Medical uses of interferon

Rebif (tradename) is an rIFN-P-la first approved for medical use in the EU in 1998 and subsequently in the USA in 2002. It is indicated for the treatment of patients with relapsing-remitting MS, to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability. 

Rebif is produced via recombinant DNA technology in a CHO cell line. It displays an identical amino acid sequence to that of native human IFN-P-la and, like the native product, is glycosylated. After cell culture the interferon is purified using a series of chromatographic steps (affinity, ion-exchange, gel-filtration and reverse-phase liquid chromatography). It is formulated as a sterile solution in pre-filled syringes and contains mannitol, HSA, sodium acetate, acetic acid and sodium hydroxide as excipients. It is administered subcutaneously three times weekly. 

Product pharmacokinetics were evaluated in healthy volunteers and a single s.c. injection (60 pg) resulted in a peak serum concentration Cmax = 5.1 IU ml with a median time of peak serum concentration Tmax = 16 h. The serum elimination half-life t1/2 was of the order of 70 h. 

The product was evaluated in two multicentre clinical studies that established safety and efficacy. The first (the PRISMS study) was a randomized, double blind placebo-controlled study involving 187 patients. The primary efficacy end-point was the number of clinical relapses recorded. The mean number of relapses over 2 years for the placebo group patients was 2.56, whereas that of the Rebif-treated group was 1.73, a relative reduction of 32 per cent. Rebif treatment also provided positive relative outcomes for several secondary end-points, including the proportion of patients with sustained disability progression. 

The most common side effects noted included injection site reactions and flu-like symptoms with serious potential side effects including depression, as well as liver and blood abnormalities. Rebif is manufactured and marketed by Serono Inc. 

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