Tapering towards DMARD-free remission in established rheumatoid arthritis: 2-year results of the TARA trial

• Published in: Annals of the rheumatic diseases Vol. 79; no. 9; pp. 1174 - 1181
• Main Authors: van Mulligen, Elise, Weel, Angelique E, Hazes, J M, van der Helm-van Mil, Annette, de Jong, Pascal Hendrik Pieter
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.09.2020; BMJ Publishing Group
• Subjects: Antirheumatic Agents - administration & dosage; Arthritis, Rheumatoid - drug therapy; Disease; Drug Administration Schedule; Drug dosages; Female; Follow-Up Studies; Humans; Induction Chemotherapy - methods; Joint diseases; Male; Methotrexate; Methotrexate - administration & dosage; Middle Aged; Patients; Remission; Remission (Medicine); Rheumatoid Arthritis; Rheumatology; Severity of Illness Index; Single-Blind Method; Studies; Symptom Flare Up; Time Factors; TNF inhibitors; Treatment Outcome; Tumor necrosis factor; Tumor Necrosis Factor Inhibitors - administration & dosage; Tumor necrosis factor-TNF; Tumors; Withholding Treatment; Netherlands; methotrexate; outcome assessment; arthritis; tumor necrosis factor inhibitors; health care; rheumatoid
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2020-217485

ObjectivesTo evaluate the 2-year clinical effectiveness of two gradual tapering strategies. The first strategy consisted of tapering the conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) first (i.e., methotrexate in ~90%), followed by the tumour necrosis factor inhibitor (TNF-inhibitor), the second strategy consisted of tapering the TNF-inhibitor first, followed by the csDMARD.MethodsThis multicentre single-blinded randomised controlled trial included patients with rheumatoid arthritis (RA) with well-controlled disease for ≥3 consecutive months, defined as a Disease Activity Score (DAS) measured in 44 joints ≤2.4 and a swollen joint count ≤1, which was achieved with a csDMARD and a TNF-inhibitor. Eligible patients were randomised into gradual tapering the csDMARD followed by the TNF-inhibitor, or vice versa. The primary outcome was the number of disease flares. Secondary outcomes were DMARD-free remission (DFR), DAS, functional ability (Health Assessment Questionnaire Disability Index (HAQ-DI)) and radiographic progression.Results189 patients were randomly assigned to tapering their csDMARD (n=94) or TNF-inhibitor (n=95) first. The cumulative flare rate after 24 months was, respectively, 61% (95% CI 50% to 71%) and 62% (95% CI 52% to 72%). The patients who tapered their csDMARD first were more often able to go through the entire tapering protocol and reached DFR more often than the group that tapered the TNF-inhibitor first (32% vs 20% (p=0.12) and 21% vs 10% (p=0.07), respectively). Mean DAS and HAQ-DI over time, and radiographic progression did not differ between groups (p=0.45, p=0.17, p=0.8, respectively).ConclusionThe order of tapering did not affect flare rates, DAS or HAQ-DI. DFR was achievable in 15% of patients with established RA, slightly more frequent in patients that first tapered csDMARDs. Because of similar effects from a clinical viewpoint, financial arguments may influence the decision to taper TNF-inhibitors first.