Thursday, July 15, 2010

Treat RA Early, Aggressively, Researchers Say

ArthritisAccording to a recent clinical trial, disease-modifying antirheumatic drugs (DMARDs) should be used early and aggressively at the first signs of rheumatoid arthritis (RA). Results of an 11-year study, published in the open-access journal Arthritis Research & Therapy, show that active treatment with multiple DMARDS from the outset is effective both short- and long-term.

A team of researchers in Finland randomized 199 patients with early active RA to receive either treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone (COMBO), or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone (SINGLE) [Rantalaiho et al. 2010]. After 2 years, the drug-treatment strategy became unrestricted, but still targeted to achieving remission. Radiographs (x-rays) of hands and feet were analyzed by using the Larsen score at baseline, 2, 5, and 11 years, and the radiographs of large joints (eg, knee) were assessed at 11 years. The Larsen scoring method [more info here] incorporates both erosions and joint space narrowing in each joint determined from radiographs as a single score on a scale of 0 to 5.

At the end of the study, there were reference radiographs of hands and feet available at baseline and at 11 years for 65 subjects in each group. The mean Larsen score change from baseline to 11 years was significantly 37% less in the COMBO group than in the SINGLE group (p = 0.037). For large joints, 87% (95% CI, 74-94) and 72% (95% CI, 58-84) of the patients in the COMBO and the SINGLE treatment arms, respectively, had no erosive changes at 11 years. The authors conclude that patients treated initially with a combination of DMARDs have less short- and long-term radiologic damage than do those treated initially with DMARD monotherapy.

COMMENTARY: The authors note that with current therapies there is less radiographic damage found in patients with RA today than during previous decades. In their study, both treatment arms — combination therapy and monotherapy — demonstrated excellent small and large peripheral joint outcomes compared with historic cohorts, and this persisted for up to 11 years. Consequently, the need for joint-replacement operations decreased. Similarly, a new review in the Journal of Rheumatology discusses mounting evidence for adopting an early, aggressive, tight control approach to the management of RA, which yields superior clinical outcomes including inhibition of progressive structural damage [Mease 2010]. However, while this approach has been successfully implemented in other chronic diseases, such as diabetes, its use in RA has been less straightforward.

Curiously, none of the above authors comment on potential adverse effects of therapy with multiple as opposed to single DMARD agents, or the relative economic costs of the two approaches. Since both strategies produced favorable outcomes in the Finnish trial, albeit combination therapy appeared superior in radiographic analyses, it could be important to also consider comparative risks versus benefits from quality of life and economic perspectives.

> Mease PJ. Improving the routine management of rheumatoid arthritis: the value of tight control. J Rheumatol. 2010(July); online ahead of print [
PDF available here].
> Rantalaiho V, Korpela M, Laasonen L, et al. Early combination disease-modifying antirheumatic drug therapy and tight disease control improve long-term radiologic outcome in patients with early rheumatoid arthritis: the 11-year results of the Finnish Rheumatoid Arthritis Combination Therapy trial. Arthritis Res Ther. 2010(June),12(3):R122 [
article available here].