Alemtuzumab Reduces Disease Progression in RRMS: Long-Term Results of the CAMMS223 Trial

OBJECTIVE: To assess clinically disease-free status and safety of alemtuzumab-treated MS patients at 4 years follow-up. BACKGROUND: Alemtuzumab demonstrated efficacy superior to subcutaneous IFNB-1a in a 3-year, phase 2 trial with relapsing-remitting MS (RRMS) patients, significantly reducing the relapse rate and risk for sustained accumulation of disability (SAD) (all comparisons p<0.001). "Clinically disease-free" was defined as the absence of both relapses and SAD. The proportion of clinically disease-free patients was significantly higher for alemtuzumab compared with IFNB-1a at years 1, 2 and 3 (all p-values < 0.0001). DESIGN/METHODS: 334 early, active RRMS patients were randomized 1:1:1 to IFNB-1a (44mcg SC 3x/week), 24 mg or 12 mg/day alemtuzumab IV administered during 2 or 3 brief annual cycles. No alemtuzumab was administered after 24 months. IFNB-1a was administered through 36 months. Post hoc analyses of 4-year patient follow-up compared treatment groups on the proportion of relapse-free, 6 month SAD-free, and clinically disease-free patients. Additional safety data were analyzed. RESULTS: At year 4, 77% of alemtuzumab-treated patients were relapse-free compared to 49% of IFNB-1a-treated patients; 91% of alemtuzumab patients were SAD-free vs. 68% of IFNB-1a patients (p<0.001). 71% of alemtuzumab patients were clinically disease-free v. 35% for IFNB-1a at year 4 (p<0.001). Similar results were observed when restricting analyses to patients receiving only 2 cycles of alemtuzumab. Updated safety results will also be reported. CONCLUSIONS/RELEVANCE: Alemtuzumab-treated patients maintained a clinically disease-free status in greater proportions than IFNB-1a-treated patients at year 4. These data support the ability of alemtuzumab to achieve clinically disease-free status and to halt clinical progression in the vast majority of RRMS patients receiving alemtuzumab. This treatment effect at year 4 is observed even for those patients who completed 2 annual cycles of alemtuzumab during the first 12 months.