P Verschueren1, D De Cock2, L Corluy3, R Joos4, C Langenaken3, V Taelman5, F Raeman4, I Ravelingien6, K Vandevyvere7, J Lenaerts3, E Geens4, P Geusens8, J Vanhoof9, A Durnez7, J Remans10, B Vander Cruyssen6, E Van Essche11, A Sileghem12, G De Brabanter13, J Joly14, S Meyfroidt2, K Van der Elst15, R Westhovens1. 1. Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Leuven, Belgium Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. 2. Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration, Leuven, Belgium. 3. Reuma-instituut Hasselt, Hasselt, Belgium Jessa Ziekenhuis Hasselt, Hasselt, Belgium. 4. ZNA Jan Palfijn Antwerpen, Antwerpen, Belgium. 5. Heilig Hart Ziekenhuis Leuven, Leuven, Belgium. 6. Department of Rheumatology, Onze-Lieve-Vrouw Ziekenhuis Aalst, Aalst, Belgium. 7. AZ Groeninge Hospital Kortrijk, Kortrijk, Belgium. 8. ReumaClinic Genk & UHasselt, Hasselt, Belgium Maastricht UMC, Maastricht, the Netherlands. 9. ReumaClinic Genk & UHasselt, Hasselt, Belgium. 10. Reuma-instituut Genk, Genk, Belgium. 11. Imeldaziekenhuis Bonheiden, Bonheiden, Belgium. 12. ReumaClinic Hasselt, Hasselt, Belgium. 13. AZ Sint Lucas Brugge, Brugge, Belgium. 14. Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. 15. Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium Skeletal Biology and Engineering Research Center, KU Leuven Department of Public Health and Primary Care, Leuven, Belgium.
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. 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.
RCT Entities:
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. 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.
Entities:
Keywords:
Corticosteroids; DMARDs (synthetic); Early Rheumatoid Arthritis; Methotrexate; Outcomes research