Alemtuzumab: evidence for its potential in relapsing-remitting multiple sclerosis

Alemtuzumab (previously known as Campath(®)) is a humanized monoclonal antibody directed against the CD52 antigen on mature lymphocytes that results in lymphopenia and subsequent modification of the immune repertoire. Here we explore evidence for its efficacy and safety in relapsing-remitting multip...

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Vydáno v:	Drug design, development and therapy Ročník 7; s. 131 - 138
Hlavní autoři:	Brown, William, Coles, Alasdair
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New Zealand Dove Medical Press Limited 01.01.2013 Taylor & Francis Ltd Dove Press Dove Medical Press
Témata:	Adjuvants, Immunologic - adverse effects Adjuvants, Immunologic - therapeutic use Alemtuzumab Antibodies, Monoclonal, Humanized - adverse effects Antibodies, Monoclonal, Humanized - immunology Antibodies, Monoclonal, Humanized - therapeutic use Antigens, CD - immunology Antigens, Neoplasm - immunology Atrophy Autoimmunity Brain Campath CD52 Antigen Clinical trials Drug therapy efficacy Glycoproteins - immunology Hemorrhage Humans Immunotherapy Interferon Interferon beta-1a Interferon-beta - adverse effects Interferon-beta - pharmacology Interferon-beta - therapeutic use Lymphocytes Lymphopenia Monoclonal antibodies Multiple sclerosis Multiple Sclerosis, Relapsing-Remitting - drug therapy Multiple Sclerosis, Relapsing-Remitting - immunology Multiple Sclerosis, Relapsing-Remitting - physiopathology Patients Pharmaceutical research Purpura relapsing-remitting multiple sclerosis Review Therapy Thrombocytopenic purpura Thyroid Treatment Outcome relapsing–remitting multiple sclerosis alemtuzumab efficacy Campath
ISSN:	1177-8881, 1177-8881
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Shrnutí:	Alemtuzumab (previously known as Campath(®)) is a humanized monoclonal antibody directed against the CD52 antigen on mature lymphocytes that results in lymphopenia and subsequent modification of the immune repertoire. Here we explore evidence for its efficacy and safety in relapsing-remitting multiple sclerosis. One Phase II and two Phase III trials of alemtuzumab versus active comparator (interferon beta-1a) have been reported. Two of these rater-blinded randomized studies assessed clinical and radiological outcomes in treatment-naïve patients; one explored patients who had relapsed despite first-line therapy. Compared to interferon beta-1a, alemtuzumab reduced the relapse rate by 49%-74% (P < 0.0001), and in two studies it reduced the risk of sustained disability accumulation by 42%-71% (P < 0.01). In one study (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CARE-MS1), there was no significant difference compared to interferon, perhaps reflecting the surprisingly low frequency of disability events in the comparator group. After alemtuzumab, the Expanded Disability Status Scale score improved by 0.14-1.2 points, culminating in a net advantage with alemtuzumab of 0.41-0.77 points over interferon in the CAMMS223 and CARE-MS2 trials (both P < 0.001). Radiological markers of new lesion formation and brain atrophy following alemtuzumab were significantly improved when compared to interferon in all studies. Adverse events were more common following alemtuzumab than interferon beta-1a (7.2-8.66 versus 4.9-5.7 events per person-year). While infusion reactions are the most common, autoimmunity is the most concerning; within Phase III studies, thyroid disorders (17%-18% versus 5%-6%) and immune thrombocytopenic purpura (1% versus 0%) were reported in patients taking alemtuzumab and interferon beta-1a, respectively. All patients responded to conventional therapy. One patient taking alemtuzumab in the Phase II study suffered a fatal intracranial hemorrhage following immune thrombocytopenic purpura, heralding assiduous monitoring of all patients thereafter. Alemtuzumab has been submitted for licensing in relapsing-remitting multiple sclerosis in the United States and Europe.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 ObjectType-Review-3 content type line 23
ISSN:	1177-8881 1177-8881
DOI:	10.2147/DDDT.S32687