Serial combination therapy: is immune modulation in multiple sclerosis enhanced by initial immune suppression?

Multiple Sclerosis Journal - Tập 15 Số 8 - Trang 959-964 - 2009
Amit Bar‐Or1, Joël Oger2, Emma Gibbs2, Masaaki Niino1, T Aziz2, Christel Renoux1, Sudabeh Alatab1, Fu‐Dong Shi3, Denise I. Campagnolo3, Farzaneh Jalili1, Susan Rhodes3, T Yamashita1, Bingbing Fan1, Marc Freedman4, Hillel Panitch5, Douglas L. Arnold1, Timothy Vollmer6
1Montreal Neurological Institute, Montreal, Quebec, Canada
2Division of Neurology, Department of Medicine, Multiple Sclerosis Clinic and Brain Research Centre, The University of British Columbia, Vancouver, British Columbia, Canada
3Barrow Neurology Institute of St Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA
4Multiple Sclerosis Research Unit The Ottawa Hospital General Campus, University of Ottawa, Ottawa, Canada
5Department of Neurology, Multiple Sclerosis Center, University of Vermont, College of Medical, Burlington, Vermont, USA
6Department of Neurology, Rocky Mountain MS Center, Anschutz Medical Center, University of Colorado, Denver, Colorado, USA

Tóm tắt

Background Although the concept that an initial course of immune-suppression facilitates subsequent immune-modulation (such as Th1 to Th2 deviation) is attractive for several autoimmune diseases, such a mechanism for serial-combination therapy has never been formally demonstrated. Recently, brief mitoxantrone induction-chemotherapy followed by immune-modulation with glatiramer acetate (GA) was significantly more effective at reducing multiple sclerosis disease activity than with GA alone. Objective To examine whether the benefit of initial immune suppression with mitoxantrone before GA treatment is associated with more efficient immune modulation. Methods IgG1/IgG4 GA-reactive antibody profiles, previously established as markers of GA-induced Th2 immune-deviation, were prospectively measured in vivo in patients treated with GA alone or with mitoxantrone induction therapy followed by GA. Results Significant and sustained increase in IgG4 antibodies (and the anticipated reversal of the IgG1/IgG4 ratio) was seen in patients treated with GA alone. Combination therapy resulted in lesser IgG4 induction (and no reversal of IgG1/IgG4 ratio). Thus, the enhanced efficacy of mitoxantrone–GA combination regimen was associated with decreased, rather than increased, efficiency of shifting the GA-reactive IgG1/IgG4 antibody profile. Conclusion These results provide important insights into mechanisms of combination therapy and therapeutic strategies for autoimmune diseases.

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Multiple Sclerosis Journal

Tập 15 Số 8

959-964

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