The Canadian Methotrexate and Etanercept Outcome Study: a randomised trial of discontinuing versus continuing methotrexate after 6 months of etanercept and methotrexate therapy in rheumatoid arthritis. Issue 12 (26th August 2013)

• Record Type: Journal Article
• Authors: Pope, Janet E; Haraoui, Boulos; Thorne, J Carter; Vieira, Andrew; Poulin-Costello, Melanie; Keystone, Edward C
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Issue 12(2014)
• Page Start: 2144
• Page End: 2151
• Publication Date: 2013-08-26
• Subjects: Rheumatoid Arthritis -- Methotrexate -- Anti-TNF -- DMARDs (biologic); Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-203684
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objective: To determine if withdrawing methotrexate (MTX) after 6 months of combination etanercept (ETN)+MTX, in MTX-inadequate responders with active rheumatoid arthritis (RA), is non-inferior to continuing ETN+MTX. Methods: Tumour necrosis factor-inhibitor naïve RA patients with disease activity score 28 (DAS28)≥3.2, swollen joint count≥3, despite stable MTX, were treated with ETN+MTX for 6 months, followed by randomisation to either continue ETN+MTX or switch to ETN monotherapy for an additional 18 months. The primary endpoint was change in DAS28 from 6-month randomisation to 12 months. The non-inferiority margin of change in DAS28 was 0.6, with prespecified analyses (DAS28<3.2 vs DAS28≥3.2). Results: 205 patients were randomised. DAS28 was stable in patients on ETN+MTX and increased slightly in patients on ETN monotherapy from 6 to 12 months. Non-inferiority was not achieved, with an adjusted difference of 0.4 (0.1 to 0.7) between the ETN and the ETN+MTX groups, for the month 6–12 change in DAS28. However, patients who achieved low disease activity (LDA; DAS28<3.2) at 6 months had a similar disease activity at 12 months, whether on monotherapy or combination therapy (DAS28 change 0.7 ETN vs 0.57 ETN+MTX, p=0.8148). Conversely, for patients who did not reach LDA at 6 months, those on ETN monotherapy had increased disease activity at 12 months, while disease activity continued to decrease for patients on combination therapy, at 12 months (DAS28 change 0.4 ETN vs −0.4 ETN+MTX, p=0.0023). Conclusions: Non-inferiority was not achieved. Withdrawing MTX after 6 months of continuation ETN+MTX in MTX inadequate responders did not yield the same degree of improvement between 6 and 12 months compared with continuing ETN+MTX. Trial Registration: ClinicalTrials.gov−NCT00654368.