Comparative Effectiveness of Bimekizumab and Ustekinumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

INTRODUCTION: A matching-adjusted indirect comparison (MAIC) was conducted to assess the relative efficacy at 52 weeks (Wk52) of bimekizumab 160 mg every 4 weeks (Q4W) and ustekinumab 45 or 90 mg every 12 weeks (Q12W) in patients with psoriatic arthritis (PsA) who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or who had a previous inadequate response or an intolerance to tumor necrosis factor inhibitors (TNFi-IR). METHODS: Relevant trials were systematically identified. Individual patient data from the bimekizumab trials BE OPTIMAL (NCT03895203; N = 431) and BE COMPLETE (NCT03896581; N = 267) were matched with summary data on patients receiving ustekinumab in the PSUMMIT 1 trial (NCT01009086; 45 mg, N = 205; 90 mg; N = 204) and a subgroup of TNFi-IR patients receiving ustekinumab in the PSUMMIT 2 trial (NCT01077362; 45 mg, N = 60; 90 mg, N = 58), respectively. Patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of the ustekinumab trial patients. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Non-placebo-adjusted comparisons of recalculated bimekizumab and ustekinumab outcomes for the American College of Rheumatology (ACR) 20/50/70 response criteria (non-responder imputation) were analyzed. RESULTS: In patients who were bDMARD naïve, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (odds ratio [95% confidence interval] 45 mg: 2.14 [1.35, 3.40]; 90 mg: 1.98 [1.24, 3.16]), ACR50 (45 mg: 2.74 [1.75, 4.29]; 90 mg: 2.29 [1.48, 3.55]), and ACR70 (45 mg: 3.33 [2.04, 5.46]; 90 mg: 3.05 [1.89, 4.91]). In patients who were TNFi-IR, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (45 mg: 4.17 [2.13, 8.16]; 90 mg: 4.19 [2.07, 8.49]), ACR50 (45 mg: 5.00 [2.26, 11.05]; 90 mg: 3.86 [1.70, 8.79]), and ACR70 (45 mg: 9.85 [2.79, 34.79]; 90 mg: 6.29 [1.98, 20.04]). CONCLUSIONS: Using MAIC, bimekizumab showed greater efficacy than ustekinumab in achieving all ACR responses in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52. TRIAL REGISTRATION: NCT03895203, NCT03896581, NCT01009086, NCT01077362.

Comparative Effectiveness of Bimekizumab and Risankizumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

INTRODUCTION: The relative efficacy of bimekizumab and risankizumab in patients with PsA who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR) was assessed at 52 weeks (Wk52) using matching-adjusted indirect comparisons (MAIC). METHODS: Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons. RESULTS: In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95% confidence interval]: 1.52 [1.11, 2.09]) and ACR70 (1.80 [1.29, 2.51]). In patients who were TNFi-IR, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR20 (1.78 [1.08, 2.96]), ACR50 (3.05 [1.74, 5.32]), ACR70 (3.69 [1.82, 7.46]), and MDA (2.43 [1.37, 4.32]). CONCLUSIONS: Using MAIC, bimekizumab demonstrated a greater likelihood of efficacy in most ACR and MDA outcomes than risankizumab in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52. TRIAL REGISTRATION: NCT03895203, NCT03896581, NCT03675308, NCT03671148.

Association Between Achievement of Clinical Disease Control and Improvement in Patient-Reported Outcomes and Quality of Life in Patients With Psoriatic Arthritis in the Phase 3 SELECT-PsA 1 and 2 Randomized Controlled Trials.

OBJECTIVE: We explored the relationship between achievement of clinical disease control and improvements in and normative values for patient-reported outcomes (PROs), including quality of life (QoL) measures, in patients with psoriatic arthritis (PsA). METHODS: This was a post hoc analysis of 104-week data from the SELECT-PsA 1 and 2 trials in adults with PsA and inadequate response to one or more conventional synthetic (SELECT-PsA 1) or biologic (SELECT-PsA 2) disease-modifying antirheumatic drug. Patients were initially randomized to upadacitinib 15 mg once daily (QD) to placebo switched to upadacitinib 15 mg QD at week 24 or to adalimumab 40 mg every other week (SELECT-PsA 1 only), and data were pooled across treatments and analyzed. We evaluated several clinical disease control measures (minimal disease activity [MDA]; very low disease activity [VLDA]; and low disease activity [LDA] and/or remission by Disease Activity in Psoriatic Arthritis [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and Routine Assessment of Patient Index Data 3 [RAPID3]) and examined their associations with improvements and normative values for various PROs. RESULTS: A total of 1,069 and 317 patients were analyzed for SELECT-PsA 1 and 2, respectively. In both studies, responders (patients who achieved MDA or VLDA, and DAPSA, PASDAS, and RAPID3 LDA or remission) at week 104 achieved more marked changes from baseline, and more responders achieved normative values in PROs compared with nonresponders (most nominal P < 0.0001). Furthermore, numerically larger proportions of responders achieved minimal clinically important differences across PROs compared with nonresponders in both studies. In addition, patients who achieved MDA or VLDA were more likely to achieve DAPSA, PASDAS, and RAPID3 LDA or remission (all nominal P < 0.0001) for upadacitinib 15 mg QD and when treatment arms were pooled. CONCLUSION: Patients with PsA who achieve clinical disease control are more likely to achieve improvements and normative values in PROs and QoL measures, which reinforces disease control as a treatment target.

Adherence, Persistence, Healthcare Resource Use, and Costs in Tofacitinib-Treated Patients with Psoriatic Arthritis: Data from Two United States Claims Databases.

INTRODUCTION: Associations between increased functional disability and higher healthcare resource utilization (HCRU) and costs were reported in patients with psoriatic arthritis (PsA). We assessed characteristics/outcomes of patients with PsA receiving tofacitinib monotherapy vs combination therapy with conventional synthetic disease-modifying antirheumatic drugs. METHODS: Claims data from Optum® Clinformatics® Data Mart (OC) and Merative™ MarketScan® (MS) databases between December 2017 and February 2020 were analyzed. Outcomes assessed were adherence/persistence by therapy type (monotherapy/combination therapy); HCRU/costs (per patient per month) by periods on-treatment (sum time on tofacitinib) and off-treatment (sum time off tofacitinib [gap of > 60 days]) plus therapy type. RESULTS: This analysis included 274 and 395 tofacitinib-treated patients in OC (70.4% female, mean age 54.4 years) and MS (68.9% female, mean age 51.4 years), respectively. Percentages of patients with a proportion of days covered ≥ 0.8 at 12 months for monotherapy vs combination therapy were OC, 44.5% vs 53.8%; MS, 36.4% vs 45.7%. Generally similar trends were seen over 24 months and for medication possession ratio ≥ 0.8. Median (95% confidence interval) times to treatment discontinuation for monotherapy vs combination therapy were OC, 10.1 (7.4-11.8) vs 16.7 (8.3-26.6) months; MS, 6.9 (5.6-9.4) vs 11.0 (6.1-13.9) months. During off-treatment vs on-treatment periods, numerical decreases were observed for all-cause (OC, $5383 vs $6149; MS, $4145 vs $5180) and PsA-related costs (OC, $3237 vs $4515; MS, $2703 vs $3907) regardless of therapy type. During off-treatment vs on-treatment periods, numerical increases in outpatient visits for all-cause (OC, 2.37 vs 2.05; MS, 2.15 vs 1.99) and PsA-related visits (OC, 0.60 vs 0.46; MS, 0.47 vs 0.44) were observed, and PsA-related medications numerically decreased (OC, 1.21 vs 1.53; MS, 1.05 vs 1.48). CONCLUSION: In this USA-based claims analysis, tofacitinib adherence was numerically lower for patients with PsA receiving monotherapy vs combination therapy. Costs numerically decreased off-treatment vs on-treatment, irrespective of therapy type, driven by lower medication costs.

A secukinumab dose-escalation study in patients with ankylosing spondylitis not achieving inactive disease after 16 weeks of treatment.

OBJECTIVE: To investigate the clinical response at week 52 in patients with ankylosing spondylitis (AS) who received secukinumab 300 vs 150 mg after inadequate response to 150 mg at week 16. METHODS: ASLeap (NCT03350815) was a randomized, double-blind, parallel-group, multicentre, phase 4 trial. After 16 weeks of open-label secukinumab 150 mg (Treatment Period 1), patients who did not achieve inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] <1.3) at both Weeks 12 and 16 were considered to have an inadequate response and were randomized 1:1 to receive secukinumab 300 or 150 mg every 4 weeks until week 52 (Treatment Period 2). The primary efficacy variable was achievement of ASDAS <1.3 at week 52 using week 16 as baseline. Safety was evaluated by the incidence of treatment-emergent adverse events through week 52. RESULTS: Of 322 patients treated with secukinumab in Treatment Period 1, 207 (64.3%) had inadequate response. Similar proportions of patients with inadequate response randomized to secukinumab 300 mg (n = 101) and 150 mg (n = 105) in Treatment Period 2 completed the study (83.8% and 84.3%, respectively). At week 52, 8.8% and 6.7% of patients receiving secukinumab 300 and 150 mg, respectively, achieved ASDAS <1.3. The incidence of treatment-emergent adverse events was similar in both groups through week 52. No new safety signals were observed. CONCLUSION: Patients with AS who did not achieve ASDAS <1.3 after receiving secukinumab 150 mg for 16 weeks experienced similar clinical response and safety through week 52 regardless of dose escalation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03350815.

Comparison of Real-World On-Label Treatment Persistence in Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Tumor Necrosis Factor Inhibitors.

BACKGROUND: Treatment persistence among patients with psoriatic arthritis (PsA) is essential for achieving optimal treatment outcomes. Guselkumab, a fully human interleukin-23p19-subunit inhibitor, was approved by the United States (US) Food and Drug Administration for the treatment of active PsA in July 2020, with a dosing regimen of 100 mg at week 0, week 4, then every 8 weeks. In the Phase 3 DISCOVER-1 and DISCOVER-2 studies of patients with active PsA, 94% of guselkumab-randomized patients completed treatment through 1 year and 90% did so through 2 years (DISCOVER-2). Real-world evidence is needed to compare treatment persistence while following US prescribing guidelines (i.e., on-label persistence) for guselkumab versus subcutaneous (SC) tumor necrosis factor inhibitors (TNFis). METHODS: Adults with PsA receiving guselkumab or their first SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or golimumab) between 14 July 2020 and 31 March 2022 were identified in the IQVIA PharMetrics® Plus database (first claim defined the treatment start date [index date]). Baseline characteristics and biologic use (biologic-naïve/biologic-experienced) were assessed during the 12-month period preceding the index date. Baseline characteristics were balanced between cohorts using propensity-score weighting based on the standardized mortality ratio approach. The follow-up period spanned from the index date until the earlier of the end of continuous insurance eligibility or end of data availability. On-label persistence, defined as the absence of treatment discontinuation (based on a gap of 112 days for guselkumab or 56 days for SC TNFi) or any dose escalation/reduction during follow-up, was assessed in the weighted treatment cohorts using Kaplan-Meier (KM) curves. A Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between the weighted cohorts. RESULTS: The guselkumab cohort included 526 patients (mean age 49.8 years; 61.2% female) and the SC TNFi cohort included 1953 patients (mean age: 48.5 years; 60.2% female). After weighting, baseline characteristics were well balanced with a mean follow-up of 12.3-12.4 months across cohorts; 51.5% of patients in the guselkumab cohort and 16.7% in the SC TNFi cohort received biologics in the 12-month baseline period. Respective rates of treatment persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5% for the guselkumab cohort versus 77.3%, 61.6%, 50.0%, and 43.7% for the SC TNFi cohort (all log-rank p < 0.001). At 12 months, patients in the guselkumab cohort were 3.0 times more likely than patients in the SC TNFi cohort to remain persistent on treatment (p < 0.001). Median time to discontinuation was not reached for the guselkumab cohort and was 8.9 months for the SC TNFi cohort. CONCLUSION: This real-world study employing US commercial health-plan claims data to assess on-label treatment persistence in PsA demonstrated that, at 12 months, guselkumab was associated with a 3 times greater likelihood of persistence compared with SC TNFi.

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.

GRAPPA 2023: Major Projects, Key Advances, and Milestones.

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, members were updated on a number of ongoing activities during the key project update session. These activities included the Axial Involvement in Psoriatic Arthritis (AXIS) cohort, the Axial Psoriatic Arthritis Molecular and Clinical Characterization study, the Diagnostic Ultrasound Enthesitis Tool (DUET) study, the Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies in Psoriatic Arthritis (SAGE-PsA) study, the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES), the GRAPPA slide library, and the GRAPPA treatment recommendations.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Celebrates Its 20th Anniversary.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) started in August 2003 with 40 initial participants and celebrated its 20th anniversary with 1036 members, many of whom attended the annual meeting in Dublin, Ireland, on July 15 to 17, 2023. GRAPPA arose from a need experienced by psoriatic arthritis (PsA) and psoriasis (PsO) investigators to meet to address questions related to psoriatic disease (PsD). Though other groups were meeting at the time to classify and discuss PsA, GRAPPA arose from a desire to include international clinical and investigational researchers of both dermatology and rheumatology. The organization has built awareness of PsO and PsA, developed and validated research assessment tools to measure clinical status and disease outcomes, published multiple treatment recommendations, supported basic and clinical research on PsD pathophysiology, fostered interactions across research fields, and educated the future generation of PsO and PsA researchers. The group continues to focus on major priorities affecting patients with PsD and will continue evolving in the next decades.

GRAPPA 2023 Collaborative Research Network Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Collaborative Research Network (CRN)/research committee met during the GRAPPA 2023 annual meeting. Updates were provided on GRAPPA research projects, including the Axial Involvement in Psoriatic Arthritis (AXIS), Axial Psoriatic Arthritis Molecular and Clinical Characterisation Study, Diagnostic Ultrasound Enthesitis Tool (DUET), and Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies (SAGE) studies, as well as the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES) and Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium (ELLIPSS) studies. The highlight of the meeting was a presentation and discussion on the use of digital tools to study psoriatic disease.

Durable control of psoriatic arthritis with guselkumab across domains and patient characteristics: post hoc analysis of a phase 3 study.

OBJECTIVES: Evaluate patterns of stringent disease control with 2 years of guselkumab across key disease-identified domains and patient-reported outcomes (PROs) in subgroups of patients with psoriatic arthritis (PsA) defined by baseline characteristics. METHOD: This post hoc analysis of DISCOVER-2 (Clinicaltrials.gov NCT03158285) evaluated biologic-naïve PsA patients (≥ 5 swollen/ ≥ 5 tender joints, C-reactive protein [CRP] ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W); guselkumab at Weeks 0 and 4, then Q8W; or placebo with crossover to guselkumab Q4W at Week 24. Achievement of American College of Rheumatology 50/70% improvement (ACR50/70), Investigator's Global Assessment (IGA) 0, dactylitis/enthesitis resolution, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue response (≥ 4-point improvement), HAQ-Disability Index (HAQ-DI) response (≥ 0.35-point improvement), PsA Disease Activity Score (PASDAS) low disease activity (LDA), and minimal disease activity (MDA) was assessed at Weeks 24, 52, and 100 in subgroups defined by sex and baseline medication use, body mass index, PsA duration, swollen/tender joints, CRP, and psoriasis severity/extent. Patients with missing categorical response data were considered nonresponders. RESULTS: 442/493 (90%) guselkumab-randomized patients completed treatment through Week 100. Significant multi-domain efficacy of guselkumab versus placebo was shown across adequately sized patient subgroups. A pattern of continuous improvement was observed across key PsA domains and PROs within patient subgroups: 65%-85% of guselkumab-randomized patients had enthesitis/dactylitis resolution, 50%-70% achieved complete skin clearance, 60%-80% reported meaningful improvements in function/fatigue, 40%-65% achieved PASDAS LDA, and 35%-50% achieved MDA at Week 100. CONCLUSION: Patients with active PsA receiving guselkumab demonstrated durable achievement of stringent endpoints associated with disease control across key PsA domains and PROs, regardless of baseline characteristics. Key Points • Among biologic-naïve patients with highly active psoriatic arthritis (PsA), efficacy of guselkumab across stringent disease endpoints and patient-reported outcomes (PROs) at Week 24 was consistent regardless of baseline demographics and disease characteristics. • Within guselkumab-randomized PsA patient subgroups, major improvements in joint disease activity, complete skin clearance, dactylitis/enthesitis resolution, clinically meaningful improvements in PROs, and achievement of low overall disease activity were maintained through Week 100. • Durable stringent endpoint achievement indicating disease control was observed with guselkumab, regardless of baseline patient or disease characteristics.

Deciphering difficult-to-treat psoriatic arthritis (D2T-PsA): a GRAPPA perspective from an international survey of healthcare professionals.

Objectives: This study contributes to the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)'s effort to define 'difficult-to-treat' PsA (D2T-PsA), leveraging insights of healthcare professionals who are GRAPPA members. The primary objective is to inform GRAPPA's D2T PsA project, ensuring the consensus definition reflects clinical experience and expertise. Methods: An online survey was conducted among GRAPPA's healthcare professionals managing PsA patients. The survey covered demographic details, structured questions, and open-ended queries to gather comprehensive insights into the experts' viewpoints. Results: About 223 physicians completed the survey, comprising 179 (80.2%) rheumatologists and 40 (17.9%) dermatologists. The majority, 184 (82.5%), favoured establishing distinct definitions for D2T-PsA and complex-to-manage PsA (C2M-PsA). Furthermore, 202 (90.5%) supported a definition that includes objective inflammation signs (clinical, laboratory, imaging, among others). However, opinions varied on the criteria for prior treatment failures, with most (93, 41.7%) favouring a definition that includes at least one conventional synthetic disease-modifying anti-rheumatic drug and two or more biological- or targeted-synthetic-DMARDs with different mechanisms of action. Conclusion: The survey reveals a majority opinion among GRAPPA experts favouring the differentiation between D2T-PsA and C2M-PsA, and the inclusion of objective inflammatory markers in these definitions. However, there is less than 50% agreement on the specific treatment failure criteria, particularly regarding the number of therapies needed to classify PsA as D2T. These findings suggest a need for continued discussion to reach a more unified approach in defining D2T-PsA, reflecting the complexity of the condition.

Phase 2 Trial of Deucravacitinib in Psoriatic Arthritis: Biomarkers Associated With Disease Activity, Pharmacodynamics, and Clinical Responses.

OBJECTIVE: Our objective was to evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and the relationship between biomarkers and clinical responses to deucravacitinib. METHODS: The phase 2 trial (ClinicalTrials.gov identifier: NCT03881059) randomly assigned 203 patients with PsA 1:1:1 to placebo, deucravacitinib at 6 mg once daily (QD), or deucravacitinib at 12 mg QD. Serum biomarkers associated with the interleukin 23 (IL-23) pathway (IL-17A, ß-defensin [BD-2], and IL-19), type I interferon pathway, inflammation, and collagen matrix turnover were measured by immunoassay. Clinical responses (≥75% improvement from baseline in the Psoriasis Area and Severity Index [PASI75] and ≥20% improvement from baseline in American College of Rheumatology criteria [ACR20] responses) were measured at week 16. Hematologic variables were also assessed. RESULTS: IL-17A, BD-2, and IL-19 had a modest association with PASI scores (r = 0.4, r = 0.56, and r = 0.5, respectively) at baseline. In deucravacitinib groups, IL-17A, BD-2, IL-19, C-X-C motif ligand 9 (CXCL9), CXCL10, C-reactive protein, matrix metalloproteinase 3, and collagen type 4 degradation marker levels were significantly reduced at week 16 versus baseline (P < 0.01); higher levels of IL-23 pathway-associated biomarkers predicted higher PASI75 and ACR20 response rates in deucravacitinib-treated patients. Significantly higher PASI75 response rates were seen in patients with high baseline IL-17A (odds ratio 15.76) and BD-2 levels (odds ratio 15.41) versus low baseline IL-17A and BD-2 levels. Changes in hematologic variables that are characteristic of JAK inhibition were not observed with deucravacitinib. CONCLUSION: Deucravacitinib significantly impacted biomarkers associated with Tyk2 signaling pathways of key inflammatory cytokines, including IL-23 and type I interferon, and those related to collagen matrix turnover. These biomarkers may predict treatment responses to deucravacitinib.

BASDAI versus ASDAS in evaluating axial involvement in patients with psoriatic arthritis: a pooled analysis of two phase 3 studies.

Objective: In the absence of axial psoriatic arthritis (axPsA)-specific tools, the BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) are used to assess axial symptoms in patients with PsA. Here, we assessed the performance of BASDAI and ASDAS in patients with PsA. Methods: Patients with active PsA in DISCOVER-1 and DISCOVER-2 (ClinicalTrials.gov: NCT03162796 and NCT03158285, respectively) with or without axPsA but with available baseline BASDAI information were analysed; those with investigator-identified axial symptoms and imaging-confirmed sacroiliitis comprised the axPsA cohort. Correlations between BASDAI/ASDAS and clinical variables were assessed with Pearson's coefficient (r). Longitudinal effects of enthesitis (Leeds Enthesitis Index [LEI]), swollen joint count and presence versus absence of axPsA on BASDAI/ASDAS (normalized 0-10 scale) were analysed with mixed models for repeated measures. Results: At baseline in the axPsA (n = 312) and non-axPsA (n = 124) cohorts, BASDAI scores showed no or weak correlation with swollen joint count (0.18-0.20), tender joint count (0.12-0.29), LEI (-0.04 to 0.24) and physician global assessment (0.35-0.43); moderate correlation with fatigue (both -0.56); and strong correlation with patient global assessment of disease activity (0.62-0.69) and patient-reported pain (0.66-0.70). Similar correlations were observed for ASDAS. Axial involvement versus non-involvement was associated with higher BASDAI scores and ASDAS (all ß ≥ 0.5), without differences between instruments; longitudinal associations between swollen joint count (ß ≤ 0.06)/LEI (ß ≤ 0.19) and BASDAI/ASDAS were clinically unimportant. Conclusion: BASDAI and ASDAS performed similarly in patients with active PsA and axial involvement, independent of peripheral disease involvement, supporting their performance in assessing axial disease activity. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03162796 and NCT03158285.

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.

Navigating the complexity of pain in psoriatic arthritis and axial spondyloarthritis.

PURPOSE OF REVIEW: Pain is the most common and often most troublesome feature of chronic autoimmune diseases such as psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). A predominant concept is that the main source of pain is from disease-induced tissue inflammation and structural damage, activating peripheral nerve fibers which relay to the central nervous system. This mechanism is nociceptive pain and the presumption has been that controlling inflammation will be sufficient to reduce this form of pain. However, despite control of inflammation, patients may still have significant residual pain. RECENT FINDINGS: We are learning that there are additional pain mechanisms, neuropathic and nociplastic, that are often operative in patients with rheumatologic conditions, that can significantly influence pain experience, quantitation of disease activity, and may benefit from therapeutic approaches distinct from immunotherapy. Neuropathic pain arises from diseased or damaged nerve tissue and nociplastic pain reflects sensitization of the central nervous system due to multiple genetic, neurobiologic, neural network dysregulation, and psychosocial factors. Pain arising from these mechanisms influence assessment of disease activity and thus needs to be factored into decision-making about immunotherapy efficacy. SUMMARY: This review addresses the importance of accurately assessing the complex mechanisms of pain experience in patients with PsA and AxSpA to more appropriately manage immunomodulatory, neuromodulatory, and nonpharmacologic therapies.

The Burden of Work Productivity and Activity Impairment in Patients with Psoriasis, Psoriatic Arthritis, Ulcerative Colitis, and Crohn's Disease.

BACKGROUND: Comparisons among autoimmune diseases enable understanding of the burden and factors associated with work productivity loss and impairment. AIMS: The objective was to compare work productivity and activity and associated factors among patients with inflammatory bowel diseases and other autoimmune conditions. METHODS: This cross-sectional study included employed, adult patients (age 20-64 years) in the CorEvitas Inflammatory Bowel Disease, Psoriasis, and Psoriatic Arthritis/Spondyloarthritis Registries between 5/2017 and 6/2020. Any patient-reported impairment on four domains of the Work Productivity and Activity Index (WPAI) was collected across registries. Prevalence for each autoimmune disease was reported and stratified by disease activity using direct age-sex-standardization. Factors associated with the presence of any WPAI were identified in logistic regression models. RESULTS: A total of 7,169 patients with psoriasis (n = 4,768, 67%), psoriatic arthritis (n = 1,208, 17%), Crohn's disease (CD, n = 621, 9%), and ulcerative colitis (UC, n = 572, 8%) met inclusion criteria. Among patients not in remission across all disease cohorts, the age-sex-standardized prevalence of any presenteeism, work productivity loss, and activity impairment ranged from 54 to 97%. Patients with CD in remission had higher standardized prevalence of presenteeism (53% [48-57%]) and work productivity loss (54% [49-59%]), compared to those from other cohorts (presenteeism [range: 33-39%] and work productivity loss [range: 37-41%]). For all WPAI domains, the strongest adjusted associations were for moderate to severe disease activity and psychosocial symptoms. CONCLUSIONS: Patients with moderate to severe disease activity reported the highest WPAI burden. However, patients in remission or mild disease activity also report some WPAI burden, emphasizing a multidisciplinary treatment approach to improve work productivity loss and impairment.

Prevalence of Fibromyalgia and Widespread Pain in Psoriatic Arthritis: Association With Disease Severity Assessment in a Large US Registry.

OBJECTIVE: The classic conception of pain etiology in rheumatologic disease is nociceptive pain-tissue injury and inflammation signaling through peripheral and central nerve fibers. But this can be mixed with other pain etiologies, including nociplastic, which is augmented pain experience due to central sensitization. The pain of fibromyalgia (FM) is nociplastic, occurs in 10% to 30% of patients with rheumatologic disease, and its presence can influence disease severity assessment. The objective of our study was to (1) ascertain the prevalence of FM and widespread pain (WP) in the CorEvitas psoriatic arthritis (PsA) registry as assessed by the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) questionnaires; (2) characterize the demographic and clinical factors associated with FM and WP; and (3) ascertain the association of FM and WP on the Clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score and other disease activity measures. METHODS: PsA registry patients completing the WPI/SSS questionnaires since May 2020, at their most recent visit recorded in the registry, were analyzed. RESULTS: The analysis included 1,823 patients with PsA; 11.1% fulfilled the FM definition and 20.6% fulfilled the WP definition. Several factors were associated with the FM definition, including female sex, depression and/or anxiety, impaired function, increased body mass index, and increased number of comorbidities. cDAPSA, patient pain and global assessment, and tender joint count were twice as severe in patients with FM compared to those without. CONCLUSION: FM prevalence is elevated in PsA and is associated with elevated disease measures, confounding reliable disease assessment for treat-to-target goals. Identification of FM as an influential contextual factor in disease assessment is recommended.