Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial

Barnett ML, Kremer JM, St Clair EW, Clegg DO, Furst D, Weisman M, Trentham DE · Arthritis and Rheumatism

A dose-ranging trial including Trentham himself, and essentially null. Only the LOWEST dose (20 mcg/day) separated from placebo, on only one of three composite criteria (Paulus, p=0.035), failing both ACR criteria and the 30% joint-count criterion. Baseline anti-CII antibodies predicted response. The authors frame the low-dose finding as consistent with oral tolerance biology; it is equally consistent with multiple testing.

Population

Patients with active rheumatoid arthritis at 6 sites

Intervention

Oral type II collagen at 20, 100, 500 or 2500 micrograms/day for 24 weeks

Comparator

Placebo

Limitations

Non-monotonic dose response with only the lowest of four doses significant, on one of three endpoints — a pattern that should invite caution. Erratum published (Arthritis Rheum 1998;41:938) and a critical comment followed (Arthritis Rheum 1999;42:585-7).