Expression of IL-4 in Tumors: A Safety Surrogate to Predict Cancer Survival Associated With Biologic Therapies.

Interleukin (IL)-4-targeted therapies have revolutionized management of inflammatory dermatoses.

Bimekizumab Safety in Patients With Moderate to Severe Plaque Psoriasis: Pooled Results From Phase 2 and Phase 3 Randomized Clinical Trials.

Importance: Psoriasis is a chronic disease requiring long-term management; understanding the long-term safety profiles of psoriasis treatments, such as bimekizumab, is important. Objective: To evaluate the 2-year safety profile of bimekizumab in patients with moderate to severe plaque psoriasis. Design, Setting, and Participants: Safety data were pooled from a cohort of patients from 4 phase 2 randomized clinical trials (BE ABLE 1, BE ABLE 2, PS0016, and PS0018) and 4 phase 3 randomized clinical trials (BE VIVID, BE READY, BE SURE, and BE BRIGHT) to include 2 years of study treatment. Data were obtained on adults with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index level ≥12, ≥10% body surface area affected by psoriasis, and an Investigator's Global Assessment score ≥3 on a 5-point scale) who were eligible for systemic psoriasis therapy and/or phototherapy. Interventions: Included patients received 1 or more doses of bimekizumab during the phase 2 or phase 3 trials. Main Outcomes and Measures: Treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation are reported using exposure-adjusted incidence rates (EAIRs) per 100 person-years. Results: A total of 1789 patients (1252 [70.0%] men; mean [SD] age, 45.2 [13.5] years) were treated with 1 or more doses of bimekizumab across the phase 2/3 trials and were included in these analyses; total bimekizumab exposure was 3109.7 person-years. TEAEs occurred at an EAIR of 202.4 per 100 person-years and did not increase with longer duration of bimekizumab exposure. The 3 most frequently reported TEAEs were nasopharyngitis (19.1 per 100 person-years; 95% CI, 17.4-20.9 per 100 person-years), oral candidiasis (12.6 per 100 person-years; 95% CI, 11.3-14.0 per 100 person-years), and upper respiratory tract infection (8.9 per 100 person-years; 95% CI, 7.8-10.1 per 100 person-years). Most oral candidiasis events were mild or moderate; 3 events led to discontinuation. The EAIRs of inflammatory bowel disease (0.1 per 100 person-years; 95% CI, 0.0-0.3 per 100 person-years), adjudicated suicidal ideation and behavior (0.0 per 100 person-years; 95% CI, 0.0-0.2 per 100 person-years), and adjudicated major adverse cardiac events (0.5 per 100 person-years; 95% CI, 0.3-0.8 per 100 person-years) were low. Conclusions and Relevance: In these pooled analyses of data from a cohort of patients from 8 randomized clinical trials, bimekizumab was well tolerated aside from an increased incidence of mild to moderate oral candidiasis. No safety signals were observed compared with previous reports, and there was no increased risk of AEs with longer duration of bimekizumab exposure.

Predictors of nonresponse to dupilumab in patients with atopic dermatitis: A machine learning analysis.

BACKGROUND: Many patients with atopic dermatitis (AD) have a suboptimal response to systemic therapy. OBJECTIVE: This study assessed predictors of nonresponse to dupilumab in patients with AD. METHODS: Data (April 2017 through June 2019) for patients aged 12 years and above with AD (International Classification of Diseases-9/10-Clinical Modification: 691.8/L20.x) who initiated dupilumab on or after April 1, 2017 (index date) were collected from an electronic health record and insurance claims database. Nonresponse indicators (dupilumab discontinuation, addition of another systemic therapy or phototherapy, addition of a high-potency topical corticosteroid, AD-related hospital visit, AD-related emergency department visit, incident skin infection) were predicted from available demographic and clinical variables using machine learning. RESULTS: Among 419 patients (mean age: 45 years), 145 (35%) experienced at least 1 indicator of nonresponse in the 6-month postindex period. In patients with at least 1 indicator, the most common was dupilumab discontinuation (47% [68/145]). Of note, this analysis could not capture nonmedical reasons for dupilumab discontinuation (eg, cost, access). The most common predictors of nonresponse were a claim for ibuprofen (in 69% of patients with a nonresponse indicator) and a Quan-Charlson Comorbidity Index value of 3 to 4 (59%). CONCLUSION: Systemic dupilumab therapy for AD can be associated with a relatively high prevalence of nonresponse indicators. Factors associated with these indicators-that is, predictors of nonresponse-may be used to optimize disease management.

Does biologic therapy impact the development of PsA among patients with psoriasis?

OBJECTIVE: To examine the association of biologic therapy use for psoriasis with incident psoriatic arthritis (PsA) diagnosis. METHODS: A retrospective cohort study was conducted in the OptumInsights Electronic Health Record Database between 2006 and 2017 among patients with psoriasis between the ages of 16 and 90 initiating a therapy for psoriasis (oral, biologic or phototherapy). The incidence of PsA was calculated within each therapy group. Multivariable Cox models were used to calculate the HR for biologic versus oral or phototherapy using biologics as a time-varying exposure and next in a propensity score-matched cohort. RESULTS: Among 1 93 709 patients with psoriasis without PsA, 14 569 biologic and 20 321 cumulative oral therapy and phototherapy initiations were identified. Mean age was lower among biologic initiators compared with oral/phototherapy initiators (45.9 vs 49.8). The incidence of PsA regardless of therapy exposure was 9.75 per 1000 person-years compared with 77.26 among biologic users, 61.99 among oral therapy users, 26.11 among phototherapy users and 5.85 among those without a prescription for one of the target therapies. Using a multivariable adjustment approach with time-varying exposure, adjusted HR (95% CI) for biologic users was 4.48 (4.23 to 4.75) compared with oral or phototherapy users. After propensity score matching, the HR (95% CI) was 2.14 (2.00 to 2.28). CONCLUSIONS: In this retrospective cohort study, biologic use was associated with the development of PsA among patients with psoriasis. This may be related to confounding by indication and protopathic bias. Prospective studies are needed to address this important question.

Efficacy of ixekizumab in patients with moderate-to-severe plaque psoriasis and prediabetes or type 2 diabetes.

Objective: Patients with psoriasis have an increased prevalence of type 2 diabetes when compared to the general population. Research suggests that type 2 diabetes (T2D) as well as obesity may have an impact on patients' response to treatment. This post-hoc analysis reports the efficacy of ixekizumab in treating moderate-to-severe psoriasis in patients with prediabetes or T2D. Method and materials: UNCOVER-1, UNCOVER-2, and UNCOVER-3 were three Phase 3, multicenter, randomized, double-blind, placebo-controlled trials that evaluated the efficacy and safety of ixekizumab in adult patients with moderate-to-severe psoriasis. Patients were aged ≥18 years with chronic moderate-to-severe psoriasis (defined as ≥10% body surface area affected, static Physician Global Assessment ≥3, and Psoriasis Area and Severity Index [PASI] ≥12 at screening and baseline) who were candidates for phototherapy or systemic therapy. UNCOVER-1, UNCOVER-2, and UNCOVER-3 participants received ixekizumab as per label (that is, an initial dose of two subcutaneous injections [160 mg in total] at Week 0, followed by 80 mg every 2 weeks through Week 12 and 80 mg every 4 weeks thereafter through Week 60). Results: The proportions of patients with prediabetes, T2D and normoglycemia that achieved PASI75, PASI90, and PASI100 at Week 60 were similar. Results suggest that patients with T2D were slower to achieve PASI100 than patients with prediabetes or those with normoglycemia. Ixekizumab had no effect on any metabolic markers in patients receiving the treatment. Conclusions: Despite the higher rate of obesity and extreme obesity in patients with prediabetes and T2D, ixekizumab was an efficacious treatment in treating patients with psoriasis.

Consensus terminology for preclinical phases of psoriatic arthritis for use in research studies: results from a Delphi consensus study.

The concept of psoriatic arthritis (PsA) prevention is gaining increased interest owing to the physical limitation, poor quality of life and low remission rates that are achieved with current therapies for PsA. The psoriasis-to-PsA transition offers a unique opportunity to identify individuals at increased risk of developing PsA and to implement preventive strategies. However, identifying individuals at increased risk of developing PsA is challenging as there is no consensus on how this population should be defined. This Consensus Statement puts forward recommended terminology from the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) for defining specific subgroups of individuals during the preclinical and early clinical phases of PsA to be used in research studies. Following a three-round Delphi process, consensus was reached for three terms and definitions: 'increased risk for PsA', 'psoriasis with asymptomatic synovio-entheseal imaging abnormalities' and 'psoriasis with musculoskeletal symptoms not explained by other diagnosis'. These terms and their definitions will enable improved identification and standardization of study populations in clinical research. In the future, as increasing evidence emerges regarding the molecular and clinical features of the psoriasis-to-PsA continuum, these terms and definitions will be further refined and updated.

Comparative safety of systemic immunomodulatory medications in adults with atopic dermatitis.

BACKGROUND: Severe atopic dermatitis (AD) is increasingly treated with systemic immunomodulatory drugs, yet their safety is unclear. OBJECTIVE: We evaluated the comparative risk of serious bacterial and opportunistic infections among patients with severe AD using systemic immunomodulatory medications in routine care. METHODS: In a population-based claims data study, we identified adult patients with AD who were treated with systemic drugs. The incidence of serious bacterial and opportunistic infections leading to hospitalization was computed by using International Classification of Disease diagnosis codes. Relative risks (RRs) were computed after 1-to-1 propensity score matching. RESULTS: Up to 232,611 patients with AD were eligible. The incidence of serious infections was 7.53 (7.18-7.89) risk per 1,000 patients among systemic nonbiologic-treated patients, 7.38 (5.68-9.57) risk per 1,000 patients among phototherapy-treated patients, and 2.6 (0.45-14.3) risk per 1,000 patients among dupilumab users. After matching, cyclosporine had a significantly reduced 6-month risk (RR 0.87) and prednisone (RR 1.78), azathioprine (RR 1.89), and mycophenolate (RR 3.31) showed increased risks compared with methotrexate. A small number of dupilumab users showed no increased risk (RR 0.33, 95% confidence interval 0.03-3.20). LIMITATIONS: Some comparisons involved small population sizes. CONCLUSION: In this population-based study of adult AD patients, cyclosporine and methotrexate have the lowest 6-month risks of serious infections. Increased risks were observed for prednisone, azathioprine, and mycophenolate relative to methotrexate.

Serious infection risk in children with psoriasis on systemic treatment: A propensity score-matched population-based study.

BACKGROUND: Psoriasis is increasingly treated with systemic medications, yet their safety is not well characterized in children. OBJECTIVE: We sought to estimate the 6-month risk of serious infections in children with psoriasis treated with biologics, systemic nonbiologics, and phototherapy. METHODS: Using insurance claims data, we identified children aged <18 years with psoriasis and compared the frequency of serious infections in those initiating biologics, systemic nonbiologics, and phototherapy. Relative risks were estimated before and after 1:1 propensity score matching. RESULTS: Among 57,323 children with psoriasis, the 6-month risk of infection was 4.2 per 1000 patient-years in 722 biologic initiators, 5.1 in 988 systemic nonbiologic initiators, and 1.1 in 2657 phototherapy initiators. The relative risk (95% confidence interval) of infection in biologics vs nonbiologics was 0.67 (0.11-3.98), in biologics vs phototherapy was 1.50 (0.25-8.95), and in nonbiologics vs phototherapy was 5.00 (0.59-42.71). The background risk of infection in children with psoriasis was 1 per 1000, almost double the risk compared with children without psoriasis (relative risk, 1.84; 95% confidence interval, 1.15-1.97). CONCLUSIONS: We found no meaningful difference in infection risk between biologics vs nonbiologics and no robust difference between systemic users vs phototherapy. Independent of treatment, children with psoriasis had a higher risk of infection than those without psoriasis.

Treatment of Medicare Patients with Moderate-to-Severe Psoriasis who Cannot Afford Biologics or Apremilast.

Elderly patients are a group with a high frequency of psoriasis. Their disease burden has negative impacts on their quality of life. While there is a clear need to treat these patients, there are challenges in doing so. This work seeks to define the challenges that exist in treating elderly Medicare patients, as well as to provide treatment suggestions for providers to follow if they encounter one or more of these challenges. Providers face the following challenges when creating treatment plants for elderly patients with psoriasis: difficulty in obtaining drug coverage through Medicare, increased medical comorbidities, and polypharmacy. Providers aim for regimens that are affordable, safe, and efficacious, but it is not always clear how to achieve this combination, especially in elderly Medicare patients. This work is relevant in that it aims to explain the logistical roadblocks posed by Medicare coverage and provide solutions for commonly encountered issues in the treatment of a disabling and common disease in a high-risk population. Specifically, alternative treatment options to biologics and small-molecule inhibitors are discussed and include topical therapies, phototherapy, methotrexate, acitretin, and cyclosporine and for psoriatic arthritis include corticosteroids and leflunomide. The specific risks and benefits of these therapies in the elderly population are provided, allowing providers to make patient-specific decisions about optimal regimens.

Bridging the Gaps in the Care of Psoriasis and Psoriatic Arthritis: the Role of Combined Clinics.

PURPOSE OF REVIEW: Despite a robust therapeutic landscape, significant gaps exist in the quality of care of psoriatic disease. Thus, an improved understanding of the challenges in providing quality care and the implementation of effective strategies to overcome them is needed. In this review, we summarize the burden of psoriatic disease, discuss the challenges in the care of psoriatic patients, and outline how combined dermatology-rheumatology clinics bridge many of these gaps. RECENT FINDINGS: Multiple challenges are faced in providing high-quality care to patients with psoriasis and psoriatic arthritis from the pre-diagnosis phase of disease to the follow-up period. Challenges are mainly driven by lack of education of patients and healthcare providers, inefficient communication between specialists, lack of a holistic approach to patients, and limitations of available therapies. The Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) is working on demonstrating the effectiveness of combined dermatology-rheumatology clinics in addressing some of these challenges. Recent findings show that combined clinic models may improve quality of care by raising awareness of psoriatic disease, fostering educational activities for both patients and physicians, and allowing for comprehensive evaluation and management of patients through improved communications between disciplines. Psoriasis and psoriatic arthritis are complex diseases that often require an interdisciplinary approach. Thus, combined dermatology-rheumatology clinics and local-regional partnerships are potentially effective in improving quality of care in psoriatic disease.

Dietary Recommendations for Adults With Psoriasis or Psoriatic Arthritis From the Medical Board of the National Psoriasis Foundation: A Systematic Review.

Importance: Psoriasis is a chronic, inflammatory skin disease and has significant associated morbidity and effect on quality of life. It is important to determine whether dietary interventions help reduce disease severity in patients with psoriatic diseases. Objective: To make evidence-based dietary recommendations for adults with psoriasis and/or psoriatic arthritis from the Medical Board of the National Psoriasis Foundation. Evidence Review: We used literature from prior systematic reviews as well as additional primary literature from the MEDLINE database from January 1, 2014, to August 31, 2017, that evaluated the impact of diet on psoriasis. We included observational and interventional studies of patients with psoriasis or psoriatic arthritis. The quality of included studies was assessed using the Newcastle-Ottawa scale for observational studies and the Cochrane Risk of Bias Tool for interventional studies. We made evidence-based dietary recommendations, which were voted on by the National Psoriasis Foundation Medical Board. Findings: We identified 55 studies meeting the inclusion criteria for this review. These studies represent 77 557 unique participants of which 4534 have psoriasis. Based on the literature, we strongly recommend dietary weight reduction with a hypocaloric diet in overweight and obese patients with psoriasis. We weakly recommend a gluten-free diet only in patients who test positive for serologic markers of gluten sensitivity. Based on low-quality data, select foods, nutrients, and dietary patterns may affect psoriasis. For patients with psoriatic arthritis, we weakly recommend vitamin D supplementation and dietary weight reduction with a hypocaloric diet in overweight and obese patients. Dietary interventions should always be used in conjunction with standard medical therapies for psoriasis and psoriatic arthritis. Conclusions and Relevance: Adults with psoriasis and/or psoriatic arthritis can supplement their standard medical therapies with dietary interventions to reduce disease severity. These dietary recommendations from the National Psoriasis Foundation Medical Board will help guide clinicians regarding the utility of dietary interventions in adults with psoriatic diseases.

Skin Signs of Rheumatoid Arthritis and its Therapy-Induced Cutaneous Side Effects.

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that primarily affects the joints, but may exhibit extra-articular, including cutaneous, manifestations such as rheumatoid nodules, rheumatoid vasculitis, granulomatous skin disorders, and neutrophilic dermatoses. A large burden of cutaneous disease may be an indication of RA disease activity and the need for more aggressive treatment. Many of the therapeutic agents used to treat RA can also result in cutaneous adverse effects, which pose their own diagnostic and therapeutic challenges. Anti-TNFα agents, in particular, have a wide variety of adverse effects including psoraisiform eruptions, granulomatous conditions, and cutaneous connective tissue disorders. Herein we provide an update on the clinical presentations and management of RA-associated cutaneous findings as well as drug-induced cutaneous effects, with particular attention to the adverse effects of biologic disease-modifying agents.

Psoriasis, psoriatic arthritis and risk of gout in US men and women.

BACKGROUND AND OBJECTIVE: Individuals with psoriasis have increased blood levels of uric acid. However, there is no prospective data on the association between psoriasis and uric acid levels and subsequent development of gout. In this study, we examined the risk of gout among individuals with psoriasis and psoriatic arthritis (PsA) in two cohorts of men and women, the Health Professionals Follow-up Study (HPFS) (1986-2010) and Nurses' Health Study (NHS) (1998-2010). METHODS: 27 751 men and 71 059 women were included in the analysis. Lifetime history of physician-diagnosed incident psoriasis and PsA was confirmed by validated supplementary questionnaires. Incident gout diagnoses were confirmed based on the American College of Rheumatology survey criteria. We used Cox proportional hazards models controlling for potential risk factors to calculate the HRs with 95% CIs of incident gout while simultaneously adjusting for several common risk factors. RESULTS: We documented 2217 incident cases of gout during follow-up. Psoriasis was associated with an increased risk of subsequent gout with a multivariate HR of 1.71 (95% CI 1.36 to 2.15) in the pooled analysis. Risk of gout was substantially augmented among those with psoriasis and concomitant PsA (pooled multivariate HR: 4.95, 95% CI 2.72 to 9.01) when compared to participants without psoriasis. CONCLUSIONS: In this prospective study of US women and men, psoriasis and PsA were associated with an increased risk of gout.

No association between vitamin D intake and incident psoriasis among US women.

We investigated the association between dietary, supplementary and total vitamin D intake and incident psoriasis in women. A prospective study was performed of 70,437 US female nurses aged 47-74 enrolled in the Nurses' Health Study who did not have psoriasis at baseline in 1994 and who completed semi-quantitative food frequency questionnaires in 1994, 1998, 2002 and 2006. The incidence of clinician-diagnosed psoriasis was ascertained and validated by self-reported questionnaires. 502 confirmed incident psoriasis cases were documented during 973,057 person-years of follow-up from 1994 June to 2008 June. Association between vitamin D intake and incident psoriasis was assessed using multivariable-adjusted cox regression analysis. After adjusting for age, smoking, body mass index, calorie intake, UV flux, exercise and alcohol use, there was no significant association between vitamin D intake (dietary, supplementary and total vitamin D) and the risk of incident psoriasis. Compared with women whose dietary vitamin D intake was <100 IU/day, multivariate relative risks for psoriasis was 1.13 (95 % CI 0.66-1.92) for ≥400 IU/day (P trend = 0.88). The multivariate relative risk for women who took supplementary vitamin D ≥400 IU/day was 1.18 (95 % CI 0.88-1.58) compared with women who did not take supplementary vitamin D. The multivariate risk for women who had total vitamin D intake of 300-399 IU/day was no different than at higher and lower doses of vitamin D intake. Our study does not support preventive roles of dietary or supplemental vitamin D intake for incident psoriasis.