Abstract: P1262
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Introduction: Chronic black holes (BHs) indicate severe tissue injury and are used as a surrogate marker of therapeutic outcomes in relapsing-remitting multiple sclerosis (RRMS). The number of chronic BHs that evolve from acute MRI lesions can quantify the neuroprotective effects of multiple sclerosis therapy.
Objectives: Evaluate the effect of peginterferon beta-1a every 2 weeks on the number of chronic BHs that evolve from acute lesions over 2 years in newly and non-newly diagnosed RRMS patients.
Methods: ADVANCE was a 2-year, double-blind phase 3 trial of peginterferon beta-1a in 1512 patients with RRMS. Patients were randomised to placebo or peginterferon beta-1a 125 mcg every 2 or 4 weeks (continuous-treatment). At year 1, placebo patients were re-randomised to peginterferon beta-1a every 2 or 4 weeks (delayed-treatment). The number of BHs at week 96 that evolved from new/enlarging T2-weighted (NET2) lesions or gadolinium-enhancing (Gd+) lesions at baseline (Gd+ only), week 24 or week 48 were compared in the peginterferon beta-1a every-2-weeks continuous-treatment and peginterferon beta-1a delayed-treatment groups. The adjusted annualised relapse rate (ARR) by BH conversion status was also assessed. Newly diagnosed (ND; RRMS diagnosis ≤1 year prior to study enrolment and no prior disease-modifying therapy use) and non-newly diagnosed (NND) subgroups of patients were evaluated.
Results: The ADVANCE intent-to-treat (ITT) population included 231 ND and 281 NND patients in the every-2-weeks continuous-treatment group and 229 ND and 271 NND patients in the delayed-treatment group. There were fewer BHs at week 96 that evolved from NET2 lesions at week 24 or week 48 in continuous- vs delayed-treatment patients in both ND (P< 0.0001) and NND (P< 0.0001) subgroups. Likewise, there were fewer BHs at week 96 that evolved from Gd+ lesions at BL, week 24 or week 48 in continuous- vs delayed-treatment patients in both ND (P< 0.0001) and NND (P< 0.0001) groups. ARR over 2 years was lower in patients without vs with BH evolution in the ND (P=0.011) and NND (P=0.004) ITT subgroups. All ND and NND subgroup results were consistent with the overall patient population.
Conclusions: The lower risk of chronic BHs evolving from acute MRI lesions with peginterferon beta-1a therapy suggests the potential to provide treatment benefits to patients with RRMS, including newly diagnosed patients, by reducing long-term disability through prevention of irreversible tissue damage.
Disclosure: Supported by Biogen.
DA: 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.
OM, MLN: employees of and may hold stock and/or stock options in Biogen.
Abstract: P1262
Type: Poster Sessions
Abstract Category: Therapy - Tools for detecting therapeutic response
Introduction: Chronic black holes (BHs) indicate severe tissue injury and are used as a surrogate marker of therapeutic outcomes in relapsing-remitting multiple sclerosis (RRMS). The number of chronic BHs that evolve from acute MRI lesions can quantify the neuroprotective effects of multiple sclerosis therapy.
Objectives: Evaluate the effect of peginterferon beta-1a every 2 weeks on the number of chronic BHs that evolve from acute lesions over 2 years in newly and non-newly diagnosed RRMS patients.
Methods: ADVANCE was a 2-year, double-blind phase 3 trial of peginterferon beta-1a in 1512 patients with RRMS. Patients were randomised to placebo or peginterferon beta-1a 125 mcg every 2 or 4 weeks (continuous-treatment). At year 1, placebo patients were re-randomised to peginterferon beta-1a every 2 or 4 weeks (delayed-treatment). The number of BHs at week 96 that evolved from new/enlarging T2-weighted (NET2) lesions or gadolinium-enhancing (Gd+) lesions at baseline (Gd+ only), week 24 or week 48 were compared in the peginterferon beta-1a every-2-weeks continuous-treatment and peginterferon beta-1a delayed-treatment groups. The adjusted annualised relapse rate (ARR) by BH conversion status was also assessed. Newly diagnosed (ND; RRMS diagnosis ≤1 year prior to study enrolment and no prior disease-modifying therapy use) and non-newly diagnosed (NND) subgroups of patients were evaluated.
Results: The ADVANCE intent-to-treat (ITT) population included 231 ND and 281 NND patients in the every-2-weeks continuous-treatment group and 229 ND and 271 NND patients in the delayed-treatment group. There were fewer BHs at week 96 that evolved from NET2 lesions at week 24 or week 48 in continuous- vs delayed-treatment patients in both ND (P< 0.0001) and NND (P< 0.0001) subgroups. Likewise, there were fewer BHs at week 96 that evolved from Gd+ lesions at BL, week 24 or week 48 in continuous- vs delayed-treatment patients in both ND (P< 0.0001) and NND (P< 0.0001) groups. ARR over 2 years was lower in patients without vs with BH evolution in the ND (P=0.011) and NND (P=0.004) ITT subgroups. All ND and NND subgroup results were consistent with the overall patient population.
Conclusions: The lower risk of chronic BHs evolving from acute MRI lesions with peginterferon beta-1a therapy suggests the potential to provide treatment benefits to patients with RRMS, including newly diagnosed patients, by reducing long-term disability through prevention of irreversible tissue damage.
Disclosure: Supported by Biogen.
DA: 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.
OM, MLN: employees of and may hold stock and/or stock options in Biogen.