Bimekizumab in patients with psoriatic arthritis, naive to biologic treatment: a randomised, double-blind, placebo-controlled, phase 3 trial (BE OPTIMAL).

BACKGROUND: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17A and IL-17F. We assessed the efficacy and safety of bimekizumab in patients with active psoriatic arthritis who were naive to biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: BE OPTIMAL was a 52-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, active reference (adalimumab) trial done at 135 sites (hospitals, clinics, doctors' offices, and research centres) in 14 countries. Eligible patients were 18 years or older with a documented diagnosis of adult-onset psoriatic arthritis that met the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening. Participants were randomly assigned with an interactive-voice and web-response system on the basis of a predetermined randomisation schedule (3:2:1, stratified by region and bone erosion number at baseline) to bimekizumab 160 mg every 4 weeks, placebo every 2 weeks, or the reference group (adalimumab 40 mg every 2 weeks), all administered subcutaneously. At week 16, patients randomly assigned to placebo switched to bimekizumab 160 mg every 4 weeks. The primary endpoint was the proportion of patients reaching 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses included all patients who were randomly assigned (intention-to-treat population); the safety analysis set comprised patients who received one or more doses of treatment. Data are presented to week 24 (preplanned analysis). This trial is registered at ClinicalTrials.gov, NCT03895203. FINDINGS: Between April 3, 2019, and Oct 25, 2021, 1163 patients were screened and 852 were randomly assigned to bimekizumab (n=431), placebo (n=281), and reference (adalimumab; n=140) groups. At week 16, significantly more patients receiving bimekizumab (189 [44%] of 431) reached ACR50 response versus placebo (28 [10%] of 281; odds ratio 7·1 [95% CI 4·6-10·9], p<0·0001; adalimumab 64 [46%] of 140). All secondary hierarchical endpoints were met. Treatment-emergent adverse events up to week 16 were reported in 258 [60%] of 431 patients receiving bimekizumab, 139 [49%] of 281 patients receiving placebo, and 83 [59%] of 140 patients receiving adalimumab. No deaths occurred. INTERPRETATION: Bimekizumab treatment had superior improvements in joint, skin, and radiographic efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis who were naive to biologic DMARDs. The safety profile of bimekizumab, including the occurrence of fungal infections, was consistent with previous phase 3 studies in patients with plaque psoriasis, and with IL-17A inhibitors. FUNDING: UCB Pharma.

Bimekizumab in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α inhibitors: a randomised, double-blind, placebo-controlled, phase 3 trial (BE COMPLETE).

BACKGROUND: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A. This study compared the efficacy and safety of bimekizumab with placebo over 16 weeks in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α (TNFα) inhibitors. METHODS: BE COMPLETE was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial conducted across 92 sites (including hospitals, clinics, and research centres) in 11 countries (Australia, Canada, Czech Republic, Germany, Hungary, Italy, Japan, Poland, Russia, the UK, and the USA). Eligible patients were aged 18 years or older with adult-onset psoriatic arthritis (meeting the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening) with a history of inadequate response or intolerance to treatment with one or two TNFα inhibitors for either psoriatic arthritis or psoriasis. We stratified patients with active psoriatic arthritis by region and previous TNFα inhibitor use. Patients were randomly assigned (2:1) to receive subcutaneous bimekizumab 160 mg every 4 weeks or placebo by an interactive-voice and web-response system on the basis of a predetermined randomisation schedule. The primary endpoint was the proportion of patients with 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses were done in the randomised population. The safety analysis set comprised patients who received one or more doses of study treatment. This trial was registered at ClinicalTrials.gov, NCT03896581, and is completed. FINDINGS: Between March 28, 2019, and Feb 14, 2022, 556 patients were screened and 400 patients were randomly assigned to bimekizumab 160 mg every 4 weeks (n=267) or placebo (n=133). The primary and all hierarchical secondary endpoints were met at week 16. 116 (43%) of 267 patients receiving bimekizumab reached ACR50, compared with nine (7%) of 133 patients receiving placebo (adjusted odds ratio [OR] 11·1 [95% CI 5·4-23·0], p<0·0001). 121 (69%) of 176 patients with psoriasis affecting at least 3% body surface area at baseline who received bimekizumab reached 90% or greater improvement in the Psoriasis Area and Severity Index (PASI90), compared with six (7%) of 88 patients who received placebo (adjusted OR 30·2 [12·4-73·9], p<0·0001). Treatment-emergent adverse events up to week 16 were reported in 108 (40%) of 267 patients receiving bimekizumab and 44 (33%) of 132 patients receiving placebo. There were no new safety signals and no deaths. INTERPRETATION: Bimekizumab treatment led to superior improvements in joint and skin efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis and inadequate response or intolerance to TNFα inhibitors. The safety profile of bimekizumab was consistent with previous phase 3 studies in patients with plaque psoriasis, and studies of IL-17A inhibitors. FUNDING: UCB Pharma.

Patient research partner involvement in rheumatology research: a systematic literature review informing the 2023 updated EULAR recommendations for the involvement of patient research partners.

BACKGROUND: Patient research partners (PRPs) are people with a disease who collaborate in a research team as partners. The aim of this systematic literature review (SLR) was to assess barriers and facilitators to PRP involvement in rheumatology research. METHODS: The SLR was conducted in PubMed/Medline for articles on PRP involvement in rheumatology research, published between 2017 and 2023; websites were also searched in rheumatology and other specialties. Data were extracted regarding the definition of PRPs, their role and added value, as well as barriers and facilitators to PRP involvement. The quality of the articles was assessed. Quantitative data were analysed descriptively, and principles of thematic content analysis was applied to qualitative data. RESULTS: Of 1016 publications, 53 articles were included; the majority of these studies were qualitative studies (26%), opinion articles (21%), meeting reports (17%) and mixed-methods studies (11%). Roles of PRPs ranged from research partners to patient advocates, advisors and patient reviewers. PRPs were reported/advised to be involved early in the project (32% of articles) and in all research phases (30%), from the conception stage to the implementation of research findings. The main barriers were challenges in communication and support for both PRPs and researchers. Facilitators of PRP involvement included more than one PRP per project, training of PRPs and researchers, a supportive environment for PRPs (including adequate communication, acknowledgement and compensation of PRPs) and the presence of a PRP coordinator. CONCLUSION: This SLR identified barriers and facilitators to PRP involvement, and was key to updating the European Alliance of Associations for Rheumatology recommendations for PRP-researcher collaboration based on scientific evidence.

EULAR recommendations for the involvement of patient research partners in rheumatology research: 2023 update.

BACKGROUND: Since the publication of the 2011 European Alliance of Associations for Rheumatology (EULAR) recommendations for patient research partner (PRP) involvement in rheumatology research, the role of PRPs has evolved considerably. Therefore, an update of the 2011 recommendations was deemed necessary. METHODS: In accordance with the EULAR Standardised Operational Procedures, a task force comprising 13 researchers, 2 health professionals and 10 PRPs was convened. The process included an online task force meeting, a systematic literature review and an in-person second task force meeting to formulate overarching principles (OAPs) and recommendations. The level of agreement of task force members was assessed anonymously (0-10 scale). RESULTS: The task force developed five new OAPs, updated seven existing recommendations and formulated three new recommendations. The OAPs address the definition of a PRP, the contribution of PRPs, the role of informal caregivers, the added value of PRPs and the importance of trust and communication in collaborative research efforts. The recommendations address the research type and phases of PRP involvement, the recommended number of PRPs per project, the support necessary for PRPs, training of PRPs and acknowledgement of PRP contributions. New recommendations concern the benefits of support and guidance for researchers, the need for regular evaluation of the patient-researcher collaboration and the role of a designated coordinator to facilitate collaboration. Agreements within the task force were high and ranged between 9.16 and 9.96. CONCLUSION: The updated EULAR recommendations for PRP involvement are more substantially based on evidence. Together with added OAPs, they should serve as a guide for researchers and PRPs and will ultimately strengthen the involvement of PRPs in rheumatology research.

Efficacy and safety of pharmacological treatment of psoriatic arthritis: a systematic literature research informing the 2023 update of the EULAR recommendations for the management of psoriatic arthritis.

OBJECTIVES: To obtain an overview of recent evidence on efficacy and safety of pharmacological treatments in psoriatic arthritis (PsA). METHODS: This systematic literature research (SLR) investigated the efficacy and safety of conventional synthetic (cs), biological (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) in patients with PsA. A systematic database search using Medline, EMBASE, Cochrane CENTRAL was conducted to identify relevant articles published since the previous update in 2019 until 28 December 2022. Efficacy was assessed in trials while for safety observational data were also considered. Adverse events of special interest were infections (including herpes zoster, influenza and tuberculosis), malignancies, major adverse cardiovascular events, venous thromboembolisms, liver disease, laboratory changes and psychiatric adverse events. No meta-analyses were performed. RESULTS: For efficacy, of 3946 articles screened, 38 articles (30 trials) were analysed. The compounds investigated included csDMARDs (leflunomide, methotrexate), bDMARDs inhibiting IL17 (bimekizumab, brodalumab, ixekizumab, izokibep, secukinumab,), IL-23 (guselkumab, risankizumab, tildrakizumab), IL-12/23 (ustekinumab) as well as TNF (adalimumab, certolizumab-pegol, etanercept, infliximab, golimumab) and Janus Kinase inhibitors (JAKi) (brepocitinib, deucravacitinib, tofacitinib, upadacitinib). The compounds investigated were efficacious in improving signs and symptoms of PsA, improving physical functioning and quality of life. For safety, 2055 abstracts were screened, and 24 articles analysed: 15 observational studies and 9 long-term follow-ups of trials, assessing glucocorticoids, TNFi, IL-17i, JAKi, IL-12/23i and PDE4i (apremilast). Safety indicators were generally coherent with the previous SLR in 2019. CONCLUSION: The results of this SLR informed the task force responsible for the 2023 update of the European Alliance of Associations for Rheumatology recommendations for pharmacological management of PsA.

Factors associated with disease flare following SARS-CoV-2 vaccination in people with inflammatory rheumatic and musculoskeletal diseases: results from the physician-reported EULAR Coronavirus Vaccine (COVAX) Registry.

OBJECTIVES: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs). METHODS: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors. RESULTS: The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment. CONCLUSION: I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination.

EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update.

OBJECTIVE: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. METHODS: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. RESULTS: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. CONCLUSION: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

Effect of Bimekizumab on Patient-Reported Disease Impact in Patients with Psoriatic Arthritis: 1-Year Results from Two Phase 3 Studies.

OBJECTIVES: To evaluate 1-year bimekizumab efficacy in psoriatic arthritis (PsA) from the patient perspective using the 12-item PsA Impact of Disease (PsAID-12) questionnaire. METHODS: BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; inadequate response/intolerance to tumour necrosis factor inhibitors [TNFi-IR]) and BE VITAL (NCT04009499; open-label extension) assessed bimekizumab 160 mg every 4 weeks in patients with PsA. Post hoc analyses of patient-reported disease impact, assessed by the PsAID-12 questionnaire, are reported to 1 year (collected to week 40 in BE COMPLETE). RESULTS: Overall, 1,112 total patients were included (698 bimekizumab, 414 placebo). Rapid improvements observed with bimekizumab treatment at week 4 continued to week 16 and were sustained to 1 year. At 1 year, mean (standard error) change from baseline in PsAID-12 total score was comparable between bimekizumab-randomized patients and patients who switched to bimekizumab at week 16 (bDMARD-naïve bimekizumab -2.3 [0.1], placebo/bimekizumab -2.2 [0.1]; TNFi-IR bimekizumab -|2.5 [0.1], placebo/bimekizumab -2.2 [0.2]). Proportions of bimekizumab-randomized patients achieving clinically meaningful within-patient improvement (≥3-point decrease from baseline) at week 16 were sustained to 1 year (bDMARD-naïve 49.0%; TNFi-IR 48.5%) and were similar for placebo/bimekizumab patients (bDMARD-naïve 44.4%; TNFi-IR 40.6%). Across studies and arms, 35.3% to 47.8% of patients had minimal or no symptom impact at 1 year. Improvements were observed to 1 year across all single-item domains, including pain, fatigue and skin problems. CONCLUSION: Bimekizumab treatment resulted in rapid and sustained clinically meaningful improvements in disease impact up to 1 year in bDMARD-naïve and TNFi-IR patients with PsA.

How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients.

OBJECTIVES: The ASSIST study investigated prescribing in routine psoriatic arthritis (PsA) care and whether the patient reported outcome: PsA Impact of Disease questionnaire (PsAID-12), impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification. METHODS: Patients with PsA were selected across the UK and Europe between July 2021-March 2022. Patients completed the PsAID questionnaire, with the results shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded. RESULTS: 503 patients recruited. 36.2% had changes made to treatment, 88.8% of this had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; the PsAID-12 score was associated with odds of treatment escalation (OR: 1.58; p< 0.0001). However, most clinicians reported PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician's assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation, (OR = 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact. CONCLUSION: This study highlights multiple factors impacting treatment decision making for individuals with PsA. PsAID-12 scoring correlates with multiple measures of disease severity and odds of treatment escalation. However, most clinicians reported the PsAID-12 did not influence treatment escalation decisions. PsAID scoring could be used to increase confidence in treatment de-escalation.

Psychometric Properties of Patient Global Assessment in Psoriatic Arthritis: A Systematic Literature Review.

OBJECTIVE: Patient global assessment (PtGA) is a patient-reported outcome (PRO) that reflects a patient's judgment of their health/disease activity (DA). The objective of this systematic literature review was to assess the psychometric properties of PtGA in psoriatic arthritis (PsA). METHODS: Research articles reporting the assessment of psychometric properties of PtGA in PsA, listed in PubMed and extracted according to the Outcome Measures in Rheumatology (OMERACT) Filter 2.1 and the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) terminology, were selected. Validity was assessed for comprehensiveness (content), correlation with other DA instruments (construct), and with quality of life measurements (criterion). A metaanalysis regarding construct validity was performed. Correlations between PtGA variations and other indices' variations (external responsiveness) and PtGA variations after treatment (internal responsiveness) were collected. Data on the formulation of PtGA and its discordance with physician global assessment (PGA) were also collected. METHODS: Of 60 articles analyzed (comprising 17,453 patients), 44 were observational studies and 16 were trials. PtGA was assessed through 27 different formulations. In all the retrieved studies, PtGA assessed DA, and in 3 studies, PtGA was assessed as a variable of global health status. The correlation between PtGA and PROs was strong (ρ > 0.50), whereas with other DA indices and PGA, it ranged from weak to moderate (ρ 0.20-0.50). Three studies described a positive discordance (PtGA > PGA). Responsiveness, assessed in 24 studies, showed a strong correlation with joint count index variations (ρ 0.51-0.52). CONCLUSION: PtGA is a valid and responsive tool in PsA. Correlations were higher with PROs and weaker with DA composite indices and PGA. PGA was usually scored lower than PtGA. A standardized formulation of PtGA would be useful.

Disease activity and widespread pain are main contributors to patient-reported global health in axial spondyloarthritis: an analysis of 6064 patients.

Global health (GH) and health-related quality of life are patient priorities in axial spondyloarthritis (axSpA). Our objective was to assess the relative importance of disease-related factors including disease activity, and patient-related factors including comorbidities, to explain GH in axSpA. Post hoc cross-sectional analyses of 4 sets (COMOSPA, PERSPA, COMEDSPA, and DESIR) of patients fulfilling ASAS criteria for axSpA. GH was assessed through the ASAS Health Index (ASAS-HI) or the EuroQoL-5D-3L (EQ-5D). Disease-related factors included disease activity (ASDAS, psoriasis, arthritis, enthesitis, and CRP), disease duration, diagnostic delay, bamboo spine, and treatment. Non-disease-related factors included sociodemographic characteristics, comorbidities and chronic widespread pain. Multivariable logistic and linear regressions and partial variances (R2) were applied to identify independent determinants of GH. In 6064 patients (range 284-2756 across datasets), mean age ranged 38.9-45.8 years, 51-68% were male. GH was generally moderate: median ASAS-HI ranged 5.0-7.0. GH was explained by ASDAS (range of odds ratios, OR, 2.60-4.48) and chronic widespread pain (range of OR 2.19-8.39); other determinants included comorbidities and sociodemographic characteristics. Only 47-57% of the total variance in GH could be explained by the models; disease activity (partial variance, 16-26%) and chronic widespread pain (partial variance 12-15%) were the key contributing variables. A wide range of disease and non-disease-related variables usually collected in studies could only explain 47-57% of the variability in GH. Among these, disease activity and chronic widespread pain were most relevant and of similar magnitude of importance. These findings will be helpful for shared decision-making.

Is the patient-perceived impact of psoriatic arthritis a global concept? An international study in 13 Arab countries (TACTIC study).

The Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire, a recommended measure of patient-reported impact for psoriatic arthritis (PsA), was initially developed in Europe and may lack universal validity. Recognizing the need for a culturally appropriate tool for Arab patients, this study aimed to TranslAte, CulTurally adapt, and validate the PsAID in ArabIC (TACTIC). The PsAID-12 was translated into Arabic using a rigorous process of double translation, back-translation, and cognitive debriefing. The Arabic version was then validated through a study conducted in 13 Arab countries in 2022. Participants were consecutive literate adult patients diagnosed with PsA and fulfilling the CASPAR criteria. Collected data included PsAID-12, disease activity, and legacy patient-reported outcomes. Psychometric properties, such as internal consistency, construct validity, and test-retest reliability, were examined. Factors associated with high PsAID-12 total scores (> 4) were explored using multivariable binary logistic regression. A culturally adapted Arabic PsAID-12 questionnaire was achieved with minor rephrasing. The validation study included 554 patients from 13 countries (mean age 45 years, 59% females), with a mean PsAID score of 3.86 (SD 2.33). The Arabic PsAID-12 demonstrated excellent internal consistency (Cronbach's α = 0.95), and correlations with other measures ranged from 0.63 to 0.78. Test-retest reliability (N = 138 patients) was substantial (intraclass correlation coefficient, ICC 0.90 [0.86-0.93]; Cohen's kappa 0.80). Factors associated with a high PsAID score were disability (odds ratio, OR 3.15 [2.03-4.89]), depression (OR 1.56 [1.35-1.81]), widespread pain (OR 1.31 [1.12-1.53]), and disease activity (OR 1.29 [1.13-1.47]). Pain and fatigue were identified as the most impactful PsAID-12 domains for PsA patients. The Arabic PsAID is a valid and reliable measure that reflects the priorities of patients with PsA. PsAID scores correlated with disease activity and legacy outcome measures, as expected, indicating PsAID is a consistent measure of PsA impact across cultures. These findings highlight the potential of the Arabic PsAID in improving the care provided to Arabic-speaking patients worldwide.

Long-term effectiveness and persistence of ustekinumab and TNF inhibitors in patients with psoriatic arthritis: final 3-year results from the PsABio real-world study.

OBJECTIVES: To evaluate real-world persistence and effectiveness of the IL-12/23 inhibitor, ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis over 3 years. METHODS: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or a TNFi. Persistence and effectiveness (achievement of clinical Disease Activity for PSA (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very LDA (MDA/VLDA)) were assessed every 6 months. Safety data were collected over 3 years. Analyses to compare the modes of action were adjusted on baseline differences by propensity scores (PS). RESULTS: In 895 patients (mean age 49.8 years, 44.7% males), at 3 years, the proportion of patients still on their initial treatments was similar with ustekinumab (49.9%) and TNFi (47.8%). No difference was seen in the risk of stopping/switching; PS-adjusted hazard ratio (95% CI) for stopping/switching ustekinumab versus TNFi was 0.87 (0.68 to 1.11). In the overall population, cDAPSA LDA/remission was achieved in 58.6%/31.4% ustekinumab-treated and 69.8%/45.0% TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63 to 1.26) for cDAPSA LDA; 0.72 (0.50 to 1.05) for remission. MDA/VLDA was achieved in 41.4%/19.2% of ustekinumab-treated and 54.2%/26.9% of TNFi-treated patients with overlapping PS-adjusted ORs. A greater percentage of TNFi-treated patients achieved effectiveness outcomes. Both treatments exhibited good long-term safety profiles, although ustekinumab-treated patients had a lower rate of adverse events (AEs) versus TNFi. CONCLUSION: At 3 years, there was generally comparable persistence after ustekinumab or TNFi treatment, but AE rates were lower with ustekinumab.

Bimekizumab treatment in biologic DMARD-naïve patients with active psoriatic arthritis: 52-week efficacy and safety results from the phase III, randomised, placebo-controlled, active reference BE OPTIMAL study.

OBJECTIVES: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. BKZ treatment has demonstrated superior efficacy versus placebo (PBO) at Week 16 in biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with active psoriatic arthritis (PsA). Here, we report long-term efficacy and safety to Week 52. METHODS: BE OPTIMAL comprised a 16-week, double-blind, PBO-controlled period, then 36 weeks treatment-blind. Patients were randomised 3:2:1 to subcutaneous BKZ 160 mg every 4 weeks, PBO with switch to BKZ at Week 16, or reference arm (adalimumab (ADA) 40 mg every 2 weeks). Efficacy outcomes included the American College of Rheumatology (ACR) response criteria 20/50/70, Psoriasis Area and Severity Index (PASI) 75/90/100 in patients with baseline psoriasis affecting ≥3% body surface area and minimal disease activity (MDA); non-responder imputation. RESULTS: ACR20/50/70, PASI75/90/100 and MDA responses were sustained with BKZ to Week 52, consistent with results observed at Week 16. Patients who switched to BKZ at Week 16 demonstrated improvements in efficacy with similar results to BKZ-randomised patients by Week 52.To Week 52, 555/702 (79.1%) patients had ≥1 treatment-emergent adverse event (TEAE) during BKZ treatment; 113/140 (80.7%) on ADA. On BKZ, 46 (6.6%) patients had serious TEAEs. 54 (7.7%) Candida infections occurred during BKZ treatment and 1 (0.7%) during ADA; all cases were localised and non-serious. One death occurred in a BKZ-treated patient, unrelated to treatment. CONCLUSIONS: The efficacy of BKZ in bDMARD-naïve patients with PsA was sustained from Week 16 to Week 52. BKZ was well tolerated with no new safety signals observed. TRIAL REGISTRATION NUMBER: NCT03895203.

EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis.

BACKGROUND: The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. OBJECTIVE: To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. METHODS: A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. RESULTS: Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. CONCLUSION: These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development.

Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis: data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression. RESULTS: Of 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19. CONCLUSION: Older age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

Evaluation of the agreement between the ACR 1990 fibromyalgia tender points and an enthesitis score in patients with axial spondyloarthritis.

OBJECTIVES: Coexistence of FM represents a challenge in the evaluation of enthesitis in patients with axial spondyloarthritis (axSpA) due to a possible overlap between the tender points (TP) due to enthesitis and those of FM. The objective was to assess the agreement between the MASES enthesitis score and the tender points of the ACR 1990 criteria in patients with axSpA. METHODS: This was a cross-sectional ancillary analysis of the Predict-SpA study (NCT03039088). Patients had a diagnosis of axSpA according to their rheumatologist and an indication to start a TNFα blocker. All patients were screened for FM according to the FiRST questionnaire. A physician was asked to assess 31 anatomically described sites in a random order without knowing to which instrument the site belonged (i.e. the 18 ACR 1990 TP and the 13 MASES sites). Agreement between the MASES and the ACR 1990 TPs by the intraclass correlation coefficient (ICC), also stratified by the presence/absence of concomitant FM according to the FiRST. RESULTS: Among the 526 patients, 53% were men and 202 (38%) had FM. Radiographic sacroiliitis and MRI sacroiliitis were present in 56% and 68% patients, respectively. Patients were mostly men (53.4%) with radiographic and MRI sacroiliitis in 56% and 68% patients, respectively. Mean number of ACR 1990 TP was 5.4 (s.d. 4.6) and mean MASES was 4.2 (s.d. 3.6). ICC between both scores was 0.7 [95% CI (0.6, 0.8)]. ICC between both scores was 0.6 [95% CI (0.3, 0.8)] and 0.7 [95% CI (0.6, 0.7)] for patients with and without FM, respectively. CONCLUSION: These results suggest a significant overlap between both scores in patients with axSpA, including in those without concomitant FM. TRIAL REGISTRATION: clinicaltrials.gov, https://clinicaltrials.gov, NCT03039088.

Effect of bimekizumab on symptoms and impact of disease in patients with psoriatic arthritis over 3 years: results from BE ACTIVE.

OBJECTIVES: Evaluate effects of long-term bimekizumab treatment on patient-reported outcome (PRO) measures, symptoms and the impact of PsA on patients. METHODS: Patients with active PsA were enrolled into BE ACTIVE, a 48-week randomised controlled trial (NCT02969525). After Week 48, patients could enter a 104-week open-label extension (NCT03347110), receiving bimekizumab 160 mg every four weeks. PRO measures assessed included arthritis pain visual analogue scale (VAS), PsA Impact of Disease (PsAID)-9, 36-Item Short Form Survey (SF-36) and HAQ-Disability Index (HAQ-DI). Results were analysed as mean (S.E.M.) changes from baseline (CfB) from Week 0 to the end of the open-label extension (3 years) and as percentage of patients reaching patient-acceptable symptom state (PASS) for global impact (PsAID-9 total score ≤4) and normal function (HAQ-DI total score <0.5). Non-responder imputation was applied to missing binary outcomes. RESULTS: In 206 patients (mean age 49.3 years, 51.0% male), completion rate was high; 161 (78.2%) patients completed Week 152. Bimekizumab treatment was associated with long-term sustained improvements in pain [arthritis pain VAS CfB; Week 48: -29.9 (1.9); Week 152: -32.0 (1.9)] and fatigue [PsAID-9 fatigue CfB; -2.4 (0.2); -2.7 (0.2)]. High percentages of patients achieved acceptable symptom state (PsAID-9 PASS: 75.2%; 65.0%) and normalised function (HAQ-DI <0.5: 49.0%; 46.1%). Improvements in patient global assessment and SF-36 Physical Component Summary were also sustained. CONCLUSIONS: Bimekizumab treatment was associated with long-term sustained improvements in pain and fatigue, reducing overall impact of PsA on patients. Physical function and quality of life improved up to 3 years. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02969525, NCT03347110.

Guselkumab provides sustained domain-specific and comprehensive efficacy using composite indices in patients with active psoriatic arthritis.

OBJECTIVES: To evaluate the efficacy of guselkumab for the treatment of active PsA utilizing composite indices. METHODS: Data were pooled from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies. In both studies, patients were randomized 1:1:1 to subcutaneous guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then Q8W; or placebo Q4W with crossover to guselkumab 100 mg Q4W at week 24. Composite indices used to assess efficacy through week 52 included Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA), and very low disease activity (VLDA). Through week 24, treatment failure rules were applied. Through week 52, non-responder imputation was used for missing data. RESULTS: Greater proportions of guselkumab- than placebo-treated patients achieved DAPSA low disease activity (LDA) and remission, PASDAS LDA and VLDA, MDA, and VLDA at week 24 vs placebo (all unadjusted P < 0.05). At week 52, in the guselkumab Q4W and Q8W groups, respectively, response rates were as follows: DAPSA LDA, 54.2% and 52.5%; DAPSA remission, 18.2% and 17.6%; PASDAS LDA, 45.3% and 41.9%; PASDAS VLDA, 16.9% and 19.5%; MDA, 35.9% and 30.7%; and VLDA, 13.1% and 14.4%. In the placebo-crossover-to-guselkumab group, response rates for all composite indices increased after patients switched to guselkumab, from week 24 through week 52. CONCLUSION: Treatment with guselkumab provided robust and sustained benefits across multiple PsA domains through 1 year, indicating that guselkumab is an effective therapy for the diverse manifestations of PsA. TRIAL REGISTRATION: NCT03162796; NCT03158285.

Gender-specific differences in patients with psoriatic arthritis receiving ustekinumab or tumour necrosis factor inhibitor: real-world data.

OBJECTIVE: Investigate effects of gender on disease characteristics and treatment impact in patients with PsA. METHODS: PsABio is a non-interventional European study in patients with PsA starting a biological DMARD [bDMARD; ustekinumab or TNF inhibitor (TNFi)]. This post-hoc analysis compared persistence, disease activity, patient-reported outcomes and safety between male and female patients at baseline and 6 and 12 months of treatment. RESULTS: At baseline, disease duration was 6.7 and 6.9 years for 512 females and 417 males respectively. Mean (95% CI) scores for females vs males were: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), 32.3 (30.3, 34.2) vs 26.8 (24.8, 28.9); HAQ-Disability Index (HAQ-DI), 1.3 (1.2, 1.4) vs 0.93 (0.86, 0.99); total PsA Impact of Disease-12 (PsAID-12) score, 6.0 (5.8, 6.2) vs 5.1 (4.9, 5.3), respectively. Improvements in scores were smaller in female than male patients. At 12 months, 175/303 (57.8%) female and 212/264 (80.3%) male patients achieved cDAPSA low disease activity, 96/285 (33.7%) and 137/247 (55.5%), achieved minimal disease activity (MDA), respectively. HAQ-DI scores were 0.85 (0.77, 0.92) vs 0.50 (0.43, 0.56), PsAID-12 scores 3.5 (3.3, 3.8) vs 2.4 (2.2, 2.6), respectively. Treatment persistence was lower in females than males (P ≤ 0.001). Lack of effectiveness was the predominant reason to stop, irrespective of gender and bDMARD. CONCLUSIONS: Before starting bDMARDs, females had more severe disease than males and a lower percentage reached favourable disease states, with lower persistence of treatment after 12 months. A better understanding of the mechanisms underlying these differences may improve therapeutic management in females with PsA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02627768.