BARCELONA—Alemtuzumab’s benefits for patients with relapsing-remitting multiple sclerosis (MS) may persist for five years, according to data from an extension study presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Participants who received alemtuzumab in the phase III pivotal studies CARE-MS I and CARE-MS II had positive outcomes throughout the course of the two-year trials. These benefits were maintained through three additional years in the extension study. In the pivotal studies, courses of treatment were administered at month zero and at month 12. After the initial two courses of treatment, 68% of treated patients from CARE-MS I and 60% of treated patients from CARE-MS II did not receive additional alemtuzumab during the following four years (ie, through month 60).
The low annualized relapse rates observed in patients who received alemtuzumab in CARE-MS I (0.18) and CARE-MS II (0.27) were maintained from year three (0.19 and 0.22, respectively) to year five (0.15 and 0.18, respectively). Through year five, 80% and 76% of patients who received alemtuzumab in CARE-MS I and CARE-MS II, respectively, did not have worsening of disability progression confirmed over six months, as measured by the Expanded Disability Status Scale (EDSS). Through year five, 33% and 43% of patients who had disability before receiving alemtuzumab in CARE-MS I and CARE-MS II, respectively, had improvement in EDSS score confirmed over at least six months, as compared with pretreatment baseline.
Furthermore, through year five, patients who received alemtuzumab in CARE-MS I and II had a slowing of brain atrophy, as measured by brain parenchymal fraction on MRI. In years three, four, and five, the median yearly brain volume loss was 0.20% or less, which was lower than the rate observed during the two-year pivotal studies. In each of years three, four, and five, most patients had no evidence of MRI disease activity (70–72% in CARE-MS I and 68–70% in CARE-MS II).
Through year five, the incidence of most adverse events during the extension study was comparable to or lower than that of the pivotal studies. The frequency of thyroid adverse events was highest in year three and declined in the subsequent years.
The phase III trials of alemtuzumab were randomized, rater-blinded, two-year pivotal studies comparing alemtuzumab with high-dose subcutaneous interferon beta-1a in patients with relapsing-remitting MS who had active disease and were either new to treatment (ie, in CARE-MS I) or who had had an inadequate response to another therapy (ie, in CARE-MS II).
More than 90% of the patients who received alemtuzumab in the CARE-MS phase III trials enrolled in the extension study. These patients were eligible to receive additional treatment with alemtuzumab in the extension study if they had at least one relapse or at least two new or enlarging brain or spinal cord lesions.
“These data illustrate that most alemtuzumab patients experienced sustained effects of treatment, despite the absence of additional treatment courses,” said Eva Havrdová, MD, PhD, Professor of Neurology at Charles University in Prague. “It is encouraging to see consistent effects maintained across multiple meaningful outcomes through five years.”
Serious side effects associated with alemtuzumab included infusion-associated reactions, autoimmune disorders (eg, thyroid disease, autoimmune cytopenias, and nephropathies), infections, and pneumonitis. The most common side effects of alemtuzumab are rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in an extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting.