Differential Effects of Three Interferon Betas on Neutralising Antibodies in Patients with Multiple Sclerosis: a Follow Up Study in an Independent Laboratory

Overview

Journal J Neurol Neurosurg Psychiatry

Publisher BMJ Publishing Group

Specialties Neurology
Neurosurgery
Psychiatry

Date 2002 Jul 18

PMID 12122172

Citations 31

Authors

A Bertolotto

S Malucchi

A Sala

G Orefice

P B Carrieri

M Capobianco

E Milano

F Melis

M T Giordana

Affiliations

Soon will be listed here.

Abstract

Objective: To evaluate the incidence and the prevalence of neutralising antibodies (NABs) to three interferon beta (IFNbeta) products in patients with multiple sclerosis (MS).

Methods: Sera were tested from 125 patients with relapsing-remitting MS. Patients were treated with IFNbeta-1b (Betaferon, n = 29) 8 MIU subcutaneously every other day, IFNbeta-1a (Avonex, n = 44) 30 microg intramuscularly once weekly, or IFNbeta-1a (Rebif, n = 36) 22 microg subcutaneously three times weekly for 6 to 18 months. An additional 16 patients were treated with Rebif 22 microg 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 IFNbeta 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 IFNbeta.

Citing Articles

Epidemiological parameters of multiple sclerosis in Chaharmahal and Bakhtiari Province, Iran.

Omrani M, Bayati A, Sahraian M, Eskandarieh S Curr J Neurol. 2023; 22(2):103-109.

PMID: 38011364 PMC: 10460920. DOI: 10.18502/cjn.v22i2.13337.

Machine Learning Techniques for Personalised Medicine Approaches in Immune-Mediated Chronic Inflammatory Diseases: Applications and Challenges.

Peng J, Jury E, Donnes P, Ciurtin C Front Pharmacol. 2021; 12:720694.

PMID: 34658859 PMC: 8514674. DOI: 10.3389/fphar.2021.720694.

Using Serum Metabolomics to Predict Development of Anti-drug Antibodies in Multiple Sclerosis Patients Treated With IFNβ.

Waddington K, Papadaki A, Coelewij L, Adriani M, Nytrova P, Kubala Havrdova E Front Immunol. 2020; 11:1527.

PMID: 32765529 PMC: 7380268. DOI: 10.3389/fimmu.2020.01527.

Subvisible Particles in IVIg Formulations Activate Complement in Human Serum.

Chisholm C, Behnke W, Pokhilchuk Y, Frazer-Abel A, Randolph T J Pharm Sci. 2019; 109(1):558-565.

PMID: 31672401 PMC: 6948146. DOI: 10.1016/j.xphs.2019.10.041.

Immunogenicity of Protein Pharmaceuticals.

Dingman R, Balu-Iyer S J Pharm Sci. 2019; 108(5):1637-1654.

PMID: 30599169 PMC: 6720129. DOI: 10.1016/j.xphs.2018.12.014.

References

Trojano M, Avolio C, Liuzzi G, Ruggieri M, Defazio G, Liguori M . Changes of serum sICAM-1 and MMP-9 induced by rIFNbeta-1b treatment in relapsing-remitting MS. Neurology. 1999; 53(7):1402-8. DOI: 10.1212/wnl.53.7.1402. View

Arnason B, Dianzani F . Correlation of the appearance of anti-interferon antibodies during treatment and dimunition of efficacy: summary of an International Workshop on Anti-Interferon Antibodies. J Interferon Cytokine Res. 1998; 18(8):639-44. DOI: 10.1089/jir.1998.18.639. View

Kivisakk P, Alm G, Fredrikson S, Link H . Neutralizing and binding anti-interferon-beta (IFN-beta) antibodies. A comparison between IFN-beta-1a and IFN-beta-1b treatment in multiple sclerosis. Eur J Neurol. 2000; 7(1):27-34. DOI: 10.1046/j.1468-1331.2000.00002.x. View

Bertolotto A, Malucchi S, Milano E, Castello A, Capobianco M, Mutani R . Interferon beta neutralizing antibodies in multiple sclerosis: neutralizing activity and cross-reactivity with three different preparations. Immunopharmacology. 2000; 48(2):95-100. DOI: 10.1016/s0162-3109(00)00182-x. View

Jacobs L, Beck R, Simon J, Kinkel R, Brownscheidle C, Murray T . Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med. 2000; 343(13):898-904. DOI: 10.1056/NEJM200009283431301. View

Ross C, Clemmesen K, Svenson M, Sorensen P, Koch-Henriksen N, Skovgaard G . Immunogenicity of interferon-beta in multiple sclerosis patients: influence of preparation, dosage, dose frequency, and route of administration. Danish Multiple Sclerosis Study Group. Ann Neurol. 2000; 48(5):706-12. View

Myhr K, Ross C, Nyland H, Bendtzen K, Vedeler C . Neutralizing antibodies to interferon (IFN) alpha-2a and IFN beta-1a or IFN beta-1b in MS are not cross-reactive. Neurology. 2000; 55(10):1569-72. DOI: 10.1212/wnl.55.10.1569. View

Poser C, Paty D, Scheinberg L, McDonald W, Davis F, Ebers G . New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983; 13(3):227-31. DOI: 10.1002/ana.410130302. View

Kurtzke J . Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983; 33(11):1444-52. DOI: 10.1212/wnl.33.11.1444. View

10.

KAWADE Y . Quantitation of neutralization of interferon by antibody. Methods Enzymol. 1986; 119:558-73. DOI: 10.1016/0076-6879(86)19076-8. View

11.

Knobler R, Greenstein J, Johnson K, Lublin F, Panitch H, Conway K . Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up. J Interferon Res. 1993; 13(5):333-40. DOI: 10.1089/jir.1993.13.333. View

12.

Jacobs L, Cookfair D, Rudick R, Herndon R, Richert J, Salazar A . Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol. 1996; 39(3):285-94. DOI: 10.1002/ana.410390304. View

13.

Khan O, Xia Q, Bever Jr C, Johnson K, Panitch H . Interferon beta-1b serum levels in multiple sclerosis patients following subcutaneous administration. Neurology. 1996; 46(6):1639-43. DOI: 10.1212/wnl.46.6.1639. View

14.

Lublin F, Reingold S . Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996; 46(4):907-11. DOI: 10.1212/wnl.46.4.907. View

15.

Galazka A, Revel M, Biffoni M, Borden E . Incidence of antibodies to interferon-beta in patients treated with recombinant human interferon-beta 1a from mammalian cells. Cytokines Cell Mol Ther. 1997; 3(1):27-32. View

16.

Pachner A . Anticytokine antibodies in beta interferon-treated MS patients and the need for testing: plight of the practicing neurologist. Neurology. 1997; 49(3):647-50. DOI: 10.1212/wnl.49.3.647. View

17.

Deisenhammer F, Reindl M, Harvey J, Gasse T, Dilitz E, Berger T . Bioavailability of interferon beta 1b in MS patients with and without neutralizing antibodies. Neurology. 1999; 52(6):1239-43. DOI: 10.1212/wnl.52.6.1239. View

18.

Antonelli G, Simeoni E, Bagnato F, Pozzilli C, Turriziani O, Tesoro R . Further study on the specificity and incidence of neutralizing antibodies to interferon (IFN) in relapsing remitting multiple sclerosis patients treated with IFN beta-1a or IFN beta-1b. J Neurol Sci. 1999; 168(2):131-6. DOI: 10.1016/s0022-510x(99)00185-9. View

19.

Runkel L, Meier W, Pepinsky R, Karpusas M, Whitty A, KIMBALL K . Structural and functional differences between glycosylated and non-glycosylated forms of human interferon-beta (IFN-beta). Pharm Res. 1998; 15(4):641-9. DOI: 10.1023/a:1011974512425. View

20.

Rudick R, Simonian N, Alam J, Campion M, Scaramucci J, Jones W . Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis. Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology. 1998; 50(5):1266-72. DOI: 10.1212/wnl.50.5.1266. View