RA Treatment - FK506

Alan Matsumoto, M.D.

Abstract 1206 Efficacy of FK506 in Rheumatoid Arthritis (RA): A 6 month Dose Ranging Study in RA Patients Failing Methotrexate (MTX)

DE Furst, Y Sherrer, RM Fleishman, J Block, J Rutstein, D Stamler Seattle WA, Boca Raton FL, Dallas TX, Chicago IL, San Antonio TX, Deerfield IL

This abstract reports the results of a multi-center, placebo trial of FK506 (Tacrolimus, Prograf) in patients who have failed methotrexate therapy. FK506 is currently approved as an anti-rejection drug for liver and renal transplantation and inhibits T cell function by inhibiting IL-2. The study randomized 268 patients to receive placebo, 1 mg, 2 mg, 3 mg or 5 mg daily of FK506. Primary outcome was ACR 20 response. The protocol specified that patients were discontinued if serum creatinine rose 40% over baseline values.

% ACR 20 Responders % discontinuing due to creatinine

elevation 40% over baseline

Placebo 15.5% 7%

1 mg 29% (p< 0.10) 9%

3 mg 34.4% (p< 0.05) 19%

5 mg 50% (p< 0.001) 29%

Editorial comment: The current study is well designed and because of its similarity to cyclosporin A, it is reasonable to expect that FK506 might have a role in the treatment of RA. A good dose response was seen. Unfortunately at the clinically significant effective doses, renal toxicity becomes a problem and will limit the usefulness of FK506 as a single agent. What remains to be shown in future trials is whether FK506 might be used in combination with other drugs such as methotrexate, similar to the role of cyclosporin.