Contributions
Abstract: P611
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: MS patients (pts) on biologic therapies develop anti-drug antibodies (ADA) that may affect the treatment pharmacodynamic (PD) profile and/or efficacy. Alemtuzumab, a humanized, anti-CD52 monoclonal antibody approved for RRMS pts, is administered as 2 initial courses (12 mg/day; baseline: 5 consecutive days; 12 months later: 3 consecutive days) with up to 2 additional courses (3 consecutive days; ≥12 months apart) as needed for disease control. In the CARE-MS studies (NCT00530348, NCT00548405), 2 courses of alemtuzumab significantly improved clinical/MRI outcomes vs SC IFNB-1a; efficacy was maintained in a 4-year extension (NCT00930553), wherein pts could receive additional courses as needed.
Aims: To determine the effect of alemtuzumab ADA on PD and efficacy in CARE-MS pts.
Methods: Alemtuzumab-binding ADA status (ever positive or always negative) was evaluated in pts receiving Course 2 (C2; all pts) and Course 3 (at any time point; median interval from C2, 2.2 years). Other assessments for correlation: lymphocyte counts (total, CD4+ T cells), annualised relapse rates (ARR), and new Gd-enhancing lesions.
Results: Of 811 pts from the pooled CARE-MS studies, 87.8% were positive for binding ADA at any time point during the 2-year alemtuzumab treatment period; 292 (90.4%) pts who received C3 were ADA positive. Median ADA titres peaked 1 month after C2 and C3, and decreased 100-fold 12 months later (defined treatment interval); titres were higher post-C3 vs post-C2. No discernible difference was detected in total or CD4+ lymphocyte depletion and repopulation patterns or efficacy measures after C2 between pts who were ADA positive or negative. The mean total lymphocyte count nadir was lower post-C2 vs post-C3. The ADA effect was minimal on CD4+ T cell depletion after C3, with limited non-significant changes in pts in the highest titre quartile. ADA had no effect a year after C3 on ARR (ADA negative: 0.19; titre quartiles 1-4: 0.16, 0.15, 0.26, and 0.15) or the percentage of pts free of Gd-enhancing lesions (ADA negative: 89%; titre quartiles 1-4: 87%, 90%, 90%, and 82%). There was no consistent trend for an ADA impact on efficacy through Year 5 post-C3.
Conclusion: Although the incidence of ADA was high at mid-course determinations with marked reduction prior to each course, it had minimal impact on long-term alemtuzumab PD/efficacy in CARE-MS pts. Peak ADA titres dropped precipitously by 12 months, the required treatment interval post-alemtuzumab.
Disclosure: AJ, LC, QU, and IF are employees of Sanofi. STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.
Abstract: P611
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: MS patients (pts) on biologic therapies develop anti-drug antibodies (ADA) that may affect the treatment pharmacodynamic (PD) profile and/or efficacy. Alemtuzumab, a humanized, anti-CD52 monoclonal antibody approved for RRMS pts, is administered as 2 initial courses (12 mg/day; baseline: 5 consecutive days; 12 months later: 3 consecutive days) with up to 2 additional courses (3 consecutive days; ≥12 months apart) as needed for disease control. In the CARE-MS studies (NCT00530348, NCT00548405), 2 courses of alemtuzumab significantly improved clinical/MRI outcomes vs SC IFNB-1a; efficacy was maintained in a 4-year extension (NCT00930553), wherein pts could receive additional courses as needed.
Aims: To determine the effect of alemtuzumab ADA on PD and efficacy in CARE-MS pts.
Methods: Alemtuzumab-binding ADA status (ever positive or always negative) was evaluated in pts receiving Course 2 (C2; all pts) and Course 3 (at any time point; median interval from C2, 2.2 years). Other assessments for correlation: lymphocyte counts (total, CD4+ T cells), annualised relapse rates (ARR), and new Gd-enhancing lesions.
Results: Of 811 pts from the pooled CARE-MS studies, 87.8% were positive for binding ADA at any time point during the 2-year alemtuzumab treatment period; 292 (90.4%) pts who received C3 were ADA positive. Median ADA titres peaked 1 month after C2 and C3, and decreased 100-fold 12 months later (defined treatment interval); titres were higher post-C3 vs post-C2. No discernible difference was detected in total or CD4+ lymphocyte depletion and repopulation patterns or efficacy measures after C2 between pts who were ADA positive or negative. The mean total lymphocyte count nadir was lower post-C2 vs post-C3. The ADA effect was minimal on CD4+ T cell depletion after C3, with limited non-significant changes in pts in the highest titre quartile. ADA had no effect a year after C3 on ARR (ADA negative: 0.19; titre quartiles 1-4: 0.16, 0.15, 0.26, and 0.15) or the percentage of pts free of Gd-enhancing lesions (ADA negative: 89%; titre quartiles 1-4: 87%, 90%, 90%, and 82%). There was no consistent trend for an ADA impact on efficacy through Year 5 post-C3.
Conclusion: Although the incidence of ADA was high at mid-course determinations with marked reduction prior to each course, it had minimal impact on long-term alemtuzumab PD/efficacy in CARE-MS pts. Peak ADA titres dropped precipitously by 12 months, the required treatment interval post-alemtuzumab.
Disclosure: AJ, LC, QU, and IF are employees of Sanofi. STUDY SUPPORT: Sanofi and Bayer HealthCare Pharmaceuticals.