Combination therapy of interferon Beta-1b and tacrolimus: a pilot safety study

Abstract

Tacrolimus is a calcineurin inhibitor which works to induce immune suppression by preventing cytokine transcription and lymphocyte activation. Combining the immunomodulator interferon beta-1b (Betaseron) with the immunosuppressant tacrolimus (Prograf) may have the potential of additive therapeutic benefit through the complementary mechanisms of action of these two therapeutics. In this randomized, open-label, multicenter, two-arm pilot study, the authors examined the safety and tolerability of the combination of interferon beta-1b and tacrolimus in relapsing remitting (RRMS) and secondary progressive (SPMS) multiple sclerosis patients who have failed one or more immunomodulatory therapies. Patients (n = 25) received a combination of interferon beta-1b subcutaneously every other day and oral tacrolimus (low blood level tacrolimus, 1-5 ng/mL, or high blood level tacrolimus, 5-10 ng/mL) for a period of 38 weeks. The combination therapy of interferon beta-1b and tacrolimus over the 10-month period of the study was shown to be safe and relatively well tolerated. There were no unexpected adverse events occurring as the result of the combination therapy. Further study of this combination therapy in patients with multiple sclerosis unresponsive to conventional therapy is warranted.

Figure 1

Study design. Relapse remitting and secondary progressive patients were randomized into low-blood-level (LBL) or high-blood-level (HBL) tacrolimus groups, in combination with Betaseron. Betaseron was administered subcutaneously every other day, while tacrolimus was given orally. Combination therapy was administered over a 38-week period.

Figure 2

Patient enrollment flow chart. 25 patients who had met all required enrolment criteria were randomly assigned to receive low-blood-level tacrolimus (LBL) or high-blood-level tacrolimus (HBL). 10 LBL patients and 10 HBL patients completed the study and were included in the ITT analysis.