Objective: To determine the safety and potential clinical efficacy of primary and booster injections of a DR4/1 peptide in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS. Subjects with active RA were enrolled in a randomized, placebo controlled, double blind, dose-escalating clinical trial of synthetic DR4/1 peptide containing the shared epitope. The primary injection of the DR4/1 peptide in alum adjuvant was administered at one of 3 doses, 1.3, 4.0, and 13 mg, followed by up to 3 or 4 booster injections every 6 or 8 weeks at the same dose. The primary outcomes were the occurrence of adverse effects and changes in measures of immune function. Clinical efficacy was assessed using the American College of Rheumatology 20% criteria for clinical improvement.
Results: Fifty-three patients were entered into the trial, including 44 who completed the study. In the absence of any observations of a dose response to the DR4/1 peptide injections, the 3 dosage groups were combined for subsequent analysis into 3 groups: patients receiving DR4/1 peptide injections every 6 weeks, patients receiving DR4/1 peptide injections every 8 weeks, and a placebo group. At all doses and each dosing interval the primary and booster injections of synthetic DR4/1 peptide were well tolerated and did not produce any significant changes in lymphocyte counts or evidence of generalized immunosuppression. Analysis of clinical efficacy showed that the 6 week group had trends toward improvement in disease measures.
Conclusion: Primary and booster injections of the DR4/1 peptide containing the shared epitope were safe and did not broadly suppress immune function.