Rheumatoid arthritis (RA) is prevalent in Yakima Indians, a Native American tribe. HLA–DR4, the HLA specificity commonly associated with RA in Caucasians, is rare among the Yakima. Using a specific oligonucleotide probe that recognizes DR4 nucleotide sequences associated with RA, a rare HLA–Dw16 gene was identified in 83% of Yakima patients with RA and in 60% of Yakima control subjects. This shared sequence encodes a discrete class II epitope that is highly correlated with RA in both DR4 positive and DR4 negative individuals.

Objective. To assess the relative efficacy of methotrexate (MTX), azathioprine (AZA), and their combination in the treatment of rheumatoid arthritis (RA) in a double-blind, prospective, multicenter, controlled trial.Methods. Two hundred nine patients with active RA were treated with escalating doses of MTX (5-15 mg/week), AZA (50-150 mg/day), or combination (5 mg MTXIweek plus 50 mg AZAlday-7.5 mg MTXlweek plus 100 mg AZMday), with opportunity to increase the dosage at 6-week intervals. The patients were evaluated for significant clinical and laboratory improvement and assessed for radiologic progression at 48 weeks.Results. One hundred ten patients remained on the initial, randomly assigned therapeutic regimen. The percentage of patients who were responders, defined as those who had 30% or greater improvement in at least 3 of 4 variables, was 38% for the combination treatment, 26% for AZA, and 45% for MTX (P = 0.06). A trend toward decreased radiologic progression was seen in the MTX-treated patients. Termination of treatment due to adverse experience occurred more frequently with combination and AZA treatments than with MTX treatment. Lack of effectiveness, adverse gastrointestinal effects, and liver enzyme elevation were the most frequent causes of treatment discontinuation.Conclusion. This study establishes that the combination of MTX and AZA in the dosages utilized is not associated with more toxicity than treatment with single agents; however, enhanced efficacy is also not seen. There is a trend toward decreased radiologic progression in patients treated with MTX.

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