Contributions
Abstract: P1592
Type: LB Poster
Abstract Category: Late Breaking News
Background: No evidence of disease activity (NEDA) status is thought to be an important endpoint for clinical trials in MS, but its use is largely based on short-term data. Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) in RRMS can be used to assess the importance of different definitions of NEDA in predicting long-term outcomes.
Objective: To examine the predictive value of clinical and MRI components of NEDA for negative disability outcomes (NDOs).
Methods: The predictive capacity of NEDA, including clinical/MRI components, for NDOs at 16 years and survival at 21 y post-randomization was assessed with logistic regression models. NEDA was defined in four ways; 1) Clinical NEDA: no relapses and no EDSS worsening from Baseline to Year 2; 2) NEDA3a: no relapses and no new T2-active lesions since Baseline during the first 2 years of treatment, and no confirmed 1-point EDSS progression by Year 2; 3) NEDA3b: no relapses and no EDSS/T2 burden of disease (BOD) worsening from Baseline, and 4) NEDA4: no relapses, no EDSS/T2 BOD worsening, and no enlargement in 3rd ventricle size from Baseline to Year 2. NDOs at Year 16 were death, need for a wheelchair, progression to unremitting EDSS ≥6, or secondary progressive MS after Year 2.
Results: Following the randomized trial (N=376), 245 and 371 total patients were evaluated at 16 and 21 years, respectively. At 16 y, NEDA3a did not predict NDOs. By contrast, clinical NEDA did predict NDOs (p=0.0029), as did baseline EDSS (p< 0.0001), baseline T2 BOD (p< 0.0001), and change in T2 BOD from Baseline to Year 2 (p=0.0033) with a trend for change in 3rd ventricular size from Baseline to Year 2 (p=0.0854). NEDA3b and NEDA4 did not significantly predict NDOs. NEDA 3a did not predict survival after 21 years but there was a trend for clinical NEDA to predict time to death (p=0.0865), as did IFNB-1b treatment (p=0.0251), relapse rate in the 2 years before study start (p=0.0260), T2 BOD at Baseline (p=0.0014), and change in T2 BOD from Baseline to Year 2 (p=0.0129). Similar to NDOs at 16 y, NEDA3b and NEDA4 did not significantly predict survival at 21 y.
Conclusions: Although MRI measures of T2 BOD and brain atrophy predicted long-term outcomes, the inclusion of these variables in the definition of NEDA (ie, NEDA3a, NEDA3b, and NEDA4) did not increase its predictive capacity. Clinical NEDA, however, did predict long-term NDOs, underscoring the value of clinical measures for predicting long-term outcomes.
Disclosure: DSG has received either personal compensation (for consulting, serving on a scientific advisory board, or speaking) or financial support for scholarly activities from pharmaceutical companies that develop products for multiple sclerosis, including Bayer-Schering Pharma, Merck-Serono, Teva Pharmaceuticals, Questcor/Malinkrodt, and Novartis
ATR has received either personal compensation (for consulting, serving on a scientific advisory board, or speaking) or financial support for scholarly activities from the American Medical Association, Institute for Health Care Quality, NARCOMS, and National Multiple Sclerosis Society and from pharmaceutical companies that develop products for multiple sclerosis, including Abbott Laboratories, Astra Merck, Athena Neurosciences, Aventis Pharma, Bayer Schering Pharma, Berlex Laboratories, Biogen and Biogen Idec, BioMS Medical Corp., Blue Cross, Blue Shield, Caremark Rx, , Genentech, Genzyme Corporation, GlaxoSmithKline, Hoechst Marion Roussel Canada Research, Inc., Hoffman-LaRoche, Idec, Immunex, Neurocrine Biosciences, Novartis Corporation, Parke-Davis, Pfizer Inc, Pharmacia and Upjohn, Questcor/Malinkrodt, Quintiles, Inc., Serono Sandoz (now Novartis), Smith Kline-Beecham, Takeda Pharmaceuticals, and Teva-Marion
RK is a salaried employee of PAREXEL International
EMW is a salaried employee of Bayer Pharma AG
Abstract: P1592
Type: LB Poster
Abstract Category: Late Breaking News
Background: No evidence of disease activity (NEDA) status is thought to be an important endpoint for clinical trials in MS, but its use is largely based on short-term data. Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) in RRMS can be used to assess the importance of different definitions of NEDA in predicting long-term outcomes.
Objective: To examine the predictive value of clinical and MRI components of NEDA for negative disability outcomes (NDOs).
Methods: The predictive capacity of NEDA, including clinical/MRI components, for NDOs at 16 years and survival at 21 y post-randomization was assessed with logistic regression models. NEDA was defined in four ways; 1) Clinical NEDA: no relapses and no EDSS worsening from Baseline to Year 2; 2) NEDA3a: no relapses and no new T2-active lesions since Baseline during the first 2 years of treatment, and no confirmed 1-point EDSS progression by Year 2; 3) NEDA3b: no relapses and no EDSS/T2 burden of disease (BOD) worsening from Baseline, and 4) NEDA4: no relapses, no EDSS/T2 BOD worsening, and no enlargement in 3rd ventricle size from Baseline to Year 2. NDOs at Year 16 were death, need for a wheelchair, progression to unremitting EDSS ≥6, or secondary progressive MS after Year 2.
Results: Following the randomized trial (N=376), 245 and 371 total patients were evaluated at 16 and 21 years, respectively. At 16 y, NEDA3a did not predict NDOs. By contrast, clinical NEDA did predict NDOs (p=0.0029), as did baseline EDSS (p< 0.0001), baseline T2 BOD (p< 0.0001), and change in T2 BOD from Baseline to Year 2 (p=0.0033) with a trend for change in 3rd ventricular size from Baseline to Year 2 (p=0.0854). NEDA3b and NEDA4 did not significantly predict NDOs. NEDA 3a did not predict survival after 21 years but there was a trend for clinical NEDA to predict time to death (p=0.0865), as did IFNB-1b treatment (p=0.0251), relapse rate in the 2 years before study start (p=0.0260), T2 BOD at Baseline (p=0.0014), and change in T2 BOD from Baseline to Year 2 (p=0.0129). Similar to NDOs at 16 y, NEDA3b and NEDA4 did not significantly predict survival at 21 y.
Conclusions: Although MRI measures of T2 BOD and brain atrophy predicted long-term outcomes, the inclusion of these variables in the definition of NEDA (ie, NEDA3a, NEDA3b, and NEDA4) did not increase its predictive capacity. Clinical NEDA, however, did predict long-term NDOs, underscoring the value of clinical measures for predicting long-term outcomes.
Disclosure: DSG has received either personal compensation (for consulting, serving on a scientific advisory board, or speaking) or financial support for scholarly activities from pharmaceutical companies that develop products for multiple sclerosis, including Bayer-Schering Pharma, Merck-Serono, Teva Pharmaceuticals, Questcor/Malinkrodt, and Novartis
ATR has received either personal compensation (for consulting, serving on a scientific advisory board, or speaking) or financial support for scholarly activities from the American Medical Association, Institute for Health Care Quality, NARCOMS, and National Multiple Sclerosis Society and from pharmaceutical companies that develop products for multiple sclerosis, including Abbott Laboratories, Astra Merck, Athena Neurosciences, Aventis Pharma, Bayer Schering Pharma, Berlex Laboratories, Biogen and Biogen Idec, BioMS Medical Corp., Blue Cross, Blue Shield, Caremark Rx, , Genentech, Genzyme Corporation, GlaxoSmithKline, Hoechst Marion Roussel Canada Research, Inc., Hoffman-LaRoche, Idec, Immunex, Neurocrine Biosciences, Novartis Corporation, Parke-Davis, Pfizer Inc, Pharmacia and Upjohn, Questcor/Malinkrodt, Quintiles, Inc., Serono Sandoz (now Novartis), Smith Kline-Beecham, Takeda Pharmaceuticals, and Teva-Marion
RK is a salaried employee of PAREXEL International
EMW is a salaried employee of Bayer Pharma AG