PMID- 31958280 OWN - NLM STAT- MEDLINE DCOM- 20210419 LR - 20210419 IS - 2056-5933 (Electronic) IS - 2056-5933 (Linking) VI - 6 IP - 1 DP - 2020 Jan TI - Methotrexate effect on immunogenicity and long-term maintenance of adalimumab in axial spondyloarthritis: a multicentric randomised trial. LID - 10.1136/rmdopen-2019-001047 [doi] LID - e001047 AB - 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 seems to increase adalimumab long-term maintenance. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Ducourau, Emilie AU - Ducourau E AD - Department of Rheumatology, University of Tours, EA 7501 GICC, CHRU de Tours, Tours, France. AD - Department of Rheumatology, CHR d'Orleans, Orleans, France. FAU - Rispens, Theo AU - Rispens T AD - Landsteiner Laboratory, Sanquin Research, Amsterdam, Netherlands. FAU - Samain, Marine AU - Samain M AD - Department of Rheumatology, University of Tours, EA 7501 GICC, CHRU de Tours, Tours, France. FAU - Dernis, Emmanuelle AU - Dernis E AD - Department of Rheumatology, CH du Mans, Le Mans, France. FAU - Le Guilchard, Fabienne AU - Le Guilchard F AD - Department of Rheumatology, CH de Blois, Blois, France. FAU - Andras, Lucia AU - Andras L AD - Department of Rheumatology, CH de Blois, Blois, France. FAU - Perdriger, Aleth AU - Perdriger A AD - Department of Rheumatology, CHRU de Rennes, Rennes, France. FAU - Lespessailles, Eric AU - Lespessailles E AD - Department of Rheumatology, CHR d'Orleans, Orleans, France. FAU - Martin, Antoine AU - Martin A AD - Department of Rheumatology, CH de Saint-Brieuc, Saint-Brieuc, France. FAU - Cormier, Gregoire AU - Cormier G AD - Department of Rheumatology, CHD Vendee, La Roche-sur-Yon, France. FAU - Armingeat, Thomas AU - Armingeat T AD - Department of Rheumatology, CH de Saint-Nazaire, Saint-Nazaire, France. FAU - Devauchelle-Pensec, Valerie AU - Devauchelle-Pensec V AD - Department of Rheumatology, Universite de Brest, Inserm UMR1227 LBAI, CHRU de Brest, Brest, France. FAU - Gervais, Elisabeth AU - Gervais E AD - Department of Rheumatology, CHRU de Poitiers, Poitiers, France. FAU - Le Goff, Benoit AU - Le Goff B AUID- ORCID: 0000-0002-4540-4549 AD - Department of Rheumatology, CHRU de Nantes, Nantes, France. FAU - de Vries, Annick AU - de Vries A AD - Biologicals Lab, Sanquin Diagnostic Services, Amsterdam, Netherlands. FAU - Piver, Eric AU - Piver E AD - Department of Biochemistry, University of Tours, Inserm U 1259, CHRU de Tours, Tours, France. FAU - Paintaud, Gilles AU - Paintaud G AD - Department of Pharmacology-Toxicology, University of Tours, EA GICC, CHRU de Tours, Tours, France. FAU - Desvignes, Celine AU - Desvignes C AD - Department of Pharmacology-Toxicology, University of Tours, EA GICC, CHRU de Tours, Tours, France. FAU - Ternant, David AU - Ternant D AD - Department of Pharmacology-Toxicology, University of Tours, EA GICC, CHRU de Tours, Tours, France. FAU - Watier, Herve AU - Watier H AUID- ORCID: 0000-0002-2139-4171 AD - Department of Immunology, University of Tours, EA 7501 GICC, CHRU de Tours, Tours, France. FAU - Goupille, Philippe AU - Goupille P AD - Department of Rheumatology, University of Tours, EA 7501 GICC, CHRU de Tours, Tours, France. AD - Inserm CIC1415, Tours, France. FAU - Mulleman, Denis AU - Mulleman D AUID- ORCID: 0000-0003-4089-7513 AD - Department of Rheumatology, University of Tours, EA 7501 GICC, CHRU de Tours, Tours, France denis.mulleman@univ-tours.fr. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200109 PL - England TA - RMD Open JT - RMD open JID - 101662038 RN - 0 (Antirheumatic Agents) RN - FYS6T7F842 (Adalimumab) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adalimumab/*administration & dosage/pharmacokinetics MH - Adolescent MH - Adult MH - Aged MH - Antirheumatic Agents/*administration & dosage MH - Arthritis, Rheumatoid/chemically induced MH - Drug Therapy, Combination MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Maintenance Chemotherapy/methods MH - Male MH - Methotrexate/*administration & dosage MH - Middle Aged MH - Prospective Studies MH - Spondylarthritis/*drug therapy MH - Treatment Outcome MH - Young Adult PMC - PMC7046954 OTO - NOTNLM OT - anti-TNF OT - methotrexate OT - spondyloarthritis COIS- Competing interests: EDu was invited to attend international congresses by Roche and UCB; she has acted as a consultant and given lectures on behalf of her institution for BMS and Abbvie. eDe participated on behalf of her institution in clinical trials sponsored by Abbvie, Roche, BMS, Novartis, P fi zer, UCB and Sanofi; she has given lectures for Abbvie, BMS, Janssen, P fi zer, UCB, Novartis; she has acted as a consultant for BMS and UCB, Novartis; she has been invited to attend international congresses by MSD, Roche, BMS Abbvie and Novartis. FLG has been invited to attend an international congress by Abbvie, Pfizer. LA was invited to attend international congress by Abbvie, Novartis, Pfizer and UCB. EL has received speaker and consultant fees from Amgen, Expanscience, Lilly, and MSD; and research grants from Abbvie, Amgen, Lilly, MSD and UCB. GC was invited to attend international congress by Abbvie. VD-P has received speaker and consultant fees from MSD, BMS, UCB, Roche; and research grants from Roche-Chugai. EG has participated on behalf of his institution in clinical trials sponsored by Roche, Lilly, Novartis, Amgen, and BMS; she has acted as a consultant and given lectures for Abbvie, BMS, MSD, P fi zer, Roche, UCB, Novartis; she has been invited to attend international congresses by MSD, Roche, Novartis and BMS. BLG has participated on behalf of his institution in clinical trials sponsored by Roche, Lilly, Novartis, P fi zer, UCB and MSD; he has acted as a consultant and given lectures for Abbvie, BMS, Janssen, MSD, P fi zer, Sano fi -Genzyme, UCB, Novartis; he has been invited to attend international congresses by MSD, Roche, Abbvie, Sanofi and Pfizer. EP was invited to attend an international congress by Buhlmann. GP reports grants received by his research team from Novartis, Roche Pharma, Sanofi-Genzyme, Chugai, Pfizer and Shire, outside of the submitted work. DT has acted as a consultant and given lectures for Sanofi, Amgen, PG participated on behalf of his institution in clinical trials sponsored by Abbvie, Roche, BMS, Boehringer, Lilly, Novartis, P fi zer, UCB, Janssen and MSD; he has acted as a consultant and given lectures for Abbvie, Biogaran, BMS, Hospira, Janssen, MSD, P fi zer, Sano fi -Genzyme, UCB; he has been invited to attend international congresses by MSD, Roche, BMS and Abbvie. DM has acted as a consultant and given lectures on behalf of his institution for Pfizer and Novartis; he has been invited to attend an international congress by Janssen-Cilag. His institution received grants for research from the non-governmental organisation Lions Club Tours Val de France. TR, MS, AP, CD, AdV, TA, AM and HW declared that they have no disclosure with the manuscript. EDAT- 2020/01/21 06:00 MHDA- 2021/04/20 06:00 PMCR- 2020/01/09 CRDT- 2020/01/21 06:00 PHST- 2019/07/02 00:00 [received] PHST- 2019/12/04 00:00 [revised] PHST- 2019/12/06 00:00 [accepted] PHST- 2020/01/21 06:00 [entrez] PHST- 2020/01/21 06:00 [pubmed] PHST- 2021/04/20 06:00 [medline] PHST- 2020/01/09 00:00 [pmc-release] AID - rmdopen-2019-001047 [pii] AID - 10.1136/rmdopen-2019-001047 [doi] PST - ppublish SO - RMD Open. 2020 Jan;6(1):e001047. doi: 10.1136/rmdopen-2019-001047. Epub 2020 Jan 9.