快樂小藥師 Im pharmacist nichts glücklich

Alemtuzumab (Lemtrada, Genzyme Corporation/sanofi-aventis) benefits the hardest-to-treat multiple sclerosis (MS) patients, even when the efficacy bar is set at the high possible level, a new study suggests.

The study showed that after 2 years, almost a quarter of patients had achieved a disease activity–free state compared with none of those treated with interferon.

The new results were presented at the 5th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Alemtuzumab, an anti-CD52 monoclonal antibody, is awaiting approval by the US Food and Drug Administration (FDA) for use in MS following completion and publication of 2 phase 3 trials: CARE-MS I in treatment naïve patients with relapsing-remitting MS, and CARE-MS II in MS patients with disease activity despite treatment.

Both studies compared alemtuzumab with interferon beta-1a (Rebif, EMD Serono, Inc.), and both showed reduction in relapse rates for those taking the new agent. In CARE-MS II, for example, the relapse rate was reduced by 49%, and disability by 42%, compared with interferon, and magnetic resonance imaging (MRI) numbers were "favorable," said Stephen Krieger, assistant professor of neurology, Mount Sinai Medical Center, New York City, who presented the results.

Alemtuzumab is delivered intravenously (12 mg) on 5 consecutive days and then on 3 consecutive days a year later.

New Analysis

This new analysis assessed a subgroup of patients in CARE-MS II who had the most active disease — 2 or more relapses in the year before randomization, and 1 or more baseline gadolinium-enhancing lesions. "They had MRI and clinical evidence of active, relapsing MS despite being on medicines," said Dr. Krieger.

Results showed that 24.2% of 101 hard-to-treat patients who received alemtuzumab were disease activity–free at the end of 2 years (P = .0002) compared with 0% of 42 similarly hard-to-treat patients taking interferon. Disease activity–free was defined as no relapse, no sustained accumulation of disability (SAD), as measured by Expanded Disability Status Scale (EDSS), and no new gadolinium-enhancing lesions or new or enlarging T2-hyperintense lesions.

Dr. Krieger stressed that the drug was not compared with placebo but against a proven effective treatment. "This is important, as it shows an unmet need. This subgroup had very active disease, and our existing medicines, which are very good, achieved total disease suppression in zero patients in that group."

In addition, the analysis showed that 35.8% of the alemtuzumab group had relapses compared with 60.0% for those on interferon. The respective numbers for SAD were 7.4% and 17.5%; for gadolinium-enhancing lesion activity, 22.1% and 52.5%; and for T2 lesion activity, 60.0% and 92.5%.

The "quieting down" of disability in the patients taking the monoclonal antibody "happened very quickly," said Dr. Krieger. "The cellular effects of the drug take place within a couple of days; the cells that alemtuzumab affect drop down to zero, and then they take a long time to come back."

Some patients who received the drug in the earlier phase 2 trial in 2004 and 2005 have not needed further treatment of any kind since, said Dr. Krieger. "There are people who still have disease, but for the ones this drug affects, it can affect them for a very long time."

The side effect and adverse events profiles for this subgroup were not different from those seen in the overall trial, said Dr. Krieger.

Careful Monitoring

In an interview, Robert Lisak, MD, professor of neurology, Wayne State University School of Medicine, Detroit, Michigan, pointed out that side effects of the drug have encompassed potentially serious autoimmune diseases, including thyroid disorders and immune thrombocytopenia, both of which require careful monitoring and management.

Dr. Lisak also noted that although phase 2 trial results for alemtuzumab were "strikingly positive," the later-phase studies were less so and suggested that the drug "didn't work forever."

"This drug, in phase 2 trials especially, and to some degree in phase 3, did look like a bit of a game changer," said Dr. Lisak. "But it doesn't look like it's that way for every patient anymore."

During the presentation of the new results, Dr. Lisak also said that the state of disease "freedom" can only be measured using current tools — MRI and clinical picture — and that this may change with time.

"He's right," said Dr. Krieger. "As we get more modern ways of looking at MS, such as new MRI techniques, we will be able to know about subtle disease activity that we can't see right now."

Dr. Krieger has received consulting fees from Acorda Therapeutics, Bayer Healthcare Pharmaceuticals, Biogen Idec Inc, EMD Serono, Genzyme Corporation, Novartis Pharmaceuticals Corporation, Questcor, and Teva Neuroscience, Inc.; a grant/research support from Bayer Healthcare Pharmacaeuticals; and fees for non-CME services from commercial interest or their agents from Teva Neuroscience, Inc.

5th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS). Oral Presentation DX01. Presented May 31, 2013.