Ana-Maria Orbai

Objective: To assess two‐year impact of bimekizumab on patient‐reported outcomes (PROs), and their association with objective measures of inflammation, in patients with psoriatic arthritis (PsA) who were biologic disease‐modifying antirheumatic drug (bDMARD)‐naïve or had tumor necrosis factor inhibitor inadequate response or intolerance (TNFi‐IR). Methods: BE OPTIMAL (NCT03895203; bDMARD‐naïve) and BE COMPLETE (NCT03896581; TNFi‐IR) were phase 3 studies that assessed subcutaneous bimekizumab 160 mg every four weeks. Both were double‐blind, placebo‐controlled to week16, then placebo patients switched to bimekizumab. BE OPTIMAL week52 or BE COMPLETE week16 completers could enter BE VITAL (NCT04009499; open‐label extension), where all patients received bimekizumab. PROs, disease impact (Psoriatic Arthritis Impact of Disease‐12 questionnaire [PsAID‐12]), and their association with inflammation (assessed using swollen joint count [SJC]) are reported to year 2. Results: Among 712 bDMARD‐naïve and 400 TNFi‐IR patients, bimekizumab resulted in long‐term sustained improvements in PROs for pain, fatigue, and function (Health Assessment Questionnaire–Disability Index) to year 2. Mean change from baseline (year 2) in bimekizumab‐randomized patients for pain and disease impact (PsAID‐12) was −33.9 to −29.2 and −2.5 to −2.2, respectively. An achievement of SJC = 0 was associated with the greatest reduction in pain. Decreased SJC was associated with improved pain, fatigue, function, and reduced disease impact to year 2. By year 2, 44.4% to 54.3% of patients originally randomized to placebo or bimekizumab reported no or low disease impact (PsAID‐12 ≤1.95), and 88.0% to 92.0% of bimekizumab‐randomized patients achieved a patient acceptable symptom state for disease impact (PsAID‐12 ≤4), associated with concurrent improvement in SJC and skin involvement. Conclusion: Bimekizumab treatment resulted in sustained clinically meaningful improvements in PROs and reduced disease impact to two years in bDMARD‐naïve and TNFi‐IR patients with PsA. Stringent inflammation control was associated with symptom relief and reduced disease impact.

Objective: The previously developed FLARE questionnaire assesses the multidimensional aspects of a flare of psoriatic arthritis (PsA). We aimed to further validate this questionnaire. Methods: Reanalysis of data from the ReFLAP study (ClinicalTrials.gov: NCT03119805 ), a longitudinal observational study carried out in 14 countries. Demographic, clinical, and patient-reported data were collected at baseline and 1 follow-up visit. The FLARE questionnaire (range 0-10) was completed at both timepoints (mean interval 4.5 months). Using a patient anchor question for perceived flare (yes/no), the optimal cutoff for defining a flare was obtained using receiver-operating characteristic curve analysis. Based on this cutoff, patients were compared for flare (yes/no) using clinical and patient-reported data, including composite measures of disease activity. The magnitude of score differences in patients experiencing a new flare at second visit were compared with independent samples t -scores. Results: Of 147 patients, 61 (41%) reported a flare at baseline; the optimal score cutoff from the FLARE questionnaire was 4 (sensitivity 0.86, specificity 0.76) and, using this cutoff, patients in flare had significantly worse clinical and patient-reported outcomes. Of those patients reporting a flare, the most frequently affirmed items from the questionnaire referred to pain, mobility, frustration, and fatigue. Those with a new flare at the second visit had patient-reported and clinical change scores significantly worse than those not reporting a flare. Conclusion: This study has provided further data on the FLARE questionnaire performance and validity. The questionnaire is ready for use in clinical trials and longitudinal observational studies.

Objective: In complex diseases, it is challenging to assess a patient's disease state, trajectory, treatment exposures, and risk of multiple outcomes simultaneously, efficiently, and at the point of care. Methods: We developed an interactive patient‐level data visualization and analysis tool (VAT) that automates illustration of the trajectory of a patient with scleroderma across multiple organs and illustrates this relative to a reference population, including patient subgroups who share risk factors with the index patient, to improve estimation of disease state. We conducted VAT usability testing with patients and clinicians. We then embedded results from internally cross‐validated, Bayesian multivariate mixed models that calculate an individual's risk of critical events, using baseline risk factors, patient‐level information in past trajectories in multiple dimensions, and known outcomes from the entire population and relevant subgroups. Results: The web‐based application aggregates complex, longitudinal data to illustrate patient‐, subgroup‐, and population‐level health trajectories across multiple organ systems. Patients (n = 7) exposed to the VAT reported increased knowledge about their disease and confidence in medical decision‐making. Rheumatologists (n = 4) were able to access 8.6 times more data in 81.5% of the time using two‐thirds fewer clicks using the VAT compared with an electronic medical record system. Statistical modeling was successfully embedded in the VAT, enabling real‐time estimation of a patient's risks of multiple complications. Conclusion: Systematic analysis and visualization of individual‐ and population‐level data in a complex disease has potential to improve medical decision‐making and warrants further study. Individualized risk estimation disseminated at the point of care may enable targeted screening and early intervention in high‐risk patients.

J Rheumatol 2025; doi: 10.3899/jrheum.2025-0268 The affiliation for Tommy Kok Annfeldt should be Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. This correction applies only to the August 5 First Release. The correct affiliation appears in the print and online issues. doi: 10.3899/jrheum.2025-0268.C1

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)–Outcome Measures in Rheumatology (OMERACT) psoriatic arthritis (PsA) working group provided updates at the GRAPPA 2024 annual meeting on their assessment of composite outcome measures for PsA. The group presented the progress of a systematic literature review on the psychometric properties of the following candidate composite outcome measures using the OMERACT filter 2.2: (1) minimal disease activity (MDA), (2) Disease Activity for Psoriatic Arthritis (DAPSA), (3) American College of Rheumatology (ACR) response criteria, (4) Psoriatic Arthritis Disease Activity Score (PASDAS), (5) Composite Psoriatic Disease Activity Index (CPDAI), (6) 3-item visual analog scale (3VAS), and (7) 4VAS. A Delphi exercise for patient research partners (PRPs) on domain match and feasibility is ongoing. Following analysis and endorsement of domain match and feasibility by PRPs, the working group will seek endorsement from the GRAPPA community. In addition, the group illustrated a new research proposal for using network metaanalysis to quantitatively compare the responsiveness of these various composite outcome measures.

Objective: To assess the long-term safety profile of bimekizumab (BKZ) in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Methods: Safety data pooled from six integrated phase IIb/III studies in axSpA and PsA are reported (to the July 2022 data-cut for phase III) for patients who received ≥1 dose of BKZ 160 mg every 4 weeks. Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rate per 100 patient-years (EAIR/100 PY). Results: The axSpA and PsA safety pools included 848 (total BKZ exposure: 2034.4 PY) and 1407 patients (2590.8 PY), respectively. TEAEs occurred at an EAIR/100 PY of 136.9 in axSpA and 139.6 in PsA; study discontinuation due to TEAEs was low (axSpA: 2.7/100 PY; PsA: 3.1/100 PY). The three most frequently reported TEAEs were SARS-CoV-2 (COVID-19) infection (axSpA: 7.8/100 PY; PsA: 8.8/100 PY), nasopharyngitis (axSpA: 8.2/100 PY; PsA: 7.7/100 PY) and upper respiratory tract infection (axSpA: 5.0/100 PY; PsA: 5.6/100 PY). EAIR/100 PY of oral candidiasis was 3.7 in axSpA and 4.2 in PsA; most events were mild/moderate. EAIR of BKZ discontinuation due to oral candidiasis was low (both axSpA and PsA: 0.3/100 PY). No systemic fungal infections or cases of active tuberculosis were reported. EAIRs of adjudicated definite/probable inflammatory bowel disease, uveitis, adjudicated major adverse cardiovascular events and adjudicated suicidal ideation/behaviour were low. Conclusion: Overall, BKZ demonstrated good tolerability, with TEAE EAIRs comparable between axSpA and PsA cohorts, remaining stable over extended treatment periods. No new safety signals were identified. Trial registration numbers: NCT02963506 (BE AGILE); NCT03355573 (BE AGILE 2); NCT03928704 (BE MOBILE 1); NCT03928743 (BE MOBILE 2); NCT04436640 (BE MOVING); NCT02969525 (BE ACTIVE); NCT03347110 (BE ACTIVE 2); NCT03895203 (BE OPTIMAL); NCT03896581 (BE COMPLETE); NCT04009499 (BE VITAL).

Objectives: Psoritic arthritis (PsA) is an inflammatory arthritis with infrequent antibodies. We present a case–control study of six PsA patients with antibodies against PCNA and observed clinical associations. Methods: We conducted a study to identify autoantibodies in PsA. Sera from 81 PsA patients were assayed by immunoprecipitation from radiolabelled cell extracts. From this study, serum that immunoprecipitated a ≈32-kDa band was selected for mass spectrometry–based antibody discovery, which identified anti-PCNA antibodies. These were validated using immunoprecipitation of 35S-methionine-labelled PCNA from in vitro transcription and translation. This assay tested 222 PsA sera for anti-PCNA antibodies. This study included sera from 39 healthy controls. Descriptive statistics were used to assess clinical associations with anti-PCNA status. Results: Anti-PCNA antibodies were identified in 6/222 PsA patients. In 4/6 patients, banked longitudinal sera were available. In patients with anti-PCNA positivity compared with negativity, the mean age was 46 years (s.d. 14) and 52 years (s.d. 13), PsA disease duration was 8 years (s.d. 7) and 7 years (s.d. 8), BMI was 27 (s.d. 4) and 31 (s.d. 7), 67% and 44% were male, 100% and 89% were White, mean clinical DAPSA was 16 (s.d. 22) and 21 (s.d. 16), psoriasis body surface area was 2% (s.d. 4) and 5% (s.d. 12), HLA-B27 positivity was 0 and 12% and sulfasalazine (SSZ) use was 83% and 10%, respectively. Of these, only SSZ use was significant (Fisher’s exact test P-value <0.001). Among anti-PCNA-positive patients with longitudinal sera, low/absent anti-PCNA coincided with articular low disease activity/remission. Conclusion: Anti-PCNA antibodies were found in 6/222 (2.7%) PsA patients. Given the low prevalence of anti-PCNA, additional studies are needed to identify the clinical associations and significance.

Objective: The aim of this study was to evaluate whether meeting minimal disease activity (MDA) as measured by the MDA criteria was perceived as good disease control by patients with psoriatic arthritis (PsA) regardless of which MDA components were not met.Methods: We analyzed data from the Remission/Flare in PsA (ReFlaP) study (ClinicalTrials.gov:NCT03119805), a cross-sectional international study of adult patients with PsA. Patients self-reported if they felt their PsA was in remission (REM), low disease activity (LDA), or neither. The relationship between patient-reported status and the MDA components met was analyzed using point-biserial correlation, chi-square test, odds ratios, and specificity.Results: Of the study participants who met MDA, 88.4% reported good disease status (REM/LDA). Pain was the most commonly unmet component. A moderate to strong correlation was found between meeting more MDA components and patient-reported good status irrespective of component unmet. On individual component testing, MDA state and patient-reported REM/LDA were significantly associated irrespective of unmet component, with the exception of entheses. Specificity of the MDA score irrespective of the unmet component was > 90%. The odds of MDA patients reporting poor disease status were significant only for when pain visual analog score (VAS) < 1 was the unmet component. This significance was not supported by the sensitivity analysis.Conclusion: This study suggests strong agreement between MDA status and patient-reported good status irrespective of unmet component. Pain < 1 or 2 on a 0-10 VAS was the hardest component to meet. The high specificity regardless of the unmet MDA component suggests patients who feel their disease is active are minimally misclassified by the score.