MANCHESTER, UK—TNF inhibitors and other flashy biologicals get more press, but lower-cost "old standy" drugs, such as methotrexate (MTX) and sulfasalazine (SSZ) are still doing most of the work of first-line treatment of early inflammatory or rheumatoid arthritis (RA). There have been surprisingly few studies examining how well these drugs perform over the long term. SL Hider, MD, and colleagues at the University of Manchester in the UK have contributed to this area by comparing long-term outcomes with MTX and with SSZ. They report in Annals of the Rheumatic Diseases that the two drugs have similar clinical efficacy at 2 years and at 5 years, but MTX appears to be somewhat more effective at protecting against bone erosions.1

"Both SSZ and MTX are effective agents, but there is good evidence, despite the shortfalls of an observational approach, that MTX has a much stronger potential for suppressing the development of erosions, which would support its being the preferred DMARD." —SL Hider, MD
"Our study aimed to investigate whether there were differences in the 2-year and 5-year outcome in a large inception cohort of patients prescribed MTX or SSZ as their first DMARD," Dr. Hider says.

The prospective cohort study followed up patients who had been recruited from primary care practices to the Norfolk Arthritis Register, a large population-based registry of patients with inflammatory polyarthritis. The follow-up included patients who had begun treatment with either MTX at 7.5 mg/week (n = 85) or SSZ at 2 g/day (n = 258) within 3 months of their baseline visit and had been followed up for at least 2 years.

Fewer erosions with MTX

Outcome measures included the Disease Activity Score (DAS) 28, the Health Assessment Questionnaire (HAQ), radiological erosions (Larsen Score), and cumulative mortality.

Clinical outcomes were similar at 2 years and 5 years. The SSZ patients had a higher proportion of erosive and mean Larsen Scores. After adjustment for baseline values, the odds of erosions at 5 years in the MTX group were 0.3 of those in the SSZ group, and the mean difference in Larsen Score was 31% lower (P = NS).

Furthermore, more of the MTX patients were still taking MTX as their first DMARD (34% vs 22%). "Continuation on MTX was substantially more in patients [initially] treated with MTX, and this agent was also associated with a considerable reduction in the likelihood of erosions at 5 years," Dr. Hider writes.

Because the patients in this study were unselected as much as possible, the researchers think that the results should have side applicability to other newly diagnosed patients with inflammatory polyarthritis.

"We conclude that both SSZ and MTX are effective agents, but there is good evidence, despite the shortfalls of an observational approach, that MTX has a much stronger potential for suppressing the development of erosions, which would support its being the preferred DMARD," Dr. Hider concludes.

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Reference

1. Hider SL, Silman A, Bunn D, et al. Comparing the long-term clinical outcome of treatment with methotrexate or sulfasalazine prescribed as the first disease-modifying antirheumatic drug in patients with inflammatory polyarthritis. Ann Rheum Dis. 2006;65:1449-1455.