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]
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