Treatment of rheumatoid arthritis with a DR4/1 peptide

Objective, To determine the safety and potential clinical efficacy of prima ry and booster injections of a DR4/1 peptide in patients with active rheuma toid arthritis (RA) despite methotrexate therapy. Methods. Subjects with active RA were enrolled in a randomized, placebo con trolled, double blind, dose-escalating clinical trial of synthetic DR4/1 pe ptide containing the shared epitope. The primary injection of the DR4/1 pep tide 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 s ame dose. The primacy outcomes were the occurrence of adverse effects and c hanges 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 sub sequent 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 n ot produce any significant changes in lymphocyte counts or evidence of gene ralized 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.