Rheumatoid Arthritis Treatments - T-cell Receptor Peptides
Abstract 281 Results of a Phase IIb Rheumatoid Arthritis Clinical Trial Using T-cell Receptor Peptides
AK Matsumoto, LW Moreland for the Study group, V Strand, EE Morgan, CJ Nardo, SP Richieri, SW Brostoff Baltimore, MD, Birmingham AL, Stanford CA, Carlsbad CA
A prior study (Arthritis and Rheumatism 1998. 41:1919) demonstrated the efficacy of a T cell receptor peptide vaccine in patients with active rheumatoid arthritis. The IR501 therapeutic vaccine consists of three 20 amino acid peptides derived from the Vb regions of T cell receptors from autoreactive T cells identified in rheumatoid synovium. The current double blind placebo controlled trial randomized 340 patients with active RA. In addition to using 30 and 90 mg doses of IR501 vaccine from the earlier study, the current trial tested 30 and 90 mg doses of the IR703 vaccine consisting of three 40 amino acid peptides containing the sequence from the previously tested peptides. All vaccines were mixed with incomplete Freund's adjuvant and injected intramuscularly at Weeks 0, 4, 8 and 20.
Using the ACR 20 criteria, a statistically significant response was seen in the IR501 30 mg group compared with placebo (34% vs 18%) at week 16 but not at week 24 (study endpoint). The treatment effect appeared to wane after week 12 but dosing at week 20 boosted the clinical response. A post hoc analysis of patients with disease duration less than 3 years showed a much greater response at week 24 in both the IR501 30 mg and IR703 90 mg groups compared with placebo (50% vs 50% vs 8%.
Editorial comment: T cell receptor peptide vaccination remains a controversial therapy for RA and these results will add debating points for both the believers and non-believers. The current study fails to show a statistically significant ACR 20 response at study endpoint, however this may represent the lack of dosing between week 8 and 20. Sustained treatment effect would appear to require monthly dosing. It is also intriguing that the limited number of patients with early disease did better, adding to the hypothesis that autoreactive T cells may play a greater role in early disease. The treatment effect appears to be modest but the vaccine is very well tolerated. Further trials will need to be done to establish the viability of this approach to RA therapy.