ObjectivesTo investigate whether the transient reduction in rheumatology services imposed by virus containment measures during the COVID-19 pandemic was associated with disease worsening in axial spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA).MethodsPatient-reported disease activity assessed during face-to-face visits and/or via a smartphone application were compared between three periods of each 2 months duration (before, during and after the COVID-19-wave) from January to June 2020 in 666 patients with axSpA, RA and PsA in the Swiss Clinical Quality Management cohort.ResultsThe number of consultations dropped by 52%, whereas the number of remote assessments increased by 129%. The proportion of patients with drug non-compliance slightly increased during the pandemic, the difference reaching statistical significance in axSpA (19.9% vs 13.2% before the pandemic, p=0.003). The proportion of patients with disease flares remained stable (<15%). There was no increase in mean values of the Bath Ankylosing Disease Activity Index, the Rheumatoid Arthritis Disease Activity Index-5 and the Patient Global Assessment in patients with axSpA, RA and PsA, respectively.ConclusionA short interruption of in-person patient–rheumatologist interactions had no major detrimental impact on the disease course of axSpA, RA and PsA as assessed by patient-reported outcomes.

ObjectivesTo integrate published single-cell RNA sequencing (scRNA-seq) data and assess the contribution of synovial fibroblast (SF) subsets to synovial pathotypes and respective clinical characteristics in treatment-naïve early arthritis.MethodsIn this in silico study, we integrated scRNA-seq data from published studies with additional unpublished in-house data. Standard Seurat, Harmony and Liger workflow was performed for integration and differential gene expression analysis. We estimated single cell type proportions in bulk RNA-seq data (deconvolution) from synovial tissue from 87 treatment-naïve early arthritis patients in the Pathobiology of Early Arthritis Cohort using MuSiC. SF proportions across synovial pathotypes (fibroid, lymphoid and myeloid) and relationship of disease activity measurements across different synovial pathotypes were assessed.ResultsWe identified four SF clusters with respective marker genes: PRG4+ SF (CD55, MMP3, PRG4, THY1neg); CXCL12+ SF (CXCL12, CCL2, ADAMTS1, THY1low); POSTN+ SF (POSTN, collagen genes, THY1); CXCL14+ SF (CXCL14, C3, CD34, ASPN, THY1) that correspond to lining (PRG4+ SF) and sublining (CXCL12+ SF, POSTN+ + and CXCL14+ SF) SF subsets. CXCL12+ SF and POSTN+ + were most prominent in the fibroid while PRG4+ SF appeared highest in the myeloid pathotype. Corresponding, lining assessed by histology (assessed by Krenn-Score) was thicker in the myeloid, but also in the lymphoid pathotype + the fibroid pathotype. PRG4+ SF correlated positively with disease severity parameters in the fibroid, POSTN+ SF in the lymphoid pathotype whereas CXCL14+ SF showed negative association with disease severity in all pathotypes.ConclusionThis study shows a so far unexplored association between distinct synovial pathologies and SF subtypes defined by scRNA-seq. The knowledge of the diverse interplay of SF with immune cells will advance opportunities for tailored targeted treatments.

ObjectiveTo compare effectiveness of treatment with secukinumab (SEC) with that of alternative tumour necrosis factor inhibitors (TNFis) in patients with axial spondyloarthritis (axSpA) after withdrawal from one or more TNFis.MethodsPatients diagnosed as having axSpA in the Swiss Clinical Quality Management cohort were included if they had initiated SEC (n=106) or an alternative TNFi (n=284) after experiencing TNFi failure. Drug retention was investigated with matching weights propensity score (PS) analyses and multiple adjusted Cox proportional hazards models. Matching weights PS-based analyses and multiple-adjusted logistic regression analyses were used to assess the proportion of patients reaching 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 1 year.ResultsSEC was more often used as third-line or later-line biological drug (76% vs 40% for TNFi). Patients starting SEC had higher BASDAI, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and C reactive protein levels. A comparable risk of drug discontinuation was found for SEC versus TNFi (HR 1.14, 95% CI 0.78 to 1.68 in the PS-based analysis and HR 1.16, 95% CI 0.79 to 1.71 in the multiple-adjusted analysis). No significant difference in BASDAI50 responses at 1 year was demonstrated between the two modes of biological drug action, with CI of estimates being, however, wide (OR for SEC vs TNFi 0.76, 95% CI 0.26 to 2.18 and 0.78, 95% CI 0.24 to 2.48 in the PS-based and the covariate-adjusted model, respectively).ConclusionOur data suggest a comparable effectiveness of SEC versus an alternative TNFi after prior TNFi exposure.

Background Sex differences with regard to clinical manifestations and response to tumor necrosis factor inhibitors (TNFi) have been delineated for the radiographic form of axial spondyloarthritis (axSpA). More limited evidence for a differential effectiveness of treatment in genders exists for the nonradiographic disease state (nr-axSpA). The aim of the study was to compare demographics, clinical parameters, and response to TNFi in women versus men with nr-axSpA. Methods We compared disease characteristics of 264 women and 231 men with nr-axSpA at inclusion in the prospective Swiss Clinical Quality Management Cohort. Response to a first TNFi was assessed in 85 women and 78 men without diagnosed co-morbid fibromyalgia. The primary outcome was the proportion of patients achieving the 40% improvement in the Assessment of SpondyloArthritis international Society criteria (ASAS40) at 1 year. Additional response outcomes were evaluated as secondary outcomes. Patients having discontinued TNFi were considered non-responders. Logistic regression analyses were adjusted for baseline differences, which might potentially mediate the effect of sex on treatment response. Results Compared to men, women had a longer diagnostic delay, a higher level of perceived disease activity, and more enthesitis and were in a lower percentage HLA-B27 positive. An ASAS40 response was achieved by 17% of women and 38% of men (OR 0.34; 95% CI 0.12, 0.93; p = 0.02). A significantly lower response rate in women was confirmed in the adjusted analysis (OR 0.19; 95% CI 0.05, 0.62; p = 0.009) as well as for the other outcomes assessed. Conclusion Despite only few sex differences in patient characteristics in nr-axSpA, response rates to TNFi are significantly lower in women than in men.

Objective To investigate whether spinal radiographic progression relates to structural damage at the sacroiliac level in axial spondyloarthritis (axSpA). Methods Patients classified as nonradiographic (nr-) and radiographic (r-) axSpA in the Swiss Clinical Quality Management cohort with radiographs performed every 2 years, scored according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), were included. The relationship between classification status and spinal progression during 2 years was investigated using binomial generalized estimating equations models with adjustment for sex, ankylosing spondylitis disease activity score (ASDAS) and tumour necrosis factor inhibitor treatment. Baseline spinal damage was considered an intermediate variable and included in sensitivity analyses. Results In total, 88 nr-axSpA and 418 r-axSpA patients contributed to data for 725 radiographic intervals. R-axSpA patients were more frequently male, had a longer disease duration and higher structural damage at baseline. Mean (SD) mSASSS change over 2 years was 0.16