Contributions
Abstract: P733
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Natalizumab (NAT) is a high-efficacy therapy for relapsing-remitting multiple sclerosis (RRMS). After 2 years on NAT, many patients discontinue, mainly due to progressive multifocal leukoencephalopathy risk concerns. Data on predictors of post-NAT disease activity may be important for physician consideration. We assessed this in the TYSABRI Observational Program (TOP), an ongoing, 10-year observational study of NAT-treated RRMS patients.
Objectives: To compare outcomes in patients who switched to an oral or injectable (INJ) therapy with those who stayed on NAT and to analyze predictors of post-NAT relapse.
Methods: TOP data as of 1 November 2016 were analyzed for patients who stayed on NAT (≥3 years NAT and only NAT during follow-up; n=2466; mean time on NAT: 5.5 years) vs patients who switched to oral (n=660) or INJ (n=95) therapies for ≥1 year after ≥2 years on NAT (mean post-NAT follow-up: 2.5 years and 2.4 years, respectively). Annualized relapse rates (ARRs) were compared. Disability worsening was defined as an Expanded Disability Status Scale (EDSS) score increase of ≥1.5 from 0.0, ≥1.0 from 1.0-5.5, or ≥0.5 from ≥6.0, confirmed at ≥24 weeks. Risks and predictors of disease activity were compared using adjusted Cox models (covariates: age, sex, symptom onset, EDSS, prior relapses, washout (WO) time, and time on NAT).
Results: Relapse risk was higher for patients who switched to oral (hazard ratio [HR]=2.18; P< .001) or INJ (HR=3.02; P< .001) therapies than for patients who stayed on NAT after 2 years. EDSS worsening risk was similar for oral (HR=1.19; P=.266) and higher for INJ (HR=2.52; P< .001) switchers compared to stayed-on-NAT patients. ARRs decreased after the first 2 years by 20.2% for stayed-on-NAT patients but increased from rates on NAT by 17.8% and 108.1% for oral and INJ switchers, respectively (P< .001 for each). In oral switchers, lower relapse risk was predicted by shorter WO time (>12 weeks vs ≤4 weeks; HR=1.97; P=.001), fewer pre-NAT relapses (HR=1.24/relapse in the prior year; P< .001), lower EDSS at NAT start (>3.5 vs ≤3.5; HR=1.44; P=.007), and longer time on NAT (HR=0.87/additional year on NAT; P=.019).
Conclusions: Staying on NAT for >2 years yields better clinical outcomes than switching to oral or INJ therapies. For those discontinuing NAT, switching to an oral yields better outcomes than switching to an INJ. Disease activity risk in oral switchers is predicted by WO time, pre-NAT disease activity and EDSS, and time on NAT.
Supported by Biogen.
Disclosure: 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, and 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.
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.
QD, SL, P-RH, NC: employees of and own stock and/or stock options in Biogen.
Abstract: P733
Type: Poster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Natalizumab (NAT) is a high-efficacy therapy for relapsing-remitting multiple sclerosis (RRMS). After 2 years on NAT, many patients discontinue, mainly due to progressive multifocal leukoencephalopathy risk concerns. Data on predictors of post-NAT disease activity may be important for physician consideration. We assessed this in the TYSABRI Observational Program (TOP), an ongoing, 10-year observational study of NAT-treated RRMS patients.
Objectives: To compare outcomes in patients who switched to an oral or injectable (INJ) therapy with those who stayed on NAT and to analyze predictors of post-NAT relapse.
Methods: TOP data as of 1 November 2016 were analyzed for patients who stayed on NAT (≥3 years NAT and only NAT during follow-up; n=2466; mean time on NAT: 5.5 years) vs patients who switched to oral (n=660) or INJ (n=95) therapies for ≥1 year after ≥2 years on NAT (mean post-NAT follow-up: 2.5 years and 2.4 years, respectively). Annualized relapse rates (ARRs) were compared. Disability worsening was defined as an Expanded Disability Status Scale (EDSS) score increase of ≥1.5 from 0.0, ≥1.0 from 1.0-5.5, or ≥0.5 from ≥6.0, confirmed at ≥24 weeks. Risks and predictors of disease activity were compared using adjusted Cox models (covariates: age, sex, symptom onset, EDSS, prior relapses, washout (WO) time, and time on NAT).
Results: Relapse risk was higher for patients who switched to oral (hazard ratio [HR]=2.18; P< .001) or INJ (HR=3.02; P< .001) therapies than for patients who stayed on NAT after 2 years. EDSS worsening risk was similar for oral (HR=1.19; P=.266) and higher for INJ (HR=2.52; P< .001) switchers compared to stayed-on-NAT patients. ARRs decreased after the first 2 years by 20.2% for stayed-on-NAT patients but increased from rates on NAT by 17.8% and 108.1% for oral and INJ switchers, respectively (P< .001 for each). In oral switchers, lower relapse risk was predicted by shorter WO time (>12 weeks vs ≤4 weeks; HR=1.97; P=.001), fewer pre-NAT relapses (HR=1.24/relapse in the prior year; P< .001), lower EDSS at NAT start (>3.5 vs ≤3.5; HR=1.44; P=.007), and longer time on NAT (HR=0.87/additional year on NAT; P=.019).
Conclusions: Staying on NAT for >2 years yields better clinical outcomes than switching to oral or INJ therapies. For those discontinuing NAT, switching to an oral yields better outcomes than switching to an INJ. Disease activity risk in oral switchers is predicted by WO time, pre-NAT disease activity and EDSS, and time on NAT.
Supported by Biogen.
Disclosure: 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, and 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.
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.
QD, SL, P-RH, NC: employees of and own stock and/or stock options in Biogen.