Methotrexate reduces immunogenicity in adalimumab treated rheumatoid arthritis patients in a dose dependent manner

• Published in: Annals of the rheumatic diseases Vol. 71; no. 11; pp. 1914 - 1915
• Main Authors: Krieckaert, Charlotte L, Nurmohamed, Michael T, Wolbink, Gerrit Jan
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.11.2012; BMJ Publishing Group; Elsevier Limited
• Subjects: Adalimumab; Antibodies, Anti-Idiotypic - blood; Antibodies, Anti-Idiotypic - drug effects; Antibodies, Anti-Idiotypic - immunology; Antibodies, Monoclonal, Humanized - immunology; Antibodies, Monoclonal, Humanized - therapeutic use; Antirheumatic Agents - immunology; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Disease; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Drug Interactions; Humans; Immunogenetic Phenomena - drug effects; Immunomodulators; Immunosuppressive Agents - pharmacology; Inflammatory joint diseases; Medical sciences; Methotrexate - pharmacology; Pharmacology. Drug treatments; Rheumatoid arthritis; Studies; Antineoplastic agent; Human; Immunopathology; Diseases of the osteoarticular system; Antipsoriatic agent; Rheumatology; Autoimmune disease; Inflammatory joint disease; Immunomodulator; Chronic; Treatment; Immunogenicity; Rheumatoid arthritis; Antirheumatic agent; Adalimumab; Methotrexate; Dose
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2012-201544

[...]in psoriasis patients, before the initiation of adalimumab therapy, MTX was discontinued. 3 Additionally, in ankylosing spondylitis patients with axial symptoms there is no proof for efficacy of MTX. 4 In a murine Pompe disease model, low dose administration of MTX (0.5 mg/kg) within 24 h after enzyme replacement treatment induced a significant reduction in antidrug antibody formation. 5 In this model, 0.5 mg/kg, administered three times, represented a human dose of 0.6 mg/week for a 5 kg infant, which is lower than the MTX dose prescribed for the treatment of adult RA. 5 Furthermore, this model showed that MTX should be initiated at the start of the immunogenic therapy because with MTX therapy it was not possible to abolish ongoing antidrug antibody formation. 5 6 In a human study with infliximab treated RA patients, 7.5 mg MTX weekly was sufficient in reducing immunogenicity of infliximab; however, in that study there was no comparison with other MTX doses. 7 The mechanism whereby MTX acts on the immune response remained unsolved; however, we hypothesise that suppression of early T and B cell expansion might be responsible for the modulation of the immune response.