HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bertolotto, A Articles by Gilli, F Search for Related Content PubMed PubMed Citation Articles by Bertolotto, A Articles by Gilli, F

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:
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.multipla{at}sanluigi.piemonte.it

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.

Abbreviations: 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

Keywords: multiple sclerosis; interferon beta; neutralising antibodies; MxA mRNA; non-responders; treatment

This article has been cited by other articles:

				P. Sorensen, N Koch-Henriksen, E. Flachs, and K Bendtzen Is the treatment effect of IFN-{beta} restored after the disappearance of neutralizing antibodies? Multiple Sclerosis, July 1, 2008; 14(6): 837 - 842. [Abstract] [PDF]

				S. Malucchi, F. Gilli, M. Caldano, F. Marnetto, P. Valentino, L. Granieri, A. Sala, M. Capobianco, and A. Bertolotto Predictive markers for response to interferon therapy in patients with multiple sclerosis Neurology, March 25, 2008; 70(13_Part_2): 1119 - 1127. [Abstract] [Full Text] [PDF]

				A.R. Pachner Real-time TaqMan assay for myxovirus resistance protein (MxA) mRNA: a robust marker of interferon beta bioactivity in patients with multiple sclerosis Multiple Sclerosis, May 1, 2007; 13(1_suppl): 49 - 52. [Abstract] [PDF]

				F Gilli, F Marnetto, M Caldano, A Sala, S Malucchi, M Capobianco, and A Bertolotto Biological markers of interferon-beta therapy: comparison among interferon-stimulated genes MxA, TRAIL and XAF-1 Multiple Sclerosis, February 1, 2006; 12(1): 47 - 57. [Abstract] [PDF]

				G Giovannoni Is it time to consider rationalising IFN-{beta} treatment in individuals with multiple sclerosis? J. Neurol. Neurosurg. Psychiatry, September 1, 2004; 75(9): 1234 - 1234. [Full Text] [PDF]