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

Objective. To determine if tacrolimus (FK506) has potential as a therapeuti c agent in patients with severe and/or refractory rheumatoid arthritis (RA) . Methods. 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 a ssessed monthly with respect to RA outcomes and drug related toxicities. Results. Of the 12 patients, 7 were able to complete 6 months of treatment. In these 7 patients, significant improvements were seen in tender joint co unt (from 26.4 +/- 4.2 to 11.7 +/- 3.2; p = 0.007), swollen joint count (fr om 17.7 +/- 2.5 to 4.1 +/- 1.3; p = 0.001), and other RA outcomes. All 7 pa tients achieved the 20% response criteria of the American College of Rheuma tology (ACR), and 5 of 7 patients met the ACR 50% response criteria. The ot her 5 patients withdrew in the first 3 months of treatment due to gastroint estinal symptoms (3, chest pain (1), and neuropathic pain (1). Serum creati nine levels were unchanged in all patients, and hypertension was not seen. Conclusion. 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.