ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

Objective: To evaluate the efficacy of anti-tumour necrosis factor (TNF) treatments (given for rheumatological manifestations) in reducing uveitis flares in patients with spondylarthropathy in daily practice. Methods: A retrospective observational study of all patients with spondylarthropathy with at least one uveitis flare treated with anti-TNF in one centre (December 1997-December 2004. The number of uveitis flares per 100 patient-years was compared before and during anti-TNF treatment; each patient was his or her own control. The relative risk (RR) and the number needed to treat (NNT) were calculated. Results: 46 patients with spondylarthropathy treated with anti-TNF drugs had at least one uveitis flare (33 treated with anti-TNF antibodies, infliximab or adalimumab, and 13 with soluble TNF receptor, etanercept). The mean age at first symptoms was 26 years, 71% were men. Patients were followed for 15.2 years (mean) before anti-TNF versus 1.2 years during anti-TNF treatment. The number of uveitis flares per 100 patient-years before and during anti-TNF were, respectively: for all anti-TNF treatments,-51.8 v 21.4 (p = 0.03), RR = 2.4, NNT = 3 (95% confidence interval (CI) 2 to 5); for soluble TNF receptor-54.6 v 58.5 (p = 0.92), RR = 0.9; and for anti-TNF antibodies-50.6 v 6.8 (p = 0.001), RR = 7.4, NNT = 2 (95% CI 2 to 5). Conclusion: Anti-TNF treatments were efficacious in decreasing the number of uveitis flares in patients with spondylarthropathy. Anti-TNF antibodies decreased the rate of uveitis flares, whereas soluble TNF receptor did not seem to decrease this rate. These results could have consequences for the choice of anti-TNF treatment in certain patients.

The rate of serious infections during TNF-alpha blocker treatment observed in daily practice conditions was much higher than in phase III trials evaluating TNF-alpha blockers. Serious infections are frequent in daily practice and close monitoring is required.

Macrophages contribute to the pathogenesis of rheumatoid arthritis (RA). They can display different states of activation or “polarization,” notably the so-called inflammatory “M1” and the various alternative “M2” polarizations, characterized by distinct functions. Data regarding the effects of RA anti-cytokine biological disease-modifying anti-rheumatic drugs (bDMARDs) on macrophage polarization are scarce. We aimed to assess in vitro modulation of macrophage polarization by bDMARDs targeting pro-inflammatory cytokines in RA. We generated monocyte derived macrophages using blood samples from 20 RA patients with active RA and 30 healthy controls. We evaluated in vitro the impact on M1 inflammatory macrophages of: etanercept (ETA), adalimumab (ADA), certolizumab (CZP), tocilizumab (TCZ), and rituximab (RTX). We assessed the impact on macrophage polarization using flow cytometry and RTqPCR to study the expression of surface markers and perform functional studies of cytokine production, phagocytosis, and negative feedback control of inflammation. Among evaluated bDMARDs, anti-TNF agents modulated the polarization of inflammatory macrophages by decreasing inflammatory surface markers (CD40, CD80) and favoring alternative markers (CD16, CD163, MerTK). Anti-TNF agents also induced alternative functions in macrophages activated in inflammatory condition with (i) the inhibition of inflammatory cytokines (TNF, IL-6, IL-12), (ii) an increase in phagocytosis. These findings were mechanistically related to an increase in early IL-10 production, responsible for higher negative feedback control of inflammation involving SOCS3 and Gas6. This IL-10 effect was STAT3-dependent. Anti-TNF agents not only inhibit in vitro inflammatory functions of macrophages, but also favor resolution of inflammation through polarization toward alternative features specifically involving the IL-10/STAT3 axis.

US-detected residual synovitis is frequent and predicts the risk of relapse and structural progression in RA patients with CR.

Vertebral size should be considered as a potential independent vertebral fracture risk factor.

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The 158V/F polymorphism of FCGR3A seems to influence the response to RTX in patients with RA after failure, intolerance or contraindication to TNF blockers.