RESEARCH - Combining DMARDs nearly always better in RA

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Combining DMARDs nearly always better in RA

Rheumawire

Nov 10, 2005

Janis

London, UK - Disease-modifying antirheumatic-drug (DMARD) combinations are

better than monotherapy for most rheumatoid-arthritis (RA) patients and for

early-stage as well as established disease, according to Dr Ernest HS Choy

(King's College Hospital, London, UK). Reporting in the November 2005 issue

of Rheumatology, Choy writes that a major meta-analysis of randomized

controlled trials (RCTs) from papers published from 1975 to 2004 shows that

the increased efficacy of combination treatment more than outweighs the

increased toxicity [1].

" I think the key issue in this study is that there is definitive evidence to

argue for more assertive management of early-RA patients, " Choy tells

rheumawire. " In patients with bad prognostic factors, combination therapy

should be the treatment of choice. "

Benefits outweigh risks for DMARD combinations

This meta-analysis identified 53 potentially relevant RCTs of combination

drug therapy for RA, of which 36 met the quality criteria and were included

in the analysis. This included 13 step-up, 16 parallel-group, and seven

step-down trials. Nine trials were in patients with early RA and 27 in

patients with established RA. The trials included more than 1800 patients.

The combinations included steroids added to DMARD monotherapy or DMARD

combinations, methotrexate (MTX) plus TNF inhibitors, and MTX plus

sulfasalazine or antimalarials (chloroquine or hydroxychloroquine).

To cut through the confusion surrounding efficacy and toxicity measures in

the various studies, Choy et al used two simple measures: the numbers of

patients withdrawn because of lack of efficacy, and the numbers of patients

withdrawn because of adverse events. Secondary end points were the number of

patients who achieved ACR20 responses or major clinical responses (ACR70 or

recorded as having entered remission).

" Overall, combination DMARD therapy was more effective than monotherapy (RR

0.35; 95% CI 0.28-0.45), although risk of toxicity was also slightly higher

(RR 1.37; 95% CI 1.16-1.62). Combinations of MTX with TNF inhibitors and MTX

with sulfasalazine or antimalarials showed good efficacy/toxicity ratios, "

the authors write.

Adding steroids to a single DMARD as bridging therapy had little effect.

Combination therapy was better both in established RA (RR 0.31; 95% CI

0.24-0.4; p=0.0001) and in early RA (RR 0.56; 95% CI 0.35-0.91; p=0.02).

Combination therapy was also better in all of the different types of trial

design.

Although combination therapy was associated with more toxicity, the

investigators found that fewer patients withdrew from combination therapy

than from monotherapy. The risk of withdrawal because of lack of effect was

75% lower with combination DMARD therapy than with monotherapy, whereas

withdrawals because of toxicity were 37% greater.

" The risk of side effects is higher with combination therapy, but the

benefit appears to outweigh the risk, " Choy says.

Choy adds, " Certainly early-RA patients with bad prognostic factors, such as

RF positive, erosive disease, and high HAQ score at onset, should be

considered for combination therapy at the onset of disease. Patients with

established RA inadequately controlled by monotherapy should be given

combination therapy. Whether early-RA patients with mild disease and good

prognostic factors should be given combination therapy is unclear. "

Source

1. Choy EHS, C, Dore CJ, DL. A meta-analysis of

the efficacy and toxicity of combining disease-modifying anti-rheumatic

drugs in rheumatoid arthritis based on patient withdrawal. Rheumatology

2005; 44:1414-1421.

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Mayo Clinic in Rochester

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s Hopkins Medicine

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