Tacrolimus (FK506) in the treatment of severe, refractory rheumatoid arthritis: initial experience in 12 patients

To determine if tacrolimus (FK506) has potential as a therapeutic agent in patients with severe and/or refractory rheumatoid arthritis (RA).

Twelve patients with RA who had severe and active disease and had failed an average of 5.3 disease modifying antirheumatic drugs (DMARD) were treated with tacrolimus 2-6 mg/day in an open label study. Patients were assessed monthly with respect to RA outcomes and drug related toxicities.

Of the 12 patients, 7 were able to complete 6 months of treatment. In these 7 patients, significant improvements were seen in tender joint count (from 26.4 +/- 4.2 to 11.7 +/- 3.2; p = 0.007), swollen joint count (from 17.7 +/- 2.5 to 4.1 +/- 1.3; p = 0.001), and other RA outcomes. All 7 patients achieved the 20% response criteria of the American College of Rheumatology (ACR), and 5 of 7 patients met the ACR 50% response criteria. The other 5 patients withdrew in the first 3 months of treatment due to gastrointestinal symptoms (3), chest pain (1), and neuropathic pain (1). Serum creatinine levels were unchanged in all patients, and hypertension was not seen.

Tacrolimus was tolerated by only 7 of 12 patients, but in 5 of these 7 patients with severe and refractory disease, the clinical responses were very good.