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BackgroundThe major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD.MethodsThrough an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline.ResultsOut of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern.ConclusionIn this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

BackgroundGiven the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA.MethodsUsing a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls.ResultsAnalysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone.ConclusionsWe found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).

Objectives To investigate whether the efficacy and safety data from drug-registration trials can be extrapolated to real-life RA patients receiving RTX. Methods The 'AutoImmunity and Rituximab' (AIR-PR) registry is a French multicentre, prospective cohort of RA patients treated with RTX in a real-life setting. We compared treatment responses at 12 months and serious adverse events (AEs) between eligible and non-eligible patients, by retrieving the eligibility criteria of the three rituximab-registration trials. We determined critical eligibility criteria and modelled the benefit–risk ratio according to the number of fulfilled critical eligibility criteria. Results Among 1984 RA patients, only 9–12% fulfilled all eligibility criteria. Non-eligible patients had fewer EULAR responses at 12 months (40.3% vs 46.9%, P  = 0.044). Critical inclusion criteria included swollen joints count ≥4, tender joints count ≥4, CRP ≥15 mg/l and RF positivity. Critical exclusion criteria were age >80 years, RA-associated systemic diseases, ACR functional class IV, DMARD other than MTX and prednisone >10 mg/day. Only 20.8% fulfilled those critical eligibility criteria. During the first year, serious AEs occurred for 182 (9.2%) patients (70.3% serious infections) and patients with ≥1 critical exclusion criterion were at higher risk (hazard ratio 3.03; 95% CI 2.25–4.06; for ≥3 criteria vs 0). The incremental risk–benefit ratio decreased with the number of unmet critical inclusion criteria and of fulfilled exclusion criteria. Conclusion Few real-life RA patients were eligible for the drug-registration trials. Non-eligible patients had lower chance of response, and higher risk of serious AEs. Efficacy and safety data obtained from those trials may not be generalizable to RA patients receiving RTX in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Objective: We assess the clinical and structural impact at two years of progressively spacing tocilizumab (TCZ) or abatacept (ABA) injections versus maintenance at full dose in patients with rheumatoid arthritis in sustained remission. Methods: This multicenter open‐label noninferiority (NI) randomized clinical trial included patients with established rheumatoid arthritis in sustained remission receiving ABA or TCZ at a stable dose. Patients were randomized to treatment maintenance (M) at full dose (M‐arm) or progressive injection spacing (S) driven by the Disease Activity Score in 28 joints every 3 months up to biologics discontinuation (S‐arm). The primary end point was the evolution of disease activity according to the Disease Activity Score in 44 joints during the 2‐year follow‐up analyzed per protocol with a linear mixed‐effects model, evaluated by an NI test based on the one‐sided 95% confidence interval (95% CI) of the slope difference (NI margin 0.25). Other end points were flare incidence and structural damage progression. Results: Overall, 202 of the 233 patients included were considered for per protocol analysis (90 in S‐arm and 112 in M‐arm). At the end of follow‐up, 16.2% of the patients in the S‐arm could discontinue their biologic disease‐modifying antirheumatic drug, 46.9% tapered the dose and 36.9% returned to a full dose. NI was not demonstrated for the primary outcome, with a slope difference of 0.10 (95% CI 0.10–0.31) between the two arms. NI was not demonstrated for flare incidence (difference 42.6%, 95% CI 30.0–55.1) or rate of structural damage progression at two years (difference 13.9%, 95% CI −6.7 to 34.4). Conclusion: The Towards the Lowest Efficacious Dose trial failed to demonstrate NI for the proposed ABA or TCZ tapering strategy. [ABSTRACT FROM AUTHOR]

Objective Monoclonal gammopathy of undetermined significance (MGUS) is common, but there are scarce data regarding the effect of DMARDs on this premalignant condition. We aimed to evaluate the impact of JAK inhibitors (JAKis) on MGUS when initiated for an active rheumatic disease. Methods Patients with monoclonal abnormality prior to JAKi initiation for an active rheumatic disease were identified through the MAJIK-SFR Registry, a French multicentre prospective study. Clinical and biological data were collected using a standardized case report form. Results Twenty patients were identified with a mean age of 65 years and a diagnosis of RA (n  = 15), PsA (n  = 3), and axial SpA (n  = 2). The JAKi prescribed was baricitinib (n  = 9), tofacitinib (n  = 6) or upadacitinib (n  = 5), with a mean duration of 15.5 months. Seventeen patients had individualized serum monoclonal protein (IgG kappa n  = 9; IgG lambda n  = 4; IgM kappa n  = 3; IgA lambda n  = 1) ranging from 0.16 to 2.3 g/dl, and three patients did not have an initial measurable spike but they had a positive serum immunofixation. With a follow-up of 4–28 months, the serum monoclonal protein level decreased in 8 of 17 patients (47%), remained stable in 8 patients (47%) and increased in 1 patient (6%). The maximal decrease observed was an initial IgG kappa of 2.3 g/dl, decreasing to 0.2 g/dl at month 14. Conclusion This study provides reassuring and promising data on MGUS evolution in patients treated with JAKis for rheumatic diseases, which may guide the choice of treatment in patients with both conditions. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. Methods Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. Results In total, 511 patients were included [mean (s. d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: −0.04, 0.33) for 2 vs 0 visits; and +0.08 units (−0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. Conclusions In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome. [ABSTRACT FROM AUTHOR]