Drug Safety

, Volume 34, Issue 2, pp 117–123

Incidence of Infusion-Associated Reactions with Rituximab for Treating Multiple Sclerosis

A Retrospective Analysis of Patients Treated at a US Centre
Short Communication

Abstract

Background: Rituximab is a monoclonal antibody approved for treating CD20-positive B-cell non-Hodgkin’s lymphoma and rheumatoid arthritis but is used off-label for treating many autoimmune disorders, including multiple sclerosis (MS). Similarly to other monoclonal antibodies, the incidence of infusion-related reactions to rituximab is high. Reactions to monoclonal antibodies, including rituximab, vary widely in type and severity, but may include mild pruritis and rash to more severe complications such as Stevens-Johnson syndrome and anaphylactic reactions.

Objective: To assess the incidence of infusion-associated reactions in our MS patients receiving rituximab infusions and compare it to previous trials investigating rituximab for treating MS.

Methods: From 1 to 30 November 2009, we retrospectively reviewed medical charts from Partners Multiple Sclerosis Centre, Brookline, MA, USA, of patients being treated with rituximab for MS between 20 November 2007 and 24 November 2009 for evidence of infusion-associated reactions and further classified reactions on a grading scale.

Results: During the period studied, 70 patients were infused with rituximab. Infusion-associated events occurred in 25.7% of our patients. Reactions were mild to moderate and most commonly occurred during the first infusion. Most patients were able to complete the infusion after appropriate treatment of the reaction was administered, and most patients went on to receive subsequent doses without any further reactions.

Conclusions: The occurrence of infusion-associated reactions to rituximab in patients with MS is fairly common. However, premedication that includes corticosteroids may reduce the incidence of reactions dramatically. Should they occur, proper treatment of reactions with histamine H1 or H2 receptor antagonists and infusion rate reduction is an effective management strategy in this situation.

References

  1. 1.
    Rituxan® (rituximab) [package insert]. San Francisco (CA): Biogen Idec Inc. and Genentech, 2009Google Scholar
  2. 2.
    Sailler L. Rituximab off-label use for difficult-to-treat auto-immune diseases: reappraisal of benefits and risks. Clin Rev Allergy Immunol 2008; 34: 103–10PubMedCrossRefGoogle Scholar
  3. 3.
    Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372: 1502–17PubMedCrossRefGoogle Scholar
  4. 4.
    Lassmann H. Models of multiple sclerosis: new insights into pathophysiology and repair. Curr Opin Neurol 2008; 21: 242–7PubMedCrossRefGoogle Scholar
  5. 5.
    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: 655–61CrossRefGoogle Scholar
  6. 6.
    Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995; 45: 1268–76PubMedCrossRefGoogle Scholar
  7. 7.
    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: 285–94PubMedCrossRefGoogle Scholar
  8. 8.
    PRISMS Study Group. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 1998; 352: 1498–504CrossRefGoogle Scholar
  9. 9.
    Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899–910PubMedCrossRefGoogle Scholar
  10. 10.
    Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354: 911–23PubMedCrossRefGoogle Scholar
  11. 11.
    Franciotta D, Salvetti M, Lolli F, et al. B cells in multiple sclerosis. Lancet Neurol 2008; 7: 852–8PubMedCrossRefGoogle Scholar
  12. 12.
    Dalakas MC. B cells in the pathophysiology of autoimmune neurological disorders: a credible therapeutic target. Pharmacol Ther 2006; 112: 57–70PubMedCrossRefGoogle Scholar
  13. 13.
    Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358: 676–88PubMedCrossRefGoogle Scholar
  14. 14.
    Common terminology criteria for adverse events v3.0 (CTCAE): online instructions and guidelines. Bethesda (MD): National Cancer Institute, August 9, 2006 [online]. Available from URL: http://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf [Accessed 2010 Jan 6]
  15. 15.
    Gaston RS, Zeierhoi MH, Patterson T, et al. OKT3 first dose reaction: association with T cells subset and cytokines release. Kidney Int 1991; 39: 141–7PubMedCrossRefGoogle Scholar
  16. 16.
    Albrecht H, Radosevich JA, Babich M. Fundamentals of antibody-related therapy and diagnostics. Drugs Today (Barc) 2009; 45: 199–211CrossRefGoogle Scholar
  17. 17.
    Calogiuri G, Ventura MT, Mason L, et al. Hypersensitivity reactions to last generation chimeric, humanized and human recombinant monoclonal antibodies for therapeutic use. Curr Pharm Des 2008; 14: 2883–91PubMedCrossRefGoogle Scholar
  18. 18.
    Cohen SB, Emery P, Greenwald MW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Arthritis Rheum 2006; 54(9): 2793–806PubMedCrossRefGoogle Scholar
  19. 19.
    Merrill JT, Neuwelt CM, Wallace DJ, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus. Arthritis Rheum 2010; 62(1): 222–33PubMedCrossRefGoogle Scholar
  20. 20.
    McLaughlin P, Hagemeister FB, Grill-Lopez AJ. Rituximab in indolent lymphoma: the single-agent pivotal trial. Semin Oncol 1999; 26 (5 Suppl. 14): 79–87PubMedGoogle Scholar
  21. 21.
    Hawker K, O’Connor P, Freedman MS, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multi-center trial. Ann Neurol 2009; 66: 460–71PubMedCrossRefGoogle Scholar
  22. 22.
    Bar-Or A, Calabresi PAJ, Arnold D, et al. Rituximab in relapsing-remitting multiple sclerosis: a 72-week, open-label, phase I trial. Ann Neurol 2008; 63: 395–400PubMedCrossRefGoogle Scholar
  23. 23.
    Schwartzberg LS, Stepanski EJ, Fortner BV, et al. Retrospective chart review of severe infusion reactions with rituximab, cetuximab, and bevacizumab in community oncology practices: assessment of clinical consequences. Support Care Cancer 2008; 16: 393–8PubMedCrossRefGoogle Scholar
  24. 24.
    Lenz HJ. Management and preparedness for infusion and hypersensitivity reactions. Oncologist 2007; 12: 601–9PubMedCrossRefGoogle Scholar
  25. 25.
    Lenz HJ. Anti-EGFR mechanism of action: antitumor effect and underlying cause of adverse events. Oncology 2006; 20 Suppl. 2: 5–13PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Department of PharmacyBrigham and Women’s HospitalBrookline, BostonUSA

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