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Treating Patients with Relapsing MS
San Diego—Multiple sclerosis (MS) is an autoimmune disease in which the immune system attacks the protective layer around nerves. During a science and innovation theater at AMCP, Lilly Jung Henson, MD, MMM, FAAN, director of the neurology clinic, Swed- ish Neuroscience Institute, and clinical associate professor of neurology, University of Washington, reviewed the use of alemtuzumab in patients with MS. The event was sponsored by Genzyme Corporation.
Alemtuzumab is a CD52-directed cytolytic monoclonal antibody approved for the treatment of relapsing forms of MS. “[Due to its safety profile, alemtuzumab is] recommend for patients who have had inadequate responses to a couple of the current disease modifying therapies,” said Dr. Henson.
Alemtuzumab is administered via intravenous infusion over 4 hours for 2 treatment courses. The recommended dosage for alemtuzumab is 12 mg/d for 5 consecutive days for the first year. In the second year, alemtuzumab is administered 12 mg/d for 3 consecutive days.
This drug is contraindicated in patients who are HIV positive. Annual screening for human papilloma virus is recommended for female patients. Screening for tuberculosis in all patients in recommended. Patients at high risk for hepatitis B and/or hepatitis C should be screened prior to starting alemtuzumab. All vaccinations should be administered 6 weeks prior to the initiation of treatment. Alemtuzumab received approval after its demonstrated effiicacy in 2 pivotal trials. Both trials were 2-year randomized, open-label, rater-blinded, controlled studies that utilized an active comparator (interferon beta-1a 44 micrograms) in place of placebo. “Part of the reason why [interferon beta-1a] was chosen above the other therapies on the market at the time is because the study designers felt it was the most effective therapy on the market,” said Dr. Henson
In Study 1, 628 relapsing-remitting multiple sclerosis (RRMS) patients who experienced at least 1 relapse while taking interferon beta or glatiramer acetate therapy and had an Expanded Disability Status Scale (EDSS) score of ≤5 participated in the study. Of the 628 RRMS patients, 426 received alemtuzumab and 202 received interferon beta-1a. Of the participants who received alemtuzumab, only 13% experienced disability progression at Year 2.
The study showed 65% of participants who received alemtuzumab remained relapse-free at Year 2 compared to participants receiving interferon beta-1a (47%; P<0.0001). Participants randomized to alemtuzumab experienced a 49% relative reduction in relapse rate compared to interferon beta-1a (P<0.0001). In MRI outcomes, the percent change in T2 lesion volume from baseline for participants who received alemtuzumab was -1.3% compared to patients who received interferon beta-1a (-1.2%).
In Study 2, 563 RRMS patients who had an EDSS score of ≤3 and had no prior treatment for MS were randomized to receive alemtuzumab (n=376) or interferon beta- 1a (n=187). Of the patients who received alemtuzumab, 78% remained relapse-free at Year 2 compared to participants who received interferon beta-1a (59%; P<0.0001). Those taking alemtuzumab experienced a 55% relative reduction in relapse rate compared to interferon beta-1a (P<0.0001). The MRI outcomes showed a percent change in T2 lesion volume from baseline for participants who received alem- tuzumab of -9.3% compared to patients who received interferon beta-1a (-6.5%).
The most common adverse events that occurred during the 2 studies were rash (53%), headache (52%), and pyrexia (29%). More serious adverse events that occurred were immune thrombocytopenia (2%), glomerular nephropathies (0.3%), thyroid disorders (34%), and other auto- immune cytopenias including neutropenia (0.1%), hemolytic anemia (0.2%), and pancytopenia (0.2%).
To monitor for early signs of serious adverse events, it is recommended that physicians test monthly for idiopathic thrombocytopenic purpura and glomerular nephropathies, including anti-glomerular basement membrane disease. Physicians should perform quarterly tests for thyroid disease. “We want labs drawn for up to 48 months after their last infusion,” added Dr. Henson.
Infusion reactions were common in 92% of patients taking alemtuzumab, but only 3% were considered serious reactions. “The infusion reactions are primarily cytokine release reactions as opposed to allergic reactions,” noted Dr. Henson. She suggested prescribing patients corticosteroids or antihistamines prior to treatment with alemtuzumab and monitoring patients for 2 hours after the infusion has taken place.
“It is easy to manage [infusion reactions] when you have the patients in an infusion unit where the nurses are well-trained and are used to taking care of patients with infusion reactions,” said Dr. Henson.
During the clinical trials, more infec- tions were seen in participants taking alemtuzumab (71%) compared to those taking interferon beta-1a (53%). Serious infections occurred in 3% of participants taking alemtuzumab. Dr. Henson suggested premedicating all patients receiving alemtuzumab with an acyclovir to prevent viral infections from developing. Monitor the patients taking acyclovir and only discontinue drug until they have reached a CD4+ count ≥200.
Of all the study participants, 70% received only 2 courses of the therapy; 5 doses in Year 1 and 3 doses in Year 2. Nineteen percent of participants continued therapy in Year 3 and 16% continued to therapy in Year 4. Dr. Henson noted that the cost of treatment would most likely be more expensive in Year 1 than Year 2 because of the change in recommended dosage.—Melissa D. Cooper
