Abstract
Objectives: To determine the efficacy and safety of low-dose tacrolimus (TAC), a calcinulin inhibitor, in combination with biologics agent to control the signs and symptom of rheumatoid arthritis (RA) in patients with an insufficient clinical response to biologics agent alone. Methods: Nine patients with active RA (mean±SD DAS 28; 5.3±1.3, despite treatment with biologics treatment for more than 3 months, were enrolled and given TAC at a starting dosage of 1mg/day and continued for 30 weeks while administration of biologics agent was continued at the existing stable dosage. All other disease-modifying antirheumatic drugs were discontinued; stable dosage of nonsteroidal anti-inflammatory drugs and oral corticosteroids (<10mg/day prednisone or its equivalent) were allowed. The primary endpoint was the assessment of clinical improvements using the EULAR criteria, and secondary endpoints were assessments of the changes in the modified health assessment questionnaire (mHAQ), depression scale (use the self-rating depression scale; SDS) and adverse events. Results: Administering TAC to biologics agent-refractory RA patients produced significant improvements in the DAS28 after both 14 (DAS28; 5.3 to 3.9) and 30 weeks (to 3.6). In addition, after 30 weeks all patients had respectively achieved moderate (5 of 9 patients; 55.6%) and good responses (4 of 9 patients; 44.4%) in the EULAR improvement criteria. A significant reduction was made in MHAQ and depression scale after 30 weeks (mHAQ; 0.51 to 0.26, SDS; 47.2 to 43.3), while there were no significant differences after 14 weeks in mHAQ and depression scale. Notably, clinical remission of RA was observed in 2 patients after the combination therapy. Adverse events were observed in only 1 patient, who showed common cold. Treatment was not discontinued in all patients. No abnormal laboratory data were seen during the study period. Conclusions: Although a double-blind, controlled study will be required to confirm the efficacy of TAC, the present preliminary study suggests that low-dose TAC in combination with biologics agent is safety and well-tolerated and provides clinical as well as economic benefit.
