Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory
- A Bertolotto1,
- S Malucchi1,
- A Sala1,
- G Orefice2,
- P B Carrieri2,
- M Capobianco1,
- E Milano1,
- F Melis1,
- M T Giordana1
- 1Centro di Riferimento Regionale Sclerosi Multipla & Laboratorio di Neurobiologia Clinica, Divisione Universitaria di Neurologia, Azienda Ospedaliera S Luigi, Università di Torino, Orbassano, Italy
- 2Dipartimento Scienze Neurologiche; Università Federico II, Napoli, Italy
- Correspondence to: Dr A Bertolotto, Centro Sclerosi Multipla & Laboratorio di Neurobiologia Clinica, Divisione Universitaria di Neurologia, Azienda Ospedaliera S Luigi di Orbassano, Università di Torino–Regione Piemonte, Regione Gonzole 10, 10043, Orbassano, Italy; nsglb{at}tin.it
- Received 26 November 2001
- Accepted 18 April 2002
- Revised 16 April 2002
Abstract
Objective: To evaluate the incidence and the prevalence of neutralising antibodies (NABs) to three interferon beta (IFNβ) products in patients with multiple sclerosis (MS).
Methods: Sera were tested from 125 patients with relapsing-remitting MS. Patients were treated with IFNβ-1b (Betaferon, n = 29) 8 MIU subcutaneously every other day, IFNβ-1a (Avonex, n = 44) 30 μg intramuscularly once weekly, or IFNβ-1a (Rebif, n = 36) 22 μg subcutaneously three times weekly for 6 to 18 months. An additional 16 patients were treated with Rebif 22 μg intramuscularly once or twice weekly. NABs were assessed using the cytopathic effect assay before treatment and every three months during treatment. Patients with two or more consecutive positive samples were considered to be persistent NAB positive (NAB+).
Results: At baseline, no patients were NAB+. NABs developed during the first three months of treatment and continued to develop until month 18. Over 18 months of treatment, the risk of being persistent NAB+ was 31% for Betaferon, 15% for Rebif, and 2% for Avonex (Betaferon versus Avonex, p = 0.001; Betaferon versus Rebif, p = 0.19; Rebif versus Avonex, p = 0.04). In all patients with one or more NAB+ samples, the risk of becoming NAB+ was 38% for Betaferon, 18% for Rebif, and 7% for Avonex (Betaferon versus Avonex, p = 0.0007; Betaferon versus Rebif, p = 0.10; Rebif versus Avonex, p = 0.07). At month 18, the prevalence of persistent NAB+ patients was 31.6% for Betaferon, 18.7% for Rebif, and 4% for Avonex. Numbers of NAB+ patients observed were similar with intramuscular Rebif and with subcutaneous Rebif.
Conclusion: The three IFNβ preparations have different degrees of immunogenicity, with Betaferon producing the highest incidence of NABs and Avonex the lowest. These differences should be considered by neurologists when selecting treatment for their patients with MS because NABs can reduce both bioavailability and clinical efficacy of IFNβ.
- CPE, cytopathic effect
- EDSS, expanded disability status scale
- IFNβ, interferon beta
- LU, laboratory units
- MS, multiple sclerosis
- NAB, neutralising antibody
- PRISMS, prevention of relapses and disability by interferon β-1a subcutaneously in multiple sclerosis
- WHO, World Health Organization
Footnotes
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Competing interests: AB, SM, GO, PBC, MC, and EM have been reimbursed by Farmades, Serono, and Dompé Biotech for attending several conferences; AB received fees for speaking from Serono, Dompé Biotech, and Biogen; and AB received funds for research and for members of the staff from Serono and Dompé Biotech. Farmades is the Italian distributor of Betaferon; Serono is the manufacturer of Rebif, Biogen is the manufacturer of Avonex, and Dompé Biotech is the Italian distributor of Avonex.
