ObjectivesAnti-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.MethodsA 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.ResultsWe 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).ConclusionMTX 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.

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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.

Background:Immunogenicity of anti TNF monoclonal antibodies leads to poor or secondary loss of response. Methotrexate reduces anti-drug antibodies (ADA) to adalimumab at week 26 in spondyloarthritis (SpA).1 Objectives:Herein we sought to examine adalimumab long term persistence in aDA positive versus aDA negative SpA patients.Methods:The CoMARIS study (Combination of Methotrexate and adalimumab to Reduce Immunization in patients with axial SpA) is a 26-week prospective, randomised, open-labelled, multicentre study in which patients received adalimumab 40 mg subcutaneously (s.c.) every other week either in combination with MTX 10 mg s.c. For 26 weeks or without MTX. In a post hoc analysis, we reviewed the charts of patients to assess adalimumab persistence. A Cox model analysis was performed to test the following covariates: MTX combination or not, sex, presence of aDA at week 26.Results:Data from 104 patients (54 without MTX and 50 with MTX) were reviewed, and time of adalimumab discontinuation was collected. The median time of follow-up was 210.57 weeks. ADA positivity at week 26 was the only covariate associated with adalimumab persistence. The median retention rate of adalimumab in aDA positive patients was 56.9 weeks, as compared with 98.6 weeks in those without aDA (log rank: p=0.015). In the Cox model analysis, the presence of aDA at week 26 increased the risk of adalimumab discontinuation by 1.78 [IC 95%=1.11-2.85], p=0.016.Figureadalimumab retention rate in aDA positive patients (n=38) at week 26 versus aDA negative patients (n=66), log rank: p=0.015Conclusion:Immunogenicity is a key factor that contributes to adalimumab discontinuation in SpA. MTX at initiation may therefore be considered in combination to adalimumab in SpA patients.References[1] Ducourau E, et al. Methotrexate reduces adalimumab immunogenicity in patients with spondyloarthritis: a randomized clinical trial. EULAR17-1527.Acknowledgement:This work was promoted by the Regional University Hospital Center of Tours and supported by grants from the French Ministry for Health and Sport within the framework of the Programme Hospitalier de Recherche Clinique2011.Disclosure of interests:Marine Samain: None declared, Emilie Ducourau Speakers bureau: BMS and abbvie, theo Rispens Grant/research support from: Genmab, Speakers bureau: Pfizer, abbvie, Regeneron, Emmanuelle Dernis: None declared, Fabienne Le Guilchard: None declared, Lucia andras: None declared, aleth Perdriger: None declared, Eric Lespessailles Grant/research support from: Grants/research support from amgen, Eli Lily, MSD, UCB., Consultant for: Consultant for amgen, Expanscience, Eli Lilly, MSD, UCB., antoine Martin: None declared, Grégoire Cormier: None declared, Thomas armingeat: None declared, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Elisabeth Gervais Speakers bureau: abbvie, BMS, MSD, Pfizer, Roche, UCB, Novartis, Benoit Le Goff Speakers bureau: abbvie, BMS, Janssen, MSD, Pfizer, Sanofi-Genzyme, UCB, Novartis, annick de...

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