Biological activity of interferon betas in patients with multiple sclerosis is affected by treatment regimen and neutralising antibodies
- Centro di Riferimento Regionale per la Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy
- Correspondence to: Dr A Bertolotto Centro Riferimento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Regione Gonzole 10, 10043, Orbassano, Torino, Italy; sclerosi.multiplasanluigi.piemonte.it
- Received 20 January 2004
- Accepted 14 May 2004
- Revised 21 April 2004
Abstract
Background: MxA gene expression is one of the most appropriate markers of biological activity of exogenous interferon (IFN) beta.
Methods: We quantified MxA mRNA for five consecutive days in 62 patients treated with IFN beta (16, Avonex; 10, Betaferon; 24, Rebif 22; 12, Rebif 44), by quantitative-competitive polymerase chain reaction. Every three months, IFN beta induced neutralising antibodies (NAbs) were evaluated in sera using a cytopathic effect assay.
Results: Two categories of patients were identified: one group (49/62) had a sharp post-injection increase in MxA expression (defined as “IFN beta biological responder”), whereas the other group (13/62) had no MxA induction after IFN beta administrations (defined as “IFN beta biological non-responder”). In 11/13 biological non-responders, the persistent presence of NAbs correlated with abolished biological activity, independently of treatment regimen. The two remaining IFN beta biological non-responders were NAb–. Among the 49 IFN beta biological responders, biological activity was comparable between the four preparations on day 2 and 3 (+12 and +36 hours post-injection), but it was greater in Betaferon and both Rebif preparations on day 1, 4, and 5. In biological responders treated three times a week, only 82% (59/72) of injections were considered effective, compared with 100% (13/13) of Avonex injections.
Conclusion: Our results suggest that an optimal IFN beta regimen is not yet available: Avonex, given once a week, shows lower cumulative biological activity. On the other hand, both Betaferon and Rebif, given three times a week, show 18% biologically ineffective injections and higher risk of developing NAbs, which abolish biological activity.
- AUC, area under the concentration time curve
- EDSS, Expanded Disability Status Scale
- IFN, interferon
- MS, multiple sclerosis
- MxA, myxovirus resistance protein A
- NAbs, neutralising antibodies
- OAS, oligoadenylate synthetase
- PBMC, peripheral blood mononuclear cell
- TRU, tenfold reduction unit
Footnotes
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This work was supported by Fondazione per la Ricerca Biomedica ONLUS and by Cavalieri Ottolenghi Foundation.
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Competing interests: AB, SM, MC, and ADS have been reimbursed by Farmades, Serono, and Dompè Biotech for attending several conferences; AB received fees for lectures by Serono, Dompè Biotech and Biogen; AB received funds for research and for staff members from Serono and Dompè Biotech. Farmades is the Italian distributor of Betaferon; Serono is the manufacturer of Rebif, Biogen of Avonex and Dompè Biotech is the Italian distributor of Avonex. The other authors have nothing to declare.
