Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial.

Abstract

OBJECTIVES:

To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial.

METHODS:

400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered.

RESULTS:

Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006).

CONCLUSIONS:

For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile.

EUDRACT NUMBER:

2008-007225-39.

• Authors: P Verschueren, D De Cock, L Corluy, R Joos, C Langenaken, V Taelman, F Raeman, I Ravelingien, K Vandevyvere, J Lenaerts, E Geens, P Geusens, J Vanhoof, A Durnez, J Remans, B Vander Cruyssen, E Van Essche, A Sileghem, G De Brabanter, J Joly, S Meyfroidt, K Van der Elst, R Westhovens
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 74 Issue 1 Pg. 27-34 (Jan 2015) ISSN: 1468-2060 [Electronic] England
• PMID: 25359382 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Antirheumatic Agents
• Glucocorticoids
• Isoxazoles
• Sulfasalazine
• Leflunomide
• Prednisone
• Methotrexate

Topics

• Adult
• Aged
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (diagnosis, drug therapy)
• Drug Therapy, Combination (methods)
• Early Medical Intervention
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Induction Chemotherapy (methods)
• Isoxazoles (therapeutic use)
• Leflunomide
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Prednisone (therapeutic use)
• Risk Assessment
• Severity of Illness Index
• Sulfasalazine (therapeutic use)
• Treatment Outcome