Diagnostic Delay of Psoriatic Arthritis of More Than Six Months Contributes to Poor Patient-Reported Outcome Measures in Depression, Social Ability, and Disease Impact: A Cross-sectional Study.

Objective: We sought to correlate the time lag between psoriatic arthritis (PsA) symptom onset and diagnosis to the likelihood and severity of depression, social impairment, and disease impact on quality of life. Methods: This cross-sectional study conducted by the National Psoriasis Foundation (NPF) surveyed individuals with PsA using patient-reported outcome measures. Results: The analysis cohort comprised 2,196 patients with PsA. Likelihood of depression progressively increased when time between PsA symptom onset and diagnosis was beyond six months (28.6% <6 months; 29.6% 7-12 months; 38.1% 13-24 months; 35.4% >2 years; p<0.01). Individuals with more than six months delay reported increasingly higher rates of experiencing moderate limitation in social participation (22.9% <6 months; 29.2% 7-12 months; 34.0% 13-24 months; 35.3% >2 years; p<0.001). Unacceptable PsA symptom rates (PsAID score >4) increased with time between PsA symptom onset and diagnosis (74.7% <6 months; 76.4% 7-12 months; 80.8% 13-24 months; 81.6% >2 years; p<0.05). These relationships persisted in body mass index (BMI) and age adjusted models. Limitations: The study only includes participants who were active members of the NPF, and all data was self-reported. Conclusion: Our results demonstrate that delays between PsA symptom onset and diagnosis that are greater than six months lead to increased likelihoods of depression, social disengagement, and impaired quality of life, and that longer delays lead to increasingly worse outcomes in these domains.

Complete Skin Clearance is Associated with the Greatest Benefits to Health-Related Quality of Life and Perceived Symptoms for Patients with Psoriasis.

INTRODUCTION: With newer biologics, the achievement of complete skin clearance has become an attainable treatment goal for patients with plaque psoriasis. We evaluate how improvements in Psoriasis Area and Severity Index (PASI) responses, particularly at incremental improvements approaching complete skin clearance (PASI 100), translate into improvements in health-related quality of life (HRQoL) and patient-perceived symptoms. METHODS: Data from the BE RADIANT phase 3b trial (NCT03536884) and its open-label extension (OLE), pooled across all study visits and treatments over 16 weeks (randomised patients) and 2 years (patients entering the OLE), were analysed using mixed-effects logistic regression models. Proportions of patients achieving a Dermatology Life Quality Index (DLQI) of 0/1, DLQI item scores of 0, and Psoriasis Symptoms and Impacts Measure (P-SIM) item scores of 0 for itching, scaling, and skin pain at specific PASI improvement levels were estimated. RESULTS: Seven hundred and forty-three patients were randomised to treatment; 654 entered the OLE. Using 16-week pooled data, there were incremental improvements in the proportions of patients estimated by our model to achieve DLQI 0/1 with PASI 100 compared with 95% (PASI = 95%) and 90% (PASI = 90%) improvements in PASI (93.0%, 89.3%, and 83.8% achieving DLQI 0/1, respectively). Estimated proportions achieving DLQI item scores of 0 had the greatest increases at higher PASI improvement levels for Items 1 (itchy, sore, painful, or stinging skin), 2 (embarrassment), and 4 (choice of clothing). Estimated proportions of patients achieving P-SIM = 0 were also higher for PASI 100 (itching: 61.7%; scaling: 82.2%; skin pain: 96.9%) than for PASI = 95% (50.8%; 72.3%; 95.7%) and PASI = 90% (39.8%; 59.5%; 94.0%). Similar benefits of incremental PASI improvements were estimated using 2-year data. CONCLUSIONS: Complete skin clearance translated into the greatest benefits to HRQoL and patient-perceived symptoms, over and above skin clearance between 90% and 100%, highlighting the importance of targeting PASI 100 as a treatment outcome for patients with psoriasis. TRIAL REGISTRATION NUMBER: NCT03536884. Complete skin clearance is associated with the greatest benefits to health-related quality of life and perceived symptoms for patients with psoriasis: KeyResults and Conclusions (MP4 72828 kb).

Treatment-emergent Candida infections in patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis treated with ixekizumab: an integrated safety analysis of 25 clinical studies.

BACKGROUND: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). RESEARCH DESIGN AND METHODS: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure. RESULTS: Candida infections had an IR of 1.9 per 100 PY in patients with PsO (N = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA (N = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA (N = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit. CONCLUSIONS: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications. TRIAL REGISTRATION: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material.

Ixekizumab (IXE) is a drug approved for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis. IXE belongs to the class of molecules that blocks a protein called interleukin-17A. Since interleukin-17A is involved in the defense against fungi, the clinical use of this class of drug has the potential to increase the risk of developing fungal infections, such as Candida infections.Therefore, researchers collected safety data from 25 clinical studies comprising 9225 adult patients treated with IXE: 6892 with psoriasis, 1401 with psoriatic arthritis, and 932 with axial spondyloarthritis. Researchers looked at the rate of new cases of Candida infections, the so-called incidence rate, and found that 1.9 per 100 patient-years experienced at least 1 Candida infection in the psoriasis group, 2.0 per 100 patient-years in the psoriatic arthritis group, and 1.2 per 100 patient-years in the axial spondyloarthritis group.Across indications, the majority of Candida infections (i) were experienced only once by patients, (ii) were mild or moderate in severity, (iii) involved infections caused by superficial skin fungus in the mouth or genitals, (iv) were considered recovered/resolved during the studies, (v) did not lead to IXE discontinuation, (vi) were managed with topical anti-fungal medications or no medications, and (vii) were typically resolved before next visit.In conclusion, this safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications.

GRAPPA Point-Counterpoint: Should Biologics Be Used for Mild Psoriasis?

Psoriasis (PsO) is commonly classified as mild, moderate, or severe, usually based on body surface area (BSA) or other validated measures. Although most dermatologists agree that mild PsO should be treated with topical therapies, there are circumstances where mild or limited PsO should be treated with biologics, even as first line. A debate about use of topical vs biologic therapy was presented at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting. Arguments in favor of using biologics when patients have mild disease on limited BSA included presence of psoriatic arthritis (PsA) and symptoms on special sites (ie, scalp, face, body folds, genitals, nails, palms, soles). New data suggest that treating limited or early PsO may decrease the risk of developing PsA. Arguments against using biologics for mild PsO focused on the definition of mild PsO, citing that limited BSA with PsA and significant quality of life impact should not be defined as mild. Truly mild PsO should be treated with topical agents, given their safety and relative low cost. The availability of newer agents like roflumilast and tapinarof have expanded therapeutic choice and have data supporting their use for treatment of special sites.

Prevalence and Impact of Unacceptable Symptom State among Patients with Psoriatic Arthritis: Results from the National Psoriasis Foundation's 2019 Annual Survey.

The National Psoriasis Foundation surveyed a random, stratified sample of individuals with psoriatic disease in the United States to determine the prevalence of an unacceptable psoriatic arthritis (PsA) symptom state and its effect on depression and social participation. Acceptable and unacceptable levels of PsA were defined using established cutoff points (acceptable ≤4 vs unacceptable >4) on the Psoriatic Arthritis Impact of Disease 9. Psoriasis severity was defined by body surface area: mild < 3%, moderate-severe ≥ 3%. Depression was assessed utilizing the Patient Health Questionnaire 2. Social participation was assessed by the Patient Reported Outcome Information Measurement System Ability to Participate in Social Role and Activities-SF4a. The analysis cohort comprised 801 patients with PsA. Unacceptable disease activity level (Psoriatic Arthritis Impact of Disease >4) was reported by 59.6% of participants. After adjusting for age, sex, and psoriasis severity, individuals with likely depression (OR = 0.014, P < .001) and those with limited ability to participate in social roles and activities (OR = 0.05, P < .001) were less likely to experience acceptable levels of PsA activity. Ultimately, the results demonstrated that most United States patients with PsA have unacceptable levels of disease activity, which is associated with increased prevalence of depression and limitations in social participation.

Safety of Bimekizumab for Plaque Psoriasis: An Expert Consensus Panel.

BACKGROUND: Plaque psoriasis is a chronic, relapsing systemic illness that has a significant effect on quality of life. Bimekizumab is the first monoclonal antibody to target both interleukin (IL)-17A and IL-17F, and recently received Food and Drug Administration (FDA) approval for moderate to severe plaque psoriasis. Guidance is necessary regarding the safety of bimekizumab. METHODS: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the safety of bimekizumab for moderate to severe psoriasis. A panel of 9 dermatologists and 1 rheumatologist with significant expertise in the treatment of psoriasis gathered to review the articles and create consensus statements on this new medication. A modified Delphi process was used to approve each statement, and strength of recommendation was assigned using the Strength of Recommendation Taxonomy criteria. RESULTS: The literature search produced 110 articles that met the criteria. A thorough screening of the studies for relevance to the research question resulted in 15 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 5 consensus statements and recommendations, all of which were given a strength of "A". CONCLUSION: Bimekizumab has a safety profile consistent with other biologics, except for a higher risk of oral candidiasis. Its hepatic safety profile is comparable with other currently FDA-approved biologics for plaque psoriasis. In addition, the data do not support an association of bimekizumab with suicide, and the incidence of inflammatory bowel disease is not greater than the incidence of other IL-17 blockers. J Drugs Dermatol. 2024;23(8):592-599. doi:10.36849/JDD.8246.

Benefits Over Five Years of Ixekizumab Treatment in Patients With Psoriasis Involving Challenging Body Areas.

BACKGROUND: Psoriasis involving challenging body areas, such as the scalp, face, palmoplantar surfaces, or nails, can be challenging to treat and negatively affects patient outcomes. OBJECTIVE: To assess clear responses and cumulative clinical benefits over 5 years of ixekizumab treatment of moderate-to-severe plaque psoriasis in patients with and without baseline involvement of challenging body areas. METHODS: This post hoc analysis included patients treated with ixekizumab in the UNCOVER-3 trial. We assessed PASI100 responses through the week (W) 264 and cumulative clinical benefits at W264 (calculated as least-squares mean of the percentage of maximum area under the curve for PASI100 and PASI% improvement and expressed as cumulative clearance days). Statistical differences were calculated via ANCOVA. RESULTS: A total of 385 patients were analyzed: 349 with scalp involvement, 152 with facial involvement, 96 with palmoplantar involvement, and 229 with nail involvement. Proportions of patients achieving PASI100 were numerically similar between patients with and without scalp and nail involvement. More patients without facial and palmoplantar involvement achieved PASI100 at W60 (only palmoplantar), W108, W156, W204, and W264 (only palmoplantar). At W264, cumulative clinical benefits for PASI100 and PASI% improvement were high and similar in both patient groups, with and without challenging body areas. A significant difference (P=0.006) was only observed for PASI% improvement between patients with and without nail involvement. CONCLUSION: For most efficacy measures, patients treated with ixekizumab over 5 years achieved similar clear responses and cumulative clinical benefits regardless of baseline involvement of challenging body areas. J Drugs Dermatol. 2024;23(8):619-625.  doi:10.36849/JDD.8160.

Report of the IDEOM Meeting Adjacent to the GRAPPA 2023 Annual Meeting.

The nonprofit organization International Dermatology Outcome Measures (IDEOM) is committed to improving the implementation of patient-centered outcome measures in dermatologic disease. At a conference adjacent to the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, the IDEOM Psoriatic Disease Workgroup presented updates on recent efforts in outcome measure advancement. Dr. Alice Gottlieb presented the preliminary findings of a study within the Mount Sinai Health System that aims to determine how well the IDEOM musculoskeletal (MSK) symptom framework, which uses the Psoriasis Epidemiology Screening Tool (PEST) and the Psoriatic Arthritis Impact of Disease (PsAID) instruments, functions in clinical settings. Drs. Joseph Merola and Lourdes Perez-Chada updated attendees on the IDEOM MSK-Q, a 9-item patient-reported questionnaire designed to measure the intensity and impact of MSK symptoms on the quality of life in patients with psoriasis (PsO) with or without psoriatic arthritis (PsA). Dr. Vibeke Strand summarized the Outcome Measures in Rheumatology (OMERACT) 2023 conference sessions. Dr. April Armstrong discussed the preliminary findings of a multicentered study designed to validate the 7-item Dermatology Treatment Satisfaction Instrument (DermSat-7) among patients with PsO. She also introduced the Psoriasis and Psoriatic Arthritis Treatment Satisfaction Instrument, a tool that seeks to capture the level of patient satisfaction with current therapy for PsO and PsA. This report summarizes the developments discussed at the IDEOM PsO and PsA research workgroups during the GRAPPA 2023 annual meeting.

Efficacy and Safety of Bimekizumab in Patients With Psoriatic Arthritis With or Without Methotrexate: 52-Week Results From Two Phase 3 Studies.

OBJECTIVE: The objective of this study was to assess 52-week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/-MTX) treatment at baseline. METHODS: We conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi-IR]), and the BE VITAL open-label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo-randomized patients received bimekizumab. Missing data were imputed using non-responder imputation, multiple imputation, or worst-category imputation. RESULTS: Through Week 52, similar proportions of bimekizumab-treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and -MTX (BE OPTIMAL: 54.4% +MTX, 54.7% -MTX; BE COMPLETE: 56.3% +MTX, 48.0% -MTX). Similar proportions of bimekizumab-treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and -MTX groups. Similar trends were seen in placebo/bimekizumab-treated patients. Through Week 52, the proportion of bimekizumab-treated patients with ≥1 treatment-emergent adverse event were similar between the +MTX and -MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab. CONCLUSION: Treatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD-naïve and TNFi-IR patients with PsA and was well tolerated, irrespective of concomitant MTX.

Prologue: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 Annual Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting was held on July 13 to 15, 2023, in Dublin, Ireland, and was attended by 285 rheumatologists, dermatologists, trainees, patient research partners (PRPs), representatives of patient organizations, and industry partners. The 20th anniversary of GRAPPA was celebrated with a special presentation and archival video. Ahead of the meeting, the PRP Network met, a workshop was held by the International Dermatology Outcome Measures (IDEOM) group, and there was a workshop in which researchers discussed advancing ultrasound use to improve the management of psoriatic disease (PsD). Young-GRAPPA also held a workshop and business meeting. Multiple presentations highlighted important topics currently influencing PsD, including ensuring that patients are included in advancing research, the role of depression in PsD, the use of magnetic resonance imaging for spinal lesions, and animal models of PsD, among others. Debates focused on whether biologics should be used for mild psoriasis, whether methotrexate should remain the first-line treatment for PsD, and whether PsD is really a primary enthesitis driving joint synovitis. Here we provide an overview of the features of the GRAPPA 2023 annual meeting and introduce the manuscripts published together in this supplement as a meeting report.

GRAPPA 2023 Annual Meeting Report: Hot Topic Session on Measurement of Musculoskeletal Symptoms in Psoriatic Disease.

During the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, the International Dermatology Outcome Measures (IDEOM) psoriatic disease (PsD) workgroup presented an update on their efforts toward measurement of musculoskeletal (MSK) symptoms in patients with PsD. Dr. Joseph Merola initiated the presentation emphasizing the vital importance of assessing MSK symptoms in patients with psoriasis (PsO) regardless of whether they have been diagnosed with psoriatic arthritis (PsA). He also discussed existing challenges for evaluating MSK symptoms in patients with PsO without a PsA diagnosis. Dr. Lourdes Perez-Chada then presented their work on the development and validation of the IDEOM Musculoskeletal Questionnaire (MSK-Q), a patient-reported questionnaire developed by the IDEOM to capture the intensity and impact of MSK symptoms on quality of life in patients with PsO with or without PsA. Dr. Perez-Chada also introduced a set of ongoing studies employing the IDEOM MSK-Q, highlighting the potential effects of the data collected through this innovative tool.

Psoriatic Arthritis: A Comprehensive Review for the Dermatologist. Part II: Screening and Management.

Psoriatic arthritis (PsA) is a common comorbidity of psoriasis occurring in up to a third of patients. Dermatologists hold an essential role in screening patients with psoriasis for PsA, since as many as 85% of patients develop psoriasis before PsA. Early detection and treatment of PsA are important for both short and long-term patient outcomes and quality of life. Many factors must be weighed when selecting the appropriate therapy for PsA. One must consider the 'domains of disease' that are manifested, the disease severity, patient comorbidities, patient preferences (routes of dosing or frequency, as examples) as well as factors often outside of patient-physician control, such as access to medications based on insurance coverage and formularies. As many patients will have involvement of multiple domains of psoriatic disease, selecting the therapy that best captures the patient's disease is required. In this review, we will address PsA screening, diagnosis, therapeutic approach to psoriatic disease, comorbidity considerations and co-management.

Psoriatic Arthritis: A comprehensive review for the dermatologist Part I: Epidemiology, Comorbidities, Pathogenesis, and Diagnosis.

Psoriatic arthritis (PsA) is an inflammatory seronegative arthritis strongly associated with psoriasis. Recognition of the clinical features of PsA is critical, as delayed detection and untreated disease may result in irreparable joint damage, impaired physical function, and a significantly reduced quality of life. Dermatologists are poised for the early detection of PsA, as psoriasis predates its development in as many as 80% of patients. In an effort to further acquaint dermatologists with PsA, this review provides a detailed overview, emphasizing its epidemiology, comorbidities, etiopathogenesis, and diagnostic features.

Efficacy and safety of guselkumab in patients with active psoriatic arthritis who had inadequate efficacy and/or intolerance to one prior tumor necrosis factor inhibitor: study protocol for SOLSTICE, a phase 3B, multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients. METHODS: The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator's Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel-Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively. DISCUSSION: Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021.

Ixekizumab Demonstrates Rapid and Consistent Efficacy for Patients with Psoriatic Arthritis, Regardless of Psoriasis Severity.

INTRODUCTION: Skin involvement in patients with psoriatic arthritis (PsA) worsens the severity and burden of disease. Ixekizumab (IXE), a selective interleukin (IL)-17A antagonist, was compared to placebo (PBO) in the SPIRIT-P1 (NCT01695239) and SPIRIT-P2 (NCT02349295) studies in patients with PsA and evidence of plaque psoriasis. This post hoc analysis reports musculoskeletal, skin, and nail outcomes through week 24 in patients from SPIRIT-P1 and SPIRIT-P2, stratified by mild, moderate, or psoriasis at baseline. METHODS: This post hoc analysis pooled patients from SPIRIT-P1 and SPIRIT-P2 who were randomly assigned to PBO or IXE 80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W). Efficacy outcomes were analyzed through week 24 by baseline psoriasis severity, defined by percent body surface area (BSA) affected; mild = BSA < 3%, moderate = 3% ≤ BSA ≤ 10%, severe = BSA > 10%. The primary outcomes assessed were the proportion of patients achieving American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. Secondary outcomes included musculoskeletal, disease activity, skin and nail, and health-related quality-of-life measures. RESULTS: Similar proportions of patients achieved ACR20/ACR50/ACR70 over time across all severity subgroups and treatment arms. More than one-third of IXE-treated patients achieved ACR20 at week 4, or ACR50 at week 24, with no significant differences according to psoriasis severity at baseline. Disease activity outcomes were similar through week 24 with both IXEQ4W and IXEQ2W, regardless of psoriasis severity at baseline. There were no significant differences over 24 weeks in the proportions of IXE-treated patients with mild, moderate, or severe baseline psoriasis who achieved Minimal Disease Activity (MDA). Across all severity subgroups, IXE demonstrated Psoriasis Area Severity Index 100 response as early as week 4, and approximately one-third of IXE-treated patients achieved total skin clearance at week 24. CONCLUSION: IXE demonstrated rapid and consistent efficacy in joint, skin, and nail for patients with PsA, regardless of baseline psoriasis severity. TRIAL REGISTRATION: SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295).

Efficacy and safety of bimekizumab in patients with moderate-to-severe hidradenitis suppurativa (BE HEARD I and BE HEARD II): two 48-week, randomised, double-blind, placebo-controlled, multicentre phase 3 trials.

BACKGROUND: Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with moderate-to-severe hidradenitis suppurativa. METHODS: BE HEARD I and II were two identically designed, 48-week randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Patients aged 18 years or older with moderate-to-severe hidradenitis suppurativa were randomly assigned 2:2:2:1 using interactive response technology (stratified by worst Hurley Stage at baseline and baseline systemic antibiotic use) to receive subcutaneous bimekizumab 320 mg every 2 weeks; bimekizumab 320 mg every 2 weeks to week 16, then every 4 weeks to week 48; bimekizumab 320 mg every 4 weeks to week 48; or placebo to week 16, then bimekizumab 320 mg every 2 weeks. The primary outcome was an hidradenitis suppurativa clinical response of at least 50%, defined as a reduction in total abscess and inflammatory nodule count of at least 50% from baseline with no increase from baseline in abscess or draining tunnel count (HiSCR50) at week 16. Efficacy analyses included all randomly assigned study patients (intention-to-treat population). Safety analyses included all patients who received at least one full or partial dose of study treatment in the safety set, and of bimekizumab in the active-medication set. These trials are registered at ClinicalTrials.gov, NCT04242446 and NCT04242498, and both are completed. FINDINGS: Patients for BE HEARD I were recruited from Feb 19, 2020, to Oct 27, 2021, and 505 patients were enrolled and randomly assigned. Patients for BE HEARD II were recruited from March 2, 2020, to July 28, 2021, and 509 patients were enrolled and randomly assigned. The primary outcome at week 16 was met in the group who received bimekizumab every 2 weeks using modified non-responder imputation; higher responder rates were observed with bimekizumab versus placebo in both trials: 138 (48%) of 289 patients versus 21 (29%) of 72 patients in BE HEARD I (odds ratio [OR] 2·23 [97·5% CI 1·16-4·31]; p=0·0060) and 151 (52%) of 291 patients versus 24 (32%) of 74 patients in BE HEARD II (2·29 [1·22-4·29]; p=0·0032). In BE HEARD II, HiSCR50 was also met in the group who were administered bimekizumab every 4 weeks (77 [54%] of 144 vs 24 [32%] of 74 with placebo; 2·42 [1·22-4·80]; p=0·0038). Responses were maintained or increased to week 48. Serious treatment-emergent adverse events were reported in 40 (8%) patients in BE HEARD I and in 24 (5%) patients in BE HEARD II treated with bimekizumab over 48 weeks. The most frequently reported treatment-emergent adverse events to week 48 were hidradenitis in both trials, in addition to coronavirus infection and diarrhoea in BE HEARD I, and oral candidiasis and headache in BE HEARD II. One death was reported across the two trials, and was due to congestive heart failure in a patient with substantial cardiovascular history treated with bimekizumab every 2 weeks in BE HEARD I (considered unrelated to bimekizumab treatment by the investigator). No new safety signals were observed. INTERPRETATION: Bimekizumab was well tolerated by patients with hidradenitis suppurativa and produced rapid and deep clinically meaningful responses that were maintained up to 48 weeks. Data from these two trials support the use of bimekizumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa. FUNDING: UCB Pharma.

Impact of disease, musculoskeletal symptoms and disease control in the CorEvitas Psoriasis Registry.

BACKGROUND: Early identification, diagnosis and symptom control of psoriatic arthritis (PsA) in patients with psoriasis remain unmet medical needs. OBJECTIVES: To compare the impact of disease and other characteristics between patients with psoriasis who screened positive for PsA using the Psoriasis Epidemiology Screening Tool (PEST) (screen-positive group) and patients who (i) have PsA (PsA group) or (ii) screened negative for PsA (screen-negative group). Also, to determine the proportion of patients at a patient-acceptable symptom state (PASS) in the screen-positive and PsA groups. METHODS: This was a cross-sectional analysis of the CorEvitas Psoriasis Registry. We included a convenience sample of patients with psoriasis from the screen-positive and PsA groups who completed the Psoriatic Arthritis Impact of Disease-12 (PsAID12), and a comparator screen-negative group who did not complete the PsAID12. We report descriptive summaries of demographics, comorbidities, psoriasis characteristics, patient-reported outcome measures and the proportion of patients at PASS (i.e. PsAID12 ≤ 4). RESULTS: The screen-positive, PsA and screen-negative groups included 369, 70 and 4724 patients, respectively. The screen-positive and PsA groups had a similar impact of disease, demographics, comorbidities and psoriasis characteristics (d < 0.337). Mean PsAID12 scores were 3.1 (SD 2.3) and 3.7 (SD 2.6) in the screen-positive and PsA groups, respectively. Compared with patients who screened negative for PsA, patients who screened positive exhibited higher rates of selected known predictors of PsA such as older age, longer psoriasis duration, nail disease and inverse psoriasis. The proportion of patients at PASS was 56% and 67% for the PsA and screen-positive groups, respectively. CONCLUSIONS: The similar profiles between screen-positive and PsA groups, in comparison with the screen-negative group, support observations of possible underdiagnosis of PsA and the increased impact of disease, especially musculoskeletal disease, among patients who screen positive for PsA. The high percentage of patients not at an acceptable symptom state in the PsA and screen-positive groups highlights the need to optimize care in PsA.

Bimekizumab safety in moderate to severe plaque psoriasis: Rates of hepatic events and changes in liver parameters over 2 years in randomized phase 3/3b trials.

BACKGROUND: Patients with psoriasis are at increased risk of liver function abnormalities. OBJECTIVE: Explore rates of hepatic treatment-emergent adverse events (TEAEs) and changes in liver parameters in bimekizumab-treated patients with psoriasis. METHODS: Data are reported from 5 phase 3/3b trials over 2 years. Hepatic TEAEs, laboratory elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and changes in clinical markers of liver fibrosis (Fibrosis-4 [FIB-4] Index and AST to Platelet Ratio Index [APRI]) are reported. TEAEs are presented using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY). RESULTS: 2186 patients received ≥1 bimekizumab dose. Over 2 years, the EAIR of hepatic TEAEs was 3.5/100 PY and did not increase from first to second year. 2-year EAIRs of ALT/AST elevations >3x and >5x the upper limit of normal were 2.3 and 0.6/100 PY; rates were similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods. FIB-4 and APRI scores did not increase through 2 years, regardless of fibrosis risk at baseline. LIMITATIONS: Obesity, diabetes, dyslipidemia, chronic alcohol consumption, and medication changes are confounding factors for hepatic dysfunction. CONCLUSION: Rates of hepatic adverse events (AEs) with bimekizumab were consistent through 2 years; incidences of transaminase elevations were similar to comparators during phase 3/3b controlled study periods.

Safety of Secukinumab from 1 Million Patient-Years of Exposure: Experience from Post-Marketing Setting and Clinical Trials.

INTRODUCTION: Secukinumab is an anti-interleukin (IL)-17A monoclonal antibody indicated for multiple immunological disorders. Here, we aim to summarize secukinumab safety in clinical trials (CTs) and post-marketing setting (PMS) until 25 June 2022. METHODS: Adverse events (AEs) were summarized with crude reporting rate (RR) per 100 patient-years (PY) in PMS for all reported indications and with exposure-adjusted incident rates (EAIR) per 100 PY in pooled 47 CTs for approved indications. RESULTS: Secukinumab exposure totaled 1,159,260 PY in PMS and 27,765 PY in CTs. AEs were mostly (> 80%) non-serious in PMS. EAIR for serious AEs was 7.0/100 PY. Nasopharyngitis (RR 0.59/100 PY, EAIR 16.08/100 PY) and pneumonia (RR 0.14/100 PY, EAIR 0.17/100 PY) were the most common infection and serious infection, respectively. Candida infections (RR 0.20/100 PY, EAIR 2.16/100 PY) were the most common fungal infections. Inflammatory bowel disease (IBD) was observed in PMS (0.14/100 PY) and CTs (0.26/100 PY). Most (76%) patients with prior IBD did not report IBD flare during CTs. PMS monitoring identified paradoxical skin reactions including dyshidrotic eczema (RR 0.006/100 PY) and pyoderma gangrenosum (RR 0.003/100 PY). CONCLUSION: Secukinumab safety profile with increased patient exposure remained favorable. Paradoxical skin reactions were identified in post-marketing monitoring.