Managing adverse effects of disease-modifying agents used for treatment of multiple sclerosis

ABSTRACT

Background: First-line agents approved in the United States for treatment of relapsing multiple sclerosis (MS) include intramuscular interferon beta (IFNβ)-1a, subcutaneous (SC) IFNβ-1a, SC IFNβ-1b, and SC glatiramer acetate. Intravenous mitoxantrone is the only agent approved for secondary progressive MS, progressive relapsing MS, and worsening relapsing MS. Intravenous natalizumab is approved for relapsing forms of MS generally in patients who have an inadequate response to, or are unable to tolerate, first-line therapies. Corticosteroids are commonly used to treat relapses. This paper reviews the incidence and management of common adverse events (AEs) associated with these treatments.

Methods: MEDLINE and EMBASE were searched for clinical trials and other publications between 1985 and 2007 reporting AEs associated with MS therapies, using these search terms: multiple sclerosis, interferon, Avonex, Betaseron, Rebif, glatiramer, copolymer 1, Copaxone, mitoxantrone, natalizumab, adverse events.

Results: A class-specific flu-like syndrome associated with IFNβ can be managed through initial dose escalation and administration of analgesics and antipyretics, prophylactically or symptomatically. Injection-site reactions can occur in patients receiving injectable therapies, particularly SC IFNβ or glatiramer acetate. The greatest risk to patients receiving mitoxantrone is cardiotoxicity; thus, the cumulative dose is limited. Allergic reactions occur rarely with natalizumab, and there is a potential risk of progressive multifocal leukoencephalopathy. AEs associated with short-term pulse corticosteroid therapy are usually transient and largely resolve after treatment is completed.

Conclusions: To improve adherence to therapy, it is important to educate patients regarding AEs and to manage AEs proactively.

Key Words::

• Adverse events
• Disease-modifying therapy
• Multiple sclerosis
• Treatment

Acknowledgments

Declaration of interest: This manuscript was supported by Biogen Idec, Inc. The authors acknowledge Sabrina Maurer and Matthew Hasson of Scientific Connexions, Newtown, PA, USA, for a preliminary draft and editorial assistance in preparing the manuscript. The authors provided final manuscript preparation, review, and approval. HM has received research support from Biogen Idec, Genentech, Novartis, Serono, and Teva Neurosciences, as well as honoraria and speaking fees from Bayer, Biogen Idec, Pfizer, EMD Serono, Questcor, and Teva Neurosciences. DWB has received research support from Biogen Idec and Teva Neurosciences and has served on advisory boards and speakers bureaus for Biogen Idec, Berlex (now Bayer), Elan Pharmaceuticals, Serono, and Teva Neurosciences.

Notes

a Avonex is a registered trademark of Biogen Idec, Inc., Cambridge, MA, USA

b Rebif is a registered trademark of EMD Serono, Inc., Rockland, MA, USA

c Betaseron is a registered trademark of Berlex Laboratories, Montvale, NJ, USA

d Copaxone is a registered trademark of Teva Pharmaceutical Industries, Inc., Kansas City, MO, USA

a Tysabri is a registered trademark of Biogen Idec, Inc., Cambridge, MA, USA

b Novantrone is a registered trademark of EMD Serono, Inc., Rockland, MA, USA

c Solu-Medrol is a registered trademark of Pharmacia & Upjohn Company, New York, NY, USA