Gut 1993; supplement: S144-S145 Interferon alfa-2b in mixed cryoglobulinaemia: a controlled crossover trial C Ferri, E Marzo, G Longombardo, L La Civita, F Lombardini, D Giuggioli, R Vanacore, A M Liberati, A Mazzoni, F Greco, S Bombardieri Abstract To confirm the positive results of a preliminary trial, 26 patients with mixed cryoglobulinaemia were enrolled in a con- trolled, randomised, crossover trial with interferon alfa-2b. A significant improve- ment was seen in the purpura score and alanine aminotransferase activities during six months' treatment, and was associated with a significant decrease in cryocrit and a returning to normal of the lymphocyte CD4/CD8 ratio (in eight of nine patients). No significant variations were seen during the six month period without interferon. Only six patients withdrew from treatment, three because of side effects and three because of poor compliance. (Gut 1993; supplement: S144-S 145) Mixed cryoglobulinaemia is an idiopathic lymphoproliferative disease with a variable number of visceral manifestations secondary to the tissue deposition of circulating immune complexes. The liver plays a part in the disease and chronic active hepatitis is a common complication occurring in about 70% of cases. The presence of hepatitis C virus (HCV)-RNA and anti-HCV antibodies in 90% of patients with mixed cryoglobulinaemial-' suggests that this virus may play an important pathogenetic part. Treatment for mixed cryoglobulinaemia depends largely on the extent and severity of organ involvement in the disease. Steroid and plasma exchange or both,4 and a low antigen content diet6 have been used in a large series of patients with mixed cryoglobulinaemia. Interferon alfa-2b, an antiviral and immuno- modulatory drug, has also been used in this disease with encouraging results.7 The aim of this controlled, randomised, crossover trial was to confirm the positive results of our preliminary study.8 Patients and methods Twenty six patients with mixed cryo- globulinaemia (15 women and 11 men), with a mean age of 54 years ((6) SD) were entered into the study. Clinical and serological characteristics of the patients before treatment are shown in Table I. All patients had six months without interferon alfa-2b (control period) and six months with interferon alfa-2b (INTRON A, TABLE I Clinical and serological characteristics of 26 patients with mixed cryoglobulinaemia Purpura 23 (88%) Arthralgias 24 (92%) Weakness 25 (96%) Sjogren's syndrome 8 (31%) Raynaud's phenomenon 4 (15%) Liver involvement* 19 (73%) Peripheral neuropathy 20 (77%) Nephropathy 1 (4%) Cryocrit % (mean (SD)) 5 (9) Cryo composition IgM (k) 15 (58%) IgM (k+X) 11 (42%) CH50 (normal >160 IU/1) (mean (SD)) 83 (75) C4 (normal >22 mg/dl) (mean (SD)) 11 (10) Antinuclear antibodies 1 (4%) Anti-smooth muscle antibodies 4 (15%) Antimitochondrial antibodies 1 (4%) anti-HCV positivet 24 (96%) HCV-RNA (polymerase chain reaction positive)t 20 (91/%) *On the basis of increased serum alanine aminotransferase activities and histological alterations, or both. tDetermined by second generation ELISA and RIBA (Chiron). t22 patients tested. Schering-Plough Corporation) at a dose of 2 million units (MU) daily for one month by subcutaneous injection, then every other day for five months. For those patients who started the trial on alfa-2b treatment, a one month washout period was included before the second half of the study. The low to medium steroid dosages prescribed before treatment 6-methylprednisolone; 4-8 mg/day) continued unchanged. Results During interferon alfa-2b treatment, a statistically significant improvement was seen using Wilcoxon's non-parametric test in the purpura score and in serum alanine aminotransferase activities (Table II). Clinical results were also reflected by changes in immunological parameters: cryocrit decreased TABLE II Changes in purpura score, serum alanine aminotransferase (ALT) activities, and cryocrit in treated and untreated patients Treated Untreated Before After Before After Purpura score 1-6 (0 3) 0 3 (0-2) 1-7 (0-3) 1-4 (0 3) p<001 NS Serum ALT(XULN) 2-5 (0 5) 1-5 (0 2) 2-6 (0 7) 2-2 (0-4) p<001 NS Cryocrit % 5-6 (2 4) 3 0 (1-8) 4-1 (2 2) 3-5 (1-7) p<0 02 NS All values are mean (SEM). Istituto Patologia Medica I, University of Pisa, Italy C Ferri E Marzo G Longombardo L La Civita F Lombardini D Giuggioli S Bombardieri Clinica Medica I, University of Pisa, Italy R Vanacore Clinica Medica I, University of Perugia, Italy A M Liberati Blood Center, Ospedale S Chiara, Pisa, Italy A Mazzoni F Greco Correspondence to: Professor Dr C Ferm, Istituto di Patologia Medica I, University of Pisa, Via Roma 67, 56100 Pisa, Italy. S144 on May 26, 2020 by guest. Protected by copyright. http://gut.bmj.com/ Gut: first published as 10.1136/gut.34.2_Suppl.S144 on 1 January 1993. Downloaded from