RESEARCH - Factorial randomized controlled trial of steroids and combination DMARDs in RA

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ls of the Rheumatic Diseases 2008;67:656-663

Copyright © 2008 BMJ Publishing Group Ltd & European League Against

Rheumatism

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EXTENDED REPORTS

Factorial randomised controlled trial of glucocorticoids and

combination disease modifying drugs in early rheumatoid arthritis

E H S Choy 1, C M 1, V Farewell 2, D 3, A Hassell 4, L

Chau 1, D L 1, for the CARDERA (Combination Anti-Rheumatic Drugs

in Early Rheumatoid Arhritis) Trial Group

1 Sir Alfred Baring Garrod Clinical Trials Unit, Academic Department

of Rheumatology, King's College School of Medicine, Weston Education

Centre, Cutcombe Road, London, UK

2 Medical Research Council Biostatistics Unit, University of Cambridge

Institute of Public Health, Cambridge, UK

3 Department of Rheumatology, Freeman Hospital, Freeman Road, High

Heaton, Newcastle upon Tyne, UK

4 Department of Rheumatology, Hayward Hospital, High Lane, Burslem,

Stoke-on-Trent, UK

Objective: Treating early active rheumatoid arthritis (RA) with

disease modifying antirheumatic drug (DMARD) monotherapy achieves

incomplete outcomes and intensive treatment seems preferable. As the

relative benefits of combining two DMARDs, one DMARD with

glucocorticoids and two DMARDs with glucocorticoids are uncertain we

defined them in a factorial trial.

Methods: A 2-year randomised double-blind factorial trial in patients

with RA within 2 years of diagnosis treated with methotrexate studied

the benefits of added ciclosporin, 9 months intensive prednisolone or

both (triple therapy). The primary outcome was the number of patients

with new erosions. Secondary outcomes included Larsen's x-ray scores,

disability, quality of life and adverse events.

Findings: 1391 patients were screened and 467 randomised. Over 2 years

132 (28%) changed therapy and 88 (19%) were lost to follow-up. The

number of patients with new erosions was reduced by nearly half by

adding ciclosporin or prednisolone (p = 0.01 and 0.03); both

treatments reduced increases in Larsen's x-ray scores by over 2 units

(p = 0.008 and 0.003). A further reduction in erosive damage was seen

with combined use of both treatments. Their effects on erosive damage

appeared independent. Triple therapy reduced disability and improved

quality of life compared with methotrexate; ciclosporin and

prednisolone acted synergistically. More patients withdrew because of

adverse events with triple therapy, without an increase in serious

adverse effects.

Conclusions: This study confirms the existence of a " window of

opportunity " in early RA, when intensive combination therapy produces

sustained benefits on damage and disability. Although

methotrexate–prednisolone combinations reduce erosive damage, the

synergistic effect of two DMARDs is needed to improve quality of life.

http://ard.bmj.com/cgi/content/abstract/67/5/656?etoc

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