OBJECTIVES:Mycophenolate mofetil (MMF) is routinely used in early diffuse cutaneous systemic sclerosis (dcSSc) but not in limited cutaneous (lc)SSc. This may miss an opportunity to slow disease progression. MINIMISE-Pilot tested the feasibility of an open-label event-driven randomised trial of MMF vs no immunosuppression in lcSSc. METHODS:We tested the feasibility of a trial evaluating the impact of MMF on a novel event-driven composite endpoint. The MINIMISE endpoint measures time to worsening of lcSSc determined by progressive lung fibrosis, pulmonary hypertension, scleroderma renal crisis, heart failure, severe gut involvement, major digital vascular complications or death. Prespecified 'Stop-Go' criteria were agreed. Subjects were stratified by ACA status. RESULTS:Recruitment was challenging. A total of 53 subjects were screened and 43 were randomised, 21 to the MMF arm. Since recruitment was <60 participants, MINIMISE-Pilot was terminated based upon the prespecified threshold for continuation. During the treatment period there were no clinical worsening endpoints. Adherence to MMF was generally high, with 19 participants (95%) being 100% adherent at week 1, decreasing to 9 participants (64%) at week 24. CONCLUSION:MINIMISE-Pilot achieved its goal as a feasibility trial, leading to early termination of the study due to low recruitment. The rationale and concept for this study remain very strong. However, our findings suggest that a randomised prospective trial across 12 sites in the UK with relatively short follow-up duration is not feasible. This will inform the design of future studies testing the benefit of MMF in lcSSc. TRIAL REGISTRATION:Eudract (https://eudract.ema.europa.eu/) 2019-004139-21.

OBJECTIVE:Our objective was to test the hypothesis, in a double-blind, placebo-controlled study that vipoglanstat, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1), which decreases prostaglandin E2 (PGE2) and increases prostacyclin biosynthesis, improves RP. METHODS:Patients with SSc and ≥7 RP attacks during the last screening week prior to a baseline visit were randomized to 4 weeks treatment with vipoglanstat 120 mg or placebo. A daily electronic diary captured RP attacks (duration and pain) and Raynaud's Condition Score, with change in RP attacks/week as the primary end point. Cold challenge assessments were performed at baseline and end of treatment. Exploratory end points included patients' and physicians' global impression of change, Assessment of Scleroderma-associated Raynaud's Phenomenon questionnaire, mPGES-1 activity, and urinary excretion of arachidonic acid metabolites. RESULTS:Sixty-nine subjects received vipoglanstat (n = 33) or placebo (n = 36). The mean weekly number of RP attacks [baseline; vipoglanstat 14.4 (S.D. 6.7), placebo 18.2 (12.6)] decreased by 3.4 (95% CI -5.8; -1.0) and 4.2 (-6.5; -2.0) attacks per week (P = 0.628), respectively. All patient-reported outcomes improved, with no difference between the groups. The mean change in recovery of peripheral blood flow after the cold challenge did not differ between the study groups. Vipoglanstat fully inhibited mPGES-1, resulting in 57% reduction of PGE2 and 50% increase of prostacyclin metabolites in the urine. Vipoglanstat was safe and well tolerated. CONCLUSION:Although vipoglanstat was safe, and well tolerated in a dose achieving full inhibition of mPGES-1, it was ineffective in SSc-related RP. Further development and evaluation of vipoglanstat will therefore be in other diseases where mPGES-1 plays a pathogenetic role. TRIAL REGISTRATION:ClinicalTrials.gov, https://www.clinicaltrials.gov, NCT0474420.

FILOSOPHY (NCT04871919) is an ongoing, prospective, observational real-world European study of filgotinib for RA. We report up to 1-year interim data from UK patients. Patients with moderate to severe active RA are prescribed filgotinib for the first time in daily practice. Assessments included DAS28-CRP, CDAI, pain (visual analog scale [VAS]), FACIT-Fatigue and activity impairment (WPAI-RA). Treatment-emergent adverse events (TEAEs) were reported. From October 2021 to January 2024, 155 UK patients were treated (median follow-up: 529 days). Most patients received filgotinib plus other csDMARDs (69.7%) and a daily dose of 200 mg (89.0%; Table). Improvements in DAS28-CRP and CDAI occurred from Month 1 and were maintained up to Month 12. Median (IQR) DAS28-CRP was 5.3 (4.6, 6.1) at baseline (n = 93), 4.2 (2.7, 5.5) at Month 1 (n = 35) and 3.1 (2.2, 4.4) at Month 12 (n = 37). At Month 12, 51.4% (19/37) of patients had DAS28-CRP ≤3.2. Improvements were observed in four subgroups: patients treated with filgotinib monotherapy, patients treated with filgotinib plus other csDMARDs, advanced therapy-experienced patients (who received ≥1 prior tsDMARD or bDMARD for RA) and advanced therapy-naïve patients. Improvements in VAS pain and FACIT-Fatigue scores were observed from Week 1. At Month 12, median (IQR) score was 43.5 (18.0, 62.0) for VAS pain (n = 86) and 32.0 (21.0, 40.0) for FACIT-Fatigue (n = 86). Mean (SD) activity impairment (WPAI-RA) reduced from 62.4% (21.2) at baseline to 43.8% (25.4) at Month 12. TEAEs were serious in 20 patients and led to treatment discontinuation in 19. Cardiovascular events (n = 21) included unstable angina (n = 2), stroke, transient ischemic attack and pulmonary embolism (each n = 1). Other TEAEs of interest were COVID-19 (n = 30), malignant/unspecified tumor (excluding NMSC; n = 4), fractures (n = 3) and herpes zoster (n = 3). There were no cases of deep vein thrombosis or cardiac failure. Two deaths occurred (lobar pneumonia; pneumonia and interstitial lung disease), considered unrelated to study treatment by the investigator. Interim data from UK patients with RA treated with filgotinib in FILOSOPHY show early and maintained improvements in disease activity and patient-reported pain, fatigue and activity impairment. Safety findings up to Month 12 were in line with the known safety profile of filgotinib. M.K. Nisar: Honoraria; AbbVie, Alfasigma S.p.A, BMS, Celgene, Chugai, Galapagos, Lilly, Medac, MSD, Novartis, Pfizer, Roche, UCB. Member of speakers’ bureau; AbbVie, Alfasigma S.p.A, BMS, Celgene, Chugai, Galapagos, Lilly, Medac, MSD, Novartis, Pfizer, Roche, UCB. Other; Undertakes clinical trials for AbbVie, Alfasigma S.p.A, BMS, Celgene, Chugai, Galapagos, Lilly, Medac, MSD, Novartis, Pfizer, Roche, UCB, Support for attending conferences from AbbVie, Alfasigma S.p.A, BMS, Celgene, Chugai, Galapagos, Lilly, Medac, MSD, Novartis, Pfizer, Roche, UCB. S. Bhat: Other; Support for attending a conference from Galapagos. O. Bouzid: Other; Employee of Alfasigma S.p.A. T. Daud: Other; Employee of Alfasigma S.p.A. T.P.A. Debray: Consultancies; Biogen, Daiichi Sankyo, Galapagos, Gilead, Provides consulting services to Alfasigma S.p.A. J. Galloway: Consultancies; AbbVie, Galapagos, Janssen, Lilly, Pfizer. Honoraria; AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB. Grants/research support; AstraZeneca, Janssen, Pfizer. N.D. McKay: Consultancies; Gilead, UCB. Member of speakers’ bureau; Galapagos. Other; Registration for conference fees from AbbVie, Novartis, UCB. His department has received grants and payments from a wide range of pharmaceutical companies for research and education. L. Robertson: Other; Financial support for conference attendance from UCB. H. Tahir: Consultancies; AbbVie, Alfasigma S.p.A, Galapagos, Janssen, Lilly, Novartis, UCB. Grants/research support; AbbVie, Alfasigma S.p.A, Galapagos, Janssen, Lilly, Novartis, UCB.

Background/Aims FILOSOPHY (NCT04871919), an ongoing, observational Phase 4 study, will assess the effectiveness and safety of filgotinib, a JAK1-preferential inhibitor, in patients with RA in a real-world setting in Europe. We report interim UK data. Methods FILOSOPHY will enroll approximately 1,500 adults with moderate-to-severe active RA, upon first exposure to filgotinib, prescribed according to the product label and local standard-of-care. DAS28-CRP and CDAI were assessed at baseline, Month one, three and six and pain (visual analog scale [VAS]) and FACIT-Fatigue score at baseline, Week one, two and three and Month one, three and six. A reduction of >= 10 mm in VAS pain or increase of >= 4 in FACIT-Fatigue score were considered a clinically meaningful change from baseline (CFB). Treatment-emergent adverse events (TEAEs) on study were reported. Results By January 31, 2023, 130 patients had been treated in the UK; baseline characteristics and study treatment are reported in the Table. Median (IQR) CFB in DAS28-CRP was -1.1 (-2.5, -0.5) at Month one (N = 29), -1.7 (-2.6, -1.2) at Month 3 (N = 32) and -2.5 (-3.2, -1.0) at Month six (N = 27). Median (IQR) CFB in CDAI was -15.0 (-26.0, -8.0) at Month one (N = 31), -17.0 (-27.0, -12.0) at Month three (N = 31) and -25.0 (-30.0, -16.0) at Month 6 (N = 30). The proportion of patients with a clinically meaningful CFB in FACIT-Fatigue score was 45.0% (n = 18/40) at Week 1 and 65.6% (n = 21/32) at Month six. For VAS pain, the proportions were 47.5% (n = 19/40) at Week 1 and 66.7% (n = 22/33) at Month six. Similar trends were seen in the monotherapy and combination groups. No unexpected TEAEs occurred. Six patients discontinued the study prematurely; there was one death (lobar pneumonia); none were lost to follow-up. Conclusion Interim UK data showed pain and fatigue improved with filgotinib treatment as early as Week one and disease activity as early as Month one, the first timepoint that DAS28-CRP and CDAI were assessed; improvements were maintained up to Month six. While conclusions regarding safety cannot be made due to the short follow-up and small sample size, no new safety findings were observed. Long-term follow-up is needed to further evaluate effectiveness and safety. Disclosure B. Kirkham: Consultancies; AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB. Member of speakers' bureau; AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB. Grants/research support; Eli Lilly, Novartis. N.D. McKay: Consultancies; Gilead, UCB. Member of speakers' bureau; Galapagos. Other; Registration for conference fees from AbbVie, Novartis, UCB. His department has received grants and payments from a wide range of pharmaceutical companies for research and education. A.G. Pratt: Consultancies; Inflection Biosciences (paid to Newcastle University). Grants/research support; Galapagos, GSK, Pfizer (paid to Newcastle University). J. Barry: Other; Employee of Galapagos. O. Bouzid: Consultancies; Galapagos. T.P.A. Debray: Consultancies; Biogen, Daiichi Sankyo, Galapagos, Gilead. S. Bhat: None. L. Robertson: Other; Financial support for conference attendance from UCB. J. Galloway: Consultancies; AbbVie, Galapagos, Janssen, Lilly, Pfizer. Honoraria; AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB. Member of speakers' bureau; AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB. Grants/research support; AstraZeneca, Janssen, Pfizer.

Abstract Objectives Although the painful and disabling features of early diffuse cutaneous SSc (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate-dose prednisolone in early dcSSc. Methods PRedSS set out as a Phase II, multicentre, double-blind randomized controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomized to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the HAQ Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients. Results Thirty-five patients were randomized (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was −0.10 (97.5% CI: −0.29, 0.10), P = 0.254, and in mRSS −3.90 (97.5% CI: −8.83, 1.03), P = 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (P = 0.027), anxiety (P = 0.018) and helplessness (P = 0.040) than control patients at 3 months. There were no renal crises, but sample size was small. Conclusion PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomized trial. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.

Abstract Background/Aims Giant cell arteritis (GCA) is a systemic inflammatory disease of medium to large sized arteries. Diagnosis of GCA is a medical emergency due to the consequence of permanent blindness if not treated early with glucocorticoids. The objective of this audit was to assess the effectiveness of the GCA fast track clinic (FTC) in NHS Tayside. The current practice was compared with British Society of Rheumatology (BSR) standards. Methods This was a retrospective audit from March 2019 to May 2021. All patients referred with suspicion of GCA were included. Main outcomes measured were referral time, investigations and management. Data were collected through electronic records. Results 120 patients were included (median age 71 years; F71.7%). 35% of patients were diagnosed with GCA. Most common symptoms were headache (94.2%), jaw claudication (26.7%), visual symptoms (36.7%), PMR symptoms (21.7%), systemic symptoms (50%). As seen in Table 1, 50% with visual symptoms were seen by ophthalmology within 24 hours. 70.8% were seen by rheumatology within 24 hours. 89% were given steroids within 24 hours from suspicion. 80.8% were investigated with ultrasound or biopsy. Comparing with expected standards, provision of written information, advice on recurrence of symptoms, calculation of CRP, documentation of bone protection was achieved at 100%. Immediate follow-up time was 6 weeks. One patient lost vision while on steroids. Conclusion Early recognition and prompt management of GCA is crucial for a good prognosis. NHS Tayside’s FTC has allowed for quick evaluation for most patients within 24 hours and has improved prognosis in patients. Disclosure D. Subramanian: None. S. Bhat: None.

SummaryThe human leucocyte antigen HLA‐B27 is strongly associated with ankylosing spondylitis, a form of seronegative inflammatory arthritis. In this study aspects related to several hypothesized mechanisms of disease pathogenesis have been investigated. Blood monocyte‐derived dendritic cells (DC) from a small patient cohort of 29 patients with ankylosing spondylitis and one with reactive arthritis, were compared with DC from 34 healthy control subjects, of whom four were found to be HLA‐B27 positive. The ability of HLA‐B27 to form heavy‐chain dimers reactive with monoclonal antibody HC10 was tested, along with the induction of endoplasmic reticulum (ER) stress, assessed by splicing xbp1 mRNA and immunoblotting of Immunoglobulin Binding Protein (BiP). Additionally, the protein expression levels of the ER resident aminopeptidase gene ERAP1 in patients with ankylosing spondylitis was also determined, following its recent identification as a novel disease‐associated gene. No significant difference was noted in the global levels of HC10‐reactive MHC class I dimers formed in either the patient or control DC populations. Stress on the ER, as determined by xbp1 mRNA splicing, was not detected but lower levels of BiP were observed in the DC from patients. Of further potential interest, in this patient cohort the expression of ERAP1 appeared to be higher in a number of patient DC samples when compared with controls, suggesting over‐expression of ERAP1 as a mechanism promoting ankylosing spondylitic pathogenesis.

returning to <100 or undetectable immediately with no associated clinical evidence of liver disease and no changes to treatment.Conclusions: Successful treatment of RA with anti-TNF in the setting of chronic HBV infection is possible without long term prophylactic anti-virals.Elevation of HBV DNA levels were transient and settled to <100 or undetectable without changes to treatment.