1. Methotrexate effect on immunogenicity and long-term maintenance of adalimumab in axial spondyloarthritis
- Author
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Eric Piver, Grégoire Cormier, Eric Lespessailles, Céline Desvignes, Elisabeth Gervais, Emmanuelle Dernis, Marine Samain, Hervé Watier, Antoine Martin, Gilles Paintaud, Valérie Devauchelle-Pensec, Theo Rispens, Denis Mulleman, Annick de Vries, Emilie Ducourau, Thomas Armingeat, Lucia Andras, Benoit Le Goff, Aleth Perdriger, Fabienne Le Guilchard, Philippe Goupille, David Ternant, Service de rhumatologie [Tours], CHU Trousseau [APHP], Sanquin Research and Landsteiner Laboratory [Amsterdam, The Netherlands], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Department of Immunopathology [Amsterdam, The Netherlands], University of Amsterdam [Amsterdam] (UvA), Service de Rhumatologie - CH Le Mans, Centre Hospitalier Le Mans (CH Le Mans), CHR de Blois, Service de Rhumatologie, Service de Rhumatologie, Rennes, Centre Hospitalier Universitaire [Rennes], Imagerie Multimodale Multiéchelle et Modélisation du Tissu Osseux et articulaire (I3MTO), Université d'Orléans (UO), Service de Rhumatologie [Orléans], Centre Hospitalier Régional d'Orléans (CHR), Service de Rhumatologie, CH Saint-Brieuc, Centre hospitalier Saint-Brieuc, Centre Hospitalier Départemental Vendée, CH de Saint-Nazaire, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Laboratoire de Pharmacologie-Toxicologie [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Département de Pharmacologie Médicale [CHRU Tours], Laboratory of Immunology, CHRU de Tours, Tours, France, Service de Médecine Nucléaire, CHRU de Tours, boulevard Tonnellé, 37000 Tours, France, INSERM U930, Université François Rabelais, boulevard Tonnellé, 37000 Tours, France, INSERM CIC 1415, boulevard Tonnellé, 37000 Tours, France., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Rhumatologie [CH Le Mans], Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional d'Orléans (CHRO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Landsteiner Laboratory, and AII - Inflammatory diseases
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Male ,[SDV]Life Sciences [q-bio] ,lcsh:Medicine ,Kaplan-Meier Estimate ,Gastroenterology ,Arthritis, Rheumatoid ,0302 clinical medicine ,Every other week ,immune system diseases ,Immunology and Allergy ,heterocyclic compounds ,Prospective Studies ,Axial spondyloarthritis ,skin and connective tissue diseases ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,Immunogenicity ,Long term maintenance ,Middle Aged ,spondyloarthritis ,humanities ,3. Good health ,Treatment Outcome ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Antirheumatic Agents ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Drug Therapy, Combination ,Female ,medicine.drug ,Adult ,musculoskeletal diseases ,medicine.medical_specialty ,Adolescent ,Immunology ,methotrexate ,Maintenance Chemotherapy ,Young Adult ,03 medical and health sciences ,Rheumatology ,Pharmacokinetics ,Internal medicine ,Spondylarthritis ,Adalimumab ,medicine ,Humans ,Adverse effect ,Aged ,030304 developmental biology ,030203 arthritis & rheumatology ,business.industry ,lcsh:R ,anti-TNF ,Methotrexate ,business - Abstract
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.
- Published
- 2020
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