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, Fletcher MJ, Chasan-Taber S, Finger E, Morales A, Le CH, Trentham
DE.
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215,
USA.
Objective
Oral administration of cartilage-derived type II collagen (CII) has
been shown to ameliorate arthritis in animal models of joint inflammation,
and preliminary studies have suggested that this novel therapy is
clinically beneficial and safe in patients with rheumatoid arthritis
(RA). The present study was undertaken to test the safety and efficacy
of 4 different dosages of orally administered CII in patients with
RA.
Methods
Two hundred and seventy-four patients with active RA were enrolled
at 6 different sites and randomized to receive placebo or 1 of 4 dosages
(20, 100, 500, or 2,500 microg/day) of oral CII for 24 weeks. Efficacy
parameters were assessed monthly. Cumulative response rates (percentage
of patients meeting the criteria for response at any time during the
study) were analyzed utilizing 3 sets of composite criteria: the Paulus
criteria, the American College of Rheumatology criteria for improvement
in RA, and a requirement for > or = 30 per cent reduction in both
swollen and tender joint counts.
Results
Eighty-three per cent of patients completed 24 weeks of treatment.
Numeric trends in favor of the 20 microg/day treatment group were
seen with all 3 cumulative composite measures. However, a statistically
significant increase (P = 0.035) in response rate for the 20 microg/day
group versus placebo was detected using only the Paulus criteria.
The presence of serum antibodies to CII at baseline was significantly
associated with an increased likelihood of responding to treatment.
No treatment-related adverse events were detected. The efficacy seen
with the lowest dosage is consistent with the findings of animal studies
and with known mechanisms of oral tolerance in which lower doses of
orally administered autoantigens preferentially induce disease-suppressing
regulatory cells.
Conclusion
Positive effects were observed with CII at the lowest dosage tested,
and the presence of serum antibodies to CII at baseline may predict
response to therapy. No side effects were associated with this novel
therapeutic agent. Further controlled studies are required to assess
the efficacy of this treatment approach.
Publication Types:
- Clinical Trial
- Multicenter Study
- Randomized Controlled Trial
PMID: 9485087 [PubMed - indexed for MEDLINE]
Studies/Articles/Abstacts
- Effects
of oral administration of type II collagen on rheumatoid arthritis
- Comment in:
Science. 1993 Sep 24;261(5129):1669-70.
Treatment of
Rheumatoid Arthritis with Oral Type II Collagen | Role
of Collagen Hydrolysate in Bone and Joint Disease | Oral
desensitization in the treatment of human immune diseases
