Contributions
Abstract: P1228
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Clinical trial data have shown that relapsing-remitting multiple sclerosis (RRMS) patients initiating natalizumab treatment at low levels of disability have better treatment outcomes. Real-world data over longer treatment durations are needed to confirm the importance of starting natalizumab early in the disease course. TOP is an ongoing multinational observational study following natalizumab-treated RRMS patients in clinical practice settings for ≥10 years.
Objective: To compare long-term outcomes in TOP patients initiating natalizumab at various disability levels.
Methods: Patients were grouped by baseline Expanded Disability Status Scale (EDSS) score using clinically relevant milestones: EDSS ≤1.5 (n=814), EDSS 2.0-3.5 (n=2511), EDSS 4.0-5.5 (n=1778), and EDSS ≥6.0 (n=705). Annualized relapse rates (ARRs) in the year pre- and 7 years post-natalizumab initiation, EDSS score changes, and the likelihood of 24-week confirmed EDSS worsening (score increase of ≥1.5 from 0, ≥1.0 from 1.0-5.5, or ≥0.5 from ≥6.0) or improvement (score decrease of ≥1.0 from ≥2.0) were analyzed using data through November 1, 2015.
Results: At baseline, patients with more disability tended to have longer disease duration than those with less disability (median 4.9, 6.1, 8.8, and 11.1 years for patients with EDSS scores ≤1.5, 2.0-3.5, 4.0-5.5, and ≥6.0, respectively). After starting treatment, ARRs were significantly reduced regardless of baseline disability (85.3-91.7%, each P< 0.0001), with the largest reduction observed in the group with EDSS scores ≤1.5 (P< 0.001 vs each other group). Over 7 years of treatment, mean EDSS score changes from baseline were < 1.0, and the risk of EDSS worsening was similar among patients with scores ≤1.5 (28.1%), 2.0-3.5 (23.7%), and 4.0-5.5 (25.6%) and higher in those with scores ≥6.0 (36.8%, HR 1.34 [95% CI 1.03-1.73], P=0.029 vs ≤1.5 group). A pattern was observed in which patients with EDSS scores ≤5.5 were more likely to improve than worsen, whereas those with scores ≥6.0 were more likely to worsen than improve.
Conclusions: Over 7 years of natalizumab treatment, ARRs were reduced, mean EDSS scores were stable, and EDSS worsening rates were low regardless of baseline EDSS score. RRMS patients initiating treatment with less disability had better outcomes, suggesting that, though patients benefit from natalizumab regardless of baseline disability, natalizumab use earlier in the disease course is associated with better long-term outcomes.
Disclosure: Supported by Biogen
Kappos L: Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee, advisory board, speaker fees, and consultancy fees from Actelion, Addex, Alkermes, Almirall, Bayer HealthCare, Biogen, CSL Behring, Excemed, Genentech, GeNeuro SA, Genzyme, Merck, Mitsubishi, Novartis, Octopharma, Pfizer, Receptos, Roche, Sanofi, Santhera, Teva, UCB; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen, Merck, Novartis, Roche, Swiss MS Society, the Swiss National Research Foundation, the European Union, the Roche Research Foundation.
Butzkueven H: honoraria and travel support from Biogen Australia, Genzyme, Novartis Australia; institution (University of Melbourne) received research support from Biogen, CSL Biopharma, Genzyme, Merck Serono, Novartis.
Chen Y: employees of and hold stock and/or stock options in Biogen.
Ho PR: employees of and hold stock and/or stock options in Biogen.
Köndgen H: employees of and hold stock and/or stock options in Biogen.
Campbell N: employees of and hold stock and/or stock options in Biogen.
Abstract: P1228
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Clinical trial data have shown that relapsing-remitting multiple sclerosis (RRMS) patients initiating natalizumab treatment at low levels of disability have better treatment outcomes. Real-world data over longer treatment durations are needed to confirm the importance of starting natalizumab early in the disease course. TOP is an ongoing multinational observational study following natalizumab-treated RRMS patients in clinical practice settings for ≥10 years.
Objective: To compare long-term outcomes in TOP patients initiating natalizumab at various disability levels.
Methods: Patients were grouped by baseline Expanded Disability Status Scale (EDSS) score using clinically relevant milestones: EDSS ≤1.5 (n=814), EDSS 2.0-3.5 (n=2511), EDSS 4.0-5.5 (n=1778), and EDSS ≥6.0 (n=705). Annualized relapse rates (ARRs) in the year pre- and 7 years post-natalizumab initiation, EDSS score changes, and the likelihood of 24-week confirmed EDSS worsening (score increase of ≥1.5 from 0, ≥1.0 from 1.0-5.5, or ≥0.5 from ≥6.0) or improvement (score decrease of ≥1.0 from ≥2.0) were analyzed using data through November 1, 2015.
Results: At baseline, patients with more disability tended to have longer disease duration than those with less disability (median 4.9, 6.1, 8.8, and 11.1 years for patients with EDSS scores ≤1.5, 2.0-3.5, 4.0-5.5, and ≥6.0, respectively). After starting treatment, ARRs were significantly reduced regardless of baseline disability (85.3-91.7%, each P< 0.0001), with the largest reduction observed in the group with EDSS scores ≤1.5 (P< 0.001 vs each other group). Over 7 years of treatment, mean EDSS score changes from baseline were < 1.0, and the risk of EDSS worsening was similar among patients with scores ≤1.5 (28.1%), 2.0-3.5 (23.7%), and 4.0-5.5 (25.6%) and higher in those with scores ≥6.0 (36.8%, HR 1.34 [95% CI 1.03-1.73], P=0.029 vs ≤1.5 group). A pattern was observed in which patients with EDSS scores ≤5.5 were more likely to improve than worsen, whereas those with scores ≥6.0 were more likely to worsen than improve.
Conclusions: Over 7 years of natalizumab treatment, ARRs were reduced, mean EDSS scores were stable, and EDSS worsening rates were low regardless of baseline EDSS score. RRMS patients initiating treatment with less disability had better outcomes, suggesting that, though patients benefit from natalizumab regardless of baseline disability, natalizumab use earlier in the disease course is associated with better long-term outcomes.
Disclosure: Supported by Biogen
Kappos L: Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee, advisory board, speaker fees, and consultancy fees from Actelion, Addex, Alkermes, Almirall, Bayer HealthCare, Biogen, CSL Behring, Excemed, Genentech, GeNeuro SA, Genzyme, Merck, Mitsubishi, Novartis, Octopharma, Pfizer, Receptos, Roche, Sanofi, Santhera, Teva, UCB; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen, Merck, Novartis, Roche, Swiss MS Society, the Swiss National Research Foundation, the European Union, the Roche Research Foundation.
Butzkueven H: honoraria and travel support from Biogen Australia, Genzyme, Novartis Australia; institution (University of Melbourne) received research support from Biogen, CSL Biopharma, Genzyme, Merck Serono, Novartis.
Chen Y: employees of and hold stock and/or stock options in Biogen.
Ho PR: employees of and hold stock and/or stock options in Biogen.
Köndgen H: employees of and hold stock and/or stock options in Biogen.
Campbell N: employees of and hold stock and/or stock options in Biogen.