Psoriatic Arthritis ICYMI

Key clinical point: Patients with psoriasis and concomitant psoriatic arthritis (PsA) were at greater risk of developing endometriosis.

Major finding: A history of psoriasis with concomitant PsA was associated with an increased risk for subsequent endometriosis diagnosis (hazard ratio [HR] 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease (HR 1.94; 95% CI 1.18-3.18).

Study details: Findings are from an analysis of 4,112 patients with laparoscopically confirmed endometriosis and 767 patients with psoriasis, of which 140 had concomitant PsA from the Nurses’ Health Study II.

Disclosures: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The authors reported no conflicts of interest.

Source: Harris HR et al. Am J Epidemiol. 2022 (Jan 13). Doi: 10.1093/aje/kwac009.

Key clinical point: Patients with psoriasis and concomitant psoriatic arthritis (PsA) were at greater risk of developing endometriosis.

Major finding: A history of psoriasis with concomitant PsA was associated with an increased risk for subsequent endometriosis diagnosis (hazard ratio [HR] 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease (HR 1.94; 95% CI 1.18-3.18).

Study details: Findings are from an analysis of 4,112 patients with laparoscopically confirmed endometriosis and 767 patients with psoriasis, of which 140 had concomitant PsA from the Nurses’ Health Study II.

Disclosures: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The authors reported no conflicts of interest.

Source: Harris HR et al. Am J Epidemiol. 2022 (Jan 13). Doi: 10.1093/aje/kwac009.

Key clinical point: Patients with psoriasis and concomitant psoriatic arthritis (PsA) were at greater risk of developing endometriosis.

Major finding: A history of psoriasis with concomitant PsA was associated with an increased risk for subsequent endometriosis diagnosis (hazard ratio [HR] 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease (HR 1.94; 95% CI 1.18-3.18).

Study details: Findings are from an analysis of 4,112 patients with laparoscopically confirmed endometriosis and 767 patients with psoriasis, of which 140 had concomitant PsA from the Nurses’ Health Study II.

Disclosures: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The authors reported no conflicts of interest.

Source: Harris HR et al. Am J Epidemiol. 2022 (Jan 13). Doi: 10.1093/aje/kwac009.

Key clinical point: Secukinumab showed early and clinically meaningful improvements in patient-reported outcomes (PRO) in adults with psoriatic arthritis (PsA).

Major finding: At week 16, patients in all secukinumab treatment groups vs. placebo showed significant improvement in all PRO (P ≤ .0001) except for the 36-item Short-Form Health Survey mental component summary. Patients receiving 300 mg secukinumab showed significant and clinically meaningful improvements as early as week 1 (P < .05).

Study details: Findings are from the phase 3 FUTURE 5 trial including 996 adults with active PsA who were randomly assigned to 300 mg secukinumab, 150 mg secukinumab  (with/without loading dose), or placebo.

Disclosures: This study was funded by Novartis Pharma. Some of the authors declared receiving research grants or consulting and speaker’s bureau fees from various sources including Novartis. Four authors declared being past/current employees or shareholders of Novartis.

Source: Strand V et al. Lancet Rheumatol. 2022 (Feb 1). Doi: 10.1016/S2665-9913(21)00354-4.

Key clinical point: Secukinumab showed early and clinically meaningful improvements in patient-reported outcomes (PRO) in adults with psoriatic arthritis (PsA).

Major finding: At week 16, patients in all secukinumab treatment groups vs. placebo showed significant improvement in all PRO (P ≤ .0001) except for the 36-item Short-Form Health Survey mental component summary. Patients receiving 300 mg secukinumab showed significant and clinically meaningful improvements as early as week 1 (P < .05).

Study details: Findings are from the phase 3 FUTURE 5 trial including 996 adults with active PsA who were randomly assigned to 300 mg secukinumab, 150 mg secukinumab  (with/without loading dose), or placebo.

Disclosures: This study was funded by Novartis Pharma. Some of the authors declared receiving research grants or consulting and speaker’s bureau fees from various sources including Novartis. Four authors declared being past/current employees or shareholders of Novartis.

Source: Strand V et al. Lancet Rheumatol. 2022 (Feb 1). Doi: 10.1016/S2665-9913(21)00354-4.

Key clinical point: Secukinumab showed early and clinically meaningful improvements in patient-reported outcomes (PRO) in adults with psoriatic arthritis (PsA).

Major finding: At week 16, patients in all secukinumab treatment groups vs. placebo showed significant improvement in all PRO (P ≤ .0001) except for the 36-item Short-Form Health Survey mental component summary. Patients receiving 300 mg secukinumab showed significant and clinically meaningful improvements as early as week 1 (P < .05).

Study details: Findings are from the phase 3 FUTURE 5 trial including 996 adults with active PsA who were randomly assigned to 300 mg secukinumab, 150 mg secukinumab  (with/without loading dose), or placebo.

Disclosures: This study was funded by Novartis Pharma. Some of the authors declared receiving research grants or consulting and speaker’s bureau fees from various sources including Novartis. Four authors declared being past/current employees or shareholders of Novartis.

Source: Strand V et al. Lancet Rheumatol. 2022 (Feb 1). Doi: 10.1016/S2665-9913(21)00354-4.

The COVID-19 pandemic led to a decrease in the proportion of patients with rheumatic diseases who stopped taking their disease-modifying antirheumatic drugs (DMARDs), but the percentage who interrupted DMARD treatment increased later in the pandemic, according to speakers at the 2022 Rheumatology Winter Clinical Symposium.

“People seem to be less anxious, but they’re interrupting their DMARD therapy more, more recently than in the pits of COVID, if you will,” said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS.

RWCS 2022 screenshot

Dr. Kavanaugh and his copresenter Jack Cush, MD, were discussing the results of a recent study published in Arthritis Care & Research that evaluated 2,424 patients with rheumatic diseases who completed a baseline and at least one follow-up survey issued by patient organizations between March 2020 and May 2021, with a median of five follow-up surveys completed. The patients included in the study were aged a mean of 57 years, 86.6% were women, 90.5% were White, 41.8% had rheumatoid arthritis (RA), 14.8% had antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and 12.4% had psoriatic arthritis. Overall, 52.6% were on biologics or a Janus kinase (JAK) inhibitor, 30.0% were receiving methotrexate, 21.4% were taking hydroxychloroquine, and 28.6% were receiving low-dose (24.0%) or high-dose (4.6%) glucocorticoids.

Patients’ T-scores on the anxiety short form Patient-Reported Outcomes Measurement Information System (PROMIS) survey significantly decreased from a score of 58.7 in April 2020 to a score of 53.7 in May 2021 (P < .001), but there was a significant decrease in the interruption of DMARD treatment between April and December 2020 (11.2% vs. 7.5%; P < .001). This percentage rose significantly to 14.0% by May 2021 (P < .001). Patients who stopped using DMARDs were significantly associated with predicted incidence of severe flare in the next survey in adjusted models (12.9% vs. 8.0%; odds ratio, 1.71; 95% confidence interval, 1.23-2.36).

The results tell us “that we as a discipline are not doing a good job educating our patients,” said Dr. Cush, a rheumatologist based in Dallas, Tex., and executive editor of RheumNow.com.

“I wish we – and I’m really talking about myself – but myself and my practice were more proactive when COVID happened [in] sending out regular bulletins: ‘Don’t stop your therapy; these are the things you get; get the test that you need to get done,’ ” he said. “We let a lot of things go on autopilot with the patient driving throughout COVID. Even now, it’s happening. And this is a problem, and there are going to be consequences to this.”

Dr. Kavanaugh agreed with Dr. Cush’s assessment, suggesting that the pandemic came up quickly enough that it was difficult to be proactive with the situation.
 

Patients on JAK inhibitors as new COVID-19 risk group?

Another standout study on COVID-19 from 2021 was an analysis of the COVID-19 Global Rheumatology Alliance physician registry that examined risk of COVID-19 severity for patients with RA taking biologic or targeted synthetic DMARDs (tsDMARDs), which was presented at the 2021 EULAR congress and later published in Annals of the Rheumatic Diseases.

The researchers evaluated 2,869 patients March 2020 and April 2021 who were receiving abatacept (237 patients), rituximab (364 patients), interleukin (IL)-6 inhibitors (317 patients), JAK inhibitors (563 patients), or tumor necrosis factor (TNF) inhibitors such as infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab (1,388 patients) before developing COVID-19. Data about biologics or tsDMARDs were collected as a drug class. Patients in the study were mostly White (69.0%) women (80.8%) with a mean age of 56.7 years who lived in Europe (51.8%) or North America (35.0%). The researchers examined the severity of COVID-19 among all patients studied and calculated odds ratios based on drug class, with the TNF inhibitor group serving as a reference.

“[I]n this case, they said that the baseline use of rituximab was associated with more severity, and you see the severity being hospitalization and ICU and deaths. They found a signal for the JAK inhibitors that is not found in the other studies,” Dr. Kavanaugh said.

Overall, they found 21% of patients in the registry were hospitalized and 5.5% died, with rituximab (OR, 4.15; 95% CI, 3.16-5.44) and JAK inhibitors (OR, 2.06; 95% CI, 1.60-2.65) associated with more severe COVID-19 outcomes. Specifically, rituximab was associated with greater likelihood of hospitalization (OR, 4.53; 95% CI, 3.32-6.18), hospitalization with oxygen/ventilation (OR, 2.87; 95% CI, 2.03-4.06), need for mechanical ventilation (OR, 4.05; 95% CI, 3.08-5.33), and mortality (OR, 4.57; 95% CI, 3.32-9.01), compared with TNF inhibitors. For JAK inhibitors, there was also a greater likelihood of hospitalization (OR, 2.40; 95% CI, 1.78-3.24), hospitalization with oxygen/ventilation (OR, 1.55; 95% CI, 1.04-2.18), need for mechanical ventilation (OR, 2.03; 95% CI, 1.56-2.62), and mortality (OR, 2.04; 95% CI, 1.58-2.65), compared with the TNF inhibitors group. Associations between COVID-19 severity and abatacept or IL-6 inhibitors were not identified.

Commenting on the study in a question-and-answer session, Roy Fleischmann, MD, said the part of the study that identified a signal for JAK inhibitors was “very interesting.” He called attention to a rapid response comment to the study, which questioned if it was the drug class itself that caused the risk for severe disease. “This is very important, because actually, the patients who stop the JAK [inhibitor], that’s what drove the illness. The patients [who] continued the JAK [inhibitor], very few of them had illness,” said Dr. Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical School and codirector of the Metroplex Clinical Research Center, both in Dallas, Tex.
 

Confusion among patients during COVID-19

Alvin Wells, MD, PhD, asked the copresenters during the Q&A session whether they had any clinical pearls for the audience on how they manage treatment of patients with rheumatic disease with potential COVID-19 risk. “I think the confusion with our patients and COVID is what the ACR has put out with their guidelines,” said Dr. Wells, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc.

Dr. Cush said he has three rules he follows: lower and discontinue steroids, avoid rituximab as a starting treatment and negotiate if patients are already taking it, and don’t stop any therapy.

“I want disease control. I think being under control is what keeps you away from risk of COVID and hospitalization,” Dr. Cush said. “I think being uncontrolled and inflamed, whether it’s our [patients with] inflammatory arthritis or lupus or, worse, vasculitis [or] myositis, those are the ones at high risk of progression from being just infected to being sick and in the hospital.”

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, posed the question of getting somewhat back to normal during COVID-19 with regard to recently infected patients presenting at infusion centers, whether patients are more likely to continue testing positive, and when patients are cleared to come back. Dr. Ruderman said his center has a 20-day rule for returning after having COVID-19, while Dr. Cush said his center allows patients to come in if they test negative after 7-10 days.

“One of the things we’re struggling with is our infusion center, and one of the questions that keeps coming up is when can people come back after a COVID infection?” he said. “If you’re on a drug at home, that’s up to you and the patient. But in the infusion [center], then you have other people sitting around there.”

Dr. Kavanaugh said there is no current data for how long patients with rheumatic disease shed virus, or how long a positive test can be measured. “You definitely will continue to shed, and you’ll be detectable for a while,” he said.

Dr. Cush and Dr. Kavanaugh reported having financial relationships with numerous pharmaceutical companies.

The COVID-19 pandemic led to a decrease in the proportion of patients with rheumatic diseases who stopped taking their disease-modifying antirheumatic drugs (DMARDs), but the percentage who interrupted DMARD treatment increased later in the pandemic, according to speakers at the 2022 Rheumatology Winter Clinical Symposium.

“People seem to be less anxious, but they’re interrupting their DMARD therapy more, more recently than in the pits of COVID, if you will,” said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS.

RWCS 2022 screenshot

Dr. Kavanaugh and his copresenter Jack Cush, MD, were discussing the results of a recent study published in Arthritis Care & Research that evaluated 2,424 patients with rheumatic diseases who completed a baseline and at least one follow-up survey issued by patient organizations between March 2020 and May 2021, with a median of five follow-up surveys completed. The patients included in the study were aged a mean of 57 years, 86.6% were women, 90.5% were White, 41.8% had rheumatoid arthritis (RA), 14.8% had antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and 12.4% had psoriatic arthritis. Overall, 52.6% were on biologics or a Janus kinase (JAK) inhibitor, 30.0% were receiving methotrexate, 21.4% were taking hydroxychloroquine, and 28.6% were receiving low-dose (24.0%) or high-dose (4.6%) glucocorticoids.

Patients’ T-scores on the anxiety short form Patient-Reported Outcomes Measurement Information System (PROMIS) survey significantly decreased from a score of 58.7 in April 2020 to a score of 53.7 in May 2021 (P < .001), but there was a significant decrease in the interruption of DMARD treatment between April and December 2020 (11.2% vs. 7.5%; P < .001). This percentage rose significantly to 14.0% by May 2021 (P < .001). Patients who stopped using DMARDs were significantly associated with predicted incidence of severe flare in the next survey in adjusted models (12.9% vs. 8.0%; odds ratio, 1.71; 95% confidence interval, 1.23-2.36).

The results tell us “that we as a discipline are not doing a good job educating our patients,” said Dr. Cush, a rheumatologist based in Dallas, Tex., and executive editor of RheumNow.com.

“I wish we – and I’m really talking about myself – but myself and my practice were more proactive when COVID happened [in] sending out regular bulletins: ‘Don’t stop your therapy; these are the things you get; get the test that you need to get done,’ ” he said. “We let a lot of things go on autopilot with the patient driving throughout COVID. Even now, it’s happening. And this is a problem, and there are going to be consequences to this.”

Dr. Kavanaugh agreed with Dr. Cush’s assessment, suggesting that the pandemic came up quickly enough that it was difficult to be proactive with the situation.
 

Patients on JAK inhibitors as new COVID-19 risk group?

Another standout study on COVID-19 from 2021 was an analysis of the COVID-19 Global Rheumatology Alliance physician registry that examined risk of COVID-19 severity for patients with RA taking biologic or targeted synthetic DMARDs (tsDMARDs), which was presented at the 2021 EULAR congress and later published in Annals of the Rheumatic Diseases.

The researchers evaluated 2,869 patients March 2020 and April 2021 who were receiving abatacept (237 patients), rituximab (364 patients), interleukin (IL)-6 inhibitors (317 patients), JAK inhibitors (563 patients), or tumor necrosis factor (TNF) inhibitors such as infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab (1,388 patients) before developing COVID-19. Data about biologics or tsDMARDs were collected as a drug class. Patients in the study were mostly White (69.0%) women (80.8%) with a mean age of 56.7 years who lived in Europe (51.8%) or North America (35.0%). The researchers examined the severity of COVID-19 among all patients studied and calculated odds ratios based on drug class, with the TNF inhibitor group serving as a reference.

“[I]n this case, they said that the baseline use of rituximab was associated with more severity, and you see the severity being hospitalization and ICU and deaths. They found a signal for the JAK inhibitors that is not found in the other studies,” Dr. Kavanaugh said.

Overall, they found 21% of patients in the registry were hospitalized and 5.5% died, with rituximab (OR, 4.15; 95% CI, 3.16-5.44) and JAK inhibitors (OR, 2.06; 95% CI, 1.60-2.65) associated with more severe COVID-19 outcomes. Specifically, rituximab was associated with greater likelihood of hospitalization (OR, 4.53; 95% CI, 3.32-6.18), hospitalization with oxygen/ventilation (OR, 2.87; 95% CI, 2.03-4.06), need for mechanical ventilation (OR, 4.05; 95% CI, 3.08-5.33), and mortality (OR, 4.57; 95% CI, 3.32-9.01), compared with TNF inhibitors. For JAK inhibitors, there was also a greater likelihood of hospitalization (OR, 2.40; 95% CI, 1.78-3.24), hospitalization with oxygen/ventilation (OR, 1.55; 95% CI, 1.04-2.18), need for mechanical ventilation (OR, 2.03; 95% CI, 1.56-2.62), and mortality (OR, 2.04; 95% CI, 1.58-2.65), compared with the TNF inhibitors group. Associations between COVID-19 severity and abatacept or IL-6 inhibitors were not identified.

Commenting on the study in a question-and-answer session, Roy Fleischmann, MD, said the part of the study that identified a signal for JAK inhibitors was “very interesting.” He called attention to a rapid response comment to the study, which questioned if it was the drug class itself that caused the risk for severe disease. “This is very important, because actually, the patients who stop the JAK [inhibitor], that’s what drove the illness. The patients [who] continued the JAK [inhibitor], very few of them had illness,” said Dr. Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical School and codirector of the Metroplex Clinical Research Center, both in Dallas, Tex.
 

Confusion among patients during COVID-19

Alvin Wells, MD, PhD, asked the copresenters during the Q&A session whether they had any clinical pearls for the audience on how they manage treatment of patients with rheumatic disease with potential COVID-19 risk. “I think the confusion with our patients and COVID is what the ACR has put out with their guidelines,” said Dr. Wells, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc.

Dr. Cush said he has three rules he follows: lower and discontinue steroids, avoid rituximab as a starting treatment and negotiate if patients are already taking it, and don’t stop any therapy.

“I want disease control. I think being under control is what keeps you away from risk of COVID and hospitalization,” Dr. Cush said. “I think being uncontrolled and inflamed, whether it’s our [patients with] inflammatory arthritis or lupus or, worse, vasculitis [or] myositis, those are the ones at high risk of progression from being just infected to being sick and in the hospital.”

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, posed the question of getting somewhat back to normal during COVID-19 with regard to recently infected patients presenting at infusion centers, whether patients are more likely to continue testing positive, and when patients are cleared to come back. Dr. Ruderman said his center has a 20-day rule for returning after having COVID-19, while Dr. Cush said his center allows patients to come in if they test negative after 7-10 days.

“One of the things we’re struggling with is our infusion center, and one of the questions that keeps coming up is when can people come back after a COVID infection?” he said. “If you’re on a drug at home, that’s up to you and the patient. But in the infusion [center], then you have other people sitting around there.”

Dr. Kavanaugh said there is no current data for how long patients with rheumatic disease shed virus, or how long a positive test can be measured. “You definitely will continue to shed, and you’ll be detectable for a while,” he said.

Dr. Cush and Dr. Kavanaugh reported having financial relationships with numerous pharmaceutical companies.

The COVID-19 pandemic led to a decrease in the proportion of patients with rheumatic diseases who stopped taking their disease-modifying antirheumatic drugs (DMARDs), but the percentage who interrupted DMARD treatment increased later in the pandemic, according to speakers at the 2022 Rheumatology Winter Clinical Symposium.

“People seem to be less anxious, but they’re interrupting their DMARD therapy more, more recently than in the pits of COVID, if you will,” said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS.

RWCS 2022 screenshot

Dr. Kavanaugh and his copresenter Jack Cush, MD, were discussing the results of a recent study published in Arthritis Care & Research that evaluated 2,424 patients with rheumatic diseases who completed a baseline and at least one follow-up survey issued by patient organizations between March 2020 and May 2021, with a median of five follow-up surveys completed. The patients included in the study were aged a mean of 57 years, 86.6% were women, 90.5% were White, 41.8% had rheumatoid arthritis (RA), 14.8% had antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and 12.4% had psoriatic arthritis. Overall, 52.6% were on biologics or a Janus kinase (JAK) inhibitor, 30.0% were receiving methotrexate, 21.4% were taking hydroxychloroquine, and 28.6% were receiving low-dose (24.0%) or high-dose (4.6%) glucocorticoids.

Patients’ T-scores on the anxiety short form Patient-Reported Outcomes Measurement Information System (PROMIS) survey significantly decreased from a score of 58.7 in April 2020 to a score of 53.7 in May 2021 (P < .001), but there was a significant decrease in the interruption of DMARD treatment between April and December 2020 (11.2% vs. 7.5%; P < .001). This percentage rose significantly to 14.0% by May 2021 (P < .001). Patients who stopped using DMARDs were significantly associated with predicted incidence of severe flare in the next survey in adjusted models (12.9% vs. 8.0%; odds ratio, 1.71; 95% confidence interval, 1.23-2.36).

The results tell us “that we as a discipline are not doing a good job educating our patients,” said Dr. Cush, a rheumatologist based in Dallas, Tex., and executive editor of RheumNow.com.

“I wish we – and I’m really talking about myself – but myself and my practice were more proactive when COVID happened [in] sending out regular bulletins: ‘Don’t stop your therapy; these are the things you get; get the test that you need to get done,’ ” he said. “We let a lot of things go on autopilot with the patient driving throughout COVID. Even now, it’s happening. And this is a problem, and there are going to be consequences to this.”

Dr. Kavanaugh agreed with Dr. Cush’s assessment, suggesting that the pandemic came up quickly enough that it was difficult to be proactive with the situation.
 

Patients on JAK inhibitors as new COVID-19 risk group?

Another standout study on COVID-19 from 2021 was an analysis of the COVID-19 Global Rheumatology Alliance physician registry that examined risk of COVID-19 severity for patients with RA taking biologic or targeted synthetic DMARDs (tsDMARDs), which was presented at the 2021 EULAR congress and later published in Annals of the Rheumatic Diseases.

The researchers evaluated 2,869 patients March 2020 and April 2021 who were receiving abatacept (237 patients), rituximab (364 patients), interleukin (IL)-6 inhibitors (317 patients), JAK inhibitors (563 patients), or tumor necrosis factor (TNF) inhibitors such as infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab (1,388 patients) before developing COVID-19. Data about biologics or tsDMARDs were collected as a drug class. Patients in the study were mostly White (69.0%) women (80.8%) with a mean age of 56.7 years who lived in Europe (51.8%) or North America (35.0%). The researchers examined the severity of COVID-19 among all patients studied and calculated odds ratios based on drug class, with the TNF inhibitor group serving as a reference.

“[I]n this case, they said that the baseline use of rituximab was associated with more severity, and you see the severity being hospitalization and ICU and deaths. They found a signal for the JAK inhibitors that is not found in the other studies,” Dr. Kavanaugh said.

Overall, they found 21% of patients in the registry were hospitalized and 5.5% died, with rituximab (OR, 4.15; 95% CI, 3.16-5.44) and JAK inhibitors (OR, 2.06; 95% CI, 1.60-2.65) associated with more severe COVID-19 outcomes. Specifically, rituximab was associated with greater likelihood of hospitalization (OR, 4.53; 95% CI, 3.32-6.18), hospitalization with oxygen/ventilation (OR, 2.87; 95% CI, 2.03-4.06), need for mechanical ventilation (OR, 4.05; 95% CI, 3.08-5.33), and mortality (OR, 4.57; 95% CI, 3.32-9.01), compared with TNF inhibitors. For JAK inhibitors, there was also a greater likelihood of hospitalization (OR, 2.40; 95% CI, 1.78-3.24), hospitalization with oxygen/ventilation (OR, 1.55; 95% CI, 1.04-2.18), need for mechanical ventilation (OR, 2.03; 95% CI, 1.56-2.62), and mortality (OR, 2.04; 95% CI, 1.58-2.65), compared with the TNF inhibitors group. Associations between COVID-19 severity and abatacept or IL-6 inhibitors were not identified.

Commenting on the study in a question-and-answer session, Roy Fleischmann, MD, said the part of the study that identified a signal for JAK inhibitors was “very interesting.” He called attention to a rapid response comment to the study, which questioned if it was the drug class itself that caused the risk for severe disease. “This is very important, because actually, the patients who stop the JAK [inhibitor], that’s what drove the illness. The patients [who] continued the JAK [inhibitor], very few of them had illness,” said Dr. Fleischmann, clinical professor of medicine at the University of Texas Southwestern Medical School and codirector of the Metroplex Clinical Research Center, both in Dallas, Tex.
 

Confusion among patients during COVID-19

Alvin Wells, MD, PhD, asked the copresenters during the Q&A session whether they had any clinical pearls for the audience on how they manage treatment of patients with rheumatic disease with potential COVID-19 risk. “I think the confusion with our patients and COVID is what the ACR has put out with their guidelines,” said Dr. Wells, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc.

Dr. Cush said he has three rules he follows: lower and discontinue steroids, avoid rituximab as a starting treatment and negotiate if patients are already taking it, and don’t stop any therapy.

“I want disease control. I think being under control is what keeps you away from risk of COVID and hospitalization,” Dr. Cush said. “I think being uncontrolled and inflamed, whether it’s our [patients with] inflammatory arthritis or lupus or, worse, vasculitis [or] myositis, those are the ones at high risk of progression from being just infected to being sick and in the hospital.”

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, posed the question of getting somewhat back to normal during COVID-19 with regard to recently infected patients presenting at infusion centers, whether patients are more likely to continue testing positive, and when patients are cleared to come back. Dr. Ruderman said his center has a 20-day rule for returning after having COVID-19, while Dr. Cush said his center allows patients to come in if they test negative after 7-10 days.

“One of the things we’re struggling with is our infusion center, and one of the questions that keeps coming up is when can people come back after a COVID infection?” he said. “If you’re on a drug at home, that’s up to you and the patient. But in the infusion [center], then you have other people sitting around there.”

Dr. Kavanaugh said there is no current data for how long patients with rheumatic disease shed virus, or how long a positive test can be measured. “You definitely will continue to shed, and you’ll be detectable for a while,” he said.

Dr. Cush and Dr. Kavanaugh reported having financial relationships with numerous pharmaceutical companies.

This interview is a translation of a video blog that first appeared on Medscape France. It has been edited for clarity.

Which diet should we recommend to patients with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis? Weight loss, omega-3 supplements, the Mediterranean diet? What about exclusion diets? Jérémie Sellam, MD, PhD, from Saint-Antoine Hospital in Paris, summarizes the key points of the first set of dietary recommendations of the French Society for Rheumatology.

Transcript

Jérémie Sellam, MD, PhD: Hello, everyone. I’m Professor Jérémie Sellam. I’m a rheumatologist at Saint-Antoine Hospital, which is affiliated with the Sorbonne University in Paris. And I was fortunate enough to coordinate France’s first set of dietary recommendations – in fact, the world’s first set of dietary recommendations – for patients with chronic inflammatory rheumatic diseases. I worked on this project with Claire Daien, MD, PhD, who’s a rheumatologist at Montpellier University Hospital.

The idea of coming up with dietary recommendations for patients with inflammatory rheumatic diseases came, quite simply, from our clinical practice. We see that when patients learn they have polyarthritis or spondyloarthritis, they start to experiment with different diets. Many patients start exclusion diets and experiment in all sorts of ways with the food they eat. And although rheumatologists have been able to find some information here and there in the literature, they’ve been pretty much on their own when trying to come up with advice to give their patients. It was to address this issue that [Dr.] Daien and I set out to form a working group. Because when patients aren’t able to get sound advice and authoritative guidance from their doctors, medical associations, or patient advocacy organizations, they often look for information online, and that information is not always reliable or validated.

This group was made up of rheumatologists, some who work at hospitals and others in private practice. Also involved were physician nutrition specialists and registered dietitians. Operating under the auspices of the French Society for Rheumatology, these multidisciplinary experts conducted out a systematic literature review for the purpose of establishing and drafting recommendations. The result was a declaration of eight general principles and nine recommendations.
 

General principles

The first of the general principles states that nutritional advice is not a substitute for the pharmacologic treatment of chronic inflammatory rheumatic diseases. As you know, whether it’s methotrexate or biologics, pharmacologic treatments are essential for the proper management of chronic inflammatory rheumatic diseases. We know that these medications have an anti-inflammatory effect, reduce pain, and – particularly in the case of rheumatoid arthritis – have a structural effect. In other words, they prevent joint deterioration and destruction. Now, I can tell you that there’s currently no diet, and no dietary supplement, that has proven to be structurally effective. So, yes, dietary intervention might turn out to be promising for patients with chronic inflammatory rheumatic diseases, but pharmacologic treatment must still be part of the picture.

Another general principle emphasizes that dietary intervention is a way for patients to be actively involved in the overall care of their disease, beyond just taking their medication. We know that patients, when they suffer from chronic diseases, are looking for something more, beyond just taking medications. Encouraging them to take an interest in their diet, asking them about what they eat, giving them advice, and supporting their desire to become involved in this aspect of their treatment plan can give them a sense of empowerment.

Dietary interventions can have articular effects, and I’m going to speak about which interventions you can propose, but also which can be beneficial in terms of cardiovascular health and bone health. All of this is based on the literature. In these recommendations, we’ve taken into account not only laboratory experiments – where this or that diet is given to a mouse with arthritis – but also reviewed randomized controlled trials that compare an intervention group with a control group. This is the benchmark we used to determine whether or not a diet should be recommended.
 

The recommendations

As for the recommendations themselves, we wanted to start off by emphasizing weight loss and what can be called weight-loss support. There’s a link between obesity and the risk of developing rheumatoid arthritis, and also psoriatic arthropathy. And the more overweight a patient is, the more active their disease. In other words, patients with obesity are going to experience more pain, more instances of wakefulness, and more morning stiffness than their normal-weight peers. They’re also going to show symptoms that suggest that disease activity is not controlled well.

Several randomized controlled studies have shown that weight loss will improve systemic joint symptoms. In one particular study, patients with psoriatic arthropathy were started on [tumor necrosis factor] inhibitor therapy and one group followed a prescribed diet and the other had no restrictions on eating. More patients in the diet group than in the no-diet group achieved minimal disease activity. Of course, in some cases – for example, patients with complicated morbid obesity – it might be necessary to have a discussion about bariatric surgery.

But practically speaking, how does one proceed? First of all, patients should be weighed at each visit and, if they’re overweight or obese, the subject should be broached. But even after that conversation, the reality remains that it’s not easy to lose weight. So in the recommendations, we focused on the fact that it shouldn’t be left to the rheumatologist or treating physician alone to handle this challenging aspect of treatment. They should incorporate dietary and nutritional care by reaching out to a dietician or, in the case of complicated obesity – especially when the BMI is higher than 35 kg/m² – they can refer patients to a nutrition expert who can manage the patient’s obesity, come up with a weight-loss plan, and handle any complications that might arise.

We don’t speak about a low-calorie diet in the recommendations because a diet has a beginning and an end and, quite often, patients regain weight after stopping a diet. Instead, we speak about weight-loss support to point out that weight loss maintained through dietary changes brings about long-term control of disease activity.

In addition, we make two positive recommendations, which overlap, that can help patients control their disease: a Mediterranean diet and omega-3 supplements. One study showed that after participants with rheumatoid arthritis followed the Mediterranean diet for 1 year, those who also took omega-3 fish oil supplements were twice as likely to achieve remission (40% vs. 20%). This explains the interest in having omega-3 as part of the diet. Other studies have shown a broad benefit of the Mediterranean diet.

We know this diet: Fish, especially fatty fish; meat, but not every day, and white meat is best; and fruits and vegetables. In addition, exercise and stay hydrated. All of this can help patients who want to use diet as a means to control their disease. And, as I said earlier, studies have shown that omega-3 supplements have beneficial effects. These are essential polyunsaturated fatty acids, which can help control the disease and joint symptoms.

We also provide some exclusionary recommendations. Not all studies are done well, but it’s clear that there are no major benefits – in fact, no benefit at all – from vegan diets, gluten-free diets, or dairy-free diets. And with these diets, patients run the risk of developing deficiencies, so it’s important that patients are aware of this. We also have to keep in mind that exclusion diets can increase social isolation. Patients need to take part in meals; such gatherings are times for sharing and having social interactions. And I would say that they must be told that there are no data in the literature in support of these diets. But if they ever insist on this kind of intervention, I think that it’s better to advise them to do it under the supervision of a dietician and nutritionist, especially to prevent the development of deficiencies. We’re talking about deficiencies in things like calcium, vitamin B¹², and selenium.
 

Conclusion

As you can see, we have positive recommendations when the patient wants to do something beyond pharmacologic treatment: the Mediterranean diet and omega-3 supplements. And we have negative recommendations, marked by a warning about the risk of developing deficiencies. But I think we all understand the importance of paying close attention to how our patients are experimenting with food. Their diets and eating habits can give us ideas for research and reviews that could allow us to deepen our understanding of the effect of diet on disease, because currently, the quality of the data on some of the diets and types of dietary interventions out there is rather tenuous.

Thank you for listening. I’d also like to thank Claire Daien, MD, PhD, for conducting this project with me so that we could come up with all of these recommendations. I’m also grateful to the following nutrition societies and associations who were our partners: the French Society of Nutrition, the French-Speaking Society of Clinical Nutrition and Metabolism, the French Association for the Study of Obesity, and the French Association of Dieticians and Nutritionists. And patient associations, too, must be recognized, as some of their members participated: the French National Association Against Rheumatoid Arthritis, the French Spondyloarthritis Association, and the French Association for Polyarthritis and Chronic Inflammatory Rheumatic Diseases.

This interview is a translation of a video blog that first appeared on Medscape France. It has been edited for clarity.

Which diet should we recommend to patients with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis? Weight loss, omega-3 supplements, the Mediterranean diet? What about exclusion diets? Jérémie Sellam, MD, PhD, from Saint-Antoine Hospital in Paris, summarizes the key points of the first set of dietary recommendations of the French Society for Rheumatology.

Transcript

Jérémie Sellam, MD, PhD: Hello, everyone. I’m Professor Jérémie Sellam. I’m a rheumatologist at Saint-Antoine Hospital, which is affiliated with the Sorbonne University in Paris. And I was fortunate enough to coordinate France’s first set of dietary recommendations – in fact, the world’s first set of dietary recommendations – for patients with chronic inflammatory rheumatic diseases. I worked on this project with Claire Daien, MD, PhD, who’s a rheumatologist at Montpellier University Hospital.

The idea of coming up with dietary recommendations for patients with inflammatory rheumatic diseases came, quite simply, from our clinical practice. We see that when patients learn they have polyarthritis or spondyloarthritis, they start to experiment with different diets. Many patients start exclusion diets and experiment in all sorts of ways with the food they eat. And although rheumatologists have been able to find some information here and there in the literature, they’ve been pretty much on their own when trying to come up with advice to give their patients. It was to address this issue that [Dr.] Daien and I set out to form a working group. Because when patients aren’t able to get sound advice and authoritative guidance from their doctors, medical associations, or patient advocacy organizations, they often look for information online, and that information is not always reliable or validated.

This group was made up of rheumatologists, some who work at hospitals and others in private practice. Also involved were physician nutrition specialists and registered dietitians. Operating under the auspices of the French Society for Rheumatology, these multidisciplinary experts conducted out a systematic literature review for the purpose of establishing and drafting recommendations. The result was a declaration of eight general principles and nine recommendations.
 

General principles

The first of the general principles states that nutritional advice is not a substitute for the pharmacologic treatment of chronic inflammatory rheumatic diseases. As you know, whether it’s methotrexate or biologics, pharmacologic treatments are essential for the proper management of chronic inflammatory rheumatic diseases. We know that these medications have an anti-inflammatory effect, reduce pain, and – particularly in the case of rheumatoid arthritis – have a structural effect. In other words, they prevent joint deterioration and destruction. Now, I can tell you that there’s currently no diet, and no dietary supplement, that has proven to be structurally effective. So, yes, dietary intervention might turn out to be promising for patients with chronic inflammatory rheumatic diseases, but pharmacologic treatment must still be part of the picture.

Another general principle emphasizes that dietary intervention is a way for patients to be actively involved in the overall care of their disease, beyond just taking their medication. We know that patients, when they suffer from chronic diseases, are looking for something more, beyond just taking medications. Encouraging them to take an interest in their diet, asking them about what they eat, giving them advice, and supporting their desire to become involved in this aspect of their treatment plan can give them a sense of empowerment.

Dietary interventions can have articular effects, and I’m going to speak about which interventions you can propose, but also which can be beneficial in terms of cardiovascular health and bone health. All of this is based on the literature. In these recommendations, we’ve taken into account not only laboratory experiments – where this or that diet is given to a mouse with arthritis – but also reviewed randomized controlled trials that compare an intervention group with a control group. This is the benchmark we used to determine whether or not a diet should be recommended.
 

The recommendations

As for the recommendations themselves, we wanted to start off by emphasizing weight loss and what can be called weight-loss support. There’s a link between obesity and the risk of developing rheumatoid arthritis, and also psoriatic arthropathy. And the more overweight a patient is, the more active their disease. In other words, patients with obesity are going to experience more pain, more instances of wakefulness, and more morning stiffness than their normal-weight peers. They’re also going to show symptoms that suggest that disease activity is not controlled well.

Several randomized controlled studies have shown that weight loss will improve systemic joint symptoms. In one particular study, patients with psoriatic arthropathy were started on [tumor necrosis factor] inhibitor therapy and one group followed a prescribed diet and the other had no restrictions on eating. More patients in the diet group than in the no-diet group achieved minimal disease activity. Of course, in some cases – for example, patients with complicated morbid obesity – it might be necessary to have a discussion about bariatric surgery.

But practically speaking, how does one proceed? First of all, patients should be weighed at each visit and, if they’re overweight or obese, the subject should be broached. But even after that conversation, the reality remains that it’s not easy to lose weight. So in the recommendations, we focused on the fact that it shouldn’t be left to the rheumatologist or treating physician alone to handle this challenging aspect of treatment. They should incorporate dietary and nutritional care by reaching out to a dietician or, in the case of complicated obesity – especially when the BMI is higher than 35 kg/m² – they can refer patients to a nutrition expert who can manage the patient’s obesity, come up with a weight-loss plan, and handle any complications that might arise.

We don’t speak about a low-calorie diet in the recommendations because a diet has a beginning and an end and, quite often, patients regain weight after stopping a diet. Instead, we speak about weight-loss support to point out that weight loss maintained through dietary changes brings about long-term control of disease activity.

In addition, we make two positive recommendations, which overlap, that can help patients control their disease: a Mediterranean diet and omega-3 supplements. One study showed that after participants with rheumatoid arthritis followed the Mediterranean diet for 1 year, those who also took omega-3 fish oil supplements were twice as likely to achieve remission (40% vs. 20%). This explains the interest in having omega-3 as part of the diet. Other studies have shown a broad benefit of the Mediterranean diet.

We know this diet: Fish, especially fatty fish; meat, but not every day, and white meat is best; and fruits and vegetables. In addition, exercise and stay hydrated. All of this can help patients who want to use diet as a means to control their disease. And, as I said earlier, studies have shown that omega-3 supplements have beneficial effects. These are essential polyunsaturated fatty acids, which can help control the disease and joint symptoms.

We also provide some exclusionary recommendations. Not all studies are done well, but it’s clear that there are no major benefits – in fact, no benefit at all – from vegan diets, gluten-free diets, or dairy-free diets. And with these diets, patients run the risk of developing deficiencies, so it’s important that patients are aware of this. We also have to keep in mind that exclusion diets can increase social isolation. Patients need to take part in meals; such gatherings are times for sharing and having social interactions. And I would say that they must be told that there are no data in the literature in support of these diets. But if they ever insist on this kind of intervention, I think that it’s better to advise them to do it under the supervision of a dietician and nutritionist, especially to prevent the development of deficiencies. We’re talking about deficiencies in things like calcium, vitamin B¹², and selenium.
 

Conclusion

As you can see, we have positive recommendations when the patient wants to do something beyond pharmacologic treatment: the Mediterranean diet and omega-3 supplements. And we have negative recommendations, marked by a warning about the risk of developing deficiencies. But I think we all understand the importance of paying close attention to how our patients are experimenting with food. Their diets and eating habits can give us ideas for research and reviews that could allow us to deepen our understanding of the effect of diet on disease, because currently, the quality of the data on some of the diets and types of dietary interventions out there is rather tenuous.

Thank you for listening. I’d also like to thank Claire Daien, MD, PhD, for conducting this project with me so that we could come up with all of these recommendations. I’m also grateful to the following nutrition societies and associations who were our partners: the French Society of Nutrition, the French-Speaking Society of Clinical Nutrition and Metabolism, the French Association for the Study of Obesity, and the French Association of Dieticians and Nutritionists. And patient associations, too, must be recognized, as some of their members participated: the French National Association Against Rheumatoid Arthritis, the French Spondyloarthritis Association, and the French Association for Polyarthritis and Chronic Inflammatory Rheumatic Diseases.

This interview is a translation of a video blog that first appeared on Medscape France. It has been edited for clarity.

Which diet should we recommend to patients with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis? Weight loss, omega-3 supplements, the Mediterranean diet? What about exclusion diets? Jérémie Sellam, MD, PhD, from Saint-Antoine Hospital in Paris, summarizes the key points of the first set of dietary recommendations of the French Society for Rheumatology.

Transcript

Jérémie Sellam, MD, PhD: Hello, everyone. I’m Professor Jérémie Sellam. I’m a rheumatologist at Saint-Antoine Hospital, which is affiliated with the Sorbonne University in Paris. And I was fortunate enough to coordinate France’s first set of dietary recommendations – in fact, the world’s first set of dietary recommendations – for patients with chronic inflammatory rheumatic diseases. I worked on this project with Claire Daien, MD, PhD, who’s a rheumatologist at Montpellier University Hospital.

The idea of coming up with dietary recommendations for patients with inflammatory rheumatic diseases came, quite simply, from our clinical practice. We see that when patients learn they have polyarthritis or spondyloarthritis, they start to experiment with different diets. Many patients start exclusion diets and experiment in all sorts of ways with the food they eat. And although rheumatologists have been able to find some information here and there in the literature, they’ve been pretty much on their own when trying to come up with advice to give their patients. It was to address this issue that [Dr.] Daien and I set out to form a working group. Because when patients aren’t able to get sound advice and authoritative guidance from their doctors, medical associations, or patient advocacy organizations, they often look for information online, and that information is not always reliable or validated.

This group was made up of rheumatologists, some who work at hospitals and others in private practice. Also involved were physician nutrition specialists and registered dietitians. Operating under the auspices of the French Society for Rheumatology, these multidisciplinary experts conducted out a systematic literature review for the purpose of establishing and drafting recommendations. The result was a declaration of eight general principles and nine recommendations.
 

General principles

The first of the general principles states that nutritional advice is not a substitute for the pharmacologic treatment of chronic inflammatory rheumatic diseases. As you know, whether it’s methotrexate or biologics, pharmacologic treatments are essential for the proper management of chronic inflammatory rheumatic diseases. We know that these medications have an anti-inflammatory effect, reduce pain, and – particularly in the case of rheumatoid arthritis – have a structural effect. In other words, they prevent joint deterioration and destruction. Now, I can tell you that there’s currently no diet, and no dietary supplement, that has proven to be structurally effective. So, yes, dietary intervention might turn out to be promising for patients with chronic inflammatory rheumatic diseases, but pharmacologic treatment must still be part of the picture.

Another general principle emphasizes that dietary intervention is a way for patients to be actively involved in the overall care of their disease, beyond just taking their medication. We know that patients, when they suffer from chronic diseases, are looking for something more, beyond just taking medications. Encouraging them to take an interest in their diet, asking them about what they eat, giving them advice, and supporting their desire to become involved in this aspect of their treatment plan can give them a sense of empowerment.

Dietary interventions can have articular effects, and I’m going to speak about which interventions you can propose, but also which can be beneficial in terms of cardiovascular health and bone health. All of this is based on the literature. In these recommendations, we’ve taken into account not only laboratory experiments – where this or that diet is given to a mouse with arthritis – but also reviewed randomized controlled trials that compare an intervention group with a control group. This is the benchmark we used to determine whether or not a diet should be recommended.
 

The recommendations

As for the recommendations themselves, we wanted to start off by emphasizing weight loss and what can be called weight-loss support. There’s a link between obesity and the risk of developing rheumatoid arthritis, and also psoriatic arthropathy. And the more overweight a patient is, the more active their disease. In other words, patients with obesity are going to experience more pain, more instances of wakefulness, and more morning stiffness than their normal-weight peers. They’re also going to show symptoms that suggest that disease activity is not controlled well.

Several randomized controlled studies have shown that weight loss will improve systemic joint symptoms. In one particular study, patients with psoriatic arthropathy were started on [tumor necrosis factor] inhibitor therapy and one group followed a prescribed diet and the other had no restrictions on eating. More patients in the diet group than in the no-diet group achieved minimal disease activity. Of course, in some cases – for example, patients with complicated morbid obesity – it might be necessary to have a discussion about bariatric surgery.

But practically speaking, how does one proceed? First of all, patients should be weighed at each visit and, if they’re overweight or obese, the subject should be broached. But even after that conversation, the reality remains that it’s not easy to lose weight. So in the recommendations, we focused on the fact that it shouldn’t be left to the rheumatologist or treating physician alone to handle this challenging aspect of treatment. They should incorporate dietary and nutritional care by reaching out to a dietician or, in the case of complicated obesity – especially when the BMI is higher than 35 kg/m² – they can refer patients to a nutrition expert who can manage the patient’s obesity, come up with a weight-loss plan, and handle any complications that might arise.

We don’t speak about a low-calorie diet in the recommendations because a diet has a beginning and an end and, quite often, patients regain weight after stopping a diet. Instead, we speak about weight-loss support to point out that weight loss maintained through dietary changes brings about long-term control of disease activity.

In addition, we make two positive recommendations, which overlap, that can help patients control their disease: a Mediterranean diet and omega-3 supplements. One study showed that after participants with rheumatoid arthritis followed the Mediterranean diet for 1 year, those who also took omega-3 fish oil supplements were twice as likely to achieve remission (40% vs. 20%). This explains the interest in having omega-3 as part of the diet. Other studies have shown a broad benefit of the Mediterranean diet.

We know this diet: Fish, especially fatty fish; meat, but not every day, and white meat is best; and fruits and vegetables. In addition, exercise and stay hydrated. All of this can help patients who want to use diet as a means to control their disease. And, as I said earlier, studies have shown that omega-3 supplements have beneficial effects. These are essential polyunsaturated fatty acids, which can help control the disease and joint symptoms.

We also provide some exclusionary recommendations. Not all studies are done well, but it’s clear that there are no major benefits – in fact, no benefit at all – from vegan diets, gluten-free diets, or dairy-free diets. And with these diets, patients run the risk of developing deficiencies, so it’s important that patients are aware of this. We also have to keep in mind that exclusion diets can increase social isolation. Patients need to take part in meals; such gatherings are times for sharing and having social interactions. And I would say that they must be told that there are no data in the literature in support of these diets. But if they ever insist on this kind of intervention, I think that it’s better to advise them to do it under the supervision of a dietician and nutritionist, especially to prevent the development of deficiencies. We’re talking about deficiencies in things like calcium, vitamin B¹², and selenium.
 

Conclusion

As you can see, we have positive recommendations when the patient wants to do something beyond pharmacologic treatment: the Mediterranean diet and omega-3 supplements. And we have negative recommendations, marked by a warning about the risk of developing deficiencies. But I think we all understand the importance of paying close attention to how our patients are experimenting with food. Their diets and eating habits can give us ideas for research and reviews that could allow us to deepen our understanding of the effect of diet on disease, because currently, the quality of the data on some of the diets and types of dietary interventions out there is rather tenuous.

Thank you for listening. I’d also like to thank Claire Daien, MD, PhD, for conducting this project with me so that we could come up with all of these recommendations. I’m also grateful to the following nutrition societies and associations who were our partners: the French Society of Nutrition, the French-Speaking Society of Clinical Nutrition and Metabolism, the French Association for the Study of Obesity, and the French Association of Dieticians and Nutritionists. And patient associations, too, must be recognized, as some of their members participated: the French National Association Against Rheumatoid Arthritis, the French Spondyloarthritis Association, and the French Association for Polyarthritis and Chronic Inflammatory Rheumatic Diseases.

Guselkumab (Tremfya) received Food and Drug Administration approval for the treatment of psoriatic arthritis (PsA) almost 2 years ago on the basis of a phase 3 trial, but a new substudy from that trial has now demonstrated long-term benefit in the subgroup of patients who entered the trial with axial involvement, according to data presented at the annual meeting of the Canadian Rheumatology Association.

“The symptom relief was clinically meaningful and durable through week 100,” reported Dafna D. Gladman, MD, professor of medicine and director of the psoriatic arthritis program at the University of Toronto.

In the previously published double-blind, placebo-controlled DISCOVER-2 trial, two dosing regimens of the interleukin-23 (IL-23) inhibitor guselkumab were compared with placebo in biologic-naive patients. The active regimens were similarly effective relative to placebo for the primary endpoint of 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24.

In this new long-term subgroup analysis, outcomes at 2 years were evaluated in the 246 patients with axial involvement (33.3% of the total number of 739 evaluable patients). Baseline characteristics across treatment groups in this subset of the DISCOVER-2 trial were similar.
 

Guselkumab exhibits nearly twofold advantage

At 24 weeks relative to baseline, the improvement on multiple axial involvement outcome measures was approximately twofold greater with active therapy than with placebo. For example, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score fell 2.6 points in both active treatment arms versus 1.4 on placebo.

The same relative advantage was observed when the BASDAI spinal pain subscore was isolated. There were also comparable responses on a modified BASDAI that excluded the peripheral pain response, and the Ankylosing Spondylitis Disease Activity Score (ASDAS).

When evaluated at week 52 and again at week 100, all outcomes employed to evaluate change in axial involvement were sustained. Many were further improved. In patients who initiated therapy on placebo, all of whom were switched to guselkumab at the end of the 24-week double-blind period, at least the same degree of axial symptom control relative to baseline was achieved at both time periods.

Incremental improvement observed over time

“For most measures there was further improvement at 2 years, and there was generally consistent response across patient groups stratified by HLA [human leucocyte antigen] status,” Dr. Gladman reported.

Relative to the 2.6-point reduction in the BASDAI score in the two guselkumab arms at week 24, the reductions reached 3.0, 3.1, and 3.3 at 100 weeks in the every-4-week guselkumab group, every-8-week guselkumab group, and the crossed-over placebo group, respectively. For ASDAS, the reductions at week 24 were 1.4, 1.5, and 0.7 points and reached 1.6, 1.7, and 1.6 points at 100 weeks in the every-4-week, every-8-week, and placebo crossover groups, respectively.

The sustained improvement is consistent with a previous post hoc analysis in which data from the phase 3 DISCOVER-1 trial were pooled with those from DISCOVER-2. This analysis focused on the 312 patients in these studies with axial disease documented by imaging. Again, the study showed improvement at week 24 was sustained at week 52 independent of HLA-B27 status.
 

Need for MRI confirmation seen

The potential problem with this new analysis as well as the previous analysis is the absence of MRI to provide objective evidence of axial involvement, according to Walter P. Maksymowych, MD, professor in the division of rheumatology at the University of Alberta, Edmonton.

Noting that previous studies have indicated that axial involvement assessed by investigators is not reliable even when performed with x-rays, Dr. Maksymowych said these data would be much more reassuring with MRI controls.

“We have seen little correlation between clinical symptoms and MRI manifestations of disease,” he said.

Dr. Gladman conceded this point. Baseline MRI was performed in some of the patients in this subgroup analysis, but it was not mandated. As a result, the data support benefit from guselkumab for symptomatic axial involvement, but she indicated that better evidence of a disease-modifying effect is expected from a more rigorous placebo-controlled trial of guselkumab called STAR.

This trial is requiring MRI at baseline and at week 24 and is using the Spondyloarthritis Research Consortium of Canada (SPARCC) score to assess change. Dr. Gladman said the trial is enrolling “as we speak.”

Overall, Dr. Gladman agreed with Dr. Maksymowych that objective biomarkers are important for demonstrating that treatments are improving long-term outcomes, not just relieving symptoms.

Guselkumab manufacturer Janssen supported the post hoc analysis. Dr. Gladman reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Janssen, Novartis, Pfizer, and UCB. Dr. Maksymowych reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB.

Guselkumab (Tremfya) received Food and Drug Administration approval for the treatment of psoriatic arthritis (PsA) almost 2 years ago on the basis of a phase 3 trial, but a new substudy from that trial has now demonstrated long-term benefit in the subgroup of patients who entered the trial with axial involvement, according to data presented at the annual meeting of the Canadian Rheumatology Association.

“The symptom relief was clinically meaningful and durable through week 100,” reported Dafna D. Gladman, MD, professor of medicine and director of the psoriatic arthritis program at the University of Toronto.

In the previously published double-blind, placebo-controlled DISCOVER-2 trial, two dosing regimens of the interleukin-23 (IL-23) inhibitor guselkumab were compared with placebo in biologic-naive patients. The active regimens were similarly effective relative to placebo for the primary endpoint of 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24.

In this new long-term subgroup analysis, outcomes at 2 years were evaluated in the 246 patients with axial involvement (33.3% of the total number of 739 evaluable patients). Baseline characteristics across treatment groups in this subset of the DISCOVER-2 trial were similar.
 

Guselkumab exhibits nearly twofold advantage

At 24 weeks relative to baseline, the improvement on multiple axial involvement outcome measures was approximately twofold greater with active therapy than with placebo. For example, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score fell 2.6 points in both active treatment arms versus 1.4 on placebo.

The same relative advantage was observed when the BASDAI spinal pain subscore was isolated. There were also comparable responses on a modified BASDAI that excluded the peripheral pain response, and the Ankylosing Spondylitis Disease Activity Score (ASDAS).

When evaluated at week 52 and again at week 100, all outcomes employed to evaluate change in axial involvement were sustained. Many were further improved. In patients who initiated therapy on placebo, all of whom were switched to guselkumab at the end of the 24-week double-blind period, at least the same degree of axial symptom control relative to baseline was achieved at both time periods.

Incremental improvement observed over time

“For most measures there was further improvement at 2 years, and there was generally consistent response across patient groups stratified by HLA [human leucocyte antigen] status,” Dr. Gladman reported.

Relative to the 2.6-point reduction in the BASDAI score in the two guselkumab arms at week 24, the reductions reached 3.0, 3.1, and 3.3 at 100 weeks in the every-4-week guselkumab group, every-8-week guselkumab group, and the crossed-over placebo group, respectively. For ASDAS, the reductions at week 24 were 1.4, 1.5, and 0.7 points and reached 1.6, 1.7, and 1.6 points at 100 weeks in the every-4-week, every-8-week, and placebo crossover groups, respectively.

The sustained improvement is consistent with a previous post hoc analysis in which data from the phase 3 DISCOVER-1 trial were pooled with those from DISCOVER-2. This analysis focused on the 312 patients in these studies with axial disease documented by imaging. Again, the study showed improvement at week 24 was sustained at week 52 independent of HLA-B27 status.
 

Need for MRI confirmation seen

The potential problem with this new analysis as well as the previous analysis is the absence of MRI to provide objective evidence of axial involvement, according to Walter P. Maksymowych, MD, professor in the division of rheumatology at the University of Alberta, Edmonton.

Noting that previous studies have indicated that axial involvement assessed by investigators is not reliable even when performed with x-rays, Dr. Maksymowych said these data would be much more reassuring with MRI controls.

“We have seen little correlation between clinical symptoms and MRI manifestations of disease,” he said.

Dr. Gladman conceded this point. Baseline MRI was performed in some of the patients in this subgroup analysis, but it was not mandated. As a result, the data support benefit from guselkumab for symptomatic axial involvement, but she indicated that better evidence of a disease-modifying effect is expected from a more rigorous placebo-controlled trial of guselkumab called STAR.

This trial is requiring MRI at baseline and at week 24 and is using the Spondyloarthritis Research Consortium of Canada (SPARCC) score to assess change. Dr. Gladman said the trial is enrolling “as we speak.”

Overall, Dr. Gladman agreed with Dr. Maksymowych that objective biomarkers are important for demonstrating that treatments are improving long-term outcomes, not just relieving symptoms.

Guselkumab manufacturer Janssen supported the post hoc analysis. Dr. Gladman reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Janssen, Novartis, Pfizer, and UCB. Dr. Maksymowych reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB.

Guselkumab (Tremfya) received Food and Drug Administration approval for the treatment of psoriatic arthritis (PsA) almost 2 years ago on the basis of a phase 3 trial, but a new substudy from that trial has now demonstrated long-term benefit in the subgroup of patients who entered the trial with axial involvement, according to data presented at the annual meeting of the Canadian Rheumatology Association.

“The symptom relief was clinically meaningful and durable through week 100,” reported Dafna D. Gladman, MD, professor of medicine and director of the psoriatic arthritis program at the University of Toronto.

In the previously published double-blind, placebo-controlled DISCOVER-2 trial, two dosing regimens of the interleukin-23 (IL-23) inhibitor guselkumab were compared with placebo in biologic-naive patients. The active regimens were similarly effective relative to placebo for the primary endpoint of 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24.

In this new long-term subgroup analysis, outcomes at 2 years were evaluated in the 246 patients with axial involvement (33.3% of the total number of 739 evaluable patients). Baseline characteristics across treatment groups in this subset of the DISCOVER-2 trial were similar.
 

Guselkumab exhibits nearly twofold advantage

At 24 weeks relative to baseline, the improvement on multiple axial involvement outcome measures was approximately twofold greater with active therapy than with placebo. For example, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score fell 2.6 points in both active treatment arms versus 1.4 on placebo.

The same relative advantage was observed when the BASDAI spinal pain subscore was isolated. There were also comparable responses on a modified BASDAI that excluded the peripheral pain response, and the Ankylosing Spondylitis Disease Activity Score (ASDAS).

When evaluated at week 52 and again at week 100, all outcomes employed to evaluate change in axial involvement were sustained. Many were further improved. In patients who initiated therapy on placebo, all of whom were switched to guselkumab at the end of the 24-week double-blind period, at least the same degree of axial symptom control relative to baseline was achieved at both time periods.

Incremental improvement observed over time

“For most measures there was further improvement at 2 years, and there was generally consistent response across patient groups stratified by HLA [human leucocyte antigen] status,” Dr. Gladman reported.

Relative to the 2.6-point reduction in the BASDAI score in the two guselkumab arms at week 24, the reductions reached 3.0, 3.1, and 3.3 at 100 weeks in the every-4-week guselkumab group, every-8-week guselkumab group, and the crossed-over placebo group, respectively. For ASDAS, the reductions at week 24 were 1.4, 1.5, and 0.7 points and reached 1.6, 1.7, and 1.6 points at 100 weeks in the every-4-week, every-8-week, and placebo crossover groups, respectively.

The sustained improvement is consistent with a previous post hoc analysis in which data from the phase 3 DISCOVER-1 trial were pooled with those from DISCOVER-2. This analysis focused on the 312 patients in these studies with axial disease documented by imaging. Again, the study showed improvement at week 24 was sustained at week 52 independent of HLA-B27 status.
 

Need for MRI confirmation seen

The potential problem with this new analysis as well as the previous analysis is the absence of MRI to provide objective evidence of axial involvement, according to Walter P. Maksymowych, MD, professor in the division of rheumatology at the University of Alberta, Edmonton.

Noting that previous studies have indicated that axial involvement assessed by investigators is not reliable even when performed with x-rays, Dr. Maksymowych said these data would be much more reassuring with MRI controls.

“We have seen little correlation between clinical symptoms and MRI manifestations of disease,” he said.

Dr. Gladman conceded this point. Baseline MRI was performed in some of the patients in this subgroup analysis, but it was not mandated. As a result, the data support benefit from guselkumab for symptomatic axial involvement, but she indicated that better evidence of a disease-modifying effect is expected from a more rigorous placebo-controlled trial of guselkumab called STAR.

This trial is requiring MRI at baseline and at week 24 and is using the Spondyloarthritis Research Consortium of Canada (SPARCC) score to assess change. Dr. Gladman said the trial is enrolling “as we speak.”

Overall, Dr. Gladman agreed with Dr. Maksymowych that objective biomarkers are important for demonstrating that treatments are improving long-term outcomes, not just relieving symptoms.

Guselkumab manufacturer Janssen supported the post hoc analysis. Dr. Gladman reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Janssen, Novartis, Pfizer, and UCB. Dr. Maksymowych reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB.

In the clinical experience of George Han, MD, PhD, treatment of psoriasis currently is often taxing for patients, with wait times to see a dermatologist exceeding 30 days in many markets and patients who present to him having cycled through many providers seeking relief from their disease.

“They come in with bags of topical products to show you what they’ve tried,” Dr. Han, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said during the ODAC Dermatology, Aesthetic & Surgical Conference. “And you’re supposed to see this patient, talk to them, and counsel them in about 10 minutes. How do you make time to conduct an efficient psoriasis visit?”

Patients have a long-term battle to get clear, and spending a little longer on the initial visit “pays a lot of dividends,” he said. “Some of these patients are the most thankful patients in our practices, and it truly is gratifying” to see how much they can improve.
 

Questions about diet

Dr. Han said that psoriasis patients often ask him if, what, or how much they’re eating affects their disease. “But how do you counsel patients about diet when we’re not dietitians? We can at least give some guidance based on available data.”

He referred to a nationwide study of psoriasis patient-reported outcomes and dietary behaviors, which found that the percentage of patients who reported skin improvement was greatest after reducing intake of alcohol (53.8%); gluten (53.4%); and nightshade vegetables, such as tomatoes, potatoes, and peppers (52.1%); and after adding fish oil/omega-3 (44.6%), vegetables (42.5%), and oral vitamin D (41%). He noted that there is a threefold increased incidence of celiac disease in patients with psoriasis.

As for nightshade vegetables, intake leads to increased alkaloids, “which have been known to worsen bowel inflammation such as in IBD [inflammatory bowel disease], but there is a lack of controlled trials examining this in the overall psoriasis population,” Dr. Han said. The Mediterranean diet, he added, “is sensible, and adding olive oil to your diet seems to have a positive effect on ... PASI, while fish oil seems to reduce C-reactive protein.” The data on the effect of vitamin D supplements are mixed, he said.

A separate randomized study evaluated the impact of weight loss in overweight or obese patients with psoriasis, who had not achieved clearance after 4 weeks of systemic treatment. Significantly more of those in the dietary intervention arm reached the weight loss goal of 5% at 20 weeks, and patients in this arm had a median reduction in the Psoriasis Area and Severity Index (PASI) score of almost 50%, compared with almost 26% among those without an active dietary intervention.
 

Joint pain, PsA

For psoriasis patients who complain of joint pain, he recommends administering quick measures like the five-question Psoriasis Epidemiology Screening Test (PEST) to screen for psoriatic arthritis (PsA), which is available on the National Psoriasis Foundation web site. “I ask patients about swollen, tender joints – specifically hands, wrists, ankles, feet, and toes,” Dr. Han said. Joint stiffness in the morning is a “concerning finding,” which is “more indicative of psoriatic arthritis than vague knee or back pain that worsens with use. If you have a younger patient with back pain who has a reduced ability to flex their spine, think axial disease.”

Tumor necrosis factor (TNF)–alpha inhibitors are considered first- and second-line treatment for PsA, but interleukin (IL)–17 inhibitors are generally considered just as effective overall. “The IL-23 inhibitors have mixed signals,” said Dr. Han, who is also on the NPF’s medical board. “We know that guselkumab is effective against psoriatic arthritis, but there is no inhibition of joint progression at the approved dosage on the label – though it was pretty close.”

Risankizumab (Skyrizi), an IL-23 inhibitor, was approved in January 2022 for adults with PsA and while the American College of Rheumatology response data “look reasonably good, the results for inhibition of radiographic progression are quite far off and it’s not in the label,” he said. Tildrakizumab (Ilumya), an IL-23 inhibitor, “looks impressive in phase 2b trials. It will be interesting to see if there is differentiation between the IL-23 agents in treating joint disease going forward.”

Dr. Han considers biologic therapy a good option for patients with questionable joint involvement or very limited joint disease. “If the patient has some evidence of PsA, as long as it’s a medication that has approval for that, I’m OK with starting it,” he said. “However, for patients whose joint pain dominates over the skin, or [who] have severe joint disease at presentation, I would prioritize the TNF-alpha inhibitors and IL-17s and refer them to rheumatology for shared management.”
 

Topical, oral treatments

As for topical approaches to treating psoriasis, adding halobetasol propionate 0.01% to tazarotene 0.045% may have a synergistic effect, while tapinarof 1% cream holds promise, he said. Tapinarof, which is expected to be approved this year, is an investigative aryl hydrocarbon agonist that inhibits an array of proinflammatory cytokines, including interferon-gamma and TNF-alpha. “It has been shown to have inhibitory effects both on Th17 cytokines and Th2 cytokines,” Dr. Han said. “What’s nice about this is that patients still appear to have treatment effect 1-2 months after stopping the drug.”

Another topical agent now under FDA review for psoriasis, is roflumilast, a phosphodiesterase type 4 (PDE4) inhibitor, which has been shown to have a treatment efficacy of 30% or more. “We’ll see how this works into our treatment regimen for psoriasis,” he said, as strategies targeting PDE4 have already been reported to help treat psoriasis.

With regards to oral therapies, he said that there are concerns about the efficacy of the oral PDE4 inhibitor apremilast, approved for psoriasis, compared with other biologics. Deucravacitinib, an oral selective tyrosine kinase 2 (TYK2) inhibitor also under FDA review for psoriasis, “may fill this gap, because its efficacy seems much stronger and really capitalizes on blocking IL-23, which we know is a central pathway in the pathogenesis of psoriasis.”

Phototherapy is another treatment option. Home narrowband-UVB devices cost $3,000-$5,000, “which is a fraction of 1 year of biologic treatment,” Dr. Han said. Older data on phototherapy suggest that “lesions can clear within 2-3 months, depending on how often you do the phototherapy, while newer data suggest that 75% of patients can achieve clear or minimal disease” with phototherapy.

Biologic therapy

If patients meet criteria for treatment with a biologic, he begins the conversation by saying, “I don’t want to give you an immunosuppressant, but your psoriasis represents an overactivation of inflammation in your body, so in some way we have to bring that down. Ideally, we would target your immune system in a way that targets psoriasis very narrowly, while leaving it to do what it needs to: protecting against infections and neoplasia.”

XXXIL-17 inhibitors generally have the fastest onset of action, Dr. Han noted. Authors of a review paper found that achievement of Psoriasis Area and Severity Index (PASI) 50 was 1.8 weeks with brodalumab, 1.9 weeks for ixekizumab, 3 weeks for high-dose secukinumab, 3.5 weeks for adalimumab, 3.7 weeks for infliximab, 5.1 weeks for low-dose ustekinumab, 6.5 weeks for high-dose etanercept, and 10.9 weeks with low-dose etanercept, while achievement of PASI 50 was closer to 1 month for IL-23 inhibitors.

“The conversation I have with patients on IL-23 inhibitors is, ‘we’re in this for the long haul,’ otherwise they come in 2 months later,” he said. “They may have gotten clearer but we’re talking about getting well over half of our patients to PASI 100, or to clear or minimal disease, and they may not have gotten there yet. It helps to frame expectations.”

Dr. Han disclosed that he is a consultant to, a speaker for, or has received research support from Beiersdorf, CeraVe, Celgene, Janssen, Lilly, MC2, Pfizer, UCB, Boehringer Ingelheim, Bond Avillion, Athenex, Amgen, AbbVie, Regeneron/Sanofi, LEO Pharma, Ortho Dermatologics, BMS, Sun Pharma, Dermavant, Dermtech, MedX, Novartis, and Castle Biosciences.

In the clinical experience of George Han, MD, PhD, treatment of psoriasis currently is often taxing for patients, with wait times to see a dermatologist exceeding 30 days in many markets and patients who present to him having cycled through many providers seeking relief from their disease.

“They come in with bags of topical products to show you what they’ve tried,” Dr. Han, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said during the ODAC Dermatology, Aesthetic & Surgical Conference. “And you’re supposed to see this patient, talk to them, and counsel them in about 10 minutes. How do you make time to conduct an efficient psoriasis visit?”

Patients have a long-term battle to get clear, and spending a little longer on the initial visit “pays a lot of dividends,” he said. “Some of these patients are the most thankful patients in our practices, and it truly is gratifying” to see how much they can improve.
 

Questions about diet

Dr. Han said that psoriasis patients often ask him if, what, or how much they’re eating affects their disease. “But how do you counsel patients about diet when we’re not dietitians? We can at least give some guidance based on available data.”

He referred to a nationwide study of psoriasis patient-reported outcomes and dietary behaviors, which found that the percentage of patients who reported skin improvement was greatest after reducing intake of alcohol (53.8%); gluten (53.4%); and nightshade vegetables, such as tomatoes, potatoes, and peppers (52.1%); and after adding fish oil/omega-3 (44.6%), vegetables (42.5%), and oral vitamin D (41%). He noted that there is a threefold increased incidence of celiac disease in patients with psoriasis.

As for nightshade vegetables, intake leads to increased alkaloids, “which have been known to worsen bowel inflammation such as in IBD [inflammatory bowel disease], but there is a lack of controlled trials examining this in the overall psoriasis population,” Dr. Han said. The Mediterranean diet, he added, “is sensible, and adding olive oil to your diet seems to have a positive effect on ... PASI, while fish oil seems to reduce C-reactive protein.” The data on the effect of vitamin D supplements are mixed, he said.

A separate randomized study evaluated the impact of weight loss in overweight or obese patients with psoriasis, who had not achieved clearance after 4 weeks of systemic treatment. Significantly more of those in the dietary intervention arm reached the weight loss goal of 5% at 20 weeks, and patients in this arm had a median reduction in the Psoriasis Area and Severity Index (PASI) score of almost 50%, compared with almost 26% among those without an active dietary intervention.
 

Joint pain, PsA

For psoriasis patients who complain of joint pain, he recommends administering quick measures like the five-question Psoriasis Epidemiology Screening Test (PEST) to screen for psoriatic arthritis (PsA), which is available on the National Psoriasis Foundation web site. “I ask patients about swollen, tender joints – specifically hands, wrists, ankles, feet, and toes,” Dr. Han said. Joint stiffness in the morning is a “concerning finding,” which is “more indicative of psoriatic arthritis than vague knee or back pain that worsens with use. If you have a younger patient with back pain who has a reduced ability to flex their spine, think axial disease.”

Tumor necrosis factor (TNF)–alpha inhibitors are considered first- and second-line treatment for PsA, but interleukin (IL)–17 inhibitors are generally considered just as effective overall. “The IL-23 inhibitors have mixed signals,” said Dr. Han, who is also on the NPF’s medical board. “We know that guselkumab is effective against psoriatic arthritis, but there is no inhibition of joint progression at the approved dosage on the label – though it was pretty close.”

Risankizumab (Skyrizi), an IL-23 inhibitor, was approved in January 2022 for adults with PsA and while the American College of Rheumatology response data “look reasonably good, the results for inhibition of radiographic progression are quite far off and it’s not in the label,” he said. Tildrakizumab (Ilumya), an IL-23 inhibitor, “looks impressive in phase 2b trials. It will be interesting to see if there is differentiation between the IL-23 agents in treating joint disease going forward.”

Dr. Han considers biologic therapy a good option for patients with questionable joint involvement or very limited joint disease. “If the patient has some evidence of PsA, as long as it’s a medication that has approval for that, I’m OK with starting it,” he said. “However, for patients whose joint pain dominates over the skin, or [who] have severe joint disease at presentation, I would prioritize the TNF-alpha inhibitors and IL-17s and refer them to rheumatology for shared management.”
 

Topical, oral treatments

As for topical approaches to treating psoriasis, adding halobetasol propionate 0.01% to tazarotene 0.045% may have a synergistic effect, while tapinarof 1% cream holds promise, he said. Tapinarof, which is expected to be approved this year, is an investigative aryl hydrocarbon agonist that inhibits an array of proinflammatory cytokines, including interferon-gamma and TNF-alpha. “It has been shown to have inhibitory effects both on Th17 cytokines and Th2 cytokines,” Dr. Han said. “What’s nice about this is that patients still appear to have treatment effect 1-2 months after stopping the drug.”

Another topical agent now under FDA review for psoriasis, is roflumilast, a phosphodiesterase type 4 (PDE4) inhibitor, which has been shown to have a treatment efficacy of 30% or more. “We’ll see how this works into our treatment regimen for psoriasis,” he said, as strategies targeting PDE4 have already been reported to help treat psoriasis.

With regards to oral therapies, he said that there are concerns about the efficacy of the oral PDE4 inhibitor apremilast, approved for psoriasis, compared with other biologics. Deucravacitinib, an oral selective tyrosine kinase 2 (TYK2) inhibitor also under FDA review for psoriasis, “may fill this gap, because its efficacy seems much stronger and really capitalizes on blocking IL-23, which we know is a central pathway in the pathogenesis of psoriasis.”

Phototherapy is another treatment option. Home narrowband-UVB devices cost $3,000-$5,000, “which is a fraction of 1 year of biologic treatment,” Dr. Han said. Older data on phototherapy suggest that “lesions can clear within 2-3 months, depending on how often you do the phototherapy, while newer data suggest that 75% of patients can achieve clear or minimal disease” with phototherapy.

Biologic therapy

If patients meet criteria for treatment with a biologic, he begins the conversation by saying, “I don’t want to give you an immunosuppressant, but your psoriasis represents an overactivation of inflammation in your body, so in some way we have to bring that down. Ideally, we would target your immune system in a way that targets psoriasis very narrowly, while leaving it to do what it needs to: protecting against infections and neoplasia.”

XXXIL-17 inhibitors generally have the fastest onset of action, Dr. Han noted. Authors of a review paper found that achievement of Psoriasis Area and Severity Index (PASI) 50 was 1.8 weeks with brodalumab, 1.9 weeks for ixekizumab, 3 weeks for high-dose secukinumab, 3.5 weeks for adalimumab, 3.7 weeks for infliximab, 5.1 weeks for low-dose ustekinumab, 6.5 weeks for high-dose etanercept, and 10.9 weeks with low-dose etanercept, while achievement of PASI 50 was closer to 1 month for IL-23 inhibitors.

“The conversation I have with patients on IL-23 inhibitors is, ‘we’re in this for the long haul,’ otherwise they come in 2 months later,” he said. “They may have gotten clearer but we’re talking about getting well over half of our patients to PASI 100, or to clear or minimal disease, and they may not have gotten there yet. It helps to frame expectations.”

Dr. Han disclosed that he is a consultant to, a speaker for, or has received research support from Beiersdorf, CeraVe, Celgene, Janssen, Lilly, MC2, Pfizer, UCB, Boehringer Ingelheim, Bond Avillion, Athenex, Amgen, AbbVie, Regeneron/Sanofi, LEO Pharma, Ortho Dermatologics, BMS, Sun Pharma, Dermavant, Dermtech, MedX, Novartis, and Castle Biosciences.

In the clinical experience of George Han, MD, PhD, treatment of psoriasis currently is often taxing for patients, with wait times to see a dermatologist exceeding 30 days in many markets and patients who present to him having cycled through many providers seeking relief from their disease.

“They come in with bags of topical products to show you what they’ve tried,” Dr. Han, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said during the ODAC Dermatology, Aesthetic & Surgical Conference. “And you’re supposed to see this patient, talk to them, and counsel them in about 10 minutes. How do you make time to conduct an efficient psoriasis visit?”

Patients have a long-term battle to get clear, and spending a little longer on the initial visit “pays a lot of dividends,” he said. “Some of these patients are the most thankful patients in our practices, and it truly is gratifying” to see how much they can improve.
 

Questions about diet

Dr. Han said that psoriasis patients often ask him if, what, or how much they’re eating affects their disease. “But how do you counsel patients about diet when we’re not dietitians? We can at least give some guidance based on available data.”

He referred to a nationwide study of psoriasis patient-reported outcomes and dietary behaviors, which found that the percentage of patients who reported skin improvement was greatest after reducing intake of alcohol (53.8%); gluten (53.4%); and nightshade vegetables, such as tomatoes, potatoes, and peppers (52.1%); and after adding fish oil/omega-3 (44.6%), vegetables (42.5%), and oral vitamin D (41%). He noted that there is a threefold increased incidence of celiac disease in patients with psoriasis.

As for nightshade vegetables, intake leads to increased alkaloids, “which have been known to worsen bowel inflammation such as in IBD [inflammatory bowel disease], but there is a lack of controlled trials examining this in the overall psoriasis population,” Dr. Han said. The Mediterranean diet, he added, “is sensible, and adding olive oil to your diet seems to have a positive effect on ... PASI, while fish oil seems to reduce C-reactive protein.” The data on the effect of vitamin D supplements are mixed, he said.

A separate randomized study evaluated the impact of weight loss in overweight or obese patients with psoriasis, who had not achieved clearance after 4 weeks of systemic treatment. Significantly more of those in the dietary intervention arm reached the weight loss goal of 5% at 20 weeks, and patients in this arm had a median reduction in the Psoriasis Area and Severity Index (PASI) score of almost 50%, compared with almost 26% among those without an active dietary intervention.
 

Joint pain, PsA

For psoriasis patients who complain of joint pain, he recommends administering quick measures like the five-question Psoriasis Epidemiology Screening Test (PEST) to screen for psoriatic arthritis (PsA), which is available on the National Psoriasis Foundation web site. “I ask patients about swollen, tender joints – specifically hands, wrists, ankles, feet, and toes,” Dr. Han said. Joint stiffness in the morning is a “concerning finding,” which is “more indicative of psoriatic arthritis than vague knee or back pain that worsens with use. If you have a younger patient with back pain who has a reduced ability to flex their spine, think axial disease.”

Tumor necrosis factor (TNF)–alpha inhibitors are considered first- and second-line treatment for PsA, but interleukin (IL)–17 inhibitors are generally considered just as effective overall. “The IL-23 inhibitors have mixed signals,” said Dr. Han, who is also on the NPF’s medical board. “We know that guselkumab is effective against psoriatic arthritis, but there is no inhibition of joint progression at the approved dosage on the label – though it was pretty close.”

Risankizumab (Skyrizi), an IL-23 inhibitor, was approved in January 2022 for adults with PsA and while the American College of Rheumatology response data “look reasonably good, the results for inhibition of radiographic progression are quite far off and it’s not in the label,” he said. Tildrakizumab (Ilumya), an IL-23 inhibitor, “looks impressive in phase 2b trials. It will be interesting to see if there is differentiation between the IL-23 agents in treating joint disease going forward.”

Dr. Han considers biologic therapy a good option for patients with questionable joint involvement or very limited joint disease. “If the patient has some evidence of PsA, as long as it’s a medication that has approval for that, I’m OK with starting it,” he said. “However, for patients whose joint pain dominates over the skin, or [who] have severe joint disease at presentation, I would prioritize the TNF-alpha inhibitors and IL-17s and refer them to rheumatology for shared management.”
 

Topical, oral treatments

As for topical approaches to treating psoriasis, adding halobetasol propionate 0.01% to tazarotene 0.045% may have a synergistic effect, while tapinarof 1% cream holds promise, he said. Tapinarof, which is expected to be approved this year, is an investigative aryl hydrocarbon agonist that inhibits an array of proinflammatory cytokines, including interferon-gamma and TNF-alpha. “It has been shown to have inhibitory effects both on Th17 cytokines and Th2 cytokines,” Dr. Han said. “What’s nice about this is that patients still appear to have treatment effect 1-2 months after stopping the drug.”

Another topical agent now under FDA review for psoriasis, is roflumilast, a phosphodiesterase type 4 (PDE4) inhibitor, which has been shown to have a treatment efficacy of 30% or more. “We’ll see how this works into our treatment regimen for psoriasis,” he said, as strategies targeting PDE4 have already been reported to help treat psoriasis.

With regards to oral therapies, he said that there are concerns about the efficacy of the oral PDE4 inhibitor apremilast, approved for psoriasis, compared with other biologics. Deucravacitinib, an oral selective tyrosine kinase 2 (TYK2) inhibitor also under FDA review for psoriasis, “may fill this gap, because its efficacy seems much stronger and really capitalizes on blocking IL-23, which we know is a central pathway in the pathogenesis of psoriasis.”

Phototherapy is another treatment option. Home narrowband-UVB devices cost $3,000-$5,000, “which is a fraction of 1 year of biologic treatment,” Dr. Han said. Older data on phototherapy suggest that “lesions can clear within 2-3 months, depending on how often you do the phototherapy, while newer data suggest that 75% of patients can achieve clear or minimal disease” with phototherapy.

Biologic therapy

If patients meet criteria for treatment with a biologic, he begins the conversation by saying, “I don’t want to give you an immunosuppressant, but your psoriasis represents an overactivation of inflammation in your body, so in some way we have to bring that down. Ideally, we would target your immune system in a way that targets psoriasis very narrowly, while leaving it to do what it needs to: protecting against infections and neoplasia.”

XXXIL-17 inhibitors generally have the fastest onset of action, Dr. Han noted. Authors of a review paper found that achievement of Psoriasis Area and Severity Index (PASI) 50 was 1.8 weeks with brodalumab, 1.9 weeks for ixekizumab, 3 weeks for high-dose secukinumab, 3.5 weeks for adalimumab, 3.7 weeks for infliximab, 5.1 weeks for low-dose ustekinumab, 6.5 weeks for high-dose etanercept, and 10.9 weeks with low-dose etanercept, while achievement of PASI 50 was closer to 1 month for IL-23 inhibitors.

“The conversation I have with patients on IL-23 inhibitors is, ‘we’re in this for the long haul,’ otherwise they come in 2 months later,” he said. “They may have gotten clearer but we’re talking about getting well over half of our patients to PASI 100, or to clear or minimal disease, and they may not have gotten there yet. It helps to frame expectations.”

Dr. Han disclosed that he is a consultant to, a speaker for, or has received research support from Beiersdorf, CeraVe, Celgene, Janssen, Lilly, MC2, Pfizer, UCB, Boehringer Ingelheim, Bond Avillion, Athenex, Amgen, AbbVie, Regeneron/Sanofi, LEO Pharma, Ortho Dermatologics, BMS, Sun Pharma, Dermavant, Dermtech, MedX, Novartis, and Castle Biosciences.

Case Report

A 39-year-old woman who was otherwise healthy presented with fatigue, malaise, a resolving rash, focal lymphadenopathy, increasing distal arthritis, dactylitis, resolving ecchymoses, and acute onycholysis of 1 week’s duration that developed 13 days after initiating ixekizumab. The patient had a history of psoriasis and psoriatic arthritis for more than 10 years. She had been successfully treated in the past for psoriasis with adalimumab for several years; however, adalimumab was discontinued after an episode of Clostridium difficile colitis. The patient had a negative purified protein derivative (tuberculin) test prior to starting biologics as she works in the health care field. Routine follow-up purified protein derivative (tuberculin) test was positive. She discontinued all therapy for psoriasis and psoriatic arthritis prior to being appropriately treated for 6 months under the care of infectious disease physicians. She then had several pregnancies and chose to restart biologic treatment after weaning her third child from breastfeeding, as her skin and joint disease were notably flaring.

Ustekinumab was chosen to shift treatment away from tumor necrosis factor (TNF) α inhibitors. The patient's condition was under relatively good control for 1 year; however, she experienced notable gastrointestinal tract upset (ie, intermittent diarrhea and constipation), despite multiple negative tests for C difficile. The patient was referred to see a gastroenterologist but never followed up. Due to long-term low-grade gastrointestinal problems, ustekinumab was discontinued, and the gastrointestinal symptoms resolved without treatment.

Given the side effects noted with TNF-α and IL-12/23 inhibitors and the fact that the patient’s cutaneous and joint disease were notable, the decision was made to start the IL-17A inhibitor ixekizumab. The patient administered 2 injections, one in each thigh. Within 12 hours, she experienced severe injection-site pain. The pain was so severe that it woke her from sleep the night of the first injections. She then developed severe pain in the right axilla that limited upper extremity mobility. Within 48 hours, she developed an erythematous, nonpruritic, nonscaly, mottled rash on the right breast that began to resolve within 24 hours without treatment. In addition, 3 days after the injections, she developed ecchymoses on the trunk and extremities without any identifiable trauma, severe acute onycholysis in several fingernails (Figure 1) and toenails, dactylitis such that she could not wear her wedding ring, and a flare of psoriatic arthritis in the fingers and ankles.

At the current presentation (2 weeks after the injections), the patient reported malaise, flulike symptoms, and low-grade intermittent fevers. Results from a hematology panel displayed leukopenia at 2.69×10³/μL (reference range, 3.54–9.06×10³/μL) and thrombocytopenia at 114×10³/μL (reference range, 165–415×10³/μL).¹ Her most recent laboratory results before the ixekizumab injections displayed a white blood cell count level at 4.6×10³/μL and platelet count at 159×10³/μL. C-reactive protein and erythrocyte sedimentation rate were within reference range. A shave biopsy of an erythematous nodule on the proximal interphalangeal joint of the fourth finger on the right hand displayed spongiotic dermatitis with eosinophils (Figure 2).

Interestingly, the psoriatic plaques on the scalp, trunk, and extremities had nearly completely resolved after only the first 2 injections. However, given the side effects, the second dose of ixekizumab was held, repeat laboratory tests were ordered to ensure normalization of cytopenia, and the patient was transitioned to pulse-dose topical steroids to control the remaining psoriatic plaques.

One week after presentation (3 weeks after the initial injections), the patient’s systemic symptoms had almost completely resolved, and she denied any further concerns. Her fingernails and toenails, however, continued to show the changes of onycholysis noted at the visit.

Comment

Ixekizumab is a human IgG4 monoclonal antibody that binds to IL-17A, one of the cytokines involved in the pathogenesis of psoriasis. The monoclonal antibody prevents its attachment to the IL-17 receptor, which inhibits the release of further cytokines and chemokines, decreasing the inflammatory and immune response.²

Ixekizumab was approved by the US Food and Drug Administration for plaque psoriasis after 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—were performed. In UNCOVER-3, the most common side effects that occurred—nasopharyngitis, upper respiratory tract infection, injection-site reaction, arthralgia, headache, and infections (specifically candidiasis)—generally were well tolerated. More serious adverse events included cardiovascular and cerebrovascular events, inflammatory bowel disease, and nonmelanoma skin cancer.³

Notable laboratory abnormalities that have been documented from ixekizumab include elevated liver function tests (eg, alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase), as well as leukopenia, neutropenia, and thrombocytopenia.⁴ Although short-term thrombocytopenia, as described in our patient, provides an explanation for the bruising noted on observation, it is unusual to note such notable ecchymoses within days of the first injection.

Onycholysis has not been documented as a side effect of ixekizumab; however, it has been reported as an adverse event from other biologic medications. Sfikakis et al⁵ reported 5 patients who developed psoriatic skin lesions after treatment with 3 different anti-TNF biologics—infliximab, adalimumab, or etanercept—for rheumatoid arthritis; 2 of those patients also developed nail changes consistent with psoriatic onycholysis. In all 5 patients, symptoms of rheumatoid arthritis improved despite the new-onset skin and nail psoriasis.⁵

The exact pathophysiology of these adverse events has not been clearly understood, but it has been proposed that anti-TNF biologics may initiate an autoimmune reaction in the skin and nails, leading to paradoxical psoriasis and nail changes such as onycholysis. Tumor necrosis factor may have a regulatory role in the skin that prevents autoreactive T cells, such as cutaneous lymphocyte antigen–expressing T cells that promote the formation of psoriasiform lesions. By inhibiting TNF, there can be an underlying activation of autoreactive T cells that leads to tissue destruction in the skin and nails.⁶ Anti-TNF biologics also could increase CXCR3, a chemokine receptor that allows autoreactive T cells to enter the skin and cause pathology.⁷

IL-17A and IL-17F also have been shown to upregulate the expression of TNF receptor II in synoviocytes,⁸ which demonstrates that IL-17 works in synergy with TNF-α to promote an inflammatory reaction.⁹ Due to the inhibitory effects of ixekizumab, psoriatic arthritis should theoretically improve. However, if there is an alteration in the inflammatory sequence, then the regulatory role of TNF could be suppressed and psoriatic arthritis could become exacerbated. Additionally, its associated symptoms, such as dactylitis, could develop, as seen in our patient.⁴ Because psoriatic arthritis is closely associated with nail changes of psoriasis, it is conceivable that acute arthritic flares and acute onycholysis are both induced by the same cytokine dysregulation. Further studies and a larger patient population need to be evaluated to determine the exact cause of the acute exacerbation of psoriatic arthritis with concomitant nail changes as noted in our patient.

Acute onycholysis (within 72 hours) is a rare side effect of ixekizumab. It can be postulated that our patient’s severe acute onycholysis associated with a flare of psoriatic arthritis could be due to idiosyncratic immune dysregulation, promoting the activity of autoreactive T cells. The pharmacologic effects of ixekizumab occur through the inhibition of IL-17. We propose that by inhibiting IL-17 with associated TNF alterations, an altered inflammatory cascade could promote an autoimmune reaction leading to the described pathology.

Case Report

A 39-year-old woman who was otherwise healthy presented with fatigue, malaise, a resolving rash, focal lymphadenopathy, increasing distal arthritis, dactylitis, resolving ecchymoses, and acute onycholysis of 1 week’s duration that developed 13 days after initiating ixekizumab. The patient had a history of psoriasis and psoriatic arthritis for more than 10 years. She had been successfully treated in the past for psoriasis with adalimumab for several years; however, adalimumab was discontinued after an episode of Clostridium difficile colitis. The patient had a negative purified protein derivative (tuberculin) test prior to starting biologics as she works in the health care field. Routine follow-up purified protein derivative (tuberculin) test was positive. She discontinued all therapy for psoriasis and psoriatic arthritis prior to being appropriately treated for 6 months under the care of infectious disease physicians. She then had several pregnancies and chose to restart biologic treatment after weaning her third child from breastfeeding, as her skin and joint disease were notably flaring.

Ustekinumab was chosen to shift treatment away from tumor necrosis factor (TNF) α inhibitors. The patient's condition was under relatively good control for 1 year; however, she experienced notable gastrointestinal tract upset (ie, intermittent diarrhea and constipation), despite multiple negative tests for C difficile. The patient was referred to see a gastroenterologist but never followed up. Due to long-term low-grade gastrointestinal problems, ustekinumab was discontinued, and the gastrointestinal symptoms resolved without treatment.

Given the side effects noted with TNF-α and IL-12/23 inhibitors and the fact that the patient’s cutaneous and joint disease were notable, the decision was made to start the IL-17A inhibitor ixekizumab. The patient administered 2 injections, one in each thigh. Within 12 hours, she experienced severe injection-site pain. The pain was so severe that it woke her from sleep the night of the first injections. She then developed severe pain in the right axilla that limited upper extremity mobility. Within 48 hours, she developed an erythematous, nonpruritic, nonscaly, mottled rash on the right breast that began to resolve within 24 hours without treatment. In addition, 3 days after the injections, she developed ecchymoses on the trunk and extremities without any identifiable trauma, severe acute onycholysis in several fingernails (Figure 1) and toenails, dactylitis such that she could not wear her wedding ring, and a flare of psoriatic arthritis in the fingers and ankles.

At the current presentation (2 weeks after the injections), the patient reported malaise, flulike symptoms, and low-grade intermittent fevers. Results from a hematology panel displayed leukopenia at 2.69×10³/μL (reference range, 3.54–9.06×10³/μL) and thrombocytopenia at 114×10³/μL (reference range, 165–415×10³/μL).¹ Her most recent laboratory results before the ixekizumab injections displayed a white blood cell count level at 4.6×10³/μL and platelet count at 159×10³/μL. C-reactive protein and erythrocyte sedimentation rate were within reference range. A shave biopsy of an erythematous nodule on the proximal interphalangeal joint of the fourth finger on the right hand displayed spongiotic dermatitis with eosinophils (Figure 2).

Interestingly, the psoriatic plaques on the scalp, trunk, and extremities had nearly completely resolved after only the first 2 injections. However, given the side effects, the second dose of ixekizumab was held, repeat laboratory tests were ordered to ensure normalization of cytopenia, and the patient was transitioned to pulse-dose topical steroids to control the remaining psoriatic plaques.

One week after presentation (3 weeks after the initial injections), the patient’s systemic symptoms had almost completely resolved, and she denied any further concerns. Her fingernails and toenails, however, continued to show the changes of onycholysis noted at the visit.

Comment

Ixekizumab is a human IgG4 monoclonal antibody that binds to IL-17A, one of the cytokines involved in the pathogenesis of psoriasis. The monoclonal antibody prevents its attachment to the IL-17 receptor, which inhibits the release of further cytokines and chemokines, decreasing the inflammatory and immune response.²

Ixekizumab was approved by the US Food and Drug Administration for plaque psoriasis after 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—were performed. In UNCOVER-3, the most common side effects that occurred—nasopharyngitis, upper respiratory tract infection, injection-site reaction, arthralgia, headache, and infections (specifically candidiasis)—generally were well tolerated. More serious adverse events included cardiovascular and cerebrovascular events, inflammatory bowel disease, and nonmelanoma skin cancer.³

Notable laboratory abnormalities that have been documented from ixekizumab include elevated liver function tests (eg, alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase), as well as leukopenia, neutropenia, and thrombocytopenia.⁴ Although short-term thrombocytopenia, as described in our patient, provides an explanation for the bruising noted on observation, it is unusual to note such notable ecchymoses within days of the first injection.

Onycholysis has not been documented as a side effect of ixekizumab; however, it has been reported as an adverse event from other biologic medications. Sfikakis et al⁵ reported 5 patients who developed psoriatic skin lesions after treatment with 3 different anti-TNF biologics—infliximab, adalimumab, or etanercept—for rheumatoid arthritis; 2 of those patients also developed nail changes consistent with psoriatic onycholysis. In all 5 patients, symptoms of rheumatoid arthritis improved despite the new-onset skin and nail psoriasis.⁵

The exact pathophysiology of these adverse events has not been clearly understood, but it has been proposed that anti-TNF biologics may initiate an autoimmune reaction in the skin and nails, leading to paradoxical psoriasis and nail changes such as onycholysis. Tumor necrosis factor may have a regulatory role in the skin that prevents autoreactive T cells, such as cutaneous lymphocyte antigen–expressing T cells that promote the formation of psoriasiform lesions. By inhibiting TNF, there can be an underlying activation of autoreactive T cells that leads to tissue destruction in the skin and nails.⁶ Anti-TNF biologics also could increase CXCR3, a chemokine receptor that allows autoreactive T cells to enter the skin and cause pathology.⁷

IL-17A and IL-17F also have been shown to upregulate the expression of TNF receptor II in synoviocytes,⁸ which demonstrates that IL-17 works in synergy with TNF-α to promote an inflammatory reaction.⁹ Due to the inhibitory effects of ixekizumab, psoriatic arthritis should theoretically improve. However, if there is an alteration in the inflammatory sequence, then the regulatory role of TNF could be suppressed and psoriatic arthritis could become exacerbated. Additionally, its associated symptoms, such as dactylitis, could develop, as seen in our patient.⁴ Because psoriatic arthritis is closely associated with nail changes of psoriasis, it is conceivable that acute arthritic flares and acute onycholysis are both induced by the same cytokine dysregulation. Further studies and a larger patient population need to be evaluated to determine the exact cause of the acute exacerbation of psoriatic arthritis with concomitant nail changes as noted in our patient.

Acute onycholysis (within 72 hours) is a rare side effect of ixekizumab. It can be postulated that our patient’s severe acute onycholysis associated with a flare of psoriatic arthritis could be due to idiosyncratic immune dysregulation, promoting the activity of autoreactive T cells. The pharmacologic effects of ixekizumab occur through the inhibition of IL-17. We propose that by inhibiting IL-17 with associated TNF alterations, an altered inflammatory cascade could promote an autoimmune reaction leading to the described pathology.

Case Report

A 39-year-old woman who was otherwise healthy presented with fatigue, malaise, a resolving rash, focal lymphadenopathy, increasing distal arthritis, dactylitis, resolving ecchymoses, and acute onycholysis of 1 week’s duration that developed 13 days after initiating ixekizumab. The patient had a history of psoriasis and psoriatic arthritis for more than 10 years. She had been successfully treated in the past for psoriasis with adalimumab for several years; however, adalimumab was discontinued after an episode of Clostridium difficile colitis. The patient had a negative purified protein derivative (tuberculin) test prior to starting biologics as she works in the health care field. Routine follow-up purified protein derivative (tuberculin) test was positive. She discontinued all therapy for psoriasis and psoriatic arthritis prior to being appropriately treated for 6 months under the care of infectious disease physicians. She then had several pregnancies and chose to restart biologic treatment after weaning her third child from breastfeeding, as her skin and joint disease were notably flaring.

Ustekinumab was chosen to shift treatment away from tumor necrosis factor (TNF) α inhibitors. The patient's condition was under relatively good control for 1 year; however, she experienced notable gastrointestinal tract upset (ie, intermittent diarrhea and constipation), despite multiple negative tests for C difficile. The patient was referred to see a gastroenterologist but never followed up. Due to long-term low-grade gastrointestinal problems, ustekinumab was discontinued, and the gastrointestinal symptoms resolved without treatment.

Given the side effects noted with TNF-α and IL-12/23 inhibitors and the fact that the patient’s cutaneous and joint disease were notable, the decision was made to start the IL-17A inhibitor ixekizumab. The patient administered 2 injections, one in each thigh. Within 12 hours, she experienced severe injection-site pain. The pain was so severe that it woke her from sleep the night of the first injections. She then developed severe pain in the right axilla that limited upper extremity mobility. Within 48 hours, she developed an erythematous, nonpruritic, nonscaly, mottled rash on the right breast that began to resolve within 24 hours without treatment. In addition, 3 days after the injections, she developed ecchymoses on the trunk and extremities without any identifiable trauma, severe acute onycholysis in several fingernails (Figure 1) and toenails, dactylitis such that she could not wear her wedding ring, and a flare of psoriatic arthritis in the fingers and ankles.

At the current presentation (2 weeks after the injections), the patient reported malaise, flulike symptoms, and low-grade intermittent fevers. Results from a hematology panel displayed leukopenia at 2.69×10³/μL (reference range, 3.54–9.06×10³/μL) and thrombocytopenia at 114×10³/μL (reference range, 165–415×10³/μL).¹ Her most recent laboratory results before the ixekizumab injections displayed a white blood cell count level at 4.6×10³/μL and platelet count at 159×10³/μL. C-reactive protein and erythrocyte sedimentation rate were within reference range. A shave biopsy of an erythematous nodule on the proximal interphalangeal joint of the fourth finger on the right hand displayed spongiotic dermatitis with eosinophils (Figure 2).

Interestingly, the psoriatic plaques on the scalp, trunk, and extremities had nearly completely resolved after only the first 2 injections. However, given the side effects, the second dose of ixekizumab was held, repeat laboratory tests were ordered to ensure normalization of cytopenia, and the patient was transitioned to pulse-dose topical steroids to control the remaining psoriatic plaques.

One week after presentation (3 weeks after the initial injections), the patient’s systemic symptoms had almost completely resolved, and she denied any further concerns. Her fingernails and toenails, however, continued to show the changes of onycholysis noted at the visit.

Comment

Ixekizumab is a human IgG4 monoclonal antibody that binds to IL-17A, one of the cytokines involved in the pathogenesis of psoriasis. The monoclonal antibody prevents its attachment to the IL-17 receptor, which inhibits the release of further cytokines and chemokines, decreasing the inflammatory and immune response.²

Ixekizumab was approved by the US Food and Drug Administration for plaque psoriasis after 3 clinical trials—UNCOVER-1, UNCOVER-2, and UNCOVER-3—were performed. In UNCOVER-3, the most common side effects that occurred—nasopharyngitis, upper respiratory tract infection, injection-site reaction, arthralgia, headache, and infections (specifically candidiasis)—generally were well tolerated. More serious adverse events included cardiovascular and cerebrovascular events, inflammatory bowel disease, and nonmelanoma skin cancer.³

Notable laboratory abnormalities that have been documented from ixekizumab include elevated liver function tests (eg, alanine aminotransferase, aspartate aminotransferase, bilirubin, and alkaline phosphatase), as well as leukopenia, neutropenia, and thrombocytopenia.⁴ Although short-term thrombocytopenia, as described in our patient, provides an explanation for the bruising noted on observation, it is unusual to note such notable ecchymoses within days of the first injection.

Onycholysis has not been documented as a side effect of ixekizumab; however, it has been reported as an adverse event from other biologic medications. Sfikakis et al⁵ reported 5 patients who developed psoriatic skin lesions after treatment with 3 different anti-TNF biologics—infliximab, adalimumab, or etanercept—for rheumatoid arthritis; 2 of those patients also developed nail changes consistent with psoriatic onycholysis. In all 5 patients, symptoms of rheumatoid arthritis improved despite the new-onset skin and nail psoriasis.⁵

The exact pathophysiology of these adverse events has not been clearly understood, but it has been proposed that anti-TNF biologics may initiate an autoimmune reaction in the skin and nails, leading to paradoxical psoriasis and nail changes such as onycholysis. Tumor necrosis factor may have a regulatory role in the skin that prevents autoreactive T cells, such as cutaneous lymphocyte antigen–expressing T cells that promote the formation of psoriasiform lesions. By inhibiting TNF, there can be an underlying activation of autoreactive T cells that leads to tissue destruction in the skin and nails.⁶ Anti-TNF biologics also could increase CXCR3, a chemokine receptor that allows autoreactive T cells to enter the skin and cause pathology.⁷

IL-17A and IL-17F also have been shown to upregulate the expression of TNF receptor II in synoviocytes,⁸ which demonstrates that IL-17 works in synergy with TNF-α to promote an inflammatory reaction.⁹ Due to the inhibitory effects of ixekizumab, psoriatic arthritis should theoretically improve. However, if there is an alteration in the inflammatory sequence, then the regulatory role of TNF could be suppressed and psoriatic arthritis could become exacerbated. Additionally, its associated symptoms, such as dactylitis, could develop, as seen in our patient.⁴ Because psoriatic arthritis is closely associated with nail changes of psoriasis, it is conceivable that acute arthritic flares and acute onycholysis are both induced by the same cytokine dysregulation. Further studies and a larger patient population need to be evaluated to determine the exact cause of the acute exacerbation of psoriatic arthritis with concomitant nail changes as noted in our patient.

Acute onycholysis (within 72 hours) is a rare side effect of ixekizumab. It can be postulated that our patient’s severe acute onycholysis associated with a flare of psoriatic arthritis could be due to idiosyncratic immune dysregulation, promoting the activity of autoreactive T cells. The pharmacologic effects of ixekizumab occur through the inhibition of IL-17. We propose that by inhibiting IL-17 with associated TNF alterations, an altered inflammatory cascade could promote an autoimmune reaction leading to the described pathology.

A dermatologist-led model of cardiovascular disease (CVD) risk management for patients with psoriatic disease – in which dermatologists do more than refer patients to a primary care physician (PCP) or a cardiologist – may be feasible, given the positive perspectives expressed by both clinicians and patients in a set of electronic surveys, researchers say.

In an analysis of survey responses from 183 dermatologists and 322 patients, John S. Barbieri, MD, MBA, and coinvestigators found that more than two-thirds of dermatologists (69.3%) agreed it “seems doable” to check lipids and calculate a 10-year cardiovascular risk score, and over one-third (36.1%) agreed they could prescribe statins when indicated.

The patient survey was distributed through the National Psoriasis Foundation to individuals who were seeing a dermatologist or rheumatologist for psoriatic disease; the clinician survey was distributed through the American Academy of Dermatology to dermatologists who reported caring for patients with psoriasis. (A survey of rheumatologists was similarly conducted, but the number of participants fell short of the needed sample size.)

Most patients surveyed indicated they would be receptive to their dermatologist (or rheumatologist) playing a larger role in screening and managing CVD risk, and that they would be similarly likely to follow recommendations regarding risk screening and management whether the advice came their dermatologist/rheumatologist or from their PCP.

The clinician survey focused on lipids and statin use, and did not address other elements of risk management. Still, the researchers see their findings as an early but promising step in finding better models to improve cardiovascular outcomes for patients with psoriatic disease, who too often do not engage with their PCPs despite their increased risk of CVD and a higher risk of premature mortality from CVD.

Fewer than half of commercially insured adults aged under 65 years visit a PCP each year, the researchers noted. And among the patients in their survey, approximately 20% did not have a PCP or had not seen their PCP in the past year.

Other research has shown that only a small minority of patients with psoriasis have an encounter with their PCP within a year of establishing care with their dermatologist, and that “over half of patients with psoriasis have undetected risk factors like dyslipidemia or hypertension,” Dr. Barbieri, of the department of dermatology at Brigham and Women’s Hospital, Boston, said in an interview.

“There’s a gap here, a missing link in the chain of cardiovascular disease prevention,” he said. “What if the dermatologist or rheumatologist could be more engaged in [CV] risk protection? ... It’s the idea of meeting the patients where they are.”
 

The surveys

The clinician survey focused on statins because of their ease of use, efficacy and safety, and the need for minimal monitoring, Dr. Barbieri said in the interview. “On the spectrum of things you can do for cardiovascular disease prevention, it’s one of the easiest ones.”

NYU Langone

In an accompanying editorial, cardiologists Michael S. Garshick, MD, MS, and Jeffrey S. Berger, MD, MS, both of the department of medicine, New York University, wrote that, “despite the well-described association between psoriasis and CVD, only 35% of patients with psoriasis diagnosed with hyperlipidemia are adequately treated with statin therapy.”

“For many of these patients, their dermatologist or rheumatologist may be their only source of contact with the health care system,” they added.

Most studies targeting CVD risk in psoriasis have focused on targeting psoriatic inflammation, and few studies have explored strategies to improve modifiable CVD risk factor control with pharmacological therapy, they said.

NYU Langone

In addition to the questions about receptiveness to identifying and potentially treating CVD risk with statins, the dermatologist survey included a best-worst scaling choice experiment to assess preferences for implementation approaches. Dermatologists were asked to rank their preferences for eight implementation strategies that have been shown in published studies to help increase statin prescribing rates.

The three highest-ranked strategies among dermatologists were clinical decision support, physician educational outreach, and patient education materials. The lowest-ranked strategies were comparisons with peers, a pay-for-performance option, and a mobile app/texting service to remind patients to undergo CVD risk screening.

Of the 183 dermatologists in the survey, 28.4% were from academic settings, 11.5% were from multispecialty groups, and 45.4% were from dermatology groups. (A low response rate of 5.2% for dermatologists raises some questions about the generalizability of the findings, Dr. Garshick and Dr. Berger noted in their editorial.)
 

Where to go from here?

Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation, Irvine, Calif., who was not involved with the study, said that a larger role in CVD risk management is “not likely to find traction with everyday dermatologists.”

“It’s already a big ask for community dermatologists to go through the approval process to get biologics for patients, so I don’t think many would be willing to add more to their plate by taking a bigger role in CVD management,” he said in an interview. He generally has not prescribed statins, “as I don’t feel that is in my scope of work.”

In the interview, Dr. Barbieri said that a parallel qualitative study, not yet published, has looked at the facilitators and barriers – including time constraints and concern about scope of practice – to statin prescribing and other elements of cardiovascular risk reduction.

All told, he said, a centralized care coordinator model may be the best approach to engage the dermatologist more in CVD prevention, including lipid management, but to also “offload some of the management responsibility.”

In this model, which is partially described by Dr. Barbieri and colleagues, the dermatologist (or rheumatologist) would educate the patient, measure blood pressure and check a lipid panel, and refer the patient to a coordinator who would, in turn, collect more information and calculate a 10-year CVD risk score.

Using a protocol-driven clinical decision support approach, the care coordinator would provide counseling about diet, exercise, and smoking cessation, and about whether statin therapy or blood pressure management is indicated.

“That coordinator would be in a good position to help the patient work with their PCP, if they have one, to find a PCP if they don’t, or to use telemedicine or work with their dermatologist or rheumatologist,” Dr. Barbieri said.

The centralized care coordinator service could be funded through grants, charitable funds, and patient assistance funds so that it is free to patients, he said, and could possibly be “housed in the National Psoriasis Foundation.”

Dr. Barbieri said he and his colleagues plan to design a clinical trial to test whether such a model can be adopted in practice and whether it can improve outcomes associated with CVD risk management.

In their editorial, Dr. Garshick and Dr. Berger, who is director of NYU Langone’s Center for the Prevention of Cardiovascular Disease, wrote that many patients with psoriatic disease have or are at risk for cardiometabolic conditions, and that CVD risk reduction should extend beyond lipid management to include blood pressure, glucose lowering, obesity management, and antiplatelet therapy.

The joint AAD-NPF guidelines for the management and treatment of psoriasis with awareness and attention to comorbidities, published in 2019, were among the first to formally recognize the enhanced CVD risk of patients with psoriasis, they noted.

The guidelines call upon dermatologists to inform patients of the psoriasis-CVD association and ensure their patients are engaged with their PCP or cardiologist for appropriate screening. Now, the editorialists say, “moving the needle forward includes refining and developing modifiable CVD risk reduction strategies for patients with psoriasis, and collaboration between the fields of dermatology, rheumatology, and cardiology is key.”

Incorporating a preventive cardiologist into combined dermatology-rheumatology clinics, or partnering as a freestanding cardioinflammatory clinic, also have potential to improve CVD risk, they wrote.

The survey study was supported by a grant from the NPF Psoriasis Prevention Initiative. Dr. Barbieri reported no conflicts of interest. Several authors disclosed consulting fees and grants from numerous pharmaceutical companies. Dr. Berger reported receiving personal fees from Janssen and grants from AstraZeneca outside of the submitted work. Dr. Garshick reported receiving personal fees from AbbVie outside of the submitted work.

A dermatologist-led model of cardiovascular disease (CVD) risk management for patients with psoriatic disease – in which dermatologists do more than refer patients to a primary care physician (PCP) or a cardiologist – may be feasible, given the positive perspectives expressed by both clinicians and patients in a set of electronic surveys, researchers say.

In an analysis of survey responses from 183 dermatologists and 322 patients, John S. Barbieri, MD, MBA, and coinvestigators found that more than two-thirds of dermatologists (69.3%) agreed it “seems doable” to check lipids and calculate a 10-year cardiovascular risk score, and over one-third (36.1%) agreed they could prescribe statins when indicated.

The patient survey was distributed through the National Psoriasis Foundation to individuals who were seeing a dermatologist or rheumatologist for psoriatic disease; the clinician survey was distributed through the American Academy of Dermatology to dermatologists who reported caring for patients with psoriasis. (A survey of rheumatologists was similarly conducted, but the number of participants fell short of the needed sample size.)

Most patients surveyed indicated they would be receptive to their dermatologist (or rheumatologist) playing a larger role in screening and managing CVD risk, and that they would be similarly likely to follow recommendations regarding risk screening and management whether the advice came their dermatologist/rheumatologist or from their PCP.

The clinician survey focused on lipids and statin use, and did not address other elements of risk management. Still, the researchers see their findings as an early but promising step in finding better models to improve cardiovascular outcomes for patients with psoriatic disease, who too often do not engage with their PCPs despite their increased risk of CVD and a higher risk of premature mortality from CVD.

Fewer than half of commercially insured adults aged under 65 years visit a PCP each year, the researchers noted. And among the patients in their survey, approximately 20% did not have a PCP or had not seen their PCP in the past year.

Other research has shown that only a small minority of patients with psoriasis have an encounter with their PCP within a year of establishing care with their dermatologist, and that “over half of patients with psoriasis have undetected risk factors like dyslipidemia or hypertension,” Dr. Barbieri, of the department of dermatology at Brigham and Women’s Hospital, Boston, said in an interview.

“There’s a gap here, a missing link in the chain of cardiovascular disease prevention,” he said. “What if the dermatologist or rheumatologist could be more engaged in [CV] risk protection? ... It’s the idea of meeting the patients where they are.”
 

The surveys

The clinician survey focused on statins because of their ease of use, efficacy and safety, and the need for minimal monitoring, Dr. Barbieri said in the interview. “On the spectrum of things you can do for cardiovascular disease prevention, it’s one of the easiest ones.”

NYU Langone

In an accompanying editorial, cardiologists Michael S. Garshick, MD, MS, and Jeffrey S. Berger, MD, MS, both of the department of medicine, New York University, wrote that, “despite the well-described association between psoriasis and CVD, only 35% of patients with psoriasis diagnosed with hyperlipidemia are adequately treated with statin therapy.”

“For many of these patients, their dermatologist or rheumatologist may be their only source of contact with the health care system,” they added.

Most studies targeting CVD risk in psoriasis have focused on targeting psoriatic inflammation, and few studies have explored strategies to improve modifiable CVD risk factor control with pharmacological therapy, they said.

NYU Langone

In addition to the questions about receptiveness to identifying and potentially treating CVD risk with statins, the dermatologist survey included a best-worst scaling choice experiment to assess preferences for implementation approaches. Dermatologists were asked to rank their preferences for eight implementation strategies that have been shown in published studies to help increase statin prescribing rates.

The three highest-ranked strategies among dermatologists were clinical decision support, physician educational outreach, and patient education materials. The lowest-ranked strategies were comparisons with peers, a pay-for-performance option, and a mobile app/texting service to remind patients to undergo CVD risk screening.

Of the 183 dermatologists in the survey, 28.4% were from academic settings, 11.5% were from multispecialty groups, and 45.4% were from dermatology groups. (A low response rate of 5.2% for dermatologists raises some questions about the generalizability of the findings, Dr. Garshick and Dr. Berger noted in their editorial.)
 

Where to go from here?

Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation, Irvine, Calif., who was not involved with the study, said that a larger role in CVD risk management is “not likely to find traction with everyday dermatologists.”

“It’s already a big ask for community dermatologists to go through the approval process to get biologics for patients, so I don’t think many would be willing to add more to their plate by taking a bigger role in CVD management,” he said in an interview. He generally has not prescribed statins, “as I don’t feel that is in my scope of work.”

In the interview, Dr. Barbieri said that a parallel qualitative study, not yet published, has looked at the facilitators and barriers – including time constraints and concern about scope of practice – to statin prescribing and other elements of cardiovascular risk reduction.

All told, he said, a centralized care coordinator model may be the best approach to engage the dermatologist more in CVD prevention, including lipid management, but to also “offload some of the management responsibility.”

In this model, which is partially described by Dr. Barbieri and colleagues, the dermatologist (or rheumatologist) would educate the patient, measure blood pressure and check a lipid panel, and refer the patient to a coordinator who would, in turn, collect more information and calculate a 10-year CVD risk score.

Using a protocol-driven clinical decision support approach, the care coordinator would provide counseling about diet, exercise, and smoking cessation, and about whether statin therapy or blood pressure management is indicated.

“That coordinator would be in a good position to help the patient work with their PCP, if they have one, to find a PCP if they don’t, or to use telemedicine or work with their dermatologist or rheumatologist,” Dr. Barbieri said.

The centralized care coordinator service could be funded through grants, charitable funds, and patient assistance funds so that it is free to patients, he said, and could possibly be “housed in the National Psoriasis Foundation.”

Dr. Barbieri said he and his colleagues plan to design a clinical trial to test whether such a model can be adopted in practice and whether it can improve outcomes associated with CVD risk management.

In their editorial, Dr. Garshick and Dr. Berger, who is director of NYU Langone’s Center for the Prevention of Cardiovascular Disease, wrote that many patients with psoriatic disease have or are at risk for cardiometabolic conditions, and that CVD risk reduction should extend beyond lipid management to include blood pressure, glucose lowering, obesity management, and antiplatelet therapy.

The joint AAD-NPF guidelines for the management and treatment of psoriasis with awareness and attention to comorbidities, published in 2019, were among the first to formally recognize the enhanced CVD risk of patients with psoriasis, they noted.

The guidelines call upon dermatologists to inform patients of the psoriasis-CVD association and ensure their patients are engaged with their PCP or cardiologist for appropriate screening. Now, the editorialists say, “moving the needle forward includes refining and developing modifiable CVD risk reduction strategies for patients with psoriasis, and collaboration between the fields of dermatology, rheumatology, and cardiology is key.”

Incorporating a preventive cardiologist into combined dermatology-rheumatology clinics, or partnering as a freestanding cardioinflammatory clinic, also have potential to improve CVD risk, they wrote.

The survey study was supported by a grant from the NPF Psoriasis Prevention Initiative. Dr. Barbieri reported no conflicts of interest. Several authors disclosed consulting fees and grants from numerous pharmaceutical companies. Dr. Berger reported receiving personal fees from Janssen and grants from AstraZeneca outside of the submitted work. Dr. Garshick reported receiving personal fees from AbbVie outside of the submitted work.

A dermatologist-led model of cardiovascular disease (CVD) risk management for patients with psoriatic disease – in which dermatologists do more than refer patients to a primary care physician (PCP) or a cardiologist – may be feasible, given the positive perspectives expressed by both clinicians and patients in a set of electronic surveys, researchers say.

In an analysis of survey responses from 183 dermatologists and 322 patients, John S. Barbieri, MD, MBA, and coinvestigators found that more than two-thirds of dermatologists (69.3%) agreed it “seems doable” to check lipids and calculate a 10-year cardiovascular risk score, and over one-third (36.1%) agreed they could prescribe statins when indicated.

The patient survey was distributed through the National Psoriasis Foundation to individuals who were seeing a dermatologist or rheumatologist for psoriatic disease; the clinician survey was distributed through the American Academy of Dermatology to dermatologists who reported caring for patients with psoriasis. (A survey of rheumatologists was similarly conducted, but the number of participants fell short of the needed sample size.)

Most patients surveyed indicated they would be receptive to their dermatologist (or rheumatologist) playing a larger role in screening and managing CVD risk, and that they would be similarly likely to follow recommendations regarding risk screening and management whether the advice came their dermatologist/rheumatologist or from their PCP.

The clinician survey focused on lipids and statin use, and did not address other elements of risk management. Still, the researchers see their findings as an early but promising step in finding better models to improve cardiovascular outcomes for patients with psoriatic disease, who too often do not engage with their PCPs despite their increased risk of CVD and a higher risk of premature mortality from CVD.

Fewer than half of commercially insured adults aged under 65 years visit a PCP each year, the researchers noted. And among the patients in their survey, approximately 20% did not have a PCP or had not seen their PCP in the past year.

Other research has shown that only a small minority of patients with psoriasis have an encounter with their PCP within a year of establishing care with their dermatologist, and that “over half of patients with psoriasis have undetected risk factors like dyslipidemia or hypertension,” Dr. Barbieri, of the department of dermatology at Brigham and Women’s Hospital, Boston, said in an interview.

“There’s a gap here, a missing link in the chain of cardiovascular disease prevention,” he said. “What if the dermatologist or rheumatologist could be more engaged in [CV] risk protection? ... It’s the idea of meeting the patients where they are.”
 

The surveys

The clinician survey focused on statins because of their ease of use, efficacy and safety, and the need for minimal monitoring, Dr. Barbieri said in the interview. “On the spectrum of things you can do for cardiovascular disease prevention, it’s one of the easiest ones.”

NYU Langone

In an accompanying editorial, cardiologists Michael S. Garshick, MD, MS, and Jeffrey S. Berger, MD, MS, both of the department of medicine, New York University, wrote that, “despite the well-described association between psoriasis and CVD, only 35% of patients with psoriasis diagnosed with hyperlipidemia are adequately treated with statin therapy.”

“For many of these patients, their dermatologist or rheumatologist may be their only source of contact with the health care system,” they added.

Most studies targeting CVD risk in psoriasis have focused on targeting psoriatic inflammation, and few studies have explored strategies to improve modifiable CVD risk factor control with pharmacological therapy, they said.

NYU Langone

In addition to the questions about receptiveness to identifying and potentially treating CVD risk with statins, the dermatologist survey included a best-worst scaling choice experiment to assess preferences for implementation approaches. Dermatologists were asked to rank their preferences for eight implementation strategies that have been shown in published studies to help increase statin prescribing rates.

The three highest-ranked strategies among dermatologists were clinical decision support, physician educational outreach, and patient education materials. The lowest-ranked strategies were comparisons with peers, a pay-for-performance option, and a mobile app/texting service to remind patients to undergo CVD risk screening.

Of the 183 dermatologists in the survey, 28.4% were from academic settings, 11.5% were from multispecialty groups, and 45.4% were from dermatology groups. (A low response rate of 5.2% for dermatologists raises some questions about the generalizability of the findings, Dr. Garshick and Dr. Berger noted in their editorial.)
 

Where to go from here?

Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation, Irvine, Calif., who was not involved with the study, said that a larger role in CVD risk management is “not likely to find traction with everyday dermatologists.”

“It’s already a big ask for community dermatologists to go through the approval process to get biologics for patients, so I don’t think many would be willing to add more to their plate by taking a bigger role in CVD management,” he said in an interview. He generally has not prescribed statins, “as I don’t feel that is in my scope of work.”

In the interview, Dr. Barbieri said that a parallel qualitative study, not yet published, has looked at the facilitators and barriers – including time constraints and concern about scope of practice – to statin prescribing and other elements of cardiovascular risk reduction.

All told, he said, a centralized care coordinator model may be the best approach to engage the dermatologist more in CVD prevention, including lipid management, but to also “offload some of the management responsibility.”

In this model, which is partially described by Dr. Barbieri and colleagues, the dermatologist (or rheumatologist) would educate the patient, measure blood pressure and check a lipid panel, and refer the patient to a coordinator who would, in turn, collect more information and calculate a 10-year CVD risk score.

Using a protocol-driven clinical decision support approach, the care coordinator would provide counseling about diet, exercise, and smoking cessation, and about whether statin therapy or blood pressure management is indicated.

“That coordinator would be in a good position to help the patient work with their PCP, if they have one, to find a PCP if they don’t, or to use telemedicine or work with their dermatologist or rheumatologist,” Dr. Barbieri said.

The centralized care coordinator service could be funded through grants, charitable funds, and patient assistance funds so that it is free to patients, he said, and could possibly be “housed in the National Psoriasis Foundation.”

Dr. Barbieri said he and his colleagues plan to design a clinical trial to test whether such a model can be adopted in practice and whether it can improve outcomes associated with CVD risk management.

In their editorial, Dr. Garshick and Dr. Berger, who is director of NYU Langone’s Center for the Prevention of Cardiovascular Disease, wrote that many patients with psoriatic disease have or are at risk for cardiometabolic conditions, and that CVD risk reduction should extend beyond lipid management to include blood pressure, glucose lowering, obesity management, and antiplatelet therapy.

The joint AAD-NPF guidelines for the management and treatment of psoriasis with awareness and attention to comorbidities, published in 2019, were among the first to formally recognize the enhanced CVD risk of patients with psoriasis, they noted.

The guidelines call upon dermatologists to inform patients of the psoriasis-CVD association and ensure their patients are engaged with their PCP or cardiologist for appropriate screening. Now, the editorialists say, “moving the needle forward includes refining and developing modifiable CVD risk reduction strategies for patients with psoriasis, and collaboration between the fields of dermatology, rheumatology, and cardiology is key.”

Incorporating a preventive cardiologist into combined dermatology-rheumatology clinics, or partnering as a freestanding cardioinflammatory clinic, also have potential to improve CVD risk, they wrote.

The survey study was supported by a grant from the NPF Psoriasis Prevention Initiative. Dr. Barbieri reported no conflicts of interest. Several authors disclosed consulting fees and grants from numerous pharmaceutical companies. Dr. Berger reported receiving personal fees from Janssen and grants from AstraZeneca outside of the submitted work. Dr. Garshick reported receiving personal fees from AbbVie outside of the submitted work.

The Food and Drug Administration on Jan. 21 approved risankizumab-rzaa (Skyrizi) for a second indication – treating adults with active psoriatic arthritis (PsA) – making it the second anti–interleukin-23 monoclonal antibody available to treat PsA, according to an announcement from manufacturer AbbVie.

The agency previously approved risankizumab in April 2019 for adults with moderate to severe plaque psoriasis.

The dosing regimen for PsA is the same as it is for patients with moderate to severe plaque psoriasis: a single 150-mg subcutaneous injection four times a year (after two starter doses at weeks 0 and 4), and it can be administered alone or in combination with disease-modifying antirheumatic drugs (DMARDs).

Two phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2, were the basis for the approval. These two trials tested the biologic agent in adults with active PsA, including those who had responded inadequately or were intolerant to biologic therapy and/or nonbiologic DMARDs. Fulfillment of the trials’ primary endpoint of at least a 20% improvement in American College of Rheumatology response criteria at 24 weeks occurred in 51.3%-57.3% of patients, compared with 26.5%-33.5% of placebo-treated patients.

Those on risankizumab also achieved significantly higher rates of ACR50 and ACR70 responses than those on placebo. In addition, patients with preexisting dactylitis and enthesitis experienced improvements in these PsA manifestations. Risankizumab was also associated with an improvement in physical function at 24 weeks on the Health Assessment Questionnaire–Disability Index, bettering placebo by a mean difference of 0.16-0.20 points in the two trials. A significantly higher percentage of patients who had psoriatic skin lesions experienced at least 90% improvement with risankizumab on the Psoriasis Area and Severity Index, compared with placebo.

AbbVie said that the safety profile of risankizumab in patients with PsA has been generally consistent with its effects in patients with plaque psoriasis.

The KEEPsAKE 1 and KEEPsAKE 2 studies are ongoing, and patients in the long-term extensions of the trials remain blinded to the original randomized allocation for the duration of the studies.

Phase 3 trials of risankizumab are also ongoing in patients with Crohn’s disease and ulcerative colitis.

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

The Food and Drug Administration on Jan. 21 approved risankizumab-rzaa (Skyrizi) for a second indication – treating adults with active psoriatic arthritis (PsA) – making it the second anti–interleukin-23 monoclonal antibody available to treat PsA, according to an announcement from manufacturer AbbVie.

The agency previously approved risankizumab in April 2019 for adults with moderate to severe plaque psoriasis.

The dosing regimen for PsA is the same as it is for patients with moderate to severe plaque psoriasis: a single 150-mg subcutaneous injection four times a year (after two starter doses at weeks 0 and 4), and it can be administered alone or in combination with disease-modifying antirheumatic drugs (DMARDs).

Two phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2, were the basis for the approval. These two trials tested the biologic agent in adults with active PsA, including those who had responded inadequately or were intolerant to biologic therapy and/or nonbiologic DMARDs. Fulfillment of the trials’ primary endpoint of at least a 20% improvement in American College of Rheumatology response criteria at 24 weeks occurred in 51.3%-57.3% of patients, compared with 26.5%-33.5% of placebo-treated patients.

Those on risankizumab also achieved significantly higher rates of ACR50 and ACR70 responses than those on placebo. In addition, patients with preexisting dactylitis and enthesitis experienced improvements in these PsA manifestations. Risankizumab was also associated with an improvement in physical function at 24 weeks on the Health Assessment Questionnaire–Disability Index, bettering placebo by a mean difference of 0.16-0.20 points in the two trials. A significantly higher percentage of patients who had psoriatic skin lesions experienced at least 90% improvement with risankizumab on the Psoriasis Area and Severity Index, compared with placebo.

AbbVie said that the safety profile of risankizumab in patients with PsA has been generally consistent with its effects in patients with plaque psoriasis.

The KEEPsAKE 1 and KEEPsAKE 2 studies are ongoing, and patients in the long-term extensions of the trials remain blinded to the original randomized allocation for the duration of the studies.

Phase 3 trials of risankizumab are also ongoing in patients with Crohn’s disease and ulcerative colitis.

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

The Food and Drug Administration on Jan. 21 approved risankizumab-rzaa (Skyrizi) for a second indication – treating adults with active psoriatic arthritis (PsA) – making it the second anti–interleukin-23 monoclonal antibody available to treat PsA, according to an announcement from manufacturer AbbVie.

The agency previously approved risankizumab in April 2019 for adults with moderate to severe plaque psoriasis.

The dosing regimen for PsA is the same as it is for patients with moderate to severe plaque psoriasis: a single 150-mg subcutaneous injection four times a year (after two starter doses at weeks 0 and 4), and it can be administered alone or in combination with disease-modifying antirheumatic drugs (DMARDs).

Two phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2, were the basis for the approval. These two trials tested the biologic agent in adults with active PsA, including those who had responded inadequately or were intolerant to biologic therapy and/or nonbiologic DMARDs. Fulfillment of the trials’ primary endpoint of at least a 20% improvement in American College of Rheumatology response criteria at 24 weeks occurred in 51.3%-57.3% of patients, compared with 26.5%-33.5% of placebo-treated patients.

Those on risankizumab also achieved significantly higher rates of ACR50 and ACR70 responses than those on placebo. In addition, patients with preexisting dactylitis and enthesitis experienced improvements in these PsA manifestations. Risankizumab was also associated with an improvement in physical function at 24 weeks on the Health Assessment Questionnaire–Disability Index, bettering placebo by a mean difference of 0.16-0.20 points in the two trials. A significantly higher percentage of patients who had psoriatic skin lesions experienced at least 90% improvement with risankizumab on the Psoriasis Area and Severity Index, compared with placebo.

AbbVie said that the safety profile of risankizumab in patients with PsA has been generally consistent with its effects in patients with plaque psoriasis.

The KEEPsAKE 1 and KEEPsAKE 2 studies are ongoing, and patients in the long-term extensions of the trials remain blinded to the original randomized allocation for the duration of the studies.

Phase 3 trials of risankizumab are also ongoing in patients with Crohn’s disease and ulcerative colitis.

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

Identifying risk factors associated with transition from cutaneous psoriasis to arthritic psoriasis remains a hot area of research. In a retrospective nested case-control study using the resources of the Rochester Epidemiology Project, Karmacharya et al¹ identified 164 patients with incident PsA between 2000 and 2017. Among the 158 total patients satisfying study criteria, 64 (41%) had concurrent psoriasis and PsA and 94 (59%) had onset of psoriasis before PsA. The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA. Early onset as well as severe psoriasis is associated with the HLA- C*06 allele as is longer psoriasis-PsA latency. Although not evaluated in this study, this genetic factor, or other factors such as detection bias, may underly these observations.

Once diagnosed, stratification of PsA severity is important for planning treatment. Towards this goal, Dubash et al² demonstrated that the presence of dactylitis indicates a more severe PsA phenotype. In a study of 177 disease-modifying antirheumatic drug (DMARD)-naive patients with early PsA, they found that those with dactylitis (46%) had significantly higher tender and swollen joint counts and C-reactive protein than those with non-dactylitic PsA. Ultrasound synovitis and erosions were also significantly more prevalent in dactylitic PsA. Thus, the presence of dactylitis indicates a more severe phenotype, and patients with dactylitis should be treated aggressively to improve long-term outcomes.

Novel therapies are being frequently evaluated in PsA and a recent target is interleukin (IL)-23, a key cytokine in the T-helper 17 (Th17) pathway and in the pathogenesis of psoriatic disease. Risankizumab is a novel monoclonal antibody targeting IL-23. In the double-blind phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to one or more conventional synthetic (cs) DMARDs. They were randomly assigned to receive 150 mg risankizumab or placebo, Kristensen et al³ demonstrated that, at week 24, at least a 20% improvement in the American College of Rheumatology score (ACR20) was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent adverse events were mild-to-moderate and reported at similar frequencies in the risankizumab (40.4%) and placebo (38.7%) groups. Thus, risankizumab was efficacious in reducing clinical manifestations of PsA in patients with inadequate response to csDMARDs with no new adverse events. An important question when treating patients with PsA with targeted therapies is the need for concomitant therapy with csDMARDs. In a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2,  1,916 patients with active PsA with an inadequate response to ≥1 non-biologic (nb) DMARDs or biologic DMARDs were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks, Nash et al⁴ demonstrated that at week 12, ACR20 response was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI 24.4%-43.1%; 30 mg: 45.7%; 95% CI 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI 27.9%-40.1%; 30 mg: 39.6%; 95% CI 33.7%-45.5%). Adverse events were generally similar between monotherapy and combination therapy. Although, we don’t have information regarding the sustainability of the response, these data indicate that upadacitinib may be used without concomitant csDMARDs in PsA.

References

1. Karmacharya P et al. Time to transition from psoriasis to psoriatic arthritis: A population-based study. Semin Arthritis Rheum. 2021(Dec 31):S0049-0172(21)00230-4.
2. Dubash S et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis. 2021(Dec 10):annrheumdis-2021-220964.
3. Kristensen LE et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022(Feb);81(2):225-231.
4. Nash P et al. Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Rheumatology (Oxford). 2021(Dec 3):keab905.

Identifying risk factors associated with transition from cutaneous psoriasis to arthritic psoriasis remains a hot area of research. In a retrospective nested case-control study using the resources of the Rochester Epidemiology Project, Karmacharya et al¹ identified 164 patients with incident PsA between 2000 and 2017. Among the 158 total patients satisfying study criteria, 64 (41%) had concurrent psoriasis and PsA and 94 (59%) had onset of psoriasis before PsA. The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA. Early onset as well as severe psoriasis is associated with the HLA- C*06 allele as is longer psoriasis-PsA latency. Although not evaluated in this study, this genetic factor, or other factors such as detection bias, may underly these observations.

Once diagnosed, stratification of PsA severity is important for planning treatment. Towards this goal, Dubash et al² demonstrated that the presence of dactylitis indicates a more severe PsA phenotype. In a study of 177 disease-modifying antirheumatic drug (DMARD)-naive patients with early PsA, they found that those with dactylitis (46%) had significantly higher tender and swollen joint counts and C-reactive protein than those with non-dactylitic PsA. Ultrasound synovitis and erosions were also significantly more prevalent in dactylitic PsA. Thus, the presence of dactylitis indicates a more severe phenotype, and patients with dactylitis should be treated aggressively to improve long-term outcomes.

Novel therapies are being frequently evaluated in PsA and a recent target is interleukin (IL)-23, a key cytokine in the T-helper 17 (Th17) pathway and in the pathogenesis of psoriatic disease. Risankizumab is a novel monoclonal antibody targeting IL-23. In the double-blind phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to one or more conventional synthetic (cs) DMARDs. They were randomly assigned to receive 150 mg risankizumab or placebo, Kristensen et al³ demonstrated that, at week 24, at least a 20% improvement in the American College of Rheumatology score (ACR20) was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent adverse events were mild-to-moderate and reported at similar frequencies in the risankizumab (40.4%) and placebo (38.7%) groups. Thus, risankizumab was efficacious in reducing clinical manifestations of PsA in patients with inadequate response to csDMARDs with no new adverse events. An important question when treating patients with PsA with targeted therapies is the need for concomitant therapy with csDMARDs. In a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2,  1,916 patients with active PsA with an inadequate response to ≥1 non-biologic (nb) DMARDs or biologic DMARDs were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks, Nash et al⁴ demonstrated that at week 12, ACR20 response was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI 24.4%-43.1%; 30 mg: 45.7%; 95% CI 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI 27.9%-40.1%; 30 mg: 39.6%; 95% CI 33.7%-45.5%). Adverse events were generally similar between monotherapy and combination therapy. Although, we don’t have information regarding the sustainability of the response, these data indicate that upadacitinib may be used without concomitant csDMARDs in PsA.

References

1. Karmacharya P et al. Time to transition from psoriasis to psoriatic arthritis: A population-based study. Semin Arthritis Rheum. 2021(Dec 31):S0049-0172(21)00230-4.
2. Dubash S et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis. 2021(Dec 10):annrheumdis-2021-220964.
3. Kristensen LE et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022(Feb);81(2):225-231.
4. Nash P et al. Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Rheumatology (Oxford). 2021(Dec 3):keab905.

Identifying risk factors associated with transition from cutaneous psoriasis to arthritic psoriasis remains a hot area of research. In a retrospective nested case-control study using the resources of the Rochester Epidemiology Project, Karmacharya et al¹ identified 164 patients with incident PsA between 2000 and 2017. Among the 158 total patients satisfying study criteria, 64 (41%) had concurrent psoriasis and PsA and 94 (59%) had onset of psoriasis before PsA. The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA. Early onset as well as severe psoriasis is associated with the HLA- C*06 allele as is longer psoriasis-PsA latency. Although not evaluated in this study, this genetic factor, or other factors such as detection bias, may underly these observations.

Once diagnosed, stratification of PsA severity is important for planning treatment. Towards this goal, Dubash et al² demonstrated that the presence of dactylitis indicates a more severe PsA phenotype. In a study of 177 disease-modifying antirheumatic drug (DMARD)-naive patients with early PsA, they found that those with dactylitis (46%) had significantly higher tender and swollen joint counts and C-reactive protein than those with non-dactylitic PsA. Ultrasound synovitis and erosions were also significantly more prevalent in dactylitic PsA. Thus, the presence of dactylitis indicates a more severe phenotype, and patients with dactylitis should be treated aggressively to improve long-term outcomes.

Novel therapies are being frequently evaluated in PsA and a recent target is interleukin (IL)-23, a key cytokine in the T-helper 17 (Th17) pathway and in the pathogenesis of psoriatic disease. Risankizumab is a novel monoclonal antibody targeting IL-23. In the double-blind phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to one or more conventional synthetic (cs) DMARDs. They were randomly assigned to receive 150 mg risankizumab or placebo, Kristensen et al³ demonstrated that, at week 24, at least a 20% improvement in the American College of Rheumatology score (ACR20) was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent adverse events were mild-to-moderate and reported at similar frequencies in the risankizumab (40.4%) and placebo (38.7%) groups. Thus, risankizumab was efficacious in reducing clinical manifestations of PsA in patients with inadequate response to csDMARDs with no new adverse events. An important question when treating patients with PsA with targeted therapies is the need for concomitant therapy with csDMARDs. In a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2,  1,916 patients with active PsA with an inadequate response to ≥1 non-biologic (nb) DMARDs or biologic DMARDs were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks, Nash et al⁴ demonstrated that at week 12, ACR20 response was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI 24.4%-43.1%; 30 mg: 45.7%; 95% CI 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI 27.9%-40.1%; 30 mg: 39.6%; 95% CI 33.7%-45.5%). Adverse events were generally similar between monotherapy and combination therapy. Although, we don’t have information regarding the sustainability of the response, these data indicate that upadacitinib may be used without concomitant csDMARDs in PsA.

References

1. Karmacharya P et al. Time to transition from psoriasis to psoriatic arthritis: A population-based study. Semin Arthritis Rheum. 2021(Dec 31):S0049-0172(21)00230-4.
2. Dubash S et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis. 2021(Dec 10):annrheumdis-2021-220964.
3. Kristensen LE et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022(Feb);81(2):225-231.
4. Nash P et al. Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Rheumatology (Oxford). 2021(Dec 3):keab905.