The overall objective of this living guideline with a fixed-interval schedule is to provide up-to-date, evidence-based recommendations for the management of Beh & ccedil;ets disease/syndrome in adults, children and young people. The literature will be reviewed at least every 6 months, with a living guideline updating cycle of 12 months. The current iteration aims to: (i) offer an appraisal of all relevant literature up to 23 May 2025 focusing on any key developments; (ii) address important, practical clinical questions relating to the primary guideline objective; and (iii) provide guideline recommendations and appropriate research recommendations.

Janus kinase inhibitors (JAKi) have proven effective for many rheumatic and musculoskeletal diseases (RMDs). Enriched treatment experience for established indications, case reports highlighting broader use and the availability of new and generic JAKi may potentially shift treatment practice. Defining prescribing habits may help predict the future treatment paradigm and understand evidence gaps. This study aimed to capture the global thoughts on JAKi utilization evolution within (1) current indications and (2) new indications where JAKi may have potential place in therapy as identified by unmet medical need, global expert medical opinion and literature evidence using a modified Delphi approach. Systematic/scoping reviews on published literature of JAKi use in RMDs were conducted to inform initial statements alongside committee clinical expertise. A 4 round online modified Delphi study was then conducted with 178 volunteer panellists (clinician’s providing Rheumatology care) from 23 countries. Global experts formed the academic and steering committees. Stable statement consensus or disagreement was a median score of ≥ 7or≤3 from two consecutive rounds on a 1-9 Likert scale, respectively. All statements were presented in ≥ 2 rounds and wording amended based on panellist suggestions, confirmed by committees. A total of 138,118,109 and113 panellists completed rounds1-4, respectively. 20 statements reached stable consensus, and 1 statement reached stable disagreement (Table 1), categorised into: Current Uses of JAKi, Potential uses of JAKi beyond currently approved indications, Potential uses of a specific class of JAKi: TYK2 inhibitors or Acquisition and access to JAKi. Clinicians provided 258 statement comments/suggestions. This study highlights global expert consensus characterisation of current uses and the evolution of JAKi use in RMDs. Clinicians were in consensus that JAKi have an important role in current indications and generic JAKi may lead to their wider use/broaden the indications for which they are utilised. Clinicians were hesitant to use JAKi without phase 3 RCT data. Work is ongoing to stratify opinion across region, income and treatment practice, and explore barriers to access. This study was sponsored by Pfizer. Pfizer employees and authors designed the study, interpreted data, and wrote the abstract. Analytical support was provided by Momentum data Ltd, funded by Pfizer. A. Barkaway: Other; Pfizer Employee. P. Mease: Consultancies; AbbVie, Acelyrin, Amgen, Bristol Myers Squib, Cullinan Biotech, Eli Lilly, Inmagene, Janssen, Moonlake, Novartis, Pfizer, Takeda, UCB. Honoraria; AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Acelyrin, Amgen, Bristol Myers Squib, Eli Lilly, Janssen, Novartis, Pfizer, UCB. Other; Genascence. R. Moots: Consultancies; Pfizer. Grants/research support; Novartis. M. Ndosi: Consultancies; Pfizer. Grants/research support; Sanofi, Vifor Pharmaceuticals. Z. Rutter-Locher: Consultancies; Pfizer. M. McLean: Other; Pfizer Employee.

Background and Objectives:Biologic therapy has been used for Behçet's Syndrome after first-line immunomodulation, but in the absence of high-quality evidence or predictive biomarkers. BIO-BEHÇET'S was a randomized controlled clinical trial to compare the two most widely used biologics for Behçet's Syndrome at that time, infliximab versus interferon-α2a, and identify potential biomarkers for response. Methods:A total of 79 patients with active Behçet's Syndrome were randomized to either infliximab (REMICADE) or interferon-α2a (ROFERON) according to the UK national treatment pathway, and follow-up with symptom-directed examination undertaken at Weeks 12 and 24. The head-to-head trial included an exploratory analysis on the potential role of single nucleotide polymorphisms (SNPs) and urinary metabolomic to act as biomarkers for drug response. Genotypic analysis was performed to determine whether four SNPs in IFNL3 and IFNL4 - selected based on known effects - impacted primary and secondary outcomes. For metabolomic analyses, urine samples were analyzed by nuclear magnetic resonance spectroscopy and principal component analysis. Results:Genetic data suggested potential association between outcomes and carriage of rs4803221 or rs7248668 variants in the IFNL3 (IL-28B) gene locus for interferon-α2a patients; however, with the relatively small sample, statistical significance was lost when corrected for multiple testing. Metabolomic analysis identified potential markers of metabolic response to infliximab. Conclusion:BIO-BEHÇET'S suggests there is potential for a novel metabolomic biomarker that can identify response to infliximab in patients with Behçet's Syndrome. Further work will characterize the appropriate metabolite (s) from existing samples to inform future prospective trials to study this in more detail clinically.

OBJECTIVE:The objective of this study was to report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD). METHODS:Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks until week 24 (treatment period [TP]1). At week 24, patients on 300 mg were rerandomized to continue 300 mg or receive placebo until week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, and patients on 5 and 50 mg directly entered posttreatment safety follow-up. Patients who discontinued treatment early or completed treatment entered safety follow-up (≥20 weeks). RESULTS:During TP1, 190 patients were randomized (placebo = 49, 5 mg = 47, 50 mg = 47, 300 mg = 47). Of these 190 patients, 90 (47.4 %; 43 continued 300 mg and 47 received placebo) entered TP2, and 81 of 90 (90.0%) completed the study treatment. By week 52, efficacy was sustained in patients who continued 300 mg in TP2 (EULAR Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, patient global assessment, and physician global assessment change from week 24: -1.45, -0.46, -4.69, and -6.86, respectively). Stimulated salivary flow rates and autoantibody levels numerically improved in the 300 mg group. Treatment-emergent adverse events were not dose-dependent, except for injection-site reactions. Cases of decreased neutrophil counts (Common Terminology Criteria for Adverse Events v4.03 grade 3 according to laboratory listings) were observed in three patients during the posttreatment follow-up, occurring at 3.5, 5.5, and 3 months, after the last ianalumab administration. None were associated with infection except one incidental finding of asymptomatic cytomegalovirus infection (IgM-positive). CONCLUSION:In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favorable safety profile up to two years of follow-up.

BACKGROUND:Treatments for osteoarthritis (OA) are limited. Previous small studies suggest that the antirheumatic drug methotrexate may be a potential treatment for OA pain. OBJECTIVE:To assess symptomatic benefits of methotrexate in knee OA (KOA). DESIGN:A multicenter, randomized, double-blind, placebo-controlled trial done between 13 June 2014 and 13 October 2017. (ISRCTN77854383; EudraCT: 2013-001689-41). SETTING:15 secondary care musculoskeletal clinics in the United Kingdom. PARTICIPANTS:A total of 207 participants with symptomatic, radiographic KOA and knee pain (severity ≥4 out of 10) on most days in the past 3 months with inadequate response to current medication were approached for inclusion. INTERVENTION:Participants were randomly assigned 1:1 to oral methotrexate once weekly (6-week escalation 10 to 25 mg) or matched placebo over 12 months and continued usual analgesia. MEASUREMENTS:The primary end point was average knee pain (numerical rating scale [NRS] 0 to 10) at 6 months, with 12-month follow-up to assess longer-term response. Secondary end points included knee stiffness and function outcomes and adverse events (AEs). RESULTS:A total of 155 participants (64% women; mean age, 60.9 years; 50% Kellgren-Lawrence grade 3 to 4) were randomly assigned to methotrexate (n = 77) or placebo (n = 78). Follow-up was 86% (n = 134; methotrexate: 66, placebo: 68) at 6 months. Mean knee pain decreased from 6.4 (SD, 1.80) at baseline to 5.1 (SD, 2.32) at 6 months in the methotrexate group and from 6.8 (SD, 1.62) to 6.2 (SD, 2.30) in the placebo group. The primary intention-to-treat analysis showed a statistically significant pain reduction of 0.79 NRS points in favor of methotrexate (95% CI, 0.08 to 1.51; P = 0.030). There were also statistically significant treatment group differences in favor of methotrexate at 6 months for Western Ontario and McMaster Universities Osteoarthritis Index stiffness (0.60 points [CI, 0.01 to 1.18]; P = 0.045) and function (5.01 points [CI, 1.29 to 8.74]; P = 0.008). Treatment adherence analysis supported a dose-response effect. Four unrelated serious AEs were reported (methotrexate: 2, placebo: 2). LIMITATION:Not permitting oral methotrexate to be changed to subcutaneous delivery for intolerance. CONCLUSION:Oral methotrexate added to usual medications demonstrated statistically significant reduction in KOA pain, stiffness, and function at 6 months. PRIMARY FUNDING SOURCE:Versus Arthritis.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of Behçets. The document aims to offer an appraisal of all relevant literature up to 25 August 2023 focusing on any key developments; to address important, practical clinical questions relating to the primary guideline objective; and to provide guideline recommendations and appropriate research recommendations.

High baseline neutrophil-to-lymphocyte ratio (NLR) in rheumatoid arthritis (RA) has been associated with positive responses to biologic tumor necrosis factor inhibition and negative responses to conventional synthetic disease-modifying antirheumatic drug (csDMARD) triple therapy. Datasets from three randomized clinical trials in patients with RA were used to test the hypothesis that baseline NLR is associated with improved clinical response to filgotinib in methotrexate (MTX)-naïve or MTX-experienced RA populations. Patients from FINCH 1 (inadequate response to MTX, MTX-IR; NCT02889796), FINCH 2 (inadequate response to biologic DMARDs; NCT02873936), and FINCH 3 (MTX-naïve; NCT02886728) were classified as baseline NLR-High or baseline NLR-Low based on a previously published cut point of 2.7. In total, 3365 patients were included across the three studies. Differences in clinical outcomes and patient-reported outcomes (PROs) were determined using linear-regression models. Control-arm patients (placebo + MTX/placebo + csDMARD) classified as NLR-High exhibited worse continuous clinical and PRO responses at week 12 across clinical trials compared to NLR-Low patients. In contrast, NLR-High patients who received FIL 200 mg + MTX/csDMARD exhibited consistently better responses after 12 weeks compared to NLR-Low patients across clinical trials, clinical endpoints, and PROs. These trends were most prominent among the MTX-IR population. The 2.7 baseline NLR cut point could be used to enrich for patients most likely to benefit from the addition of filgotinib to background MTX/csDMARD. Use of baseline NLR as part of therapeutic decision-making would not require additional diagnostics and could contribute to improved outcomes for patients with RA. Clinicaltrials.gov: NCT02889796; NCT02873936; NCT02886728. Rheumatoid arthritis is a disease that results in swollen and painful joints. There is currently no method to determine which treatment will work best for an individual patient. However, there may be identifying markers found in the blood that could indicate how a patient will respond to treatment. One of these possible markers is a ratio of two types of white blood cells, neutrophils and lymphocytes, which are part of the body’s immune system and help the body detect and fight infection and other diseases. This ratio is referred to as the neutrophil-to-lymphocyte ratio. The current study evaluated whether the neutrophil-to-lymphocyte ratio at the beginning of treatment was associated with rheumatoid arthritis treatment outcomes. Blood test results were used from 3365 patients receiving filgotinib (a medicine used to treat rheumatoid arthritis) or other therapies as part of the FINCH clinical trials. Patients were classified as having a high or low neutrophil-to-lymphocyte ratio at the start of treatment. Patients receiving filgotinib over 24 weeks who had a high neutrophil-to-lymphocyte ratio showed less disease activity than patients whose ratio was low. This study provides support for the use of the neutrophil-to-lymphocyte ratio as a way to help determine whether a patient would benefit from filgotinib as part of their rheumatoid arthritis treatment and may help improve rheumatoid arthritis treatment outcomes.

BACKGROUND:In this prospective cohort study the objective was to identify the socio-demographic and clinical factors that influence treatment response to disease-modifying antirheumatic drugs (DMARDs) at ambulatory multicenter rheumatology outpatient clinics. The subjects were patients with rheumatoid arthritis satisfying the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria with informed consent. MATERIALS AND METHODS:Pre-coded data sheets were used to capture socio-demographic and clinical characteristics. Baseline data was collected at time of patient recruitment. Only patients who had complete data at three-month follow-up were included in the study analysis. The study's outcome was achievement of remission or low disease activity. The study used the adherence in chronic disease scale and European Task Force for Patient Evaluation of General Practice tools to evaluate patient adherence and assessments of health care received. Data analysis was carried out using Prism 7 and SPSS. Categorical data were regulated as percentages, while continuous data were regulated as means and standard deviation. Prevalence (at 95% CIs) of various socio-demographic and clinical characteristics were calculated comparisons of socio-demographic characteristics, clinical characteristics between patients into achieved primary/secondary outcomes and those who didn't were carried out using the chi-square statistic (for categorical variables) and independent student T-test (for continuous variables). Logistic regression was performed to estimate the impact of moderator variables on study outcomes and to calculate adjusted odds ratio (OR) with corresponding 95% CI. Throughout analysis α < 0.05 was considered statistically significant. RESULTS:A total of 206 patients were included. The mean age was 51.2 ± 15.1 years; mostly females (n=188 patients, 91.3%). Majority had attained post-primary education (n=172 patients, 83.5%). Only 74 patients (35.9%) had formal professional employment, while only six patients (3%) paid for healthcare via government-funded/private insurance. At recruitment, nearly half of the included patients had moderate to severe disability. Majority of patients had elevated baseline erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Most of the patients (90.3%) had a positive rheumatoid factor test at recruitment, while 58% had a positive anti-cyclic citrullinated peptide test. Majority had moderate disease activity. Thirty-three patients were in remission, 9.7% had low disease activity while 12.6% had high disease activity. Majority of patients (94.2%) were on non-steroidal anti-inflammatory drugs, non-biological DMARDs (80.6%) and systemic corticosteroids (54.9%). Mean duration of follow-up was 4.6 months. At follow-up, 37.9% found the system to be acceptable, 63.6% found the system to be problematic. Majority of the patients reported to have been adherent to therapy (high adherence: 7.8%; moderate adherence: 86.9%). The proportion of patients who achieved remission or low disease activity increased significantly at three-month follow-up. CONCLUSION:Having shorter disease duration, lower unemployment rates, higher income, lower non-adherence rates, having a positive outlook towards the healthcare system, normal CRP baseline, normal ESR baseline, and lower baseline of functional disability were significantly associated with increased chances of low disease activity/remission.

Objective Understanding preferences of patients with rheumatoid arthritis (RA) can facilitate tailored patient-centric care. This study elicited trade-offs that patients with RA were willing to make during treatment selection.Methods Patients with RA completed an online discrete choice experiment, consisting of a series of choices between hypothetical treatments. Treatment attributes were selected based on literature review and qualitative patient interviews. Eligible patients were ≥18 years old, diagnosed with RA, receiving systemic disease-modifying antirheumatic drug therapy, and residents of Europe or USA. Male patients were oversampled for subgroup analyses. Data were analysed using a correlated mixed logit model.Results Of 2090 participants, 42% were female; mean age was 45.2 years (range 18–83). Estimated effects were significant for all attributes (p<0.001) but varied between patients. Average relative attribute importance scores revealed different priorities (p<0.001) between males and females. While reducing pain and negative effect on semen parameters was most important to males, females were most concerned by risk of blood clots and serious infections. No single attribute explained treatment preferences by more than 30%. Preferences were also affected by patients’ age: patients aged 18–44 years placed less importance on frequency and mode of treatment administration (p<0.05) than older age groups. Patients were willing to accept higher risk of serious infections and blood clots in exchange for improvements in pain, daily activities or administration convenience. However, acceptable trade-offs varied between patients (p<0.05).Conclusion Treatment preferences of patients with RA were individual-specific, but driven by benefits and risks, with no single attribute dominating the decision-making.

BackgroundThere is a great unmet need for the development of effective treatments to treat the symptoms of OA. Nuclear-Factor Kappa-B (NF-κB) and Nrf2 play a key roles in OA pathogenesis and have been identified as potential targets. A fixed-dose combination of apocynin and paenol in a ratio of 2:7 (APPA) has been shown to inhibit activation of NF-κB and upregulate Nrf2. [1]ObjectivesWe report the results of a phase 2a study evaluating the efficacy and safety of APPA in patients with symptomatic knee OA.MethodsThe trial was a 28-day randomized, placebo-controlled, double-blind study comparing 800 mg of APPA twice daily with matched placebo capsules. Patients with radiographic knee OA KL-grade 2-3, and a WOMAC pain score ≥40 and ≤90/100 of target knee at screening and baseline were randomized 1:1 to APPA or placebo. Main exclusion criteria included recent intraarticular surgery or injection therapy, hip pain greater than the target knee, and BMI ≥40 kg/m2. The primary endpoint was change from baseline to Day 28 in the WOMAC pain score. Safety outcomes included reported adverse events (AE), clinical laboratory parameters, ECG, and vital signs.A pre-defined subgroup analysis in subjects with a baseline PainDETECT score >12 indicated a positive effect. Accordingly, post-hoc analyses were undertaken to further assess the effects of APPA in subgroups of participants with higher disease severity.Results152 participants were randomized, and 149 (98%) completed the trial. The mean (SD) WOMAC pain score at baseline was 55.3 (10.2). The two groups were comparable in terms of baseline pain score, gender, age, and BMI.The primary endpoint was not met, mean difference (MD) between APPA and placebo was -0.89 (95 % CI: -5.62, 3.84, p=0.71, Figure 1A). Similarly, no significant differences were found on other key secondary endpoints (WOMAC Function and WOMAC total Figure 1B and C, respectively.) APPA was well tolerated and no differences in frequencies of reported AEs were noted, apart from a higher proportion of subjects reporting mild to moderate gastrointestinal discomfort reported with APPA compared to placebo (12% vs. 6.5 %).In the pre-defined subgroup of participants with baseline PainDETECT ≥ 13 (N=45), the difference in mean change in pain from baseline favored the APPA-group (MD: -11.20, 95 % CI: -20.29 to -2.11, p=0.02). Analysis of participants > 50 WOMAC pain at baseline (Group 1, N=95, Figure 1D), and a KL-grade of the non-target knee >2 (Group 2, N=105, Figure 1E), and a combination of these two criteria (Group 3, N=64, Figure 1F) found a positive effect of APPA compared to placebo (Group 1 MD: -2.61, 95 % CI: -8.98 to 3.76, p=0.42, Group 2 MD: -4.01, 95 % CI: -9.35 to 1.33, p=0.14, and Group 3 MD: -8.32, 95 % CI: -15.48 to -1.16, p=0.02).ConclusionTreatment with APPA 800 mg twice daily for 28 days in patients with symptomatic knee OA overall was not associated with significantly improved outcomes compared to placebo. The treatment was well-tolerated and safe. Subgroup analyses, however, showed a significant effect of APPA in patients with moderate to severe OA, indicating that further research in the effects of APPA in appropriate patients is warranted.References[1]Cross AL, Hawkes J, Wright HL, Moots RJ, Edwards SW. APPA (apocynin and paeonol) modulates pathological aspects of human neutrophil function, without supressing antimicrobial ability, and inhibits TNFα expression and signalling. Inflammopharmacology. 2020 Oct; 28(5):1223-1235.Disclosure of InterestsAsger Reinstrup Bihlet Shareholder of: NBCD A/S, Employee of: NBCD A/S, Inger Byrjalsen Employee of: NBCD A/S, Jeppe Ragnar Andersen Shareholder of: NBCD A/S, Employee of: NBCD A/S, Anna Metnik Shareholder of: NBCD A/S, Employee of: NBCD A/S, Alan Reynolds Shareholder of: AKL R&D, Employee of: AKL R&D, Nicholas Larkins Shareholder of: AKL R&D, Employee of: AKL R&D, Peter Alexandersen: None declared, Helene Rovsing: None declared, Ulla Schmidt: None declared, Robert Moots Speakers bureau: Pfizer, Amgen, Novartis, Gilead, Grant/research support from: University of Liverpool received grant support from AKL on Phase 1 trial where Prof. Rob Moots was principal investigator. UoL also received grant support from AKL on basic neutrophil research., Philip G Conaghan Speakers bureau: AbbVie, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer and UCB, Consultant of: AbbVie, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer and UCB

The systemic vasculitides cause considerable morbidity, not least by their potential to affect so many organs. In major referral centres, they are managed optimally, by multidisciplinary teams comprising specialists in the individual organ systems involved, working together to provide a holistic approach and the optimal environment to assess disease activity and deliver optimal therapy. For example, the National Centre for Behçet’s syndrome (BS) in Liverpool UK[1] brings together clinicians from disparate disciplines to provide patient-centred state-of-the-art care for this form of vasculitis. Unfortunately, in many countries, access to diagnostic techniques and appropriately experienced specialists in systemic vasculitis can be difficult. In this article, we will highlight the challenges of detecting and managing systemic vasculitis in the eye and consider how advances in “oculomics” and artificial intelligence (AI) may enhance the management of this major complication and help address the current inequalities of care. We will focus on ocular disease in BS, where early diagnosis and prompt treatment can be sight-preserving.

Background The rheumatoid arthritis (RA) treatment landscape is diverse, with multiple therapies available that differ in several attributes such as mode of administration and benefit-risk profile. Patients and prescribers face challenging trade-offs during treatment selection to accommodate patients' circumstances in order to ensure comprehensive disease management. EULAR recommendations for RA management emphasize the need to recognize patient preferences in shared decision-making (SDM). Therefore, it is essential to understand how preferences differ in the RA patient population. Objectives This study elicited trade-offs that RA patients were willing to make during treatment selection while accounting for preference heterogeneity. Methods An online discrete choice experiment (DCE) was conducted from September to October 2021 in which RA patients were required to elicit their preferences for attributes of treatments for RA (Figure 1) and make trade-offs between them. Attributes were selected and defined based on literature review and qualitative patient interviews, and were then tested in a quantitative pilot. Main data collection consisted of an online survey in which participants were asked to repeatedly choose between hypothetical treatments. Eligible patients were ≥18 years old, diagnosed with RA, currently received systemic disease-modifying anti-rheumatic drug therapy for RA, and were residents of France, Germany, Italy, Spain, United Kingdom, or United States. Male patients were oversampled to support subgroup analysis of preferences for effects on sperm parameters. Data were analyzed using a correlated mixed logit model and differences in preferences between sex and age were explored. Relative attribute importance (RAI) scores and maximum acceptable risk (MAR) measures were derived from the estimates. Results A total of 2,090 patients participated; 42% were female with predefined oversampling of male patients, with a mean age of 45.2 years (range 18–83). Estimated effects were significant for all attributes (p<0.001), implying that they all influenced treatment choices and suggesting preferences differed between participants. Average RAI scores revealed different priorities (p<0.001) between males and females (Figure 1). While reducing pain and negative effect on semen parameters was most important to male patients, female patients were most concerned by risk of blood clots and serious infections. The remaining attributes were of lower importance but were still relevant. However, no single attribute explained treatment preferences by more than 30%. Preferences were also affected by patients' age: patients aged 18-44 years placed less importance on frequency and mode of treatment administration (p<0.05) than older age groups. Patients were willing to make benefit-risk trade-offs; they accepted extra risks of blood clots (male: 1.8%; female: 0.8%), serious infections (male: 2.5%; female: 1.0%), or negative effects on sperm (male: 7.4%) for an oral pill every day instead of injection once a week. They also accepted extra risks of blood clots (male: 2.3%; female: 1.2%), serious infections (male: 3.2%; female: 1.6%), or negative effects on sperm (male: 10.4%) for reducing amount of pain from 30% to 10%. Similar observations were made for improved performance of daily activities. However, acceptable trade-offs varied between patients (p<0.05). Conclusion Preferences of RA patients were driven by benefits and risks of RA treatments, with no single attribute dominating the decision making. Patients were willing to accept higher risk of serious infections and blood clots in exchange for improvements in pain, daily activities, or administration convenience. These findings emphasize the importance of considering the entire treatment profile, including benefits, risks, and administration to support SDM between providers and patients.Preference drivers: males – pain, blood clots; females – blood clots, infections, pain. Sperm risk data are based on male responses only. Acknowledgements This study was funded by Galapagos NV (Mechelen, Belgium). Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Medical writing support was provided by Brooke Middlebrook (Evidera) and publications management was provided by Aspire Scientific Ltd (Bollington, UK), funded by Galapagos NV. Disclosure of Interests Rieke Alten Consultant of: AbbVie, Amgen, Biogen, BMS, Celltrion, Gilead, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, UCB, Viatris, Juan Carlos Nieto González Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, FAES Farma, Gebro, Janssen, Lilly, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, GSK, Galapagos, Janssen, Lilly, MSD, Peggy Jacques: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, BMS, Boehringer, Eli Lilly, Galapagos, Pfizer, Roche, Sanofi, Consultant of: AbbVie, BMS, Gilead, Robert Moots Speakers bureau: Amgen, Galapagos, Consultant of: Ferring, Grant/research support from: Novartis, Helga Radner Speakers bureau: Gilead Sciences, Janssen, MSD, Pfizer Corporation Austria, Sebastian Heidenreich Employee of: Evidera Inc, which is part of Thermo Fisher Scientific's Clinical Research Group. Evidera received payment for conducting the work outlined in this work., Chiara Whichello Employee of: Evidera Inc, which is part of Thermo Fisher Scientific's Clinical Research Group. Evidera received payment for conducting the work outlined in this work., Nicolas Krucien Employee of: Evidera Inc, which is part of Thermo Fisher Scientific's Clinical Research Group. Evidera received payment for conducting the work outlined in this work., Monia Zignani Shareholder of: Galapagos, Employee of: Galapagos, Harald Vonkeman Speakers bureau: AbbVie, Boehringer Ingelheim, Galapagos, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Boehringer Ingelheim, Galapagos, Janssen, Novartis, Pfizer, UCB, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos.Figure 1RAI overall and by sex

Background Behçet’s disease (BD) is a rare, and severe, multisystemic inflammatory disease characterized by recurrent oral aphthous ulcers, genital ulcers, skin lesions, and both anterior and posterior uveitis; articular, vascular, gastroenteric and neurological involvement may also occur. The multi-organ involvement and the wide spectrum of clinical manifestations make the diagnosis of BD challenging. The lack of medication adherence leads to poorer health outcomes for the patients, which affect quality of life, generate economic loss for the healthcare system and trigger uncertainty for the healthcare prescribers in dealing with the disease treatment. This challenge is particularly important in BD, and for this reason, worldwide experts in BD and patient representatives living with BD gathered to launch the IMPACT_BD study. Objectives The objectives of IMPACT_BD are to explore the unmet needs in treatment adherence and the main reasons for low- or non-adherence, to create a tool aimed at identifying and monitoring the reasons of low treatment adherence and to plan specific actions aimed at improving treatment adherence in BD. Methods The methodology includes 5 phases. Phase A. Panel creation - The first step created a multi-stakeholder panel that included clinicians, BD patient’s representatives, BD caregiver representatives and other experts (economists, psychologist, pharmacists, etc). Phase B. Co-design process – Ad hoc surveys were created in co-design with the different stakeholders to capture the different dimensions, barriers and needs related to treatment adherence. The survey was translated into 8 languages and launched across Social Media (Phase C. Launch of the survey). Phase D. Data analysis, workshop and agreement – Answers to the survey questions will be elaborated to identify the main barriers and unmet needs in treatment adherence. An online workshop will be organized to co-design a tool that will enable the identification and the monitoring of BD treatment adherence during the clinical follow-up of BD patients. Phase E. Pilot phase for validation – The final tool will be translated into different languages and will be adopted in a pilot study. The results of the pilot phase will be discussed and refined within the panel. A list of future actions aimed at improving treatment adherence in BD patients will also be produced with the support of members of the co-design panel. Results The main results of the study will be represented by: the identification of the main barriers and unmet needs related to treatment adherence in BD patients, caregivers and families; the creation of a co-designed tool aimed at assessing the causes and barriers of low- or non-adherence in BD patients; and the planning of future initiatives aimed at improving treatment adherence in BD patients. Conclusion Assessing the barriers causing low or non-adherence in BD will provide relevant information that will support the clinicians and the other healthcare professionals caring for BD patients, by improving the clinical management of the disease; by taking tangible actions aimed at increasing adherence to treatment; and therefore by improving the wellbeing of BD patients, caregivers and families. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

Background:Behçet's syndrome (BS) is a rare multi-systemic vasculitis of unknown aetiology. Fibromyalgia syndrome (FMS) is more prevalent in rheumatological conditions such-as BS, than the general population. However, there is limited research into the aetiology and characteristics of pain in BS.Objectives:To describe the pain characteristics and incidence of FMS in people with BS and investigate their relationship with BS disease activity.Methods:A cohort study of BS patients attending the Liverpool Behçet's Centre between February 2017 and March 2019. BS was defined using the International Study Group Criteria. BS severity was assessed using the Behçet's Disease Current Activity Form. FMS was determined from consultant diagnosis. Assessments of pain included: Pain Visual Analogue Scale (PVAS), Pain Mannequin, Brief Pain Inventory, EQ-5D-3L and Short Form McGill. Pain and FMS prevalence were compared between high and low disease activity.Results:90% reported moderate-severe pain with a median PVAS score of 68/100 [38, 81]. 35.6% of participants had FMS and 46.5% experienced generalized pain. 76% of participants with high disease activity reported severe pain, compared to 39.1% with low disease activity (p = .003). Pain was more generalised in high disease activity (72%) compared to low disease activity (37.7%) (p = .003). FMS was more prevalent in the high disease activity group (52%) than the low disease activity group (29%) (p = .04).Conclusions:This is the first study to explore pain in participants with BS in the United Kingdom. The majority of BS patients experience moderate-severe widespread pain. Severe widespread pain is more prevalent in those with high disease activity. We have demonstrated a relationship between high disease activity, worse pain intensity, and FMS. This paper contributes to the understanding of two conditions which remain to be fully understood, FMS and BS, and generates new hypotheses to describe the interplay between.

Background High-quality randomised trials and predictive biomarkers are required to target therapy optimally in Behçet’s syndrome (BS) - especially with high cost biologics. Objectives Utilise a Bayesian approach to design and undertake a high quality randomised, head to head, controlled clinical trial of the two most widely used biologics for BS at the time of design of the trial: the anti-TNF infliximab and interferon alpha 2a Roferon and undertake an exploratory analysis of potential predictive biomarkers. Methods A pragmatic, prospective, standard of care, single masked, randomised, two arm, parallel head-to-head trial, with the exploratory evaluation of potential biomarkers IFNL3 and IFNL4 SNPs for Roferon, and urinary metabolomics as biomarkers for response to infliximab. Patients with active BS (utilising ISG 1990 classification criteria), with inadequate response to or intolerance of first line treatment were randomised to infliximab (5mg/kg ivi every 6-8 weeks depending on organ involvement) or Roferon (subcutaneous injection: standard tapering dose). Primary outcome: modified Behçet’s disease activity index (mBDAI) at 12 weeks of therapy. Secondary outcomes: (a) mBDAI at 24 weeks, (b) significant improvement at 12 and 24 weeks in vitreous haze and best corrected visual acuity change; oral ulcer severity score; number of genital ulcers; arthritis pain; adverse events; reduction in dose of glucocorticoid; Quality of Life and Physician’s Global Assessment (disease activity). Sample size was calculated utilising a Bayesian analysis of covariance model (80% credible interval): initial sample size 45/arm (Bayesian power 90%). With anticipated 10% drop-out, recruitment of 100 patients was initially planned. Following recommendations to reduce the overall length of the trial, this was revised down to 80 patients (36/arm allowing for 10% drop out): 80% equi-tailed credibility interval, Bayesian power 88%. A stratified block randomisation scheme was employed, based on randomly permuted blocks, with random block sizes of 2 and 4. Patient follow up was undertaken at weeks 12 and 24, following standard of care. Results In this first prospective head-to-head randomised controlled clinic trial of two biologic drugs in BS, infliximab and Roferon were equally effective, with a trend for minor benefit favouring infliximab for tolerability and treatment persistence. Genetic data suggested a potential association between patient outcome and carriage of either rs4803221 or rs7248668 variants in IFNL3 (IL-28B) gene locus in the Roferon-treated arm. However, statistical significance was lost when correcting for multiple testing. Metabolomic analysis identified potential markers for response to treatment with infliximab. Conclusion We report an equivalent efficacy between infliximab and Roferon in refractory active BS, better tolerability of Roferon compared to that anticipated, together with the potential for a novel metabolomic biomarkers identifying a clinical response to infliximab. Acknowledgements This work was funded by a UK National Institute for Health Research (NIHR) Efficiency and Mechanism Evaluation programme, 12/205 Very Rare Diseases/ EME:12/205/46 Trial Registration: EudraCT: 2014-005390-36; ISRCTN: ISRCTN49793874 Disclosure of Interests None Declared.