Methotrexate effect on immunogenicity and long-term maintenance of adalimumab in axial spondyloarthritis: a multicentric randomised trial.

OBJECTIVES: Anti-drug antibodies (ADA) are responsible for decreased adalimumab efficacy in axial spondyloarthritis (SpA). We aimed to evaluate the ability of methotrexate (MTX) to decrease adalimumab immunisation. METHODS: A total of 110 patients eligible to receive adalimumab 40 mg subcutaneously (s.c.) every other week were randomised (1:1 ratio) to receive, 2 weeks before adalimumab (W-2) and weekly, MTX 10 mg s.c. (MTX+) or not (MTX-). ADA detection and adalimumab serum concentration were assessed at weeks 4 (W4), 8 (W8), 12 (W12) and 26 (W26) after starting adalimumab (W0). The primary outcome was the proportion of patients with ADA at W26. Four years after the study completion, we retrospectively analysed adalimumab maintenance in relation with MTX co-treatment duration. RESULTS: We analysed data for 107 patients (MTX+; n=52; MTX-; n=55). ADA were detected at W26 in 39/107 (36.4%) patients: 13/52 (25%) in the MTX+ group and 26/55 (47.3%) in the MTX- group (p=0.03). Adalimumab concentration was significantly higher in the MTX+ than MTX- group at W4, W8, W12 and W26. The two groups did not differ in adverse events or efficacy. In the follow-up study, MTX co-treatment >W26 versus no MTX or ≤W26 was significantly associated with adalimumab long-term maintenance (p=0.04). CONCLUSION: MTX reduces the immunogenicity and ameliorate the pharmacokinetics of adalimumab in axial SpA. A prolonged co-treatment of MTX>W26 seems to increase adalimumab long-term maintenance.

Drug maintenance of a second tumor necrosis factor alpha inhibitor in spondyloarthritis patients: A real-life multicenter study.

OBJECTIVES: Five TNF inhibitor (TNFi) agents are marketed for spondyloarthritis (SpA): 1 soluble receptor (SR) and 4 monoclonal antibodies (mAbs). From 15% to 30% of patients stop the first TNFi in the first 2 years, but we lack recommendations on the choice of the second TNFi. The aim here was to assess drug survival of a second TNFi in SpA and its determinants. METHODS: This was a multicenter observational study of SpA patients who started a first TNFi in 2013 and 2014 and were followed to 2018. For the first and second TNFi, we retrospectively collected data on initiation and discontinuation dates, type of TNFi, and reasons for withdrawal. Kaplan-Meier plots and log-rank tests were used to compare drug survival. Factors associated with drug survival of the second TNFi were analyzed by univariate Cox regression analyses. RESULTS: We included 244 patients. During a follow-up of 7,838 patient-months, 101 (41%) received 1 TNFi, and 143 (59%) switched to a second TNFi. Mean drug intake duration was significantly greater with the first than second TNFi: 21.7 (SD 19.6) and 15.4 (SD 13.6) months (P<0.001). When switching to another mAb or from an SR to an mAb (or the reverse), mean drug survival did not differ: 14.4 (SD 12.7) and 16 (SD 14.1) months (P=0.35). Factors associated with retaining the second TNFi were male sex (P=0.054) and age<41 years at SpA diagnosis (P=0.022). On multivariable analysis, only age<41 years at diagnosis remained independently associated with maintenance of the second TNFi. CONCLUSION: In SpA patients, drug survival is significantly longer with the first than second TNFi. Male sex and age<41 years at diagnosis were associated with retaining the second TNFi.

Application of Recommendations Regarding the Use of Subcutaneous Tumor Necrosis Factor Inhibitors in Spondyloarthritis by Rheumatologists in Daily Practice.

OBJECTIVE: To assess the implementation of European recommendations for use of TNF inhibitors for spondyloarthritis (SpA), rheumatologists' level of knowledge of and adherence to the recommendations, and potential barriers to the application of recommendations. METHODS: We conducted a retrospective study among 42 rheumatologists who initiated a first subcutaneous TNF inhibitor for SpA in 2013 or 2014. Thirty items from national and international recommendations were separated into 3 domains: indication, pretherapeutic monitoring, and management under TNF inhibitors. A standardized data collection procedure was used to gather data from medical files to assess the application of each recommendation. Questionnaires assessing the knowledge, level of adherence to each recommendation, and potential barriers to their implementation were sent to rheumatologists. RESULTS: Rheumatologists applied a mean of 60% of items from domains A and B, but less than 50% from domain C items. Recommendations regarding the search for previous infection and the prevention of future infections were the ones most often applied. However, < 60% of rheumatologists assessed cancer and other diseases before TNF inhibitor initiation. More than 95% of rheumatologists knew of the recommendations and had a high level of adherence. Lack of time, difficulties accessing specialized consultations, and lack of flexibility in the recommendations explained rheumatologists' difficulties in applying the recommendations. CONCLUSION: Despite high levels of knowledge of, and adherence to, recommendations for using TNF inhibitors for SpA, rheumatologists' application was limited because of a lack of human and material resources.