Abstract: P1171
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: No Evidence of Disease Activity (NEDA) is an evolving concept that was first proposed as a composite measure of whether patients with relapsing-remitting multiple sclerosis (RRMS) were meeting goals of treatment in the clinical trial setting. In the first year of the Phase 3 ADVANCE study, significantly more patients dosed with subcutaneous peginterferon beta-1a 125 mcg every 2 weeks achieved NEDA versus placebo and every-4-weeks dosing. Similar results were found for the second year of ADVANCE (after placebo-treated patients were re-randomized to peginterferon beta-1a every 2 or 4 weeks) and the first year of the ATTAIN extension study for clinical-, MRI- and overall NEDA.
Objectives: To assess NEDA status during both ADVANCE and ATTAIN by year and explore clinical outcomes in ATTAIN in patients stratified by their overall NEDA (clinical and MRI) status at the end of ADVANCE.
Methods: The proportion of patients in the ATTAIN intent-to-treat (ITT) population experiencing overall (clinical and MRI) NEDA was evaluated for patients treated with peginterferon beta-1a every 2 weeks or every 4 weeks over 4 years. Patients in all dosing groups combined were then stratified based on achievement of overall NEDA during ADVANCE (NEDA+/NEDA-). Annualised relapse rate (ARR) during ATTAIN (Years 3 and 4 since ADVANCE baseline) was analysed based on NEDA status during ADVANCE.
Results: Both peginterferon beta-1a every 2 weeks (n=376) and every 4 weeks (n=354) maintained efficacy on NEDA outcomes over 4 years of treatment, and more patients treated with peginterferon beta-1a every 2 weeks achieved overall NEDA in Years 1-4 (35-54% vs 22-35%, all p< 0.0001). Similar results were found for clinical (significantly higher % in Years 2, 3) and MRI (significantly higher % in all years) NEDA. Overall NEDA status in ADVANCE was predictive of positive clinical outcomes in ATTAIN: patients in the NEDA+ group (n=196), compared with those in the NEDA- group (n=877) had lower ARR (0.066 vs. 0.227, p< 0.0001) during ATTAIN.
Conclusions: Patients with RRMS administered peginterferon beta-1a every 2 weeks displayed maintained efficacy and increased NEDA over 4 years compared with treatment every 4 weeks. Patients who were free from disease activity at the end of ADVANCE had significantly reduced ARR during ATTAIN than patients who were not, suggesting that overall NEDA within the first 2 years of treatment is prognostic of long-term clinical outcomes.
Disclosure: Supported by: Biogen
Author disclosures:
Douglas Arnold reports an equity interest in NeuroRx during the conduct of the study and personal fees from Biogen, EMD Serono, Genentech, Genzyme, Hoffman-La Roche, Innate Immunotherapy, MedImmune, Mitsubishi, Novartis, Receptos, Acorda, Sanofi-Aventis, and Teva outside the submitted work, as well as grants from Biogen and Novartis. Shulian Shang is an employee and stockholder of Biogen. Damian Fiore is an employee and stockholder of Biogen. Carmen Castrillo-Viguera is an employee and stockholder of Biogen.
Abstract: P1171
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: No Evidence of Disease Activity (NEDA) is an evolving concept that was first proposed as a composite measure of whether patients with relapsing-remitting multiple sclerosis (RRMS) were meeting goals of treatment in the clinical trial setting. In the first year of the Phase 3 ADVANCE study, significantly more patients dosed with subcutaneous peginterferon beta-1a 125 mcg every 2 weeks achieved NEDA versus placebo and every-4-weeks dosing. Similar results were found for the second year of ADVANCE (after placebo-treated patients were re-randomized to peginterferon beta-1a every 2 or 4 weeks) and the first year of the ATTAIN extension study for clinical-, MRI- and overall NEDA.
Objectives: To assess NEDA status during both ADVANCE and ATTAIN by year and explore clinical outcomes in ATTAIN in patients stratified by their overall NEDA (clinical and MRI) status at the end of ADVANCE.
Methods: The proportion of patients in the ATTAIN intent-to-treat (ITT) population experiencing overall (clinical and MRI) NEDA was evaluated for patients treated with peginterferon beta-1a every 2 weeks or every 4 weeks over 4 years. Patients in all dosing groups combined were then stratified based on achievement of overall NEDA during ADVANCE (NEDA+/NEDA-). Annualised relapse rate (ARR) during ATTAIN (Years 3 and 4 since ADVANCE baseline) was analysed based on NEDA status during ADVANCE.
Results: Both peginterferon beta-1a every 2 weeks (n=376) and every 4 weeks (n=354) maintained efficacy on NEDA outcomes over 4 years of treatment, and more patients treated with peginterferon beta-1a every 2 weeks achieved overall NEDA in Years 1-4 (35-54% vs 22-35%, all p< 0.0001). Similar results were found for clinical (significantly higher % in Years 2, 3) and MRI (significantly higher % in all years) NEDA. Overall NEDA status in ADVANCE was predictive of positive clinical outcomes in ATTAIN: patients in the NEDA+ group (n=196), compared with those in the NEDA- group (n=877) had lower ARR (0.066 vs. 0.227, p< 0.0001) during ATTAIN.
Conclusions: Patients with RRMS administered peginterferon beta-1a every 2 weeks displayed maintained efficacy and increased NEDA over 4 years compared with treatment every 4 weeks. Patients who were free from disease activity at the end of ADVANCE had significantly reduced ARR during ATTAIN than patients who were not, suggesting that overall NEDA within the first 2 years of treatment is prognostic of long-term clinical outcomes.
Disclosure: Supported by: Biogen
Author disclosures:
Douglas Arnold reports an equity interest in NeuroRx during the conduct of the study and personal fees from Biogen, EMD Serono, Genentech, Genzyme, Hoffman-La Roche, Innate Immunotherapy, MedImmune, Mitsubishi, Novartis, Receptos, Acorda, Sanofi-Aventis, and Teva outside the submitted work, as well as grants from Biogen and Novartis. Shulian Shang is an employee and stockholder of Biogen. Damian Fiore is an employee and stockholder of Biogen. Carmen Castrillo-Viguera is an employee and stockholder of Biogen.