NutriNet-Santé prospective cohort study. JAMA Dermatol. 2020;156:854-862.
- Adebamowo CA, Spiegelman D, Berkey CS, et al. Milk consumption and acne in teenaged boys. J Am Acad Dermatol. 2008;58:787-793.
- Adebamowo CA, Spiegelman D, Berkey CS, et al. Milk consumption and acne in adolescent girls. Dermatol Online J. 2006;12:1.
- Silverberg NB. Whey protein precipitating moderate to severe acne flares in 5 teenaged athletes. Cutis. 2012;90:70-72.
- Cengiz FP, Cemil BC, Emiroglu N, et al. Acne located on the trunk, whey protein supplementation: is there any association? Health Promot Perspect. 2017;7:106-108.
- Ben-Amitai D, Laron Z. Effect of insulin-like growth factor-1 deficiency or administration on the occurrence of acne. J Eur Acad Dermatol Venereol. 2011;25:950-954.
- Jensen P, Skov L. Psoriasis and obesity [published online February 23, 2017]. Dermatology. 2016;232:633-639.
- Extreme obesity, and what you can do. American Heart Association website. https://www.heart.org/en/healthy-living/healthy-eating/losing-weight/extreme-obesity-and-what-you-can-do. Updated April 18, 2014. Accessed November 30, 2020.
- Naldi L, Conti A, Cazzaniga S, et al. Diet and physical exercise in psoriasis: a randomized controlled trial. Br J Dermatol. 2014;170:634-642.
- Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80:1073-1113.
- Phan C, Touvier M, Kesse-Guyot E, et al. Association between Mediterranean anti-inflammatory dietary profile and severity of psoriasis: results from the NutriNet-Santé cohort. JAMA Dermatol. 2018;154:1017-1024.
- Ungprasert P, Wijarnpreecha K, Kittanamongkolchai W. Psoriasis and risk of celiac disease: a systematic review and meta-analysis. Indian J Dermatol. 2017;62:41-46.
- Silverberg NB, Lee-Wong M, Yosipovitch G. Diet and atopic dermatitis. Cutis. 2016;97:227-232.
- Bieber T, Bussmann C. Atopic dermatitis. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. China: Elsevier Saunders; 2012:203-218.
- Eigenmann PA, Sicherer SH, Borkowski TA, et al. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics. 1998;101:E8.
- Age-adjusted percentages (with standard errors) of hay fever, respiratory allergies, food allergies, and skin allergies in the past 12 months for children under age 18 years, by selected characteristics: United States, 2016. CDC website. https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2016_SHS_Table_C-2.pdf. Accessed December 8, 2020.
- Du Toit G, Roberts G, Sayre PH, et al; LEAP study team. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803-813.
- Sugita K, Akdis CA. Recent developments and advances in atopic dermatitis and food allergy [published online October 22, 2019]. Allergol Int. 2020;69:204-214.
- Bowe WP, Joshi SS, Shalita AR. Diet and acne. J Am Acad Dermatol. 2010;63:124-141.
- Penso L, Touvier M, Deschasaux M, et al. Association between adult acne and dietary behaviors: findings from the NutriNet-Santé prospective cohort study. JAMA Dermatol. 2020;156:854-862.
- Adebamowo CA, Spiegelman D, Berkey CS, et al. Milk consumption and acne in teenaged boys. J Am Acad Dermatol. 2008;58:787-793.
- Adebamowo CA, Spiegelman D, Berkey CS, et al. Milk consumption and acne in adolescent girls. Dermatol Online J. 2006;12:1.
- Silverberg NB. Whey protein precipitating moderate to severe acne flares in 5 teenaged athletes. Cutis. 2012;90:70-72.
- Cengiz FP, Cemil BC, Emiroglu N, et al. Acne located on the trunk, whey protein supplementation: is there any association? Health Promot Perspect. 2017;7:106-108.
- Ben-Amitai D, Laron Z. Effect of insulin-like growth factor-1 deficiency or administration on the occurrence of acne. J Eur Acad Dermatol Venereol. 2011;25:950-954.
- Jensen P, Skov L. Psoriasis and obesity [published online February 23, 2017]. Dermatology. 2016;232:633-639.
- Extreme obesity, and what you can do. American Heart Association website. https://www.heart.org/en/healthy-living/healthy-eating/losing-weight/extreme-obesity-and-what-you-can-do. Updated April 18, 2014. Accessed November 30, 2020.
- Naldi L, Conti A, Cazzaniga S, et al. Diet and physical exercise in psoriasis: a randomized controlled trial. Br J Dermatol. 2014;170:634-642.
- Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80:1073-1113.
- Phan C, Touvier M, Kesse-Guyot E, et al. Association between Mediterranean anti-inflammatory dietary profile and severity of psoriasis: results from the NutriNet-Santé cohort. JAMA Dermatol. 2018;154:1017-1024.
- Ungprasert P, Wijarnpreecha K, Kittanamongkolchai W. Psoriasis and risk of celiac disease: a systematic review and meta-analysis. Indian J Dermatol. 2017;62:41-46.
- Silverberg NB, Lee-Wong M, Yosipovitch G. Diet and atopic dermatitis. Cutis. 2016;97:227-232.
- Bieber T, Bussmann C. Atopic dermatitis. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. China: Elsevier Saunders; 2012:203-218.
- Eigenmann PA, Sicherer SH, Borkowski TA, et al. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics. 1998;101:E8.
- Age-adjusted percentages (with standard errors) of hay fever, respiratory allergies, food allergies, and skin allergies in the past 12 months for children under age 18 years, by selected characteristics: United States, 2016. CDC website. https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2016_SHS_Table_C-2.pdf. Accessed December 8, 2020.
- Du Toit G, Roberts G, Sayre PH, et al; LEAP study team. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372:803-813.
- Sugita K, Akdis CA. Recent developments and advances in atopic dermatitis and food allergy [published online October 22, 2019]. Allergol Int. 2020;69:204-214.
Resident Pearls
- There are strong data on the relationship between dietary patterns and skin conditions.
- High glycemic index foods (eg, skim milk, whey protein, sugary beverages, fatty foods) are associated with acne vulgaris.
- Obesity is a risk factor for psoriasis; weight loss interventions such as improved dietary patterns can improve psoriasis.
- Children with atopic dermatitis (AD) are at higher risk for food allergies (both IgE and non–IgE-mediated allergies). A small subset may experience flares in their AD in relation to non–IgE-mediated food allergies.
Synovial, skin gene expression differences may explain PsA treatment responses
Differences in gene expression between the skin and synovial tissues of individuals with psoriatic arthritis could explain why treatments targeting proinflammatory mechanisms don’t improve joint symptoms in some patients.
A paper published in Annals of the Rheumatic Diseases presents the results of an observational, open-label study involving 27 patients with active psoriatic arthritis, 18 of whom were treated with anti–tumor necrosis factor (anti-TNF) therapies and 9 with the monoclonal antibody ustekinumab (Stelara). This drug targets the axis of proinflammatory cytokine interleukin-23 and effector cytokine IL-12, which are believed to play an important role both in skin and nail psoriasis, and psoriatic arthritis.
However, while anti–IL-23 antibodies seem to work well to address skin manifestations of psoriasis, they tend to improve joint symptoms only in selected patients.
“The lack of a clear mechanism to explain such divergent responses prompted this study,” said Dr. Alessandra Nerviani, lead author of the study, from the Barts and The London School of Medicine & Dentistry.
Participants also had biopsies taken from the synovium – in particular, from joints that were clinically and ultrasonographically active – and from lesional and nonlesional skin for gene expression analysis.
In terms of treatment response, the ustekinumab-treated group showed significantly higher scores for erythrocyte sedimentation rate, joint pain, and disease activity, compared with the anti–TNF-treated group. Psoriasis Area and Severity Index scores were similar in both treatment arms, but significantly more patients in the anti-TNF group met the EULAR Disease Activity Score for response (70.6% vs. 22.2%).
The gene expression analysis, which assessed the activity of 80 genes related to inflammation in 14 patient samples from synovial tissue, lesional skin, and nonlesional skin, found that patterns of expression in the synovium clustered away from those from skin.
This was particularly the case when it came to genes related to drug targets. The targets for anti-TNF showed similar levels of expression in both skin and synovial tissue. However, the targets for ustekinumab – namely interleukin (IL)–23A, IL-23R and, IL-12B – showed higher levels of expression in lesional skin than in nonlesional skin and synovial tissue.
“Interestingly, we observed that, while some patients did express IL-23 cytokines/receptor in both skin and joint, others had discordant expression, that is, active IL-23 pathway in the lesional skin but not in the synovium,” the authors wrote.
When researchers then stratified patients according to how much synovial inflammation they had, they found that patients who had higher scores also showed higher expression of genes for IL-12B and IL-23R, but not IL-23A, despite showing no other major clinical differences.
The authors also looked at the protein expression levels for IL-23p40, IL-23p19 and IL-23R, and found that while the percentage of cells positive for these proteins was significantly higher in lesional, compared with nonlesional skin, it was also higher in the synovium among patients with more inflammation.
“Except for the LIKERT patient score, we did not detect other significant correlations between IL-23 axis expression and clinical parameters at baseline, suggesting that patients with comparable disease severity may have, in fact, heterogeneous histopathological features and expression of drug targets within the diseased synovium,” they wrote.
More selective expression of IL-23 in synovium
Commenting on the findings, the authors highlighted that the expression of targets for anti-TNF was much more homogeneous across skin and synovial tissue, but the IL-23A/IL-12B/IL-23R genes generally showed higher levels of expression in lesional skin. compared with either nonlesional skin or synovium. However, even within the synovium, expression of these genes varied enormously, from levels similar to those seen in paired lesional skin to levels well below those.
“It is plausible to speculate that an overall higher presence of IL-23 in the psoriatic skin supports the concept of a generally better response in terms of skin manifestations, including almost complete clearance of psoriatic lesions,” Dr. Nerviani said in an interview. “While, on the other hand, the more selective expression of IL-23 in the synovium, namely in histologically more inflamed synovium characterized by immune cells infiltration, may explain the overall more modest success to meet stringent response criteria in the joints.“
Of particular significance was the observation that IL-12B and IL-23R transcription levels were higher in patients with higher levels of synovial tissue inflammation.
“We confirmed that IL-23 axis expression relates to the synovial histopathology not only in PsA at different stages of the disease, including early treatment-naive patients, but also in the early phase of RA, investigated as disease control,” they wrote.
Dr. Nerviani said the results could inform a more tailored “precision medicine” approach to treating patients with psoriatic arthritis.
“While randomized synovial biopsy–driven clinical trials are now a reality in rheumatoid arthritis, in psoriatic arthritis, these kinds of studies have not been performed yet but may become actual in the future,” she said. “An in-depth characterization of the synovial tissue represents the first essential step towards addressing current unmet clinical needs and, potentially, changing our practice.”
However, she stressed that the study was not powered to test the correlation between the expression level of these pathways in disease tissue and clinical response to treatment.
“Further dedicated clinical trials should be designed to look at the relationship between synovial pathology and molecular characteristics, and response to targeted treatment to address this question,” Dr. Nerviani said.
The study was supported by the Queen Mary University of London and the Fondazione Ceschina, and in part by grants from Versus Arthritis. No conflicts of interest were declared.
SOURCE: Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.
Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.
Differences in gene expression between the skin and synovial tissues of individuals with psoriatic arthritis could explain why treatments targeting proinflammatory mechanisms don’t improve joint symptoms in some patients.
A paper published in Annals of the Rheumatic Diseases presents the results of an observational, open-label study involving 27 patients with active psoriatic arthritis, 18 of whom were treated with anti–tumor necrosis factor (anti-TNF) therapies and 9 with the monoclonal antibody ustekinumab (Stelara). This drug targets the axis of proinflammatory cytokine interleukin-23 and effector cytokine IL-12, which are believed to play an important role both in skin and nail psoriasis, and psoriatic arthritis.
However, while anti–IL-23 antibodies seem to work well to address skin manifestations of psoriasis, they tend to improve joint symptoms only in selected patients.
“The lack of a clear mechanism to explain such divergent responses prompted this study,” said Dr. Alessandra Nerviani, lead author of the study, from the Barts and The London School of Medicine & Dentistry.
Participants also had biopsies taken from the synovium – in particular, from joints that were clinically and ultrasonographically active – and from lesional and nonlesional skin for gene expression analysis.
In terms of treatment response, the ustekinumab-treated group showed significantly higher scores for erythrocyte sedimentation rate, joint pain, and disease activity, compared with the anti–TNF-treated group. Psoriasis Area and Severity Index scores were similar in both treatment arms, but significantly more patients in the anti-TNF group met the EULAR Disease Activity Score for response (70.6% vs. 22.2%).
The gene expression analysis, which assessed the activity of 80 genes related to inflammation in 14 patient samples from synovial tissue, lesional skin, and nonlesional skin, found that patterns of expression in the synovium clustered away from those from skin.
This was particularly the case when it came to genes related to drug targets. The targets for anti-TNF showed similar levels of expression in both skin and synovial tissue. However, the targets for ustekinumab – namely interleukin (IL)–23A, IL-23R and, IL-12B – showed higher levels of expression in lesional skin than in nonlesional skin and synovial tissue.
“Interestingly, we observed that, while some patients did express IL-23 cytokines/receptor in both skin and joint, others had discordant expression, that is, active IL-23 pathway in the lesional skin but not in the synovium,” the authors wrote.
When researchers then stratified patients according to how much synovial inflammation they had, they found that patients who had higher scores also showed higher expression of genes for IL-12B and IL-23R, but not IL-23A, despite showing no other major clinical differences.
The authors also looked at the protein expression levels for IL-23p40, IL-23p19 and IL-23R, and found that while the percentage of cells positive for these proteins was significantly higher in lesional, compared with nonlesional skin, it was also higher in the synovium among patients with more inflammation.
“Except for the LIKERT patient score, we did not detect other significant correlations between IL-23 axis expression and clinical parameters at baseline, suggesting that patients with comparable disease severity may have, in fact, heterogeneous histopathological features and expression of drug targets within the diseased synovium,” they wrote.
More selective expression of IL-23 in synovium
Commenting on the findings, the authors highlighted that the expression of targets for anti-TNF was much more homogeneous across skin and synovial tissue, but the IL-23A/IL-12B/IL-23R genes generally showed higher levels of expression in lesional skin. compared with either nonlesional skin or synovium. However, even within the synovium, expression of these genes varied enormously, from levels similar to those seen in paired lesional skin to levels well below those.
“It is plausible to speculate that an overall higher presence of IL-23 in the psoriatic skin supports the concept of a generally better response in terms of skin manifestations, including almost complete clearance of psoriatic lesions,” Dr. Nerviani said in an interview. “While, on the other hand, the more selective expression of IL-23 in the synovium, namely in histologically more inflamed synovium characterized by immune cells infiltration, may explain the overall more modest success to meet stringent response criteria in the joints.“
Of particular significance was the observation that IL-12B and IL-23R transcription levels were higher in patients with higher levels of synovial tissue inflammation.
“We confirmed that IL-23 axis expression relates to the synovial histopathology not only in PsA at different stages of the disease, including early treatment-naive patients, but also in the early phase of RA, investigated as disease control,” they wrote.
Dr. Nerviani said the results could inform a more tailored “precision medicine” approach to treating patients with psoriatic arthritis.
“While randomized synovial biopsy–driven clinical trials are now a reality in rheumatoid arthritis, in psoriatic arthritis, these kinds of studies have not been performed yet but may become actual in the future,” she said. “An in-depth characterization of the synovial tissue represents the first essential step towards addressing current unmet clinical needs and, potentially, changing our practice.”
However, she stressed that the study was not powered to test the correlation between the expression level of these pathways in disease tissue and clinical response to treatment.
“Further dedicated clinical trials should be designed to look at the relationship between synovial pathology and molecular characteristics, and response to targeted treatment to address this question,” Dr. Nerviani said.
The study was supported by the Queen Mary University of London and the Fondazione Ceschina, and in part by grants from Versus Arthritis. No conflicts of interest were declared.
SOURCE: Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.
Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.
Differences in gene expression between the skin and synovial tissues of individuals with psoriatic arthritis could explain why treatments targeting proinflammatory mechanisms don’t improve joint symptoms in some patients.
A paper published in Annals of the Rheumatic Diseases presents the results of an observational, open-label study involving 27 patients with active psoriatic arthritis, 18 of whom were treated with anti–tumor necrosis factor (anti-TNF) therapies and 9 with the monoclonal antibody ustekinumab (Stelara). This drug targets the axis of proinflammatory cytokine interleukin-23 and effector cytokine IL-12, which are believed to play an important role both in skin and nail psoriasis, and psoriatic arthritis.
However, while anti–IL-23 antibodies seem to work well to address skin manifestations of psoriasis, they tend to improve joint symptoms only in selected patients.
“The lack of a clear mechanism to explain such divergent responses prompted this study,” said Dr. Alessandra Nerviani, lead author of the study, from the Barts and The London School of Medicine & Dentistry.
Participants also had biopsies taken from the synovium – in particular, from joints that were clinically and ultrasonographically active – and from lesional and nonlesional skin for gene expression analysis.
In terms of treatment response, the ustekinumab-treated group showed significantly higher scores for erythrocyte sedimentation rate, joint pain, and disease activity, compared with the anti–TNF-treated group. Psoriasis Area and Severity Index scores were similar in both treatment arms, but significantly more patients in the anti-TNF group met the EULAR Disease Activity Score for response (70.6% vs. 22.2%).
The gene expression analysis, which assessed the activity of 80 genes related to inflammation in 14 patient samples from synovial tissue, lesional skin, and nonlesional skin, found that patterns of expression in the synovium clustered away from those from skin.
This was particularly the case when it came to genes related to drug targets. The targets for anti-TNF showed similar levels of expression in both skin and synovial tissue. However, the targets for ustekinumab – namely interleukin (IL)–23A, IL-23R and, IL-12B – showed higher levels of expression in lesional skin than in nonlesional skin and synovial tissue.
“Interestingly, we observed that, while some patients did express IL-23 cytokines/receptor in both skin and joint, others had discordant expression, that is, active IL-23 pathway in the lesional skin but not in the synovium,” the authors wrote.
When researchers then stratified patients according to how much synovial inflammation they had, they found that patients who had higher scores also showed higher expression of genes for IL-12B and IL-23R, but not IL-23A, despite showing no other major clinical differences.
The authors also looked at the protein expression levels for IL-23p40, IL-23p19 and IL-23R, and found that while the percentage of cells positive for these proteins was significantly higher in lesional, compared with nonlesional skin, it was also higher in the synovium among patients with more inflammation.
“Except for the LIKERT patient score, we did not detect other significant correlations between IL-23 axis expression and clinical parameters at baseline, suggesting that patients with comparable disease severity may have, in fact, heterogeneous histopathological features and expression of drug targets within the diseased synovium,” they wrote.
More selective expression of IL-23 in synovium
Commenting on the findings, the authors highlighted that the expression of targets for anti-TNF was much more homogeneous across skin and synovial tissue, but the IL-23A/IL-12B/IL-23R genes generally showed higher levels of expression in lesional skin. compared with either nonlesional skin or synovium. However, even within the synovium, expression of these genes varied enormously, from levels similar to those seen in paired lesional skin to levels well below those.
“It is plausible to speculate that an overall higher presence of IL-23 in the psoriatic skin supports the concept of a generally better response in terms of skin manifestations, including almost complete clearance of psoriatic lesions,” Dr. Nerviani said in an interview. “While, on the other hand, the more selective expression of IL-23 in the synovium, namely in histologically more inflamed synovium characterized by immune cells infiltration, may explain the overall more modest success to meet stringent response criteria in the joints.“
Of particular significance was the observation that IL-12B and IL-23R transcription levels were higher in patients with higher levels of synovial tissue inflammation.
“We confirmed that IL-23 axis expression relates to the synovial histopathology not only in PsA at different stages of the disease, including early treatment-naive patients, but also in the early phase of RA, investigated as disease control,” they wrote.
Dr. Nerviani said the results could inform a more tailored “precision medicine” approach to treating patients with psoriatic arthritis.
“While randomized synovial biopsy–driven clinical trials are now a reality in rheumatoid arthritis, in psoriatic arthritis, these kinds of studies have not been performed yet but may become actual in the future,” she said. “An in-depth characterization of the synovial tissue represents the first essential step towards addressing current unmet clinical needs and, potentially, changing our practice.”
However, she stressed that the study was not powered to test the correlation between the expression level of these pathways in disease tissue and clinical response to treatment.
“Further dedicated clinical trials should be designed to look at the relationship between synovial pathology and molecular characteristics, and response to targeted treatment to address this question,” Dr. Nerviani said.
The study was supported by the Queen Mary University of London and the Fondazione Ceschina, and in part by grants from Versus Arthritis. No conflicts of interest were declared.
SOURCE: Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.
Nerviani A et al. Ann Rheum Dis. 2020 Nov 26. doi: 10.1136/annrheumdis-2020-218186.
FROM ANNALS OF THE RHEUMATIC DISEASES
Racial Disparities in Dermatology Training: The Impact on Black Patients
Although physicians commit themselves to providing equitable treatment to all patients, significant disparities remain in the dermatologic care of Black patients, who constitute 13% of the US population, which continues to grow increasingly diverse.1 Despite these changes in the population, the literature demonstrates that dermatologic training does not adequately focus on unique presentations of cutaneous pathology in the Black population.2,3 Accordingly, medical students lack proper training in how skin disorders manifest in people of color. Compounding the problem, only 3% of dermatologists are Black, creating a cultural barrier that can compromise care for Black patients.2,4 Racial disparities in dermatology training can compromise treatment, patient satisfaction, and outcomes.3
Issues in Medical Education Training and Resources
Lack of diversity in the resources used for dermatology training in medical schools affects diagnosis and treatment, as skin manifestations such as hypersensitivity reactions, rashes, and cancer can appear differently on different skin tones.5 A study of medical students’ ability to diagnose common dermatologic pathologies found that when trainees were presented with photographs of dark skin, their accuracy in identifying urticaria, squamous cell carcinoma, and even atopic dermatitis was reduced, despite these diseases being more prevalent in children of African American ancestry.4,6
Dermatologic diseases also can have different distributions in different races; for example, on non–sun-exposed sites, squamous cell carcinoma in Black patients occurs at 8.5 times the frequency of White patients.7 Failure to identify diseases accurately due to insufficient training can have grave consequences for patients. Although skin cancer is less common in individuals with skin of color, it is associated with greater morbidity and mortality, in part due to delayed diagnosis.7
Inadequate research, reporting, and instruction on dermatologic findings in patients with darker complexions further compound racial disparities in dermatology. A 2006 study of the representation of darker skin in major dermatology educational resources found that only 2% of teaching events at American Academy of Dermatology annual meetings focused on skin of color. Furthermore, the study determined that many common diseases in patients with dark skin, such as acne vulgaris and pityriasis rosea, were completely absent or limited in dermatology textbooks.8
Impact on the Black Patient Experience
Patients’ therapeutic relationship with their physician also is damaged by limitations in training in diverse skin color. A study that assessed Black patients seen in a skin of color clinic (SOCC) compared to Black patients seen in a non-SOCC found that non-SOCC patients reported a lower degree of respect, dignity, understanding, and trust compared to the patients seen in a SOCC. Black patients expressed specific concerns about non-SOCC dermatologists’ knowledge of abnormalities that present in darker skin and Black hair.3 These findings are compounded by reports suggesting that, independent of care, structural racism contributes to dermatologic disease severity by influencing patient education level, household income, and degree of exposure to harmful environmental irritants.6
Racial disparities continue to be seen in the makeup of the universe of dermatologists and skin researchers. As of 2016, only 3% of dermatologists were Black, making dermatology one of the least diverse medical specialties.2 Increasing the diversity of the dermatology workforce is important to improve patient satisfaction and treatment, both for minority and nonminority patients. Compared to race-discordant medical visits, race-concordant visits were shown to have a higher rate of satisfaction and better shared decision-making.9 Also, minority physicians are more likely to practice health care in areas that are traditionally underserved and to care for patients who do not have health insurance, making their participation essential in addressing some of the baseline disparities Black patients face in securing quality dermatologic care.1
Structural Racism in Medicine
Changing dermatology training to ensure improved treatment of Black patients requires not only increased attention to differences in disease presentation but also heightened awareness of underlying genetic, environmental, and structural factors that contribute to the disease course.6 For example, there is evidence suggesting that structural racism in the form of residential segregation, lower socioeconomic status, and lower educational attainment contribute to disease severity in conditions such as atopic dermatitis. There is additional evidence suggesting that White patients are more readily offered therapeutic options than Black patients. A study of racial disparities in psoriasis treatment found that Black patients with moderate to severe psoriasis were 70% less likely to receive treatment with a biologic than White patients, independent of socioeconomic factors, comorbidities, and insurance plans.10
Moving Forward
Although research continues to underscore racial disparities in dermatology, some leaders in the field are actively combating these problems. A recent study that looked at representations of dark skin images in medical educational resources found far greater representation of dark pigmented skin in web-based resources than in traditional printed texts. Specifically, the online resource VisualDx (https://www.visualdx.com/) features 28.5% dark skin images compared to 10.3% (on average) in printed dermatology books.11 There also is increasing public awareness of these issues, with organizations such as the Skin of Color Society (http://skinofcolorsociety.org/) helping to promote interest in racial disparities in dermatology. Physicians also have created textbooks and social media accounts focused on dermatologic manifestations in skin of color.12 The Instagram account Brown Skin Matters (@brownskinmatters) has created a publicly accessible online resource where physicians and patients can see and post dermatologic diseases in skin of color.5
Final Thoughts
It is critical that physicians be trained to identify skin and hair manifestations of disease and disorders in Black patients. Training can be improved by including more images of skin manifestations in dark skin, both in medical school curricula and in new editions of dermatology textbooks. Training also must teach students about hair in Black individuals and how to properly treat it as well as related conditions of the hair and scalp.13 More research also is needed to better understand how dermatologists can improve the patient experience for Black patients. Residency programs must work to increase diversity among dermatology trainees.
Lastly, dermatology education should increasingly be supplemented with newer, web-based resources that show dermatologic manifestations across the spectrum of skin tones. Dermatology training must be adapted to better account for diverse patient populations and increase its focus on the systems that produce baseline disparities in disease morbidity and mortality.
- Pandya AG, Alexis AF, Berger TG, et al. Increasing racial and ethnic diversity in dermatology: a call to action. J Am Acad Dermatol. 2016;74:584-587.
- Gallegos A. Dermatology lacks diversity. Dermatology News. June 1, 2016. Accessed November 18, 2020. https://www.mdedge.com/dermatology/article/108920/practice-management/dermatology-lacks-diversity.
- Gorbatenko-Roth K, Prose N, Kundu RV, et al. Assessment of black patients’ perception of their dermatology care. JAMA Dermatol. 2019;155:1129-1134.
- Fenton A, Elliott E, Shahbandi A, et al. Medical students’ ability to diagnose common dermatologic conditions in skin of color. J Am Acad Dermatol. 2020;83:957-958.
- Prichep D. Diagnostic gaps: skin comes in many shades and so do rashes. NPR website. November 14, 2019. Accessed November 19, 2020. https://www.npr.org/sections/health-shots/2019/11/04/774910915/diagnostic-gaps-skin-comes-in-many-shades-and-so-do-rashes.
- Tackett KJ, Jenkins F, Morrell DS, et al. Structural racism and its influence on the severity of atopic dermatitis in African American children. Pediatr Dermatol. 2020;37:142-146.
- Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006;55:741-760.
- Ebede T, Papier A. Disparities in dermatology educational resources. J Am Acad Dermatol. 2006;55:687-690.
- Cooper LA, Roter DL, Johnson RL, et al. Patient-centered communication, ratings of care, and concordance of patient and physician race. Ann Intern Med. 2003;139:907-915.
- Takeshita J, Eriksen WT, Raziano VT, et al. Racial differences in perceptions of psoriasis therapies: implications for racial disparities in psoriasis treatment. J Invest Dermatol. 2019;139:1672-1679.e1.
- Alvarado SM, Feng H. Representation of dark skin images of common dermatologic conditions in educational resources: a cross-sectional analysis [published online June 18, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2020.06.041.
- Rabin RC. Dermatology has a problem with skin color. The New York Times. August 30, 2020. http://www.nytimes.com/2020/08/30/health/skin-diseases-black-hispanic.html. Accessed November 19, 2020.
- Bosley RE, Daveluy S. A primer to natural hair care practices in black patients. Cutis. 2015;95:78-80.
Although physicians commit themselves to providing equitable treatment to all patients, significant disparities remain in the dermatologic care of Black patients, who constitute 13% of the US population, which continues to grow increasingly diverse.1 Despite these changes in the population, the literature demonstrates that dermatologic training does not adequately focus on unique presentations of cutaneous pathology in the Black population.2,3 Accordingly, medical students lack proper training in how skin disorders manifest in people of color. Compounding the problem, only 3% of dermatologists are Black, creating a cultural barrier that can compromise care for Black patients.2,4 Racial disparities in dermatology training can compromise treatment, patient satisfaction, and outcomes.3
Issues in Medical Education Training and Resources
Lack of diversity in the resources used for dermatology training in medical schools affects diagnosis and treatment, as skin manifestations such as hypersensitivity reactions, rashes, and cancer can appear differently on different skin tones.5 A study of medical students’ ability to diagnose common dermatologic pathologies found that when trainees were presented with photographs of dark skin, their accuracy in identifying urticaria, squamous cell carcinoma, and even atopic dermatitis was reduced, despite these diseases being more prevalent in children of African American ancestry.4,6
Dermatologic diseases also can have different distributions in different races; for example, on non–sun-exposed sites, squamous cell carcinoma in Black patients occurs at 8.5 times the frequency of White patients.7 Failure to identify diseases accurately due to insufficient training can have grave consequences for patients. Although skin cancer is less common in individuals with skin of color, it is associated with greater morbidity and mortality, in part due to delayed diagnosis.7
Inadequate research, reporting, and instruction on dermatologic findings in patients with darker complexions further compound racial disparities in dermatology. A 2006 study of the representation of darker skin in major dermatology educational resources found that only 2% of teaching events at American Academy of Dermatology annual meetings focused on skin of color. Furthermore, the study determined that many common diseases in patients with dark skin, such as acne vulgaris and pityriasis rosea, were completely absent or limited in dermatology textbooks.8
Impact on the Black Patient Experience
Patients’ therapeutic relationship with their physician also is damaged by limitations in training in diverse skin color. A study that assessed Black patients seen in a skin of color clinic (SOCC) compared to Black patients seen in a non-SOCC found that non-SOCC patients reported a lower degree of respect, dignity, understanding, and trust compared to the patients seen in a SOCC. Black patients expressed specific concerns about non-SOCC dermatologists’ knowledge of abnormalities that present in darker skin and Black hair.3 These findings are compounded by reports suggesting that, independent of care, structural racism contributes to dermatologic disease severity by influencing patient education level, household income, and degree of exposure to harmful environmental irritants.6
Racial disparities continue to be seen in the makeup of the universe of dermatologists and skin researchers. As of 2016, only 3% of dermatologists were Black, making dermatology one of the least diverse medical specialties.2 Increasing the diversity of the dermatology workforce is important to improve patient satisfaction and treatment, both for minority and nonminority patients. Compared to race-discordant medical visits, race-concordant visits were shown to have a higher rate of satisfaction and better shared decision-making.9 Also, minority physicians are more likely to practice health care in areas that are traditionally underserved and to care for patients who do not have health insurance, making their participation essential in addressing some of the baseline disparities Black patients face in securing quality dermatologic care.1
Structural Racism in Medicine
Changing dermatology training to ensure improved treatment of Black patients requires not only increased attention to differences in disease presentation but also heightened awareness of underlying genetic, environmental, and structural factors that contribute to the disease course.6 For example, there is evidence suggesting that structural racism in the form of residential segregation, lower socioeconomic status, and lower educational attainment contribute to disease severity in conditions such as atopic dermatitis. There is additional evidence suggesting that White patients are more readily offered therapeutic options than Black patients. A study of racial disparities in psoriasis treatment found that Black patients with moderate to severe psoriasis were 70% less likely to receive treatment with a biologic than White patients, independent of socioeconomic factors, comorbidities, and insurance plans.10
Moving Forward
Although research continues to underscore racial disparities in dermatology, some leaders in the field are actively combating these problems. A recent study that looked at representations of dark skin images in medical educational resources found far greater representation of dark pigmented skin in web-based resources than in traditional printed texts. Specifically, the online resource VisualDx (https://www.visualdx.com/) features 28.5% dark skin images compared to 10.3% (on average) in printed dermatology books.11 There also is increasing public awareness of these issues, with organizations such as the Skin of Color Society (http://skinofcolorsociety.org/) helping to promote interest in racial disparities in dermatology. Physicians also have created textbooks and social media accounts focused on dermatologic manifestations in skin of color.12 The Instagram account Brown Skin Matters (@brownskinmatters) has created a publicly accessible online resource where physicians and patients can see and post dermatologic diseases in skin of color.5
Final Thoughts
It is critical that physicians be trained to identify skin and hair manifestations of disease and disorders in Black patients. Training can be improved by including more images of skin manifestations in dark skin, both in medical school curricula and in new editions of dermatology textbooks. Training also must teach students about hair in Black individuals and how to properly treat it as well as related conditions of the hair and scalp.13 More research also is needed to better understand how dermatologists can improve the patient experience for Black patients. Residency programs must work to increase diversity among dermatology trainees.
Lastly, dermatology education should increasingly be supplemented with newer, web-based resources that show dermatologic manifestations across the spectrum of skin tones. Dermatology training must be adapted to better account for diverse patient populations and increase its focus on the systems that produce baseline disparities in disease morbidity and mortality.
Although physicians commit themselves to providing equitable treatment to all patients, significant disparities remain in the dermatologic care of Black patients, who constitute 13% of the US population, which continues to grow increasingly diverse.1 Despite these changes in the population, the literature demonstrates that dermatologic training does not adequately focus on unique presentations of cutaneous pathology in the Black population.2,3 Accordingly, medical students lack proper training in how skin disorders manifest in people of color. Compounding the problem, only 3% of dermatologists are Black, creating a cultural barrier that can compromise care for Black patients.2,4 Racial disparities in dermatology training can compromise treatment, patient satisfaction, and outcomes.3
Issues in Medical Education Training and Resources
Lack of diversity in the resources used for dermatology training in medical schools affects diagnosis and treatment, as skin manifestations such as hypersensitivity reactions, rashes, and cancer can appear differently on different skin tones.5 A study of medical students’ ability to diagnose common dermatologic pathologies found that when trainees were presented with photographs of dark skin, their accuracy in identifying urticaria, squamous cell carcinoma, and even atopic dermatitis was reduced, despite these diseases being more prevalent in children of African American ancestry.4,6
Dermatologic diseases also can have different distributions in different races; for example, on non–sun-exposed sites, squamous cell carcinoma in Black patients occurs at 8.5 times the frequency of White patients.7 Failure to identify diseases accurately due to insufficient training can have grave consequences for patients. Although skin cancer is less common in individuals with skin of color, it is associated with greater morbidity and mortality, in part due to delayed diagnosis.7
Inadequate research, reporting, and instruction on dermatologic findings in patients with darker complexions further compound racial disparities in dermatology. A 2006 study of the representation of darker skin in major dermatology educational resources found that only 2% of teaching events at American Academy of Dermatology annual meetings focused on skin of color. Furthermore, the study determined that many common diseases in patients with dark skin, such as acne vulgaris and pityriasis rosea, were completely absent or limited in dermatology textbooks.8
Impact on the Black Patient Experience
Patients’ therapeutic relationship with their physician also is damaged by limitations in training in diverse skin color. A study that assessed Black patients seen in a skin of color clinic (SOCC) compared to Black patients seen in a non-SOCC found that non-SOCC patients reported a lower degree of respect, dignity, understanding, and trust compared to the patients seen in a SOCC. Black patients expressed specific concerns about non-SOCC dermatologists’ knowledge of abnormalities that present in darker skin and Black hair.3 These findings are compounded by reports suggesting that, independent of care, structural racism contributes to dermatologic disease severity by influencing patient education level, household income, and degree of exposure to harmful environmental irritants.6
Racial disparities continue to be seen in the makeup of the universe of dermatologists and skin researchers. As of 2016, only 3% of dermatologists were Black, making dermatology one of the least diverse medical specialties.2 Increasing the diversity of the dermatology workforce is important to improve patient satisfaction and treatment, both for minority and nonminority patients. Compared to race-discordant medical visits, race-concordant visits were shown to have a higher rate of satisfaction and better shared decision-making.9 Also, minority physicians are more likely to practice health care in areas that are traditionally underserved and to care for patients who do not have health insurance, making their participation essential in addressing some of the baseline disparities Black patients face in securing quality dermatologic care.1
Structural Racism in Medicine
Changing dermatology training to ensure improved treatment of Black patients requires not only increased attention to differences in disease presentation but also heightened awareness of underlying genetic, environmental, and structural factors that contribute to the disease course.6 For example, there is evidence suggesting that structural racism in the form of residential segregation, lower socioeconomic status, and lower educational attainment contribute to disease severity in conditions such as atopic dermatitis. There is additional evidence suggesting that White patients are more readily offered therapeutic options than Black patients. A study of racial disparities in psoriasis treatment found that Black patients with moderate to severe psoriasis were 70% less likely to receive treatment with a biologic than White patients, independent of socioeconomic factors, comorbidities, and insurance plans.10
Moving Forward
Although research continues to underscore racial disparities in dermatology, some leaders in the field are actively combating these problems. A recent study that looked at representations of dark skin images in medical educational resources found far greater representation of dark pigmented skin in web-based resources than in traditional printed texts. Specifically, the online resource VisualDx (https://www.visualdx.com/) features 28.5% dark skin images compared to 10.3% (on average) in printed dermatology books.11 There also is increasing public awareness of these issues, with organizations such as the Skin of Color Society (http://skinofcolorsociety.org/) helping to promote interest in racial disparities in dermatology. Physicians also have created textbooks and social media accounts focused on dermatologic manifestations in skin of color.12 The Instagram account Brown Skin Matters (@brownskinmatters) has created a publicly accessible online resource where physicians and patients can see and post dermatologic diseases in skin of color.5
Final Thoughts
It is critical that physicians be trained to identify skin and hair manifestations of disease and disorders in Black patients. Training can be improved by including more images of skin manifestations in dark skin, both in medical school curricula and in new editions of dermatology textbooks. Training also must teach students about hair in Black individuals and how to properly treat it as well as related conditions of the hair and scalp.13 More research also is needed to better understand how dermatologists can improve the patient experience for Black patients. Residency programs must work to increase diversity among dermatology trainees.
Lastly, dermatology education should increasingly be supplemented with newer, web-based resources that show dermatologic manifestations across the spectrum of skin tones. Dermatology training must be adapted to better account for diverse patient populations and increase its focus on the systems that produce baseline disparities in disease morbidity and mortality.
- Pandya AG, Alexis AF, Berger TG, et al. Increasing racial and ethnic diversity in dermatology: a call to action. J Am Acad Dermatol. 2016;74:584-587.
- Gallegos A. Dermatology lacks diversity. Dermatology News. June 1, 2016. Accessed November 18, 2020. https://www.mdedge.com/dermatology/article/108920/practice-management/dermatology-lacks-diversity.
- Gorbatenko-Roth K, Prose N, Kundu RV, et al. Assessment of black patients’ perception of their dermatology care. JAMA Dermatol. 2019;155:1129-1134.
- Fenton A, Elliott E, Shahbandi A, et al. Medical students’ ability to diagnose common dermatologic conditions in skin of color. J Am Acad Dermatol. 2020;83:957-958.
- Prichep D. Diagnostic gaps: skin comes in many shades and so do rashes. NPR website. November 14, 2019. Accessed November 19, 2020. https://www.npr.org/sections/health-shots/2019/11/04/774910915/diagnostic-gaps-skin-comes-in-many-shades-and-so-do-rashes.
- Tackett KJ, Jenkins F, Morrell DS, et al. Structural racism and its influence on the severity of atopic dermatitis in African American children. Pediatr Dermatol. 2020;37:142-146.
- Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006;55:741-760.
- Ebede T, Papier A. Disparities in dermatology educational resources. J Am Acad Dermatol. 2006;55:687-690.
- Cooper LA, Roter DL, Johnson RL, et al. Patient-centered communication, ratings of care, and concordance of patient and physician race. Ann Intern Med. 2003;139:907-915.
- Takeshita J, Eriksen WT, Raziano VT, et al. Racial differences in perceptions of psoriasis therapies: implications for racial disparities in psoriasis treatment. J Invest Dermatol. 2019;139:1672-1679.e1.
- Alvarado SM, Feng H. Representation of dark skin images of common dermatologic conditions in educational resources: a cross-sectional analysis [published online June 18, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2020.06.041.
- Rabin RC. Dermatology has a problem with skin color. The New York Times. August 30, 2020. http://www.nytimes.com/2020/08/30/health/skin-diseases-black-hispanic.html. Accessed November 19, 2020.
- Bosley RE, Daveluy S. A primer to natural hair care practices in black patients. Cutis. 2015;95:78-80.
- Pandya AG, Alexis AF, Berger TG, et al. Increasing racial and ethnic diversity in dermatology: a call to action. J Am Acad Dermatol. 2016;74:584-587.
- Gallegos A. Dermatology lacks diversity. Dermatology News. June 1, 2016. Accessed November 18, 2020. https://www.mdedge.com/dermatology/article/108920/practice-management/dermatology-lacks-diversity.
- Gorbatenko-Roth K, Prose N, Kundu RV, et al. Assessment of black patients’ perception of their dermatology care. JAMA Dermatol. 2019;155:1129-1134.
- Fenton A, Elliott E, Shahbandi A, et al. Medical students’ ability to diagnose common dermatologic conditions in skin of color. J Am Acad Dermatol. 2020;83:957-958.
- Prichep D. Diagnostic gaps: skin comes in many shades and so do rashes. NPR website. November 14, 2019. Accessed November 19, 2020. https://www.npr.org/sections/health-shots/2019/11/04/774910915/diagnostic-gaps-skin-comes-in-many-shades-and-so-do-rashes.
- Tackett KJ, Jenkins F, Morrell DS, et al. Structural racism and its influence on the severity of atopic dermatitis in African American children. Pediatr Dermatol. 2020;37:142-146.
- Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006;55:741-760.
- Ebede T, Papier A. Disparities in dermatology educational resources. J Am Acad Dermatol. 2006;55:687-690.
- Cooper LA, Roter DL, Johnson RL, et al. Patient-centered communication, ratings of care, and concordance of patient and physician race. Ann Intern Med. 2003;139:907-915.
- Takeshita J, Eriksen WT, Raziano VT, et al. Racial differences in perceptions of psoriasis therapies: implications for racial disparities in psoriasis treatment. J Invest Dermatol. 2019;139:1672-1679.e1.
- Alvarado SM, Feng H. Representation of dark skin images of common dermatologic conditions in educational resources: a cross-sectional analysis [published online June 18, 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2020.06.041.
- Rabin RC. Dermatology has a problem with skin color. The New York Times. August 30, 2020. http://www.nytimes.com/2020/08/30/health/skin-diseases-black-hispanic.html. Accessed November 19, 2020.
- Bosley RE, Daveluy S. A primer to natural hair care practices in black patients. Cutis. 2015;95:78-80.
Practice Points
- Dermatologists should be aware of the existing health disparities in dermatology training, including lack of representation among dermatologists, treatment, patient satisfaction, and outcomes.
- Dermatologic diseases can present differently in different skin tones, and current dermatology training does not reflect these differences.
- We must continue to work toward increasing diversity of the dermatology workforce, including a diverse range of skin tones in images used in dermatology training, and teaching trainees how diseases present differently in different skin tones.
International expert group agrees on redefining psoriasis severity
It’s high time to say farewell to the traditional categorization of psoriasis severity into mild, moderate, or severe disease, according to the International Psoriasis Council.
The mild/moderate/severe categorization is vague and defined differently by different organizations and in different countries. It often underestimates disease severity because it ignores psoriasis involvement in particularly tough-to-treat special areas, including the scalp, palms, soles, face, nails, and genitalia, Bruce E. Strober, MD, PhD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year. He chaired an IPC project in which prominent psoriasis experts in 32 countries employed a Delphi consensus approach aimed at achieving agreement on a more practical recategorization of psoriasis severity for use in both daily clinical practice and enrolling appropriate participants in clinical trials. What emerged was a simplified dichotomous categorization system.
“What we came up with is a very sensible approach to defining whether patients should get either topical or systemic therapy. In fact, there are only two groups of patients in psoriasis: those who should get topicals alone, and those who should get systemic therapy. It’s topicals or systemics,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., who also works in private practice in Cromwell, Conn.
Under the IPC classification, psoriasis patients are candidates for systemic therapy if they meet at least one of three criteria: body surface area of involvement greater than 10%, disease involving the previously mentioned special areas, or failure of topical therapy.
“This approach is about practically treating patients who are in need,” Dr. Strober said. “If patients meet just one of these three criteria they can move on to our current toolbox of systemic therapies, be they older systemic treatments, apremilast, phototherapy, or 1 of the 11 biologics currently approved for the treatment of psoriasis. The key point is that for patients with moderate to severe psoriasis – or should I say, systemic therapy–appropriate psoriasis – treatment should be based on individual patient characteristics. We don’t work on a stepwise approach. If a patient walks in with more than 10% body surface area involved, don’t make them fail topicals; you can go right to systemics.”
European dermatologists often use the Psoriasis Area and Severity Index (PASI) score to characterize disease severity and monitor response to therapy. In contrast, American dermatologists generally find PASI too complex and time-consuming for use in clinical practice, relying instead on the amount of body surface area involved with psoriasis. Neither of these measures incorporates disease involvement in special areas, which when present ought to automatically place a patient in the systemic therapy–appropriate category, according to Dr. Strober.
“I find this [IPC recategorization] a very practical approach. I hope you write this down and use this in your own practice,” Dr. Strober said.
The full IPC report was published in the Journal of the American Academy of Dermatology.
The IPC psoriasis severity reclassification project was unfunded. Dr. Strober reported receiving institutional research funding from and serving as a paid consultant to more than two dozen pharmaceutical companies.
MedscapeLive and this news organization are owned by the same parent company.
It’s high time to say farewell to the traditional categorization of psoriasis severity into mild, moderate, or severe disease, according to the International Psoriasis Council.
The mild/moderate/severe categorization is vague and defined differently by different organizations and in different countries. It often underestimates disease severity because it ignores psoriasis involvement in particularly tough-to-treat special areas, including the scalp, palms, soles, face, nails, and genitalia, Bruce E. Strober, MD, PhD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year. He chaired an IPC project in which prominent psoriasis experts in 32 countries employed a Delphi consensus approach aimed at achieving agreement on a more practical recategorization of psoriasis severity for use in both daily clinical practice and enrolling appropriate participants in clinical trials. What emerged was a simplified dichotomous categorization system.
“What we came up with is a very sensible approach to defining whether patients should get either topical or systemic therapy. In fact, there are only two groups of patients in psoriasis: those who should get topicals alone, and those who should get systemic therapy. It’s topicals or systemics,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., who also works in private practice in Cromwell, Conn.
Under the IPC classification, psoriasis patients are candidates for systemic therapy if they meet at least one of three criteria: body surface area of involvement greater than 10%, disease involving the previously mentioned special areas, or failure of topical therapy.
“This approach is about practically treating patients who are in need,” Dr. Strober said. “If patients meet just one of these three criteria they can move on to our current toolbox of systemic therapies, be they older systemic treatments, apremilast, phototherapy, or 1 of the 11 biologics currently approved for the treatment of psoriasis. The key point is that for patients with moderate to severe psoriasis – or should I say, systemic therapy–appropriate psoriasis – treatment should be based on individual patient characteristics. We don’t work on a stepwise approach. If a patient walks in with more than 10% body surface area involved, don’t make them fail topicals; you can go right to systemics.”
European dermatologists often use the Psoriasis Area and Severity Index (PASI) score to characterize disease severity and monitor response to therapy. In contrast, American dermatologists generally find PASI too complex and time-consuming for use in clinical practice, relying instead on the amount of body surface area involved with psoriasis. Neither of these measures incorporates disease involvement in special areas, which when present ought to automatically place a patient in the systemic therapy–appropriate category, according to Dr. Strober.
“I find this [IPC recategorization] a very practical approach. I hope you write this down and use this in your own practice,” Dr. Strober said.
The full IPC report was published in the Journal of the American Academy of Dermatology.
The IPC psoriasis severity reclassification project was unfunded. Dr. Strober reported receiving institutional research funding from and serving as a paid consultant to more than two dozen pharmaceutical companies.
MedscapeLive and this news organization are owned by the same parent company.
It’s high time to say farewell to the traditional categorization of psoriasis severity into mild, moderate, or severe disease, according to the International Psoriasis Council.
The mild/moderate/severe categorization is vague and defined differently by different organizations and in different countries. It often underestimates disease severity because it ignores psoriasis involvement in particularly tough-to-treat special areas, including the scalp, palms, soles, face, nails, and genitalia, Bruce E. Strober, MD, PhD, asserted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year. He chaired an IPC project in which prominent psoriasis experts in 32 countries employed a Delphi consensus approach aimed at achieving agreement on a more practical recategorization of psoriasis severity for use in both daily clinical practice and enrolling appropriate participants in clinical trials. What emerged was a simplified dichotomous categorization system.
“What we came up with is a very sensible approach to defining whether patients should get either topical or systemic therapy. In fact, there are only two groups of patients in psoriasis: those who should get topicals alone, and those who should get systemic therapy. It’s topicals or systemics,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., who also works in private practice in Cromwell, Conn.
Under the IPC classification, psoriasis patients are candidates for systemic therapy if they meet at least one of three criteria: body surface area of involvement greater than 10%, disease involving the previously mentioned special areas, or failure of topical therapy.
“This approach is about practically treating patients who are in need,” Dr. Strober said. “If patients meet just one of these three criteria they can move on to our current toolbox of systemic therapies, be they older systemic treatments, apremilast, phototherapy, or 1 of the 11 biologics currently approved for the treatment of psoriasis. The key point is that for patients with moderate to severe psoriasis – or should I say, systemic therapy–appropriate psoriasis – treatment should be based on individual patient characteristics. We don’t work on a stepwise approach. If a patient walks in with more than 10% body surface area involved, don’t make them fail topicals; you can go right to systemics.”
European dermatologists often use the Psoriasis Area and Severity Index (PASI) score to characterize disease severity and monitor response to therapy. In contrast, American dermatologists generally find PASI too complex and time-consuming for use in clinical practice, relying instead on the amount of body surface area involved with psoriasis. Neither of these measures incorporates disease involvement in special areas, which when present ought to automatically place a patient in the systemic therapy–appropriate category, according to Dr. Strober.
“I find this [IPC recategorization] a very practical approach. I hope you write this down and use this in your own practice,” Dr. Strober said.
The full IPC report was published in the Journal of the American Academy of Dermatology.
The IPC psoriasis severity reclassification project was unfunded. Dr. Strober reported receiving institutional research funding from and serving as a paid consultant to more than two dozen pharmaceutical companies.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
The case for anti–IL-17 agents as first-line biologics in psoriatic arthritis
LAS VEGAS – at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.
“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”
Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.
A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.
“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.
Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.
“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.
The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.
“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.
Durability of response and safety
“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.
Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.
Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.
“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.
There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.
Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.
Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.
For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
What about IL-12/23 and IL-23 inhibitors in PsA?
In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.
An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.
Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.
“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”
Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.
A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.
“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.
Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.
“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.
The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.
“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.
Durability of response and safety
“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.
Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.
Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.
“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.
There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.
Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.
Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.
For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
What about IL-12/23 and IL-23 inhibitors in PsA?
In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.
An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.
Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.
“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”
Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.
A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.
“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.
Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.
“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.
The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.
“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.
Durability of response and safety
“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.
Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.
Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.
“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.
There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.
Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.
Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.
For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
What about IL-12/23 and IL-23 inhibitors in PsA?
In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.
An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.
Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
Expanded indications likely for apremilast
Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
“We’ll have , meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
Mild or moderate psoriasis
Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.
Pediatric studies
A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.
“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.
Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.
Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.
“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.
Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.
One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
Topical PDE-4 inhibitor shows promise
Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.
“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.
A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.
The phase 3 program is now recruiting participants.
Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.
MedscapeLive and this news organization are owned by the same parent company.
Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
“We’ll have , meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
Mild or moderate psoriasis
Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.
Pediatric studies
A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.
“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.
Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.
Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.
“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.
Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.
One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
Topical PDE-4 inhibitor shows promise
Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.
“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.
A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.
The phase 3 program is now recruiting participants.
Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.
MedscapeLive and this news organization are owned by the same parent company.
Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
“We’ll have , meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
Mild or moderate psoriasis
Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.
Pediatric studies
A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.
“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.
Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.
Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.
“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.
Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.
One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
Topical PDE-4 inhibitor shows promise
Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.
“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.
A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.
The phase 3 program is now recruiting participants.
Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
TNF inhibitor–induced psoriasis treatment algorithm maintains TNF inhibitor if possible
In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.
While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
IBD and RA most common
Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.
Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.
Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.
In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).
Algorithm aims at balancing control
The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.
“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”
Risk to benefit ratio favors retaining TNF inhibitors
The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.
Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.
SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.
In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.
While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
IBD and RA most common
Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.
Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.
Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.
In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).
Algorithm aims at balancing control
The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.
“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”
Risk to benefit ratio favors retaining TNF inhibitors
The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.
Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.
SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.
In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.
While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
IBD and RA most common
Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.
Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.
Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.
In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).
Algorithm aims at balancing control
The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.
“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”
Risk to benefit ratio favors retaining TNF inhibitors
The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.
Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.
SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY