Objective In rheumatoid arthritis, the association between advanced therapies (including biologic disease‐modifying antirheumatic drugs [DMARDs] and targeted synthetic DMARDs) and methotrexate (MTX) is recommended by international societies. When MTX cannot be used, other conventional synthetic DMARDs (csDMARDs) may be proposed. We aimed to compare the safety and efficacy of MTX and non‐MTX csDMARDs in combination with advanced therapies. Methods We systematically searched the literature for studies comparing the effectiveness, retention rate, and safety of MTX versus non‐MTX csDMARDs (leflunomide or others) in combination with tumor necrosis factor inhibitors (TNFi), abatacept, rituximab, tocilizumab, and JAK inhibitors. Meta‐analysis was performed with RevMan, using an inverse variance approach with fixed or random‐effects models. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated. Results The literature search revealed 3,842 articles; 41 studies were included for the systematic literature review and 21 for the meta‐analysis: 13 with TNFi, 3 with abatacept, and 5 with rituximab. For TNFi, the European Alliance of Associations for Rheumatology (EULAR) response at 6 months was lower for patients receiving non‐MTX csDMARDs than for those using MTX (RR 0.93 [95% CI 0.87, 1.0], P = 0.04; n = 3,843; I2 = 28%), with a lower retention rate at 12 months. For abatacept, effectiveness and safety were similar between the 2 groups. For rituximab, a good EULAR response was higher with leflunomide than MTX (RR 1.38 [95% CI 1.13, 1.68], P = 0.001; n = 2,078; I2 = 0%), with similar adverse event rates. Meta‐analysis for tocilizumab or JAK inhibitors could not be performed. Conclusion The different csDMARDs seem safe and efficient to combine with advanced therapies in RA patients. Although MTX seems slightly superior to other csDMARDs in combination with TNFi, leflunomide might be superior to MTX in combination with rituximab.
Background:A screening program for multimorbidities started in 2014 at the Montpellier University Hospital for primary prevention in patients with chronic inflammatory rheumatic diseases (IRD).Objectives:The objective of this work was to assess the impact of this program on morbidity by comparing the hospitalization rate of those patients in the year following the screening to the one of patients with IRD who did not benefit from this program.Methods:Patients with IRD who benefit from the screening program in 2015, 2016 and 2017 were identified in the French national health database PMSI and matched to 3 controls living in the same area on age, sex, type of IRD, use of intravenous (IV) biologic (b) DMARDs and index date. The exclusion criteria were subjects in secondary prevention identified as history of myocardial infarction in the previous 5 years or use of antiplatelet therapy. The primary outcome was the rate of all-cause hospitalization in the following year. The secondary endpoints were hospitalizations for another reason than IRD (“non-IRD”) including those for cardiovascular [CV] events and major fractures. Hospitalization rates were compared between the two groups in the year after screening (or index date) and also between the year preceding screening and the year after for each group. Univariate and multivariate odds ratios (CI95%) were calculated, taking into account the medical history (hypertension, diabetes, heart failure, CV disease, COPD, major fractures in the 5 years preceding the index date) and hospitalizations in the previous year.Results:486 patients were identified and matched with 1458 controls. 67.08% had rheumatoid arthritis and 21.81% spondyloarthritis; 7% of them had IV bDMARDs. Unscreened patients had more hypertension (19% vs 10.1%), diabetes (9% vs 4.9%), heart failure (2.3% vs 0.4%) and “non-IRD” hospitalizations (78.5% vs 72.2%) in the 5 years preceding the index date. In the year following the index date, the percentages of “all causes” and “non-IRD” hospitalizations were significantly higher in non-screened than in screened patients (n = 1944, 64.8% versus 51%, Chi2 test, p <0.001; and 47.1% versus 37.9%, p <0.001 respectively). 17 (1.17%) cardiovascular events occurred in non-screened versus 2 (0.41%) in screened patients (n = 1944, Chi2 test, p = 0.14). There was no difference in the occurrence of CV events or major fractures between the 2 groups. In multivariate analysis, screening was associated with a 49% (0.51 [0.41-0.64]) reduction in “all causes” hospitalization and a 27% (0, 73 [0.58-0.91]) decrease in “non-IRD” hospitalization, with no difference for CV or fracture cardiological events. The risk factors associated with “non-IRD” hospitalization were: history of “non-IRD” hospitalization in the previous year (2.26 [1.63-3.13]), IV bDMARDs (1.69 [1, 14-2.53]) and age> 70 years (1.44 [1.02-2.03] vs <50 years). Hospitalization in the previous year for “all causes” or “non-IRD” was associated with rehospitalization in the following year in the non-screened group (p <0.001), but not in the screened group (p = 0.750 and p = 0.066 respectively).Conclusion:Our screening and prevention program was associated with a reduction in hospitalizations in the following year and a decrease in the risk of re-hospitalization compared to unscreened patients with IRD. This suggests a positive impact of performing systematic screening for multi-morbidities in IRD patients.Acknowledgements:We thank Pfizer for their financial supportDisclosure of Interests:guillaume decarriere: None declared, Jenica PASTOR: None declared, David DEMOULIN: None declared, Gael Mouterde Speakers bureau: Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Pfizer, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Grégoire Mercier: None declared, Jacques Morel Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Claire Daien Speakers bureau: Pfizer, Roche-Chugai, Fresenius, BMS, MSD, Lilly, Novartis, Galapagos, Consultant of: Abivax, Abbbvie, BMS, Roche-Chugai, Grant/research support from: Pfizer, roche-chugai, fresenius, MSD
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