Split-dosing of subcutaneous alpha and beta interferon reduces local cutaneous complications

Abstract

RATIONALE: Interferon (IFN) therapy for multiple sclerosis (MS) and hepatitis C (HepC) is associated with severe local adverse effects.METHODS: We studied the efficacy of a split-dosing regimen for subcutaneous interferons. A MS patient receiving recombinant IFN1β 9×106 units on alternate days and a HepC patient receiving pegylated IFNα2a 180mcg weekly were referred for evaluation. Erythematous lesions evolving into necrotic ulcers presented 6 weeks after IFN1β injection. Pruritic hive-like lesions developed 2 hours after IFNα2a injection. No improvement occurred with alternate injection sites. Therapy was discontinued. Prick/intradermal skin tests and incremental challenge were performed in the HepC patient due to rapid onset of reaction. Prick tests were done with undiluted IFNα2A (180mcg/1cc), histamine (6mg/ml) and saline controls. Intradermal skin testing was performed with IFNα2A diluted in saline (1:100 concentration), histamine and saline controls. Subcutaneous incremental challenge began with undiluted IFNα2A 18mcg. Trials of split-dosing, half the standard dose given at two separate sites, were initiated in both patients. The patients were followed for site reactions over subsequent weeks after therapy re-initiation.RESULTS: No immediate or delayed hypersensitivity or irritant reaction was observed after skin testing and challenge with IFNα2a. Split dosing of interferons significantly reduced the severity of reactions and permitted the continued use of these drugs.CONCLUSION: Given the efficacy of interferon therapy and the frequency of cutaneous side-effects, an alternative dosing regimen in patients with severe local complications should be considered. RATIONALE: Interferon (IFN) therapy for multiple sclerosis (MS) and hepatitis C (HepC) is associated with severe local adverse effects. METHODS: We studied the efficacy of a split-dosing regimen for subcutaneous interferons. A MS patient receiving recombinant IFN1β 9×106 units on alternate days and a HepC patient receiving pegylated IFNα2a 180mcg weekly were referred for evaluation. Erythematous lesions evolving into necrotic ulcers presented 6 weeks after IFN1β injection. Pruritic hive-like lesions developed 2 hours after IFNα2a injection. No improvement occurred with alternate injection sites. Therapy was discontinued. Prick/intradermal skin tests and incremental challenge were performed in the HepC patient due to rapid onset of reaction. Prick tests were done with undiluted IFNα2A (180mcg/1cc), histamine (6mg/ml) and saline controls. Intradermal skin testing was performed with IFNα2A diluted in saline (1:100 concentration), histamine and saline controls. Subcutaneous incremental challenge began with undiluted IFNα2A 18mcg. Trials of split-dosing, half the standard dose given at two separate sites, were initiated in both patients. The patients were followed for site reactions over subsequent weeks after therapy re-initiation. RESULTS: No immediate or delayed hypersensitivity or irritant reaction was observed after skin testing and challenge with IFNα2a. Split dosing of interferons significantly reduced the severity of reactions and permitted the continued use of these drugs. CONCLUSION: Given the efficacy of interferon therapy and the frequency of cutaneous side-effects, an alternative dosing regimen in patients with severe local complications should be considered.