Contributions
Abstract: P908
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: The TYSABRI Observational Program (TOP) began >10 years ago to inform on long-term safety and effectiveness of natalizumab (NTZ) in relapsing-remitting multiple sclerosis (RRMS) patients in clinical practice. TOP is the largest ongoing, real-world study of NTZ-treated patients.
Objectives: Report an interim analysis of safety and effectiveness in patients with up to 10 years of NTZ treatment in TOP, an open-label, multinational, prospective, observational study.
Methods: Annualised relapse rates (ARRs) for the year prior to starting NTZ and on NTZ (and ≤84 days post discontinuation) were compared using a repeated Poisson model. Confirmed Expanded Disability Status Scale (EDSS) worsening, an increase of ≥1.5 from a baseline (BL) of 0, ≥1.0 from a BL of 1.0-5.5, or ≥0.5 from a BL ≥6.0, and improvement, a decrease of ≥1.0 from a BL ≥2.0, while on NTZ were estimated by Kaplan-Meier analysis; confirmation could occur ≤84 days post discontinuation. Serious adverse events (SAEs) were assessed at clinical visits.
Results: As of November 2017, TOP included 6149 patients. At BL, mean EDSS score was 3.5; 90.6% had prior disease-modifying therapy (DMT) use. A total of 3210 patients (52.2%) discontinued NTZ; 2118 (34.4%) withdrew from TOP. Median exposure was 38 (range, 1-135) doses; median follow-up time was 63 (range, 1-131) months. ARR while on NTZ was reduced by 89.4% (from 1.99 pre-NTZ to 0.21 on NTZ; P< .001). Similarly, for those with BL EDSS scores < 3.0 or ≥3.0, ARR decreased by 91.0% (P< .001) and 87.9% (P< .001), respectively. For those with 0, 1, or ≥2 prior DMTs, ARRs were reduced by 92.7% (P< .001), 91.0% (P< .001), and 86.7% (P< .001), respectively. At 10 years, cumulative probabilities of 24-week-confirmed EDSS worsening and improvement were 32.9% and 35.5%, respectively. Overall, 828 of 6149 patients (13.5%) experienced ≥1 SAE (most commonly reported by system organ class: infections and infestations, 253 patients [4.1%]).
Conclusions: Since the TOP 5-year interim analysis (December 2012), cohort size (N=4821), median exposure (22 doses), and median follow-up time (26 months) have grown, and this analysis reinforces the consistent effectivenessparticularly when used earlier in the disease and treatment courseand the unchanged, established safety profile of NTZ, now assessed over 10 years. The planned continued follow-up for up to 15 years in TOP will provide the longest evaluation of real-world outcomes in NTZ-treated patients.
Disclosure: Supported by Biogen.
LK: institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
HB: Compensation for steering committee, advisory board and consultancy fees from Biogen, Merck, Roche, Novartis, Teva, Oxford Pharamgenesis; research support from Novartis, Biogen, Merck, NHMRC Australia, MS Research Australia, UK MS Trust.
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.
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.
KR, NC, PH, SL: employees of and may hold stock and/or stock options in Biogen.
Abstract: P908
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: The TYSABRI Observational Program (TOP) began >10 years ago to inform on long-term safety and effectiveness of natalizumab (NTZ) in relapsing-remitting multiple sclerosis (RRMS) patients in clinical practice. TOP is the largest ongoing, real-world study of NTZ-treated patients.
Objectives: Report an interim analysis of safety and effectiveness in patients with up to 10 years of NTZ treatment in TOP, an open-label, multinational, prospective, observational study.
Methods: Annualised relapse rates (ARRs) for the year prior to starting NTZ and on NTZ (and ≤84 days post discontinuation) were compared using a repeated Poisson model. Confirmed Expanded Disability Status Scale (EDSS) worsening, an increase of ≥1.5 from a baseline (BL) of 0, ≥1.0 from a BL of 1.0-5.5, or ≥0.5 from a BL ≥6.0, and improvement, a decrease of ≥1.0 from a BL ≥2.0, while on NTZ were estimated by Kaplan-Meier analysis; confirmation could occur ≤84 days post discontinuation. Serious adverse events (SAEs) were assessed at clinical visits.
Results: As of November 2017, TOP included 6149 patients. At BL, mean EDSS score was 3.5; 90.6% had prior disease-modifying therapy (DMT) use. A total of 3210 patients (52.2%) discontinued NTZ; 2118 (34.4%) withdrew from TOP. Median exposure was 38 (range, 1-135) doses; median follow-up time was 63 (range, 1-131) months. ARR while on NTZ was reduced by 89.4% (from 1.99 pre-NTZ to 0.21 on NTZ; P< .001). Similarly, for those with BL EDSS scores < 3.0 or ≥3.0, ARR decreased by 91.0% (P< .001) and 87.9% (P< .001), respectively. For those with 0, 1, or ≥2 prior DMTs, ARRs were reduced by 92.7% (P< .001), 91.0% (P< .001), and 86.7% (P< .001), respectively. At 10 years, cumulative probabilities of 24-week-confirmed EDSS worsening and improvement were 32.9% and 35.5%, respectively. Overall, 828 of 6149 patients (13.5%) experienced ≥1 SAE (most commonly reported by system organ class: infections and infestations, 253 patients [4.1%]).
Conclusions: Since the TOP 5-year interim analysis (December 2012), cohort size (N=4821), median exposure (22 doses), and median follow-up time (26 months) have grown, and this analysis reinforces the consistent effectivenessparticularly when used earlier in the disease and treatment courseand the unchanged, established safety profile of NTZ, now assessed over 10 years. The planned continued follow-up for up to 15 years in TOP will provide the longest evaluation of real-world outcomes in NTZ-treated patients.
Disclosure: Supported by Biogen.
LK: institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
HB: Compensation for steering committee, advisory board and consultancy fees from Biogen, Merck, Roche, Novartis, Teva, Oxford Pharamgenesis; research support from Novartis, Biogen, Merck, NHMRC Australia, MS Research Australia, UK MS Trust.
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.
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.
KR, NC, PH, SL: employees of and may hold stock and/or stock options in Biogen.