Skip to main content
SpringerLink
Log in

Managing the Adverse Effects of Interferon-β Therapy in Multiple Sclerosis

  • Practical Drug Safety
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Interferon-β is an established therapy in relapsing-remitting multiple sclerosis. Recently, it has also been shown that interferon-β-1b is effective in secondary progressive multiple sclerosis. However, adverse effects of interferon-β treatment are common, particularly during the first weeks of treatment, and are a major concern. Flu-like symptoms, injection site reactions and laboratory abnormalities are the most common adverse effects, and may result in reduced compliance or even discontinuation of treatment in a number of patients. Therefore, efforts to minimise these reactions, e.g. appropriate comedication with analgesic/antipyretic drugs, use of correct preparation and injection technique and sometimes modification of the dosage of interferon-p, are of considerable importance.

This article provides an overview of the management of clinically relevant adverse effects related to treatment with interferon-β, based on a literature review and personal experience. Essential aspects of patient information are also stressed. If these recommendations are followed, adverse effects related to interferon-β may be substantially reduced in the majority of patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV

Similar content being viewed by others

References

  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: 655–61

    Google Scholar 

  2. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39: 285–94

    Article  PubMed  CAS  Google Scholar 

  3. PRISMS (Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis. Lancet 1998; 352: 1498–504

    Google Scholar 

  4. European Study Group on Interferon β-1b in Secondary Progressive MS. Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis. Lancet 1998; 352: 1491–7

    Google Scholar 

  5. Betaseron® (interferon beta-1b) product monograph. Richmond (CA): Berlex Laboratories, 1993 [revision date 10/96]

  6. Rebif® (interferon beta-1a) product monograph. Geneva: Ares-Serono International SA, 1998

  7. Avonex™ (interferon beta-1a): brief summary of full prescribing information. Cambridge (MA): Biogen Inc., 1996

  8. Logan-Clubb L, Stacy M. An open-labelled assessment of adverse effects associated with interferon 1-beta in the treatment of multiple sclerosis. J Neurosci Nurs 1995; 27: 344–7

    Article  PubMed  CAS  Google Scholar 

  9. Neilly LK, Goodin DS, Goodkin DE, et al. Side effect profile of interferon beta-1b in MS: results of an open label trial. Neurology 1996; 46: 552–4

    Article  Google Scholar 

  10. Huber S, Spycher M, Lechner-Scott J, et al. Multiple sclerosis: therapy with recombinant beta-1b interferon: initial results with 30 multiple sclerosis patients in northwest Switzerland. Schweiz Med Wochenschr 1996; 126: 1475–81

    PubMed  CAS  Google Scholar 

  11. Schwid SR, Goodman AD, Mattson DH. Autoimmune hyperthyroidism in patients with multiple sclerosis treated with interferon beta-1b. Arch Neurol 1997; 57: 1169–70

    Article  Google Scholar 

  12. Durelli L, Bongioanni MR, Ferrero B, et al. Interferon treatment for multiple sclerosis: autoimmune complications may be lethal. Neurology 1998; 50: 570–1

    Article  PubMed  CAS  Google Scholar 

  13. Rotondi M, Oliviero A, Profice P, et al. Occurence of thyroid autoimmunity and dysfunction throughout a nine-month follow-up in patients undergoing interferon-beta therapy for multiple sclerosis. J Endocrinol Invest 1998; 21: 748–52

    PubMed  CAS  Google Scholar 

  14. Durelli L, Ferrero B, Oggero A, et al. Autoimmune events during interferon beta-1b treatment for multiple sclerosis. J Neurol Sci 1999; 162: 74–83

    Article  PubMed  CAS  Google Scholar 

  15. Blake G, Murphy S. Onset of myasthenia gravis in a patient with multiple sclerosis during interferon-1b treatment. Neurology 1997; 49: 1747–8

    Article  PubMed  CAS  Google Scholar 

  16. Webster GF, Knobler RL, Lublin FD, et al. Cutaneous ulcerations and pustular psoriasis flare caused by recombinant interferon beta injections in patients with multiple sclerosis. J Am Acad Dermatol 1996; 34: 365–70

    Article  PubMed  CAS  Google Scholar 

  17. Mehta CL, Tyler RJ, Cripps DJ. Granulomatous dermatitis with focal sarcoidal features associated with recombinant interferon β-1b injections. J Am Acad Dermatol 1998; 39: 1024–8

    Article  PubMed  CAS  Google Scholar 

  18. Linden D. Severe Raynaud’s phenomenon associated with interferon-β treatmentformultiplesclerosis. Lancet 1998; 352: 878–9

    Article  PubMed  CAS  Google Scholar 

  19. Cohen BA, Greenberger PA, Saini S. Delayed occurence of a severe cutaneous reaction in a multiple sclerosis patient taking interferon beta-1b. Allergy Asthma Proc 1998; 19: 85–8

    Article  PubMed  CAS  Google Scholar 

  20. Nousari HC, Kimyai-Asadi A, Tausk FA. Subacute cutaneous lupus erythematosus associated with interferon beta-1a. Lancet 1998; 352: 1825–6

    Article  PubMed  CAS  Google Scholar 

  21. Jabaily JA, Thompson JS. Effects of interferon beta-1B in rheumatoid arthritis: acasereport. Arthritis Rheum 1997; 40: 1370

    PubMed  CAS  Google Scholar 

  22. Alsalameh S, Manger B, Kern P, et al. New onset of rheumatoid arthritis during interferon β-1B treatment in a patient with multiple sclerosis: comment on the case report by Jabaily and Thompson. Arthritis Rheum 1998; 41: 754

    Article  PubMed  CAS  Google Scholar 

  23. Levesque MC, Ward FE, Jeffery DR, et al. Interferon-β1a-induced polyarthritis in a patient with the HLA-DRB1*0404 allele. Arthritis Rheum 1999; 42: 569–73

    Article  PubMed  CAS  Google Scholar 

  24. Colosimo C, Pozzilli C, Frontoni M, et al. No increase of serum autoantibodies during therapy with recombinant human interferon-β1a in relapsing-remitting multiple sclerosis. Acta Neurol Scand 1997; 96: 372–4

    Article  PubMed  CAS  Google Scholar 

  25. Kivisakk P, Lundahl J, von Heigl Z, et al. No evidence for increased frequency of autoantibodies during interferon-β1b treatment of multiple sclerosis. Acta Neurol Scand 1998; 97: 320–3

    Article  PubMed  CAS  Google Scholar 

  26. Dayal AS, Jensen MA, Lledo A et al. Interferon-gamma-secreting cells in multiple sclerosis patients treated with interferon beta-1b. Neurology 1995; 45: 2173–7

    Article  PubMed  CAS  Google Scholar 

  27. Byskosh PV, Reder AT. Interferon β-1b effects on cytokine mRNA in peripheral mononuclear cells in multiple sclerosis. Mult Scler 1996; 1: 262–9

    PubMed  CAS  Google Scholar 

  28. Panitch HS, Hirsch RL, Haley AS, et al. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 1987; I: 893–5

    Article  Google Scholar 

  29. The IFNB Multiple Sclerosis Study Group, University of British Columbia MS/MRI Analysis Group. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology 1995; 45: 1277–85

    Google Scholar 

  30. Mohr DC, Goodkin DE, Likosky W, et al. Therapeutic expectations of patients with multiple sclerosis upon initiating interferon beta-1b: relationship to adherence to treatment. Mult Scler 1996; 2: 222–6

    PubMed  CAS  Google Scholar 

  31. Walther EU, Dietrich E, Hohlfeld R. Therapy for multiple sclerosis with interferon-beta-1b. Advice to patients, including how to deal with side effects. Nervenarzt 1996; 67: 452–6

    PubMed  CAS  Google Scholar 

  32. Munschauer FE, Kinkel RP. Managing side effects of interferon-beta in patients with relapsing-remitting multiple sclerosis. Clin Ther 1997; 19: 883–93

    Article  PubMed  Google Scholar 

  33. Lublin FD, Whitaker JN, Eidelman BH, et al. Management of patients receiving interferon beta-1b for multiple sclerosis: report of a consensus conference. Neurology 1996; 46: 12–8

    Article  PubMed  CAS  Google Scholar 

  34. Report of the quality standards subcommittee of the American Academy of Neurology. Practise advisory on selection of patients with multiple sclerosis for treatment with Betaseron. Neurology 1994, 44: 1537–40

    Google Scholar 

  35. Rio J, Nos C, Marzo ME, et al. Low-dose steroids reduce flulike symptoms at the initiation of IFNβ-1b in relapsing-remitting MS. Neurology 1998; 50: 1910–2

    Article  PubMed  CAS  Google Scholar 

  36. Martínez-Cáceres EM, Rio J, Barrau M, et al. Amelioration of flulike symptoms at the onset of interferon-β-1b therapy in multiple sclerosis by low-dose oral steroids is related to a decrease in interleukin-6 induction. Ann Neurol 1998; 44: 682–5

    Article  PubMed  Google Scholar 

  37. Rieckmann P, Weber F, Gunther A, et al. Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis. J Neuroimmunol 1996; 64: 193–200

    Article  PubMed  CAS  Google Scholar 

  38. Rieckmann P, Bitsch A, Multiple Sclerosis Study Group. Effect of pentoxifylline on disease activity and immunological markers in multiple sclerosis: results from a double-blind, placebo-controlled, cross-over trial in patients with relapsing remitting MS. Mult Scler 1998; 4: 325

    Article  Google Scholar 

  39. Weber F, Polak T, Günther A, et al. Synergistic immunomodulatory effects of interferon-β1b and the phosphodiesterase inhibitor pentoxifylline in patients with relapsing-remitting multiple sclerosis. Ann Neurol 1998; 44: 27–34

    Article  PubMed  CAS  Google Scholar 

  40. Rieckmann P, Weber F, Gunther A, et al. The phosphodiesterase inhibitor pentoxifylline reduces early side effects of interferon-β1b treatment in patients with multiple sclerosis. Neurology 1996, 47: 604

    Article  PubMed  CAS  Google Scholar 

  41. Skias DD, Reder AT. IL-10 inhibits EAE [abstract]. Neurology 1995; 45: A349

    Article  Google Scholar 

  42. Gaines AR, Varricchio F. Interferon beta-1b injection site reactions and necroses. Mult Scler 1998; 4: 70–3

    PubMed  CAS  Google Scholar 

  43. Rieger-Ziegler V, Kränke B, Soyer P, et al. Large cutaneous-subcutaneous infiltrates: a side effect of interferon beta injections. Hautarzt 1998; 49: 310–2

    Article  Google Scholar 

  44. Elgart GW, Sheremata W, Ahn YS. Cutaneous reactions to recombinant human interferon beta-1b: the clinical and histologic spectrum. J Am Acad Dermatol 1997; 37: 553–8

    Article  PubMed  CAS  Google Scholar 

  45. Weinberg JM, Wolfe JT, Sood S, et al. Cutaneous necrosis associated with recombinant interferon injection. Acta Derm Venereol (Stockh) 1997; 77: 146–8

    CAS  Google Scholar 

  46. Albani C, Albani G. A case of cutaneous necrosis during interferon-β1b (B-IFN) therapy in multiple sclerosis. J Neurol Neurosurg Psychiatry 1997; 62: 418

    Article  PubMed  CAS  Google Scholar 

  47. Feldmann R, Löw-Weiser H, Duschet P, et al. Necrotizing cutaneous lesions caused by interferon beta injections in a patient with multiple sclerosis. Dermatology 1997; 195: 52–3

    Article  PubMed  CAS  Google Scholar 

  48. Knobler RL, Kelley CL, Trantas F, et al. Interferon beta-1b induced ulcerative skin lesions in MS. J Neuroimmunol 1994; 54: 173

    Google Scholar 

  49. Bocci V, Pacini A, Bandinelli L, et al. The role of liver in the catabolism of human α- and β-interferon. J Gen Virol 1982; 60: 397–400

    Article  PubMed  CAS  Google Scholar 

  50. Renton KW, Armstrong SG. Immune-mediated downregulation of cytochrome P450 and related drug biotransformation. In: Dean JH, Luster MI, Munson AE, et al., editors. Immunotoxicology and immunopharmacology. New York: Raven Press, 1994: 501–12

    Google Scholar 

  51. Mohr DC, Goodkin DE, Likosky W, et al. Treatment of depression improves adherence to interferon beta-1b therapy for multiple sclerosis. Arch Neurol 1997; 54: 531–3

    Article  PubMed  CAS  Google Scholar 

  52. Joffe RT, Lippert GP, Gray TA, et al. Mood disorder and multiple sclerosis. Arch Neurol 1987; 44: 376–8

    Article  PubMed  CAS  Google Scholar 

  53. Sadovnick AD, Remick RA, Allen J, et al. Depression and multiple sclerosis. Neurology 1996; 46: 628–32

    Article  PubMed  CAS  Google Scholar 

  54. Sadovnick AD, Eisen K, Ebers GC, et al. Cause of deaths in patients attending multiple sclerosis clinics. Neurology 1991; 41: 1193–6

    Article  PubMed  CAS  Google Scholar 

  55. Stenager EN, Stenager E, Koch-Henriksen N, et al. Suicide and multiple sclerosis: an epidemiological investigation. J Neurol Neurosurg Psychiatry 1992; 55: 542–5

    Article  PubMed  CAS  Google Scholar 

  56. Pakulski LA, DiMarco LM. Severe vaginal bleeding associated with recombinant interferon beta-1B. Ann Pharmacother 1997; 31: 50–2

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Research Unit for Multiple Sclerosis and Neuroimmunology, Department of Neurology, University of Würzburg, Josef-Schneider-Strasse 11, 97080, Würzburg, Germany

    Antonios Bayas &  Peter Rieckmann

Authors
  1. Antonios Bayas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Rieckmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Rieckmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bayas, A., Rieckmann, P. Managing the Adverse Effects of Interferon-β Therapy in Multiple Sclerosis. Drug-Safety 22, 149–159 (2000). https://doi.org/10.2165/00002018-200022020-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200022020-00006

Keywords

Search

Navigation