Background/Purpose: Addition of a biologic disease-modifying antirheumatic drug (bDMARD) or targeted synthetic DMARD (tsDMARD) is recommended in patients with rheumatoid arthritis (RA) with inadequate response to methotrexate. Current reimbursement, but the Korean National Health Insurance Service requires moderate to high disease activity with at least 6 months’ treatment with at least two conventional synthetic DMARDs (csDMARDs). Triple therapy with the addition of hydroxychloroquine and sulfasalazine is often used. Methotrexate plus leflunomide or tacrolimus is also used. Drug levels of tacrolimus in patients with RA and their correlation with efficacy and safety were assessed

Methods: A retrospective medical record review of patients with RA who had fulfilled the 2010 ACR/EULAR classification criteria for RA and had initiated treatment with tacrolimus was performed. Serum tacrolimus concentration was measured after six months of treatment with tacrolimus. Disease Activity Score 28 (DAS28) and renal function were assessed at initiation of tacrolimus and after six months. ACR20 responses were assessed at 6 months.

Results: A total of 189 patients were assessed. The mean age was 61.4 ± 11.7 years, and 88.9% were female. Mean DAS28 at baseline was 3.48 ± 1.77 with a mean serum creatinine level of 0.7 ± 0.2 mg/dl and a mean Glomerular Filtration Rate (GFR) of 98.9 ± 15.0. Mean dose of tacrolimus was 1.3 ± 0.5 mg. At six months, the mean DAS28 was 2.98 ± 1.33 with a mean serum creatinine level of 0.7 ± 0.6 mg/dl and a mean GFR of 99.4 ± 14.8. Mean tacrolimus concentration at six months was 3.5 ± 2.6 ng/ml, with the highest being 14.8 ng/dl. A total of 117 (63.9%) patients showed tacrolimus levels below 3 ng/dl, 51 (27.9%) patients showed 3 -7 ng/d, and 21 (11.1%) showed over 7 ng/dl. ACR20 response rates at six months were 44.9% for patients with tacrolimus levels less than 3 ng/dl and 34.7% for those with greater than 3 ng/dl without significant differences. There was no significant increase in serum creatinine levels and GFR at six months, and the differences were not significant according to the serum tacrolimus drug concentration levels.

Conclusion: Tacrolimus at low doses showed clinical efficacy in patients with RA with inadequate response to methotrexate, and there was no significant increase in serum creatinine. All patients showed serum tacrolimus levels below the recommended 15 ng/dl, and there were no significant differences in efficacy and renal function by serum tacrolimus concentration.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-tacrolimus-and-its-serum-concentration-in-patients-with-rheumatoid-arthritis-with-inadequate-response-to-methotrexate/