A pilot study of the combination of cyclosporin A and interferon alfacon-1 for the treatment of hepatitis C in previous nonresponder patients.

GOALS: To evaluate the safety and efficacy of the combination of interferon and cyclosporine for the treatment of hepatitis C in previous nonresponder patients.

BACKGROUND: Preliminary data indicated that adding the immunosuppressive agent cyclosporin A to interferon might improve response rates in patients with hepatitis C.

STUDY: Ten previous virologic nonresponders with genotype 1 infection were included. Treatment consisted of interferon alfacon-1, 15 microg/d, and cyclosporine, 100 mg twice daily, for 4 weeks. The dose of interferon alfacon-1 was then decreased to 15 microg three times weekly, and cyclosporine was reduced to 50 mg twice daily. Therapy was continued for 48 weeks unless viremia persisted at week 24.

RESULTS: Three of 10 subjects had an on-treatment virologic response, although one had a breakthrough with recurrent viremia during treatment and two relapsed after therapy was completed. On treatment responders had significantly higher trough cyclosporine levels at week 4 compared with nonresponders (P = 0.025). Serum creatinine levels remained stable, and no patient developed diabetes. Triglyceride levels increased during treatment. Cyclosporine was dose reduced in two patients for hypertension.

CONCLUSIONS: Selected patients with hepatitis C tolerated therapy, including cyclosporine without severe or irreversible toxicity. Despite an association between higher cyclosporine levels and on-treatment response, the combination of cyclosporine and interferon was ineffective in producing a sustained response in previous nonresponder patients.