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Objectives: To assess the best choice of second-line therapy between tumour necrosis factor-inhibitor (TNFi) and biologics of different-mode-ofaction (BDMA-rituximab/tocilizumab/abatacept) in rheumatoid arthritis (RA) by evaluating drug-survival following discontinuation of the first-line TNFi. Methods: This retrospective drug-survival study was performed across two different hospitals by conventional-statistics and machine-learning approach. Results: From a total of 435 patients, 213 (48.9%; TNFi = 122, BDMA = 91) discontinued their second-line biologic {median drug-survival: TNFi, 27 months [95% confidence interval (95%CI) 22-32] vs BDMA, 37 months (95%CI 32-52)}. As a second-line biologic, BDMA was likely to reduce the risk of treatment-discontinuation [hazard-ratio (HR) 0.63, 95%CI 0.48-0.83] compared to TNFi, but only in seropositive-patients (HR 0.52, 95%CI 0.38-0.73), not in seronegative-RA. Drug-survival benefit of BDMA over TNFi was not observed if the seropositive-patients were previously exposed to monoclonal-TNFi (HR 0.77, 95%CI 0.49-1.22) versus soluble-TNFi (etanercept/biosimilars) or if the first-line TNFi was terminated within 23.9 months of initiation (HR 0.97, 95%CI 0.56-1.68). Conclusions: BDMA, as a second-line biologic, is more likely to be sustained in seropositive-patients, particularly without prior exposure to monoclonal-TNFi. The drug-survival benefit of BDMA was not observed in seronegative-patients or if the first-line TNFi was stopped within 2 years. [ABSTRACT FROM AUTHOR]

Objective: With the aim of assessing the response to treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) used in patients with psoriatic arthritis (PsA), data on methotrexate, sulfasalazine (SSZ), and leflunomide were analyzed from baseline and subsequent follow-up (FU) questionnaires completed by patients with either PsA or other spondyloarthritides (SpAs). Material and Methods: A single-center real-life retrospective analysis was performed by obtaining clinical data via questionnaires administered before and after treatment. The indices used were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), wellbeing (WB), and treatment effect (TxE). The indices measured at baseline were compared with those measured on one occasion in a FU visit at least 1 year later. Results: A total of 73 patients, 51 with PsA (mean age 49.8±12.8 years; male-to-female ratio [M:F]=18:33) and 22 with other SpAs (mean age 50.6±16 years; M:F=2:20), were studied. BASDAI, BASFI, and WB displayed consistent improvements during FU assessments in both PsA patients and controls in comparison to baseline values. SSZ exhibited better efficacy as confirmed by TxE in both PsA patients and controls. ESR and CRP displayed no differences in either the PsA or the SpA group between the cases before and after treatment. Conclusion: Real-life retrospective analysis of three DMARDs used in PsA (and SpAs other than PsA) demonstrated that all three DMARDs that were used brought about improvements in BASDAI, BASFI, TxE, and WB. However, the greatest improvements at FU were seen with SSZ use in both PsA and control cohorts. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the ex vivo effect of the JAK1/2 inhibitor baricitinib on expression of pro-inflammatory mediators in rheumatoid arthritis (RA) fibroblast like synoviocytes (FLS) stimulated with TNFα, IL-1β and oncostatin M (OSM), and in RA synovial membrane cells (SMCs)., Methods: RA and osteoarthritis (OA) SMCs, were isolated from arthroplasty specimens of RA (n=8) and OA (n=8) patients, respectively, using enzymatic digestion followed by cell propagation to obtain RA (n=5) and OA (n=3) FLS. Normal FLS and normal human foreskin fibroblasts (HSF) were purchased from commercial sources. Fibroblasts were stimulated with cytokines with or without baricitinib. RA SMCs were cultured in the presence of baricitinib without stimulation. JAK/STAT activation and levels of mRNA and proteins of the various inflammatory cytokines (IL-6, IL-8, MCP-1, RANTES and IP-10) were determined by qPCR, ELISA and MSD., Results: Baricitinib inhibited OSM-induced JAK signalling in RA synovial fibroblasts and effectively suppressed subsequent expression of the proinflammatory mediators IL-6, MCP-1 and IP-10. However, baricitinib was not effective in altering levels of spontaneously released TNFα, IL-6 and IL-8 in RA SMC. Although both TNFα and IL-1β signal independently of the JAK/STAT pathway, in HSF, but not in RA FLS, baricitinib significantly inhibited TNFα- and IL-1β-induced MCP-1 and IP-10 protein levels in a dose dependent manner. Furthermore, baricitinib did not inhibit TNFα- and IL-1β-induced expression of IL-6, IL-8 and MCP-1 in RA FLS., Conclusions: These findings are consistent with known signalling pathways employed by OSM, TNFα and IL-1β, but our data suggest that in HSF, baricitinib may have anti-inflammatory effects via downstream modulation of cytokines and chemokines produced in response to TNFα or IL-1β.

Background: With the aim to study Spondyloarthritis in patients originating from Africa and compare the disease with the way it is manifested in Europeans, data was analysed from 62 African patients and compared with 56 Europeans living in the same geographical area (north East London, United Kingdom) and treated under the same health system (NHS). Data analysed were demographic, social and clinical characteristics., Results: Comparisons showed differences in prevalence of psoriasis (more in Caucasians), uveitis (more in Africans), smoking (more in Europeans), and significantly fewer patients of African origin declared family history of SpA. African patients have less disease activity (but not significantly better measured by BASDAI), and statistically significant better functional ability (BASFI) compared to Europeans. No difference has been noted in gender distribution, age of disease onset, disease duration, delay in diagnosis, disease associations with IBD, night pain, or overall wellbeing., Conclusions: SpA is different in Africans in that it shows to be milder in terms of disease activity and functional ability with more uveitis less psoriasis and less family history of SpAs., (© 2021 The Mediterranean Journal of Rheumatology (MJR).)

Objectives: To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren's syndrome (PSS) in a multicentre, multiobserver phase III trial substudy., Methods: Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0-11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point., Results: 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were -1.2 (95% CI -2.1 to -0.3; P=0.0099) and -1.2 (95% CI -2.0 to -0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48., Conclusions: We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker., Trial Registration Number: 65360827, 2010-021430-64; Results., Competing Interests: Competing interests: BAF and SJB have received support from the NIHR Birmingham Biomedical Research Centre. BAF paid instructor/consultant for Novartis, Roche, BMS, Virtualscopics. W-FN is consultant for Pfizer, UCB, MedImmune, GSK, Takeda and Sanofi. MB is consultant for GSK, Amgen/MedImmune and UCB. SJB is consultant for Cellgene, Glenmark, GSK, Eli Lilly, Novartis, Roche, Takeda, UCB., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To investigate whether rituximab, an anti-B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögren's syndrome (SS)., Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that included health economic analysis. Anti-Ro-positive patients with primary SS, symptomatic fatigue, and oral dryness were recruited from 25 UK rheumatology clinics from August 2011 to January 2014. Patients were centrally randomized to receive either intravenous (IV) placebo (250 ml saline) or IV rituximab (1,000 mg in 250 ml saline) in 2 courses at weeks 0, 2, 24, and 26, with pre- and postinfusion medication including corticosteroids. The primary end point was the proportion of patients achieving a 30% reduction in either fatigue or oral dryness at 48 weeks, as measured by visual analog scale. Other outcome measures included salivary and lacrimal flow rates, quality of life, scores on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index and EULAR Sjögren's Syndrome Disease Activity Index, symptoms of ocular and overall dryness, pain, globally assessed disease activity, and cost-effectiveness., Results: All 133 patients who were randomized to receive placebo (n = 66) or rituximab (n = 67) were included in the primary analysis. Among patients with complete data, 21 of 56 placebo-treated patients and 24 of 61 rituximab-treated patients achieved the primary end point. After multiple imputation of missing outcomes, response rates in the placebo and rituximab groups were 36.8% and 39.8%, respectively (adjusted odds ratio 1.13 [95% confidence interval 0.50, 2.55]). There were no significant improvements in any outcome measure except for unstimulated salivary flow. The mean ± SD costs per patient for rituximab and placebo were £10,752 ± 264.75 and £2,672 ± 241.71, respectively. There were slightly more adverse events (AEs) reported in total for rituximab, but there was no difference in serious AEs (10 in each group)., Conclusion: The results of this study indicate that rituximab is neither clinically effective nor cost-effective in this patient population., (© 2017, American College of Rheumatology.)

Objectives: Spondyloarthritis (SpA) is often diagnosed late in the course of the disease and improved methods for early diagnosis are required. We have tested the ability of genetic profiling to diagnose axial SpA (axSpA) as a whole group, or ankylosing spondylitis (AS) alone, in a cohort of chronic back pain patients., Methods: 282 patients were recruited from centres in the United Kingdom, Germany, Taiwan, Canada, Columbia and Turkey as part of the ASAS classification criteria for axSpA study (ASAS cohort). Subjects were classified according to the ASAS axSpA criteria, and the modified New York Criteria for AS. Patients were genotyped for ~200,000 immune-mediated disease SNPs using the Illumina Immunochip., Results: We first established the predictive accuracy of genetic data comparing 9,638 healthy controls and 4,428 AS cases from the homogenous International Genetics of AS (IGAS) Consortium Immunochip study which showed excellent predictive power (AUC=0.91). Genetic risk scores had lower predictive power (AUC=0.83) comparing ASAS cohort axSpA cases meeting the ASAS imaging criteria with IGAS controls. Comparing genetic risk scores showed moderate discriminatory capacity between IGAS AS and ASAS imaging positive cases (AUC 0.67±0.05), indicating that significant differences in genetic makeup exist between the cohorts., Conclusions: In a clinical setting of referred back pain patients suspected to have axial SpA we were unable to use genetic data to construct a predictive model better than that based on existing clinical data. Potential confounding factors include significant heterogeneity in the ASAS cohort, possibly reflecting the disease heterogeneity of axSpA, or differences between centres in ascertainment or classification performance.