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.
Highlights
The autoimmune pathophysiological process by which the immune system carries out its attack of the central nervous system in multiple sclerosis (MS) is complex and multipronged and can vary between patients and even within the same patient, over time [1]
Tacrolimus (FK506) is a macrolide isolated from Streptomyces tsukubaensis and is currently used as an immunosuppressant to prevent allograft
We examined the safety and tolerability of the combination therapy consisting of interferon beta-1b and tacrolimus in relapsing remitting multiple sclerosis (RRMS) and secondary progressive (SPMS) patients who have failed one or more previous immunomodulating therapies
Summary
The autoimmune pathophysiological process by which the immune system carries out its attack of the central nervous system in multiple sclerosis (MS) is complex and multipronged and can vary between patients and even within the same patient, over time [1]. More than 15 years of experience with current immunomodulators, when used as monotherapy in multiple sclerosis, has shown that their clinical efficacy is only modest, and that new therapeutic strategies are required. Combination therapies in MS may have the potential of offering additive benefit through to patients with MS by targeting multiple autoimmune processes. As previously described with respect to MS, combination therapy with drugs utilizing complementary mechanisms of action [2] may have the potential for improving disease control by targeting multiple inflammatory or autoimmune aspects of the disease at once. Interferon beta1b (Betaseron) was the first clinically effective therapeutic agent proven to modify the disease course in MS patients and is thought to exert its therapeutic effects by downregulating expression of MHC II molecules and inhibiting the passage of immune cells into the CNS [3,4,5,6]. Tacrolimus (FK506) is a macrolide isolated from Streptomyces tsukubaensis and is currently used as an immunosuppressant to prevent allograft
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
