Safety profile of tacrolimus in patients with rheumatoid arthritis

Abstract

We assessed the safety of tacrolimus therapy for rheumatoid arthritis. Forty-two patients who started tacrolimus therapy between April 2005 and July 2006 were investigated retrospectively using data from their medical records up to June 2007. The cumulative treatment continuation rate was assessed by the Kaplan-Meier method. Fisher's exact test was used to compare gastrointestinal symptoms between different tacrolimus doses and between the presence and absence of each concomitant medication. The mean (+/-SD) observation period was 288 +/- 238 days. The cumulative treatment continuation rate was, respectively, 59.5% and 38.1% at 6 months and 1 year after the patients started treatment. Tacrolimus was discontinued in 28 patients, and was discontinued because of adverse reactions in 21 patients. Gastrointestinal symptoms were the most common adverse reactions (45.2% = 19/42 patients), followed by infections and hyperglycemia. Tacrolimus was discontinued in 9/19 patients with gastrointestinal symptoms, and was discontinued within 60 days of starting treatment in seven of them. Nausea and vomiting led to discontinuation in seven patients (within 60 days of starting treatment in six of them). The incidence of gastrointestinal symptoms was higher in patients receiving a daily dose >or=2 mg than in those receiving <2 mg/day. During treatment of rheumatoid arthritis by oral tacrolimus therapy, gastrointestinal symptoms were common, early, and dose-dependent. However, these symptoms were not severe and did not cause any serious safety problems.

Efficacy and safety of additional use of tacrolimus in patients with early rheumatoid arthritis with inadequate response to DMARDs—a multicenter, double-blind, parallel-group trial

“…The incidence of ''gastrointestinal disorders'' was significantly higher in the tacrolimus group than that in the placebo group (P = 0.003), but there were no patients who discontinued the trial because of AEs or severe events. This result is not significantly different from those of tacrolimus monotherapy trials [7,8,31,32] in patients with rheumatoid arthritis, and in the present study, good tolerability of tacrolimus was shown in patients with early rheumatoid arthritis who also received other DMARDs. Moreover, the main side effects, such as infections, gastroenterological disorders, abnormal variations in renal function test valuesand abnormal variations in glucose tolerance test valueshave been observed in previous studies [7,8,32].…”

Tacrolimus (FK506): Safety and Applications in Reconstructive Surgery

“…A final retrospective study focused on the safety profile of tacrolimus as used in a previous randomized doubleblind controlled study (2008) [2]. The findings were similar to the previous safety studies with GI symptoms being the most common and significant adverse reaction which was the main reason for discontinuation of therapy.…”

Tacrolimus therapy for systemic lupus erythematosus without renal involvement: a preliminary retrospective study

“…In our study, adverse reactions were observed in 4 patients, but all symptoms were reversible and improved after dose reduction or discontinuation of tacrolimus. We [26] previously studied the safety profile of tacrolimus and found that 21 out of 42 patients discontinued treatment due to adverse reactions during an average observation period of 288 days. In the study presented here on patients with SLE, no gastrointestinal symptoms were observed, although these were the most common adverse reaction (45.2%, 19/42 patients) [26] in patients with rheumatoid arthritis.…”