Impact of discordance between patient's and evaluator's global assessment on treatment outcomes in 14 868 patients with spondyloarthritis.

OBJECTIVES: To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (ΔPEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe. METHODS: Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by χ2 test and by logistic regression across quartiles of baseline ΔPEG, separately in female and male PsA and axSpA patients. RESULTS: We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline ΔPEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P <0.001), with 6/12/24-months' BASDAI < 2 (P ≤0.002) and ASDAS < 1.3 (P ≤0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P ≤0.04) and DAPSA28 ≤ 4 (P ≤0.01), but not DAS28CRP(3)<2.6 (P ≥0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients. CONCLUSION: High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes.

Pro-inflammatory S100A11 is elevated in inflammatory myopathies and reflects disease activity and extramuscular manifestations in myositis.

BACKGROUND: S100A11 (calgizzarin), a member of the S100 family, is associated with oncogenesis, inflammation and myocardial damage. Our aim was to analyse S100A11 in idiopathic inflammatory myopathies (IIMs) and its association with disease activity features and cancer development. METHODS: S100A11 in muscle was determined by immunohistochemistry in polymyositis (PM), dermatomyositis (DM), myasthenia gravis (MG) and in subjects without autoimmune inflammatory disease (HC). S100A11 in plasma was measured in 110 patients with IIMs (PM, DM, and cancer associated myositis (CAM) patients) and in 42 HC. Disease activity was assessed by myositis disease activity assessment (MYOACT), muscle enzymes and C-reactive protein (CRP) were measured by routine laboratory techniques; autoantibodies by immunoprecipitation or by immunoblot. RESULTS: We observed an accumulation of S100A11 in the cytoplasm of regenerating and necrotizing muscle fibres of PM and DM patients. S100A11 was increased in plasma of all myositis patients compared to HC (3.8 (1.5-16.8) vs 2.8 (1.7-11.2) ng/ml, p = 0.011) and in DM and CAM patients compared to HC (4.0 (2.2-14.9) and 4.5 (1.5-9.1) vs 2.8 (1.7-11.2) ng/ml, p < 0.001 and p = 0.022, respectively). In all myositis patients, S100A11 correlated with the levels of lactate dehydrogenase (r = 0.256, p = 0.011), aspartate aminotransferase (AST) (r = 0.312, p = 0.002), CRP (r = 0.254, p = 0.022) and MYOACT (r = 0.245, p = 0.022). S100A11 was associated with MYOACT (r = 0.377, p = 0.030) and pulmonary and cutaneous disease activity in DM patients (r = 0.408, p = 0.017 and r = 0.417, p = 0.01, respectively). S100A11 was related to the levels of AST (r = 0.412, p = 0.027) in PM and to the levels of creatine phosphokinase (r = 0.432, p = 0.028) in CAM patients. CONCLUSIONS: We show for a first time a potential implication of S100A11 in the local inflammatory and tissue remodelling processes in myositis and an association of circulating S100A11 with disease activity and extra muscular manifestations in DM.

Effect of CTLA4-Ig (abatacept) treatment on T cells and B cells in peripheral blood of patients with polymyositis and dermatomyositis.

We aimed to evaluate in vivo effects of abatacept on phenotypes of T and B cells in the circulation of myositis patients in a sub-study of the ARTEMIS trial. Twelve patients with paired frozen PBMCs before and after 6-month abatacept treatment were included in this sub-study where mass cytometry (CyTOF) was chosen as a technology to be tested for its utility in a real-life clinical immune monitoring setting. Using CyTOF, the peripheral T cell phenotypes demonstrated considerable variation over time and between individuals precluding the identification of treatment-specific changes. We therefore conclude that studies of patient cohorts displaying wide clinical heterogeneity using mass cytometry must be relatively large in order to be suited for discovery research and immune monitoring. Still, we did find some correlations with functional muscle outcome, namely positive correlations between the ratio of CD4+ T cells and CD8+ T cells (CD4/CD8) in peripheral blood samples both at baseline and after treatment with muscle endurance improvement as assessed by the functional index-2 (FI-2) test. Our data suggest that the CD4/CD8 ratio in circulation at time of active disease may be a predictor of treatment efficacy in myositis patients.

Serum levels of B-cell activating factor of the TNF family (BAFF) correlate with anti-Jo-1 autoantibodies levels and disease activity in patients with anti-Jo-1positive polymyositis and dermatomyositis.

BACKGROUND: B-cell activating factor of the tumour necrosis factor family (BAFF) plays a role in autoantibody production and is elevated in dermatomyositis (DM) and anti-Jo-1-positive polymyositis (PM). We investigated the inter-relationships between serum levels of BAFF, anti-Jo-1 autoantibodies, and disease activity. METHODS: Serum levels of BAFF and anti-Jo-1 antibodies measured by enzyme-linked immunosorbent assay (ELISA) were compared to levels of myoglobin, creatine kinase (CK), aminotransferases (alanine (ALT) and aspartate (AST)), C-reactive protein (CRP), and disease activity assessed by the Myositis Disease Activity Assessment Tool in 63 anti-Jo-1 antibody-positive DM/PM patients. Serial serum samples collected at 2 (46 cases) and 3-5 time points (23 cases) were included. Relationships between BAFF, anti-Jo-1, disease activity, CRP, and their longitudinal changes were evaluated using correlation analysis, multiple regression (MR), path analysis (PA), and hierarchical linear models (HLM). RESULTS: Cross-sectional assessment demonstrated significant correlations between the levels of BAFF and anti-Jo-1 antibodies which were associated with levels of CK, myoglobin, AST, and CRP, as well as multivariate associations between BAFF, anti-Jo-1 antibodies, and CK levels. PA revealed direct effects of anti-Jo-1 antibodies on CK (ß = 0.41) and both direct (ß = 0.42) and indirect (through anti-Jo-1 antibodies; ß = 0.17) effects of BAFF on CK. Changes in levels of both BAFF and anti-Jo-1 between two time points (Δ) were associated with Δmyoglobin and Δaminotransferases and changes of BAFF correlated with ΔCK, Δcutaneous, Δmuscle, Δglobal, and Δskeletal disease activities. The longitudinal analysis showed a high intra-individual variability of serum levels of BAFF over time (97%) which could predict 79% of the variance in anti-Jo-1 levels. The anti-Jo-1 variability was explained by inter-individual differences (68%). The close longitudinal relationship between levels of BAFF, anti-Jo-1, and disease activity was supported by high proportions of their variance explained with serum levels of CK and CRP or pulmonary and muscle activities. CONCLUSION: Our findings of associations between levels of BAFF and anti-Jo-1 antibodies in serum and myositis activity suggest a role of this cytokine in disease-specific autoantibody production as part of disease mechanisms, and support BAFF as a potential target for intervention in anti-Jo-1-positive myositis patients.

Clinical trials roundup in idiopathic inflammatory myopathies.

PURPOSE OF REVIEW: To review recent advances in the treatment of idiopathic inflammatory myopathies (IIMs) with emphasis on new biological agents and on some less commonly used immunosuppressive drugs. RECENT FINDINGS: Double-blinded comparison of oral high-dose pulse dexamethasone with standard high daily prednisolone doses showed similar efficacy in the composite score, significantly longer median time to relapse with prednisolone and fewer side effects with dexamethasone treatment. Use of intravenous immunoglobulins (IVIGs) in IIMs is associated with variable results; however, recent retrospective evaluation of IVIGs administration to steroid-resistant patients with esophageal involvement showed good effect. Whereas smaller open studies with rituximab reported a very good efficacy, even in notoriously difficult-to-treat anti-signal recognition particle-positive cases, the double-blind trial has not reached the primary endpoint. Studies with TNF neutralization are reporting results ranging from only a modest or no effect to a promising outcome in the most recent trial with etanercept. Pilot studies suggest efficacy of alemtuzumab in inclusion body myositis and allogeneic mesenchymal stem cell transplantation in polymyositis/dermatomyositis. SUMMARY: Unmet need for efficacious therapy in IIMs exists and therefore a coordinated effort is necessary to properly evaluate various new classical and biological agents.

Treatment-resistant inflammatory myopathy.

When confronted with a dermatomyositis or polymyositis patient not responding to immunosuppressive treatment, physicians must first ask whether the original diagnosis was correct. In this review, we provide a guide to the clinical features and ancillary tests, which might be helpful in the differential diagnosis of myositis. Particular attention is paid to the role of autoantibody detection, as some of them are not only relatively specific for the disease but also associated with unique clinical features including resistance to treatment. Subsequently, other possible explanations of treatment resistance are listed and a short overview of treatment options for resistant myositis patients is given.