Natural interferon-α versus its combination with 6-methyl-prednisolone in the therapy of type II mixed cryoglobulinemia: A long-term, randomized, controlled study

Abstract

Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis characterized by circulating cold-precipitable proteins that usually consists of polyclonal IgG and monoclonal IgMκ with rheumatoid factor (RF) activity. Its etiology is unknown, although recent evidence strongly suggests that hepatitis C virus (HCV) plays a major role. Plasmapheresis, corticosteroids, and cytotoxic drugs have been used in the therapy of MC patients. Recently, favorable results with recombinant interferon-alpha (rIFNα) have been reported. To further assess its effectiveness, we studied the effects of natural human interferon-α (nIFNα), alone and in combination with 6- methyl-prednisolone (PDN), in a prospective, randomized, controlled trial in patients with symptomatic MC. Sixty-five patients were enrolled onto the trial, 52 (80%) of whom presented serum anti-HCV antibodies and specific genomic RNA sequences. Fifteen patients received nIFNα (3 MU) intramuscularly (IM) three times weekly, whereas 17 patients also received 16 mg/d of PDN orally on non-IFN days. Moreover, 18 patients received 16 mg/d of PDN only, and 15 were untreated. Treatment was discontinued after 1 year and patients were monitored for 8 to 17 months (mean, 13). A complete response was achieved in eight of 15 patients (53.3%) treated with nIFNα and nine of 17 (52.9%) treated with nIFNα plus PDN, as compared with three of 18 patients (16.7%) who received PDN only (P < .05) and one of 15 (6.7%) untreated controls (P < .01). Partial response occurred in two of 15 (13.3%) patients treated with nIFNα, three of 17 (17.6%) who received nIFNα plus PDN, one of 18 (5.5%) who received PDN only, and one of 15 (6.7%) controls. A complete response in six patients (66.7%) was achieved within 3 months in the group that received nIFNα plus PDN, as compared with two patients (25%) of those who received nIFNα alone (P < .02). In anti-HCV-positive patients, the clinical response occurred in step with reduced or undetectable levels of HCV RNA and transaminase normalization. Quantification of circulating HCV RNA represented a good predictive response marker. The probability of relapse within 3 months after treatment was 100% (three of three patients) and 75% (six of eight patients), respectively, in patients who received PDN alone or nIFNα alone as compared with none of those who received nIFNα plus PDN (P < .001). Two of eight (25%) and three of nine (33.3%) patients who received nIFNα and nIFNα plus PDN, respectively, remained in remission throughout the follow-up period. nIFNα controls the activity of MC in more than 50% of patients. Its combination with PDN results in a more prompt response and delayed relapse; however, considering the increased viremia found with prednisone, the marginal effects of combined therapy do not warrant use of this protocol. In addition, relapse is common after 3 months of treatment withdrawal from both treatment modalities.