Chicken Collagen: Good for Rheumatoid Arthritis?
May 15, 1998 3 minutes read
Chicken Collagen: Good for Rheumatoid Arthritis?
ABSTRACT & COMMENTARY
Synopsis: The results of a multicenter, randomized controlled trial of oral type II collagen for patients with rheumatoid arthritis were disappointing for three of the active treatment groups. Only the study group receiving the lowest dose of oral collagen, 20 mcg per day, did significantly better than the placebo-treated group, and then only when the weakest criteria for improvement were used to define response to treatment.
Source: Barnett ML, et al. Arthritis Rheum 1998;41:290-297.
Those with good memories may recall the media "hype" that greeted the 1993 report of treatment of rheumatoid arthritis with oral type II collagen derived from chicken cartilage.1 The current report is a follow-up to that initial promising study. This time, adult patients with rheumatoid arthritis were enrolled at six sites and were withdrawn from their slow-acting anti-rheumatic drugs for 8-12 weeks before receiving either placebo or one of four different daily doses of oral type II collagen, prepared from chick sternal cartilage. The doses of 20 mcg, 100 mcg, 500 mcg, or 2500 mcg of type II collagen per day were mixed with orange juice and given once in the morning. Patients were allowed to remain on a stable dose of corticosteroid (equivalent to prednisone < 10 mg/d) and of background nonsteroidal anti-inflammatory drugs (NSAIDS). A total of 273 patients were evaluable, and 228 patients completed the six-month trial. Most of the dropouts were due to lack of efficacy. Measurement of tender joints, swollen joints, grip strength, 50-foot walking times, as well as patient and physician global assessment were used to calculate aggregate scores to determine responders and nonresponders. The Paulus criteria, the American College of Rheumatology Criteria for response, or an ad hoc criterion of 30% or greater improvement in tender and swollen joint scores were the three indicators of "response." Only the group receiving type II collagen at a dose of 20 mcg per day had a statistically significant difference from the placebo group in the number of responders. And, this difference in response was only statistically significant when the Paulus criteria were used. There was no statistically significant difference from placebo when the American College of Rheumatology or the "greater than or equal to 30% improvement" criteria were used. The placebo group had 19% responders vs. 39% responders in the 20 mcg/d group. Subjects who had antibodies that reacted with type II collagen in their serum at the time of the baseline visit were found in a post hoc analysis to have a higher likelihood of response to type II collagen administration.
COMMENT BY JERRY GREENE, MD
The concept of using an antigenic substance, in this case type II collagen, that is present at a site of inflammation to induce a T-lymphocyte response that will reduce inflammation is referred to as induction of tolerance. Animal models suggest that such tolerance can indeed be induced and can ameliorate experimental autoimmune diseases such as allergic encephalomyelitis. Sieper and colleagues found no significant differences between groups treated with type II collagen at doses of 1000 mcg day and 10,000 mcg per day compared to a group receiving placebo.2 Although the results in the current study by Barnett and colleagues of oral type II collagen in rheumatoid arthritis were disappointing with the higher doses of 100, 500, and 2500 mcg per day, the results with the lowest dose of 20 mcg per day were sufficiently promising that we can look forward to another trial, perhaps with even lower doses of collagen. It is hard to understand why the 100 mcg per day dose, which had looked so promising earlier, was ineffective in this trial.
The allure of this potential therapy, which appears to be free of any serious toxicity, seems irresistible. For now, oral type II collagen remains an investigational agent, and patients who inquire about it should be reminded that there is no evidence that any of the collagen preparations available commercially have any effect-beneficial or otherwise-on rheumatoid arthritis.
References
1. Trentham DE, et al. Science 1993;261:1727-1730.
2. Sieper J, et al. Arthritis Rheum 1996;39:41-51.
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