Effect of Alemtuzumab (CAMPATH 1-H) in patients with inclusion-body myositis

Marinos C. Dalakas, Goran Rakocevic, Jens Schmidt, Mohammad Salajegheh, Beverly McElroy, Michael O. Harris-Love, Joseph A. Shrader, Ellen W. Levy, James Dambrosia, Robert L. Kampen, David A. Bruno, Allan D. Kirk

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171 Scopus citations


Sporadic inclusion-body myositis (sIBM) is the most common disabling, adult-onset, inflammatory myopathy histologically characterized by intense inflammation and vacuolar degeneration. In spite of T cell-mediated cytotoxicity and persistent, clonally expanded and antigen-driven endomysial T cells, the disease is resistant to immunotherapies. Alemtuzumab is a humanized monoclonal antibody that causes an immediate depletion or severe reduction of peripheral blood lymphocytes, lasting at least 6 months. We designed a proof-of-principle study to examine if one series of Alemtuzumab infusions in sIBM patients depletes not only peripheral blood lymphocytes but also endomysial T cells and alters the natural course of the disease. Thirteen sIBM patients with established 12-month natural history data received 0.3 mg/kg/day Alemtuzumab for 4 days. The study was powered to capture <10 increase strength 6 months after treatment. The primary end-point was disease stabilization compared to natural history, assessed by bi-monthly Quantitative Muscle Strength Testing and Medical Research Council strength measurements. Lymphocytes and T cell subsets were monitored concurrently in the blood and the repeated muscle biopsies. Alterations in the mRNA expression of inflammatory, stressor and degeneration-associated molecules were examined in the repeated biopsies. During a 12-month observation period, the patients' total strength had declined by a mean of 14.9 based on Quantitative Muscle Strength Testing. Six months after therapy, the overall decline was only 1.9 (P < 0.002), corresponding to a 13 differential gain. Among those patients, four improved by a mean of 10 and six reported improved performance of daily activities. The benefit was more evident by the Medical Research Council scales, which demonstrated a decline in the total scores by 13.8 during the observation period but an improvement by 11.4 (P < 0.001) after 6 months, reaching the level of strength recorded 12 months earlier. Depletion of peripheral blood lymphocytes, including the naive and memory CD8 cells, was noted 2 weeks after treatment and persisted up to 6 months. The effector CD45RA CD62L cells, however, started to increase 2 months after therapy and peaked by the 4th month. Repeated muscle biopsies showed reduction of CD3 lymphocytes by a mean of 50 (P < 0.008), most prominent in the improved patients, and reduced mRNA expression of stressor molecules Fas, Mip-1a and αB-crystallin; the mRNA of desmin, a regeneration-associated molecule, increased. This proof-of-principle study provides insights into the pathogenesis of inclusion-body myositis and concludes that in sIBM one series of Alemtuzumab infusions can slow down disease progression up to 6 months, improve the strength of some patients, and reduce endomysial inflammation and stressor molecules. These encouraging results, the first in sIBM, warrant a future study with repeated infusions (Clinical Trials. Gov NCT00079768).

Original languageEnglish
Pages (from-to)1536-1544
Number of pages9
Issue number6
StatePublished - Jun 2009
Externally publishedYes


  • Alemtuxumab
  • Endomysial inflammation
  • IBM
  • Lymphocyte depletion
  • Muscle degeneration
  • Muscle inflammation
  • Stressor molecules


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