Treatment with alemtuzumab was associated with reduced relapse rates and improved MRI outcomes compared to treatment with subcutaneous interferon beta-1a.
Individuals with relapsing forms of multiple sclerosis (MS) whose disease is highly active show benefit from alemtuzumab, a humanized monoclonal antibody, according to subgroup analysis of a larger study of the drug. Stephen Krieger, MD, of Mt. Sinai Medical Center presented the findings during a poster session at the 2014 joint meeting of the Committee for Treatment and Research in Multiple Sclerosis of Europe and the Americas (ACTRIMS-ECTRIMS), held in Boston, MA.
Krieger’s presentation discussed data from the phase 3 CARE-MS I study, which showed significant reduction in annualized relapse rate (ARR) for treatment-naïve alemtuzumab takers compared with those treatment-naïve individuals who received subcutaneous interferon beta-1a (SC IFNB-1a), as well as significant improvements in magnetic resonance imaging (MRI) outcomes for those receiving alemtuzumab as compared with SC IFNB-1a.
Of the 187 individuals receiving SC IFNB 1-a and the 376 receiving alemtuzumab in the parent study, 61 and 105 patients had highly active MS, respectively, and qualified for inclusion in this analysis. Except for those characteristics that defined their disease state as highly active (number of prior-year relapses and number of patients with gadolinium (Gd)-enhancing lesions), this subgroup was similar in disease state and demographics to the full CARE-I MS population.
In examining efficacy, the highly active subgroup’s ARR was reduced by 51% for alemtuzumab takers in comparison with those receiving SC IFNB-1a (p=.0068). Additionally, relapses over 2 years were fewer for alemtuzumab recipients: 23.8% for alemtuzumab vs. 49.6% for SC IFNB-1a (HR, 0.40., p=.0007). Sustained Accumulation of Disability over six months (6-Month SAD) occurred in 8.6% of those treated with alemtuzumab and for 10.0% of those treated with SC IFNB-1a. This difference did not reach statistical significance (HR, 0.87, p=.7873).
Neuroimaging by MRI also showed differences between the two treatment groups for those with highly active disease. Overall, there were proportionately fewer patients with new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and any Gd-enhancing lesions at the end of year two of the study. No Gd-enhancing lesions were seen in 90.3% of the alemtuzumab group vs. 66.1% of the SC IFNB-1a group (p=.0401), no new T2 hyperintensities in 71.2% vs. 45.6% (p=.0496), and no T1 hypointensities in 90.4% vs. 68.4% (p=.0135). Finally, brain parenchymal fraction (BPF) in the alemtuzumab group showed a 32.2% smaller median reduction over the study period, compared with the SC IFNB-1a takers (p=.0089).
Overall, more patients taking alemtuzumab were free of clinical and MRI disease activity when compared with those treated with SC IFNB-1a (25.5% vs. 20.0%, p=.0002).
In assessing safety, adverse events (AEs) of any kind were very common for both groups, occurring in 97% of those treated with alemtuzumab and 93% of those taking SC IFNB-1a. The rates and types of AEs for the subgroup were similar to those seen in the full CARE-MS I cohort, with far fewer serious AEs (18.0 and, 16.2% respectively). There were two patients in the highly active subgroup and treated with alemtuzumab who had grade 4 serious adverse events (one with immune thrombocytopenia and one with agranulocytosis,) which were assessed as being treatment-related.
Addressing the relevance of these findings for the practicing neurologist, Krieger pointed to the value of pulling out a subgroup of patients with highly active disease. “This group of patients looks like something we recognize, that we see in practice,” he commented. He also remarked that the safety profile of this drug did not differ from the larger cohort in these patients with highly active disease.