Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients with multiple sclerosis

Multiple Sclerosis

Volumn 15, Issue 3, 2009, Pages 323-328

  Ravnborg, Mads ^a,d   Bendtzen, K ^a,b   Christensen, O ^a,b   Jensen, P E H ^a   Hesse, D ^a   Tovey, M G ^b,c   Sorensen P S ^a  

^a Rigshospitalet   (Denmark)

^b Biomonitor A/S   (Denmark)

^c INSTITUT ANDRÉ LWOFF   (France)

^d ODENSE UNIVERSITY HOSPITAL   (Denmark)

Author keywords

Azathioprine; Interferon ; Methylprednisolone; Multiple sclerosis; Neutralizing antibodies; Treatment

Indexed keywords

AZATHIOPRINE; BETA INTERFERON; BETA INTERFERON ANTIBODY; INTERFERON ANTIBODY; MESSENGER RNA; METHYLPREDNISOLONE; MYXOVIRUS RESISTANCE PROTEIN A; NEUTRALIZING ANTIBODY; UNCLASSIFIED DRUG;

ANTIBODY TITER; AROUSAL; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED STUDY; CYTOPATHOGENIC EFFECT; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG DOSE REDUCTION; DRUG RESPONSE; DYSPEPSIA; FATIGUE; GASTROINTESTINAL SYMPTOM; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; IN VIVO STUDY; INSOMNIA; MULTIPLE SCLEROSIS; OUTCOME ASSESSMENT; REAL TIME POLYMERASE CHAIN REACTION; REPORTER GENE; SIDE EFFECT; TREATMENT DURATION;

ANTIBODIES; AZATHIOPRINE; DRUG RESISTANCE; DRUG THERAPY, COMBINATION; GENES, REPORTER; GLUCOCORTICOIDS; GTP-BINDING PROTEINS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INTERFERON-BETA; METHYLPREDNISOLONE; MULTIPLE SCLEROSIS; RNA, MESSENGER; TREATMENT FAILURE;

EID: 61849151765     PISSN: 13524585     EISSN: None     Source Type: Journal    
DOI: 10.1177/1352458508099476     Document Type: Article

References (30)

1. The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993; 43: 655-661.
2. Jacobs, LD, Cookfair, DL, Rudick, RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 1996; 39: 285-294.
3. PRISMS. (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/ remitting multiple sclerosis. Lancet 1998; 352: 1498-1504.
4. Bertolotto, A, Gilli, F, Sala, A, et al. Persistent neutralizing antibodies abolish the interferon beta bioavailability in MS patients. Neurology 2003; 60: 634-639.
5. 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: 1239-1243.
6. Francis, GS, Rice, GP, Alsop, JC. Interferon beta-1a in MS: Results following development of neutralizing antibodies in PRISMS. Neurology 2005; 65: 48-55.
7. Kappos, L, Clanet, M, Sandberg-Wollheim, M, et al. Neutralizing antibodies and efficacy of interferon beta-1a: A 4-year controlled study. Neurology 2005; 65: 40-47.
8. Polman, C, Kappos, L, White, R, et al. Neutralizing antibodies during treatment of secondary progressive MS with interferon beta-1b. Neurology 2003; 60: 37-43.
9. PRISMS Study Group. PRISMS-4: Long-term efficacy of interferon-beta-1a in relapsing MS. Neurology 2001; 56: 1628-1636.
10. Sorensen, PS, Ross, C, Clemmesen, KM, et al. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet 2003; 362: 1184-1191.
11. Pachner, AR, Bertolotto, A, Deisenhammer, F. Measurement of MxA mRNA or protein as a biomarker of IFNbeta bioactivity: Detection of antibody-mediated decreased bioactivity (ADB). Neurology 2003; 61(Suppl. 5): S24-S26.
12. Farrell, RA, Giovannoni, G. Measuring and management of anti-interferon beta antibodies in subjects with multiple sclerosis. Mult Scler 2007; 13: 567-577.
13. Giovannoni, G, Goodman, A. Neutralizing anti-IFN-beta antibodies: How much more evidence do we need to use them in practice. Neurology 2005; 65: 6-8.
14. Hesse, D, Sorensen, PS. Using measurements of neutralizing antibodies: the challenge of IFN-beta therapy. Eur J Neurol 2007; 14: 850-859.
15. Sorensen, PS, Deisenhammer, F, Duda, P, et al. Guidelines on use of anti-interferon-beta antibody measurements in multiple sclerosis - report of an EFNS Task Force on IFN-beta antibodies in multiple sclerosis. Eur J Neurol 2005; 12: 817-827.
16. Rice, GP, Paszner, B, Oger, J, Lesaux, J, Paty, D, Ebers, G. The evolution of neutralizing antibodies in multiple sclerosis patients treated with interferon beta-1b. Neurology 1999; 52: 1277-1279.
17. Sorensen, PS, Koch-Henriksen, N, Ross, C, Clemmesen, KM, Bendtzen, K. Appearance and disappearance of neutralizing antibodies during interferon-beta therapy. Neurology 2005; 65: 33-39.
18. Petersen, B, Bendtzen, K, Koch-Henriksen, N, Ravnborg, M, Ross, C, Sorensen, PS. Persistence of neutralizing antibodies after discontinuation of IFNbeta therapy in patients with relapsing-remitting multiple sclerosis. Mult Scler 2006; 12: 247-252.
19. Pozzilli, C, Antonini, G, Bagnato, F, et al. Monthly corticosteroids decrease neutralizing antibodies to IFNbeta1 b: A randomized trial in multiple sclerosis. J Neurol 2002; 249: 50-56.
20. Bendtzen, K. Anti-IFN BAb and NAb antibodies: A minireview. Neurology 2003; 61(Suppl. 5): S6-S10.
21. Ravnborg, M, Gronbech Jensen, M, Jonsson, A. The MS Impairment Scale: A pragmatic approach to the assessment of impairment in patients with multiple sclerosis. Mult Scler 1997; 3: 31-42.
22. Grossberg, SE, Kawade, Y, Kohase, M, Klein, JP. The neutralization of interferons by antibody. II. Neutralizing antibody unitage and its relationship to bioassay sensitivity: The tenfold reduction unit. J Interferon Cytokine Res 2001; 21: 743-755.
23. Pachner, A, Narayan, K, Price, N, Hurd, M, Dail, D. MxA gene expression analysis as an interferon-beta bioactivity measurement in patients with multiple sclerosis and the identification of antibody-mediated decreased bioactivity. Mol Diagn 2003; 7: 17-25.
24. Rudick, RA, Simonian, NA, Alam, JA, et al. Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis. Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology 1998; 50: 1266-1272.
25. Ross, C, Svenson, M, Clemmesen, KM, Sorensen, PS, Koch-Henriksen, N, Bendtzen, K. Measuring and evaluating interferon-beta-induced antibodies in patients with multiple sclerosis. Mult Scler 2006; 12: 39-46.
26. Pachner, AR, Dail, D, Pak, E, Narayan, K. The importance of measuring IFNbeta bioactivity: Monitoring in MS patients and the effect of anti-IFNbeta antibodies. J Neuroimmunol 2005; 166: 180-188.
27. Sorensen, PS, Koch-Henriksen, N, Flachs, EM, Bendtzen, K. Is treatment effect of IFN-beta restored after disappearance of neutralizing antibodies. Mult Scler 2008; 14: 837-842.
28. Malucchi, S, Capobianco, M, Gilli, F, et al. Fate of multiple sclerosis patients positive for neutralising antibodies towards interferon beta shifted to alternative treatments. Neurol Sci 2005; 26(Suppl. 4): S213-S214.
29. Gneiss, C, Reindl, M, Lutterotti, A, et al. Interferon-beta: The neutralizing antibody (NAb) titre predicts reversion to NAb negativity. Mult Scler 2004; 10: 507-510.
30. Sorensen, PS, Tscherning, T, Mathiesen, HK, et al. Neutralizing antibodies hamper IFNbeta bioactivity and treatment effect on MRI in patients with MS. Neurology 2006; 67: 1681-1683.