Psoriatic Arthritis ICYMI

The rates of osteopenia and osteoporosis among individuals with psoriatic arthritis are comparable to those seen in the general population, research suggests.

The cohort study, published in Arthritis Care & Research, also found that clinicians are likely to refer patients for bone mineral density (BMD) testing based on osteoporosis risk factors or psoriatic arthritis disease severity markers.

Timothy S.H. Kwok, MD, of the University of Toronto, and coauthors wrote that previous research suggested a possible link between psoriatic arthritis and osteoporosis or osteopenia. However, no cohort studies appear to have examined this association.

The study involved 201 individuals with psoriatic arthritis attending a single specialist clinic, who were enrolled in a longitudinal study of psoriatic arthritis (PsA) and who were also referred for BMD testing with dual-energy x-ray absorptiometry.

Of these participants, 13% had a BMD in the osteoporotic range, 45% were in the osteopenic range, and 42% were in the normal range for BMD. The prevalence of osteoporosis observed in the general population aged 50 or above, observed in an earlier large prospective study, ranged from 7% to 16%, and osteopenia ranged from 27% to 46%.

“Our study suggests that patients with PsA have similar BMDs compared to the general population,” the authors wrote.

Researchers did note the suggestion that patients with polyarthritis had lower BMDs over time. Because of the small number of events, this did not achieve statistical significance, but “this relationship warrants further research, given that multiple cohort studies have independently demonstrated polyarticular onset of disease predicting clinical deformities and erosive disease in PsA,” they wrote.

They also saw that patients with increased body mass index had a significant 21% lower odds of having a BMD in the osteoporotic range, while those using biologics had a significant 83% lower odds.

Among participants with BMD scores in the osteopenic or osteoporotic range, these scores were seen in the lumbar spine in 63% of measurements, the femoral neck in 88%, and the total hip in 39%. Mean T-scores for the lumbar spine were –0.30±0.32, and for the femoral neck were –1.10±1.04 and the total hip, –0.45±0.42.

The study also examined what factors were associated with referral for BMD testing. They found that increasing age, menopause, elevated acute phase reactants, or use of biologics, methotrexate, and systemic glucocorticoids were associated with a higher likelihood of undergoing BMD testing.

Noting that the latest Canadian clinical practice guidelines on BMD testing advise that age, menopause, and use of systemic glucocorticoids use are risk factors that should prompt testing, the authors suggested clinicians were using a combination of traditional osteoporosis risk factors and markers of psoriatic disease severity to underpin their decision to refer.

However, they commented that none of the factors associated with a higher likelihood of having a BMD test were actually associated with lower BMD scores.

“This suggests that clinicians may be over-screening patients with PsA for osteopenia/osteoporosis, as they do not appear to be at baseline higher risk for lower BMD scores than the general population,” they wrote. “This is of importance, as there are currently no formal recommendations with regards to the optimal interval or time to commence BMD testing within the recent major PsA guidelines.”

The study was supported by a grant from the Krembil Foundation. No conflicts of interest were declared.

SOURCE: Kwok TSH et al. Arthritis Care Res. 2020 Dec 16. doi: 10.1002/acr.24538.

The rates of osteopenia and osteoporosis among individuals with psoriatic arthritis are comparable to those seen in the general population, research suggests.

The cohort study, published in Arthritis Care & Research, also found that clinicians are likely to refer patients for bone mineral density (BMD) testing based on osteoporosis risk factors or psoriatic arthritis disease severity markers.

Timothy S.H. Kwok, MD, of the University of Toronto, and coauthors wrote that previous research suggested a possible link between psoriatic arthritis and osteoporosis or osteopenia. However, no cohort studies appear to have examined this association.

The study involved 201 individuals with psoriatic arthritis attending a single specialist clinic, who were enrolled in a longitudinal study of psoriatic arthritis (PsA) and who were also referred for BMD testing with dual-energy x-ray absorptiometry.

Of these participants, 13% had a BMD in the osteoporotic range, 45% were in the osteopenic range, and 42% were in the normal range for BMD. The prevalence of osteoporosis observed in the general population aged 50 or above, observed in an earlier large prospective study, ranged from 7% to 16%, and osteopenia ranged from 27% to 46%.

“Our study suggests that patients with PsA have similar BMDs compared to the general population,” the authors wrote.

Researchers did note the suggestion that patients with polyarthritis had lower BMDs over time. Because of the small number of events, this did not achieve statistical significance, but “this relationship warrants further research, given that multiple cohort studies have independently demonstrated polyarticular onset of disease predicting clinical deformities and erosive disease in PsA,” they wrote.

They also saw that patients with increased body mass index had a significant 21% lower odds of having a BMD in the osteoporotic range, while those using biologics had a significant 83% lower odds.

Among participants with BMD scores in the osteopenic or osteoporotic range, these scores were seen in the lumbar spine in 63% of measurements, the femoral neck in 88%, and the total hip in 39%. Mean T-scores for the lumbar spine were –0.30±0.32, and for the femoral neck were –1.10±1.04 and the total hip, –0.45±0.42.

The study also examined what factors were associated with referral for BMD testing. They found that increasing age, menopause, elevated acute phase reactants, or use of biologics, methotrexate, and systemic glucocorticoids were associated with a higher likelihood of undergoing BMD testing.

Noting that the latest Canadian clinical practice guidelines on BMD testing advise that age, menopause, and use of systemic glucocorticoids use are risk factors that should prompt testing, the authors suggested clinicians were using a combination of traditional osteoporosis risk factors and markers of psoriatic disease severity to underpin their decision to refer.

However, they commented that none of the factors associated with a higher likelihood of having a BMD test were actually associated with lower BMD scores.

“This suggests that clinicians may be over-screening patients with PsA for osteopenia/osteoporosis, as they do not appear to be at baseline higher risk for lower BMD scores than the general population,” they wrote. “This is of importance, as there are currently no formal recommendations with regards to the optimal interval or time to commence BMD testing within the recent major PsA guidelines.”

The study was supported by a grant from the Krembil Foundation. No conflicts of interest were declared.

SOURCE: Kwok TSH et al. Arthritis Care Res. 2020 Dec 16. doi: 10.1002/acr.24538.

The rates of osteopenia and osteoporosis among individuals with psoriatic arthritis are comparable to those seen in the general population, research suggests.

The cohort study, published in Arthritis Care & Research, also found that clinicians are likely to refer patients for bone mineral density (BMD) testing based on osteoporosis risk factors or psoriatic arthritis disease severity markers.

Timothy S.H. Kwok, MD, of the University of Toronto, and coauthors wrote that previous research suggested a possible link between psoriatic arthritis and osteoporosis or osteopenia. However, no cohort studies appear to have examined this association.

The study involved 201 individuals with psoriatic arthritis attending a single specialist clinic, who were enrolled in a longitudinal study of psoriatic arthritis (PsA) and who were also referred for BMD testing with dual-energy x-ray absorptiometry.

Of these participants, 13% had a BMD in the osteoporotic range, 45% were in the osteopenic range, and 42% were in the normal range for BMD. The prevalence of osteoporosis observed in the general population aged 50 or above, observed in an earlier large prospective study, ranged from 7% to 16%, and osteopenia ranged from 27% to 46%.

“Our study suggests that patients with PsA have similar BMDs compared to the general population,” the authors wrote.

Researchers did note the suggestion that patients with polyarthritis had lower BMDs over time. Because of the small number of events, this did not achieve statistical significance, but “this relationship warrants further research, given that multiple cohort studies have independently demonstrated polyarticular onset of disease predicting clinical deformities and erosive disease in PsA,” they wrote.

They also saw that patients with increased body mass index had a significant 21% lower odds of having a BMD in the osteoporotic range, while those using biologics had a significant 83% lower odds.

Among participants with BMD scores in the osteopenic or osteoporotic range, these scores were seen in the lumbar spine in 63% of measurements, the femoral neck in 88%, and the total hip in 39%. Mean T-scores for the lumbar spine were –0.30±0.32, and for the femoral neck were –1.10±1.04 and the total hip, –0.45±0.42.

The study also examined what factors were associated with referral for BMD testing. They found that increasing age, menopause, elevated acute phase reactants, or use of biologics, methotrexate, and systemic glucocorticoids were associated with a higher likelihood of undergoing BMD testing.

Noting that the latest Canadian clinical practice guidelines on BMD testing advise that age, menopause, and use of systemic glucocorticoids use are risk factors that should prompt testing, the authors suggested clinicians were using a combination of traditional osteoporosis risk factors and markers of psoriatic disease severity to underpin their decision to refer.

However, they commented that none of the factors associated with a higher likelihood of having a BMD test were actually associated with lower BMD scores.

“This suggests that clinicians may be over-screening patients with PsA for osteopenia/osteoporosis, as they do not appear to be at baseline higher risk for lower BMD scores than the general population,” they wrote. “This is of importance, as there are currently no formal recommendations with regards to the optimal interval or time to commence BMD testing within the recent major PsA guidelines.”

The study was supported by a grant from the Krembil Foundation. No conflicts of interest were declared.

SOURCE: Kwok TSH et al. Arthritis Care Res. 2020 Dec 16. doi: 10.1002/acr.24538.

Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.

Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.

“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”

Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.

The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.

They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”

The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.

Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.

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Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.

“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”

Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.

Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.

The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.

Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.

Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.

“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”

Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.

The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.

They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”

The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.

Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.

SDI Productions/E+

Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.

“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”

Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.

Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.

The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.

Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.

Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.

“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”

Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.

The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.

They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”

The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.

Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.

SDI Productions/E+

Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.

“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”

Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.

Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.

The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.

SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.

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.

scyther5/thinkstock

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.

scyther5/thinkstock

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.

scyther5/thinkstock

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.

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.

SilverV/Thinkstock

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.

SilverV/Thinkstock

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.

SilverV/Thinkstock

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.

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.

[email protected]

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.

[email protected]

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.

[email protected]

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said 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.

[email protected]

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said 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.

[email protected]

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said 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.

[email protected]

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 a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, 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.

[email protected]

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 a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, 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.

[email protected]

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 a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, 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.

[email protected]

New study results from British researchers show that dactylitis may be a clinical indicator of an aggressive phenotype of psoriatic arthritis (PsA). That phenotype is marked by a significantly greater swollen joint count, tender joint count, C-reactive protein, erosive damage, and ultrasound synovitis in very early disease-modifying antirheumatic drug (DMARD)-naive PsA.

The dactylitis study is noted by Dr Saakshi Khattri, assistant professor of rheumatology and dermatology at the Icahn School of Medicine at Mount Sinai, as one of the key findings on PsA presented at ACR Convergence 2020, the American College of Rheumatology's first all-virtual annual meeting. Researchers from Leeds, United Kingdom, concluded that dactylitis may help differentiate risk among patients in an early disease stage.

Another study from researchers in the UK also addresses very early DMARD-naive PsA patients. It found that clinically, swollen joints are linked to power Doppler‒detected synovitis, but tender, nonswollen joints are not.

Also in this ReCAP, Dr Khattri discusses a population-based study from the Mayo Clinic that shows that patients with a family history of psoriasis and severe psoriasis experience a delay in transitioning to PsA. She highlights an interim report about an emerging risk-prediction model that may improve early detection of PsA. Finally, Dr Khattri shares a quality-of-life survey from the National Psoriasis Foundation about the prevalence of unacceptable symptom states in PsA, which reinforces that PsA is far from adequately treated.
--

Saakshi Khattri, MBBS, MD, Assistant Professor, Department of Internal Medicine, Divisions of Rheumatology and Dermatology, Icahn School of Medicine at Mount Sinai; Director, Center for Connective Tissue Diseases at Mount Sinai, New York, NY. 

Saakshi Khattri, MBBS, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis
Serve(d) as a speaker or a member of a speakers bureau for: Janssen
Received research grant from: Pfizer
Received income in an amount equal to or greater than $250 from: Pfizer; Novartis.

New study results from British researchers show that dactylitis may be a clinical indicator of an aggressive phenotype of psoriatic arthritis (PsA). That phenotype is marked by a significantly greater swollen joint count, tender joint count, C-reactive protein, erosive damage, and ultrasound synovitis in very early disease-modifying antirheumatic drug (DMARD)-naive PsA.

The dactylitis study is noted by Dr Saakshi Khattri, assistant professor of rheumatology and dermatology at the Icahn School of Medicine at Mount Sinai, as one of the key findings on PsA presented at ACR Convergence 2020, the American College of Rheumatology's first all-virtual annual meeting. Researchers from Leeds, United Kingdom, concluded that dactylitis may help differentiate risk among patients in an early disease stage.

Another study from researchers in the UK also addresses very early DMARD-naive PsA patients. It found that clinically, swollen joints are linked to power Doppler‒detected synovitis, but tender, nonswollen joints are not.

Also in this ReCAP, Dr Khattri discusses a population-based study from the Mayo Clinic that shows that patients with a family history of psoriasis and severe psoriasis experience a delay in transitioning to PsA. She highlights an interim report about an emerging risk-prediction model that may improve early detection of PsA. Finally, Dr Khattri shares a quality-of-life survey from the National Psoriasis Foundation about the prevalence of unacceptable symptom states in PsA, which reinforces that PsA is far from adequately treated.
--

Saakshi Khattri, MBBS, MD, Assistant Professor, Department of Internal Medicine, Divisions of Rheumatology and Dermatology, Icahn School of Medicine at Mount Sinai; Director, Center for Connective Tissue Diseases at Mount Sinai, New York, NY. 

Saakshi Khattri, MBBS, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis
Serve(d) as a speaker or a member of a speakers bureau for: Janssen
Received research grant from: Pfizer
Received income in an amount equal to or greater than $250 from: Pfizer; Novartis.

New study results from British researchers show that dactylitis may be a clinical indicator of an aggressive phenotype of psoriatic arthritis (PsA). That phenotype is marked by a significantly greater swollen joint count, tender joint count, C-reactive protein, erosive damage, and ultrasound synovitis in very early disease-modifying antirheumatic drug (DMARD)-naive PsA.

The dactylitis study is noted by Dr Saakshi Khattri, assistant professor of rheumatology and dermatology at the Icahn School of Medicine at Mount Sinai, as one of the key findings on PsA presented at ACR Convergence 2020, the American College of Rheumatology's first all-virtual annual meeting. Researchers from Leeds, United Kingdom, concluded that dactylitis may help differentiate risk among patients in an early disease stage.

Another study from researchers in the UK also addresses very early DMARD-naive PsA patients. It found that clinically, swollen joints are linked to power Doppler‒detected synovitis, but tender, nonswollen joints are not.

Also in this ReCAP, Dr Khattri discusses a population-based study from the Mayo Clinic that shows that patients with a family history of psoriasis and severe psoriasis experience a delay in transitioning to PsA. She highlights an interim report about an emerging risk-prediction model that may improve early detection of PsA. Finally, Dr Khattri shares a quality-of-life survey from the National Psoriasis Foundation about the prevalence of unacceptable symptom states in PsA, which reinforces that PsA is far from adequately treated.
--

Saakshi Khattri, MBBS, MD, Assistant Professor, Department of Internal Medicine, Divisions of Rheumatology and Dermatology, Icahn School of Medicine at Mount Sinai; Director, Center for Connective Tissue Diseases at Mount Sinai, New York, NY. 

Saakshi Khattri, MBBS, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis
Serve(d) as a speaker or a member of a speakers bureau for: Janssen
Received research grant from: Pfizer
Received income in an amount equal to or greater than $250 from: Pfizer; Novartis.

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.

The full 5-year results of a long-term extension study of tildrakizumab for psoriasis show a high rate of sustained disease control coupled with a favorable safety profile during more than 5,400 patient-years of prospective follow-up, Diamont Thaçi, MD, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

For example, 89% of patients who had a PASI-75 response on the 100-mg dose of tildrakizumab (Ilumya) – the dose approved in the United States – at week 28 in the parent reSURFACE 1 and reSURFACE 2 trials maintained their PASI-75 response throughout the next 4½ years in the long-term extension study, as did 93% of those with a week 28 PASI-75 response on 200 mg, a dose approved elsewhere, said Dr. Thaçi, professor of dermatology and director of the Comprehensive Center for Inflammation Medicine at Lübeck (Germany) University.

The same held true for PASI-90, a response achieved by 71% of participants on 100 mg of tildrakizumab at week 28 and 66% at week 244, and by 73% of those on the 200-mg dose at week 28 and 70% at 5 years. A PASI-100 response was documented at week 28 in 29% of patients on the lower dose and 37% of those on 200 mg, with week 244 PASI-100 rates of 33% and 41%, respectively.

The long-term extension study enrolled 622 patients with moderate to severe chronic plaque psoriasis with at least a PASI-75 response to 100 mg or 200 mg of the humanized monoclonal antibody interleukin-23p19 inhibitor at week 28 in reSURFACE 1 or 2, or who were partial or nonresponders to etanercept in reSURFACE 2 and were then switched to tildrakizumab at 200 mg. Five hundred and forty-five of the 622 patients (88%) completed the full 5 years of the extension study.

Very few patients left the study because of loss of efficacy or adverse events. Indeed, the exposure-adjusted rate of drug-related serious adverse events was 0.8 cases per 100 patient-years at tildrakizumab 100 mg and 0.5 per 100 patient-years at 200 mg. Moreover, the rates of drug-related serious adverse events leading to treatment continuation were 0.3 and 0.2 per 100 patient-years at the 100-mg and 200-mg doses. Rates of treatment-emergent severe infection were 1.2 and 1.3 per 100 patient-years on the lower and higher doses. Major adverse cardiovascular events occurred at rates of 0.5 and 0.7 cases per 100 patient-years.

“I think the adverse events are generally similar to what has been seen with other biologics, but slightly less with tildrakizumab. Registries will provide a clearer picture. What’s interesting is that even if you double the dosage you don’t see an increase in side effects,” Dr. Thaçi said.

Asked what happens when a tildrakizumab responder stops taking the monoclonal antibody, he replied, “This is something very interesting we see with the IL-23 inhibitors: The disease comes back very slowly. It takes months, and sometimes years, for the patient to lose the PASI-75 or even the PASI-90 response. But we still consider that continuous treatment is probably the better way to go because we cannot be sure who will lose or regain response. At the moment we don’t have a biomarker to tell us what we should do in our daily practice.”

Dr. Thaçi reported serving as an adviser to and paid investigator for Almirall, the study sponsor, and approximately 20 other pharmaceutical companies.

[email protected]

The full 5-year results of a long-term extension study of tildrakizumab for psoriasis show a high rate of sustained disease control coupled with a favorable safety profile during more than 5,400 patient-years of prospective follow-up, Diamont Thaçi, MD, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

For example, 89% of patients who had a PASI-75 response on the 100-mg dose of tildrakizumab (Ilumya) – the dose approved in the United States – at week 28 in the parent reSURFACE 1 and reSURFACE 2 trials maintained their PASI-75 response throughout the next 4½ years in the long-term extension study, as did 93% of those with a week 28 PASI-75 response on 200 mg, a dose approved elsewhere, said Dr. Thaçi, professor of dermatology and director of the Comprehensive Center for Inflammation Medicine at Lübeck (Germany) University.

The same held true for PASI-90, a response achieved by 71% of participants on 100 mg of tildrakizumab at week 28 and 66% at week 244, and by 73% of those on the 200-mg dose at week 28 and 70% at 5 years. A PASI-100 response was documented at week 28 in 29% of patients on the lower dose and 37% of those on 200 mg, with week 244 PASI-100 rates of 33% and 41%, respectively.

The long-term extension study enrolled 622 patients with moderate to severe chronic plaque psoriasis with at least a PASI-75 response to 100 mg or 200 mg of the humanized monoclonal antibody interleukin-23p19 inhibitor at week 28 in reSURFACE 1 or 2, or who were partial or nonresponders to etanercept in reSURFACE 2 and were then switched to tildrakizumab at 200 mg. Five hundred and forty-five of the 622 patients (88%) completed the full 5 years of the extension study.

Very few patients left the study because of loss of efficacy or adverse events. Indeed, the exposure-adjusted rate of drug-related serious adverse events was 0.8 cases per 100 patient-years at tildrakizumab 100 mg and 0.5 per 100 patient-years at 200 mg. Moreover, the rates of drug-related serious adverse events leading to treatment continuation were 0.3 and 0.2 per 100 patient-years at the 100-mg and 200-mg doses. Rates of treatment-emergent severe infection were 1.2 and 1.3 per 100 patient-years on the lower and higher doses. Major adverse cardiovascular events occurred at rates of 0.5 and 0.7 cases per 100 patient-years.

“I think the adverse events are generally similar to what has been seen with other biologics, but slightly less with tildrakizumab. Registries will provide a clearer picture. What’s interesting is that even if you double the dosage you don’t see an increase in side effects,” Dr. Thaçi said.

Asked what happens when a tildrakizumab responder stops taking the monoclonal antibody, he replied, “This is something very interesting we see with the IL-23 inhibitors: The disease comes back very slowly. It takes months, and sometimes years, for the patient to lose the PASI-75 or even the PASI-90 response. But we still consider that continuous treatment is probably the better way to go because we cannot be sure who will lose or regain response. At the moment we don’t have a biomarker to tell us what we should do in our daily practice.”

Dr. Thaçi reported serving as an adviser to and paid investigator for Almirall, the study sponsor, and approximately 20 other pharmaceutical companies.

[email protected]

The full 5-year results of a long-term extension study of tildrakizumab for psoriasis show a high rate of sustained disease control coupled with a favorable safety profile during more than 5,400 patient-years of prospective follow-up, Diamont Thaçi, MD, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

For example, 89% of patients who had a PASI-75 response on the 100-mg dose of tildrakizumab (Ilumya) – the dose approved in the United States – at week 28 in the parent reSURFACE 1 and reSURFACE 2 trials maintained their PASI-75 response throughout the next 4½ years in the long-term extension study, as did 93% of those with a week 28 PASI-75 response on 200 mg, a dose approved elsewhere, said Dr. Thaçi, professor of dermatology and director of the Comprehensive Center for Inflammation Medicine at Lübeck (Germany) University.

The same held true for PASI-90, a response achieved by 71% of participants on 100 mg of tildrakizumab at week 28 and 66% at week 244, and by 73% of those on the 200-mg dose at week 28 and 70% at 5 years. A PASI-100 response was documented at week 28 in 29% of patients on the lower dose and 37% of those on 200 mg, with week 244 PASI-100 rates of 33% and 41%, respectively.

The long-term extension study enrolled 622 patients with moderate to severe chronic plaque psoriasis with at least a PASI-75 response to 100 mg or 200 mg of the humanized monoclonal antibody interleukin-23p19 inhibitor at week 28 in reSURFACE 1 or 2, or who were partial or nonresponders to etanercept in reSURFACE 2 and were then switched to tildrakizumab at 200 mg. Five hundred and forty-five of the 622 patients (88%) completed the full 5 years of the extension study.

Very few patients left the study because of loss of efficacy or adverse events. Indeed, the exposure-adjusted rate of drug-related serious adverse events was 0.8 cases per 100 patient-years at tildrakizumab 100 mg and 0.5 per 100 patient-years at 200 mg. Moreover, the rates of drug-related serious adverse events leading to treatment continuation were 0.3 and 0.2 per 100 patient-years at the 100-mg and 200-mg doses. Rates of treatment-emergent severe infection were 1.2 and 1.3 per 100 patient-years on the lower and higher doses. Major adverse cardiovascular events occurred at rates of 0.5 and 0.7 cases per 100 patient-years.

“I think the adverse events are generally similar to what has been seen with other biologics, but slightly less with tildrakizumab. Registries will provide a clearer picture. What’s interesting is that even if you double the dosage you don’t see an increase in side effects,” Dr. Thaçi said.

Asked what happens when a tildrakizumab responder stops taking the monoclonal antibody, he replied, “This is something very interesting we see with the IL-23 inhibitors: The disease comes back very slowly. It takes months, and sometimes years, for the patient to lose the PASI-75 or even the PASI-90 response. But we still consider that continuous treatment is probably the better way to go because we cannot be sure who will lose or regain response. At the moment we don’t have a biomarker to tell us what we should do in our daily practice.”

Dr. Thaçi reported serving as an adviser to and paid investigator for Almirall, the study sponsor, and approximately 20 other pharmaceutical companies.

[email protected]