Campath 1-H treatment in patients with aggressive relapsing remitting multiple sclerosis

Department of Neurology, University Hospital of Wales, Heath Park, Cardiff, UK.
Journal of Neurology (Impact Factor: 3.38). 02/2008; 255(2):231-8. DOI: 10.1007/s00415-008-0696-y
Source: PubMed


Campath 1-H (Alemtuzumab) is a humanised monoclonal antibody which targets the CD52 antigen, a low molecular weight glycoprotein present on the surface of most lymphocyte lineages, causing complement mediated lysis and rapid and prolonged T lymphocyte depletion. Following encouraging initial data from other centres we report our open label experience of using Campath 1-H as a treatment in aggressive relapsing multiple sclerosis in a consecutive series of 39 highly selected patients treated across three regional centres and followed for a mean of 1.89 years.
The mean annualised relapse rate fell from 2.48 pre treatment to 0.19 post treatment with 29% of documented relapses observed in the 12 weeks following initial infusion. Mean change in EDSS was –0.36 overall and –0.15 in those patients completing ≥1 year of follow- up. Eighty-three per cent of patients had stable or improved disability following treatment. Infusion related side effects were common including rash, headache and pyrexia but were usually mild and self limiting. Transient worsening of pre-existing neurological deficits during infusion was observed in 3 patients. 12 patients developed biochemical evidence of autoimmune dysfunction, 2 patients developed thyroid disease and 1 patient autoimmune skin disease.
We conclude that relapse rates fall following Campath 1-H. Whilst side effects were common these were normally self limiting or easily managed, suggesting Campath 1-H may be of use in the treatment of very active relapsing remitting multiple sclerosis.


Available from: Adrian A Pace, Feb 21, 2015
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    • "A frequently observed side effect is thyroid autoimmune disease, which can be observed in one-quarter of treated patients (Coles et al., 1999). Allergic reactions with fever, rash, and hypotension are common in patients receiving alemtuzumab (Hirst et al., 2008). The most serious adverse event, however, was the occurrence of fatal cases of idiopathic thrombocytopenic purpura (3% of patients receiving alemtuzumab), which led to the premature cessation of the phase II trial in MS (Coles et al., 2008; Linker and Kieseier, 2008). "
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    • "CD8 + cells appear at high frequencies within CNS lesions (Babbe et al., 2000) and parenchyma and are also enriched within the CSF of patients with relapsing–remitting MS (Jilek et al., 2007; Malmestrom et al., 2008). Although depleting all lymphocytes with the anti-CD52 mAb Campath 1-H can reduce clinical signs in patients with relapsing–remitting and secondary progressive stages of MS (Coles et al., 2006; Hirst et al., 2008), trials that selectively targeted only CD4 + T cells showed limited benefit (Racadot et al., 1993; Rumbach et al., 1996; van Oosten et al., 1997), suggesting that CD8 + T cells might also be an important target. Others have suggested that transfer of myelin oligodendrocyte glycoprotein (MOG)reactive CD8 + T cells can also induce EAE (Sun et al., 2003; Ford and Evavold, 2005). "
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