Contributions
Abstract: P746
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In clinical trials and real-world studies, natalizumab (NAT) treatment has been associated with disability improvement as indicated by a decrease in Expanded Disability Status Scale (EDSS) score. Better understanding of the timing, magnitude, and duration of disability improvement during long-term NAT treatment may help inform clinical decision making.
Objective: To characterize confirmed disability improvement (CDI) in patients participating in the TYSABRI Observational Program (TOP), an ongoing 10-year observational study of relapsing-remitting multiple sclerosis patients initiating NAT in clinical practice.
Methods: Analyses included patients with CDI, defined as a decrease of ≥1.0 from a baseline EDSS score of ≥2.0 confirmed at ≥24 weeks, as of 1 November 2016. Kaplan-Meier (KM) time-to-event analyses evaluated the proportion of patients reaching EDSS improvement-from-baseline milestones of ≥1.5 and ≥2.0 and the duration of improvement (time from EDSS improvement to return to baseline).
Results: Of the 5119 patients in TOP with baseline EDSS ≥2.0, 1204 (23.5%) had CDI. The cumulative probability of CDI was 14% at year 1, 22% at year 2, 27% at year 3, 29% at year 4, and 36% at 8.5 years. CDI patients had a mean (standard deviation [SD]) EDSS score of 3.8 (1.3) at baseline and 4.2 (1.9) years of on-NAT follow-up in TOP. Among CDI patients, 683 (57%) and 414 (34%) had EDSS improvements of ≥1.5 and ≥2.0, respectively. Over 408 weeks, the KM-estimated probabilities of improvements of ≥1.5 and ≥2.0 were 69% and 44%, respectively. The estimated probability of maintaining improvement was >50% up to 408 weeks after the CDI event. In the 301 CDI patients (25%) who returned to baseline (mean [SD] time to return to baseline: 129.3 [72.4] weeks), mean (SD) EDSS change from baseline through on-NAT follow-up was −0.01 (1.15). Additional analyses will explore predictors of earlier, higher magnitude, and longer duration CDI events.
Conclusions: In TOP, >20% of patients experienced CDI. More CDI events occurred in the first year of NAT treatment. Most CDI patients had an EDSS improvement of ≥1.5 points and many had improvement of ≥2.0 points. The majority of CDI patients maintained improvement over 8 years, and in those who returned to baseline, mean EDSS score change from baseline through the last visit remained below baseline. These results highlight CDI as a functional outcome that may be an important consideration for treatment decisions.
Supported by Biogen.
Disclosure:
HW: honoraria from Abbvie, Actelion, Alexion, Biogen, Cognomed, Evgen, F. Hoffmann-La Roche Ltd, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA; research support from Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme.
HB: compensation for consulting from Biogen, Merck Serono, Novartis; research support from Biogen, Merck Serono.
LK: In last 3 years, Institution (University Hospital Basel) received and used exclusively for research support: steering committee, advisory board, consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation.
TS: honoraria for consultancy and funding for travel from Biogen, Novartis.
MT: compensation for consulting from Biogen, Merck Serono, Novartis; speaker honoraria from Biogen, Merck Serono, Novartis, Sanofi, Teva; research grants from Biogen, Merck Serono, Novartis.
QD, NC, P-RH, SL: employees of and own stock and/or stock options in Biogen.
Abstract: P746
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: In clinical trials and real-world studies, natalizumab (NAT) treatment has been associated with disability improvement as indicated by a decrease in Expanded Disability Status Scale (EDSS) score. Better understanding of the timing, magnitude, and duration of disability improvement during long-term NAT treatment may help inform clinical decision making.
Objective: To characterize confirmed disability improvement (CDI) in patients participating in the TYSABRI Observational Program (TOP), an ongoing 10-year observational study of relapsing-remitting multiple sclerosis patients initiating NAT in clinical practice.
Methods: Analyses included patients with CDI, defined as a decrease of ≥1.0 from a baseline EDSS score of ≥2.0 confirmed at ≥24 weeks, as of 1 November 2016. Kaplan-Meier (KM) time-to-event analyses evaluated the proportion of patients reaching EDSS improvement-from-baseline milestones of ≥1.5 and ≥2.0 and the duration of improvement (time from EDSS improvement to return to baseline).
Results: Of the 5119 patients in TOP with baseline EDSS ≥2.0, 1204 (23.5%) had CDI. The cumulative probability of CDI was 14% at year 1, 22% at year 2, 27% at year 3, 29% at year 4, and 36% at 8.5 years. CDI patients had a mean (standard deviation [SD]) EDSS score of 3.8 (1.3) at baseline and 4.2 (1.9) years of on-NAT follow-up in TOP. Among CDI patients, 683 (57%) and 414 (34%) had EDSS improvements of ≥1.5 and ≥2.0, respectively. Over 408 weeks, the KM-estimated probabilities of improvements of ≥1.5 and ≥2.0 were 69% and 44%, respectively. The estimated probability of maintaining improvement was >50% up to 408 weeks after the CDI event. In the 301 CDI patients (25%) who returned to baseline (mean [SD] time to return to baseline: 129.3 [72.4] weeks), mean (SD) EDSS change from baseline through on-NAT follow-up was −0.01 (1.15). Additional analyses will explore predictors of earlier, higher magnitude, and longer duration CDI events.
Conclusions: In TOP, >20% of patients experienced CDI. More CDI events occurred in the first year of NAT treatment. Most CDI patients had an EDSS improvement of ≥1.5 points and many had improvement of ≥2.0 points. The majority of CDI patients maintained improvement over 8 years, and in those who returned to baseline, mean EDSS score change from baseline through the last visit remained below baseline. These results highlight CDI as a functional outcome that may be an important consideration for treatment decisions.
Supported by Biogen.
Disclosure:
HW: honoraria from Abbvie, Actelion, Alexion, Biogen, Cognomed, Evgen, F. Hoffmann-La Roche Ltd, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA; research support from Biogen, GlaxoSmithKline GmbH, Roche Pharma AG, Sanofi-Genzyme.
HB: compensation for consulting from Biogen, Merck Serono, Novartis; research support from Biogen, Merck Serono.
LK: In last 3 years, Institution (University Hospital Basel) received and used exclusively for research support: steering committee, advisory board, consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation.
TS: honoraria for consultancy and funding for travel from Biogen, Novartis.
MT: compensation for consulting from Biogen, Merck Serono, Novartis; speaker honoraria from Biogen, Merck Serono, Novartis, Sanofi, Teva; research grants from Biogen, Merck Serono, Novartis.
QD, NC, P-RH, SL: employees of and own stock and/or stock options in Biogen.