Natural interferon-alpha versus its combination with 6-methyl-prednisolone in the therapy of type II mixed cryoglobulinemia: a long-term, randomized, controlled study.
Type II mixed cryoglobulinemia (MC) is an often progressive vasculitis characterized by circulating cold-precipitable proteins that usually consists of polyclonal IgG and monoclonal IgM kappa 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 (rIFN alpha) have been reported. To further assess its effectiveness, we studied the effects of natural human interferon-alpha (nIFN alpha), 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 nIFN alpha (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 nIFN alpha and nine of 17 (52.9%) treated with nIFN alpha 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 nIFN alpha, three of 17 (17.6%) who received nIFN alpha 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 nIFN alpha plus PDN, as compared with two patients (25%) of those who received nIFN alpha 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 nIFN alpha alone as compared with none of those who received nIFN alpha plus PDN (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Dammacco
F
F
Department of Biomedical Sciences, University of Bari Medical School, Italy.
Sansonno
D
D
Han
J H
JH
Shyamala
V
V
Cornacchiulo
V
V
Iacobelli
A R
AR
Lauletta
G
G
Rizzi
R
R
D001483:Base Sequence; D003449:Cryoglobulinemia / Q000097:blood / Q000276:immunology / Q000628:therapy*; D017931:DNA Primers; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000276:immunology / Q000302:isolation & purification; D006508:Hepatitis Antibodies / Q000097:blood; D018937:Hepatitis C Antibodies; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011336:Probability; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000097:blood; D013997:Time Factors; D005719:gamma-Globulins / Q000032:analysis
D017931:DNA Primers; D006508:Hepatitis Antibodies; D018937:Hepatitis C Antibodies; D007075:Immunoglobulin M; D016898:Interferon-alpha; D005719:gamma-Globulins; D012217:Rheumatoid Factor; D008775:Methylprednisolone