Contributions
Abstract: EP1695
Type: ePoster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Fingolimod treatment improved the clinical and MRI outcomes over 12 months in relapsing-remitting MS (RRMS) patients with highly active disease (HAD) after an exposure to previous disease-modifying therapies (DMTs)1.
Objective: To evaluate the long-term effectiveness and safety of fingolimod in RRMS patients with HAD after an exposure to previous DMTs.
Methods: LONGTERMS is a single-arm, open-label extension study of phase 2/3/3b trials of fingolimod in relapsing MS. Two cohorts of patients who received fingolimod 0.5 mg as the only dose in the core phase of three phase 3 trials were analysed: Highly active disease cohort (HADC, N=463) and overall core cohort (CC, N=1212). HADC included patients who received any DMT during the year before study entry and either (1) had as many or more relapses in the year before study entry than 2 years before study entry or (2) had ≥1 relapse in the previous year and ≥1 Gd+ T1 lesion or ≥9 T2 lesions at baseline (BL). Effectiveness evaluations included relapse (annualised relapse rate [ARR], estimated by negative binomial regression) and disability outcomes (Kaplan-Meier [KM] estimates for patients not reaching Expanded Disability Status Scale (EDSS) of ≥4, ≥6, or ≥7). Incidence rate ratios (IRRs; IR for HADC/CC) were reported for any adverse events (AEs) and serious AEs (SAEs).
Results: BL demographics and disease characteristics of patients in the HADC and CC cohorts were: women, 74% and 70%; mean age (years), 38.6 and 37.9; mean number of relapses in the year prior to enrolment in the core studies, 1.5 and 1.5; mean EDSS, 2.5 and 2.3. The median (range) exposure to fingolimod was: HADC, 1361 (2-3546) days and CC, 1545 (2-3619) days. From BL to Month (M)120, 46% and 53% of patients remained relapse free in the HADC and CC, respectively. The ARR (95% CI) remained low during M0-6 to M0-120 (HADC, 0.46 [0.38; 0.56] to 0.27 [0.24; 0.31]; CC, 0.36 [0.32; 0.41] to 0.21 [0.19; 0.23]). At M96, most patients in both HADC and CC did not reach an EDSS score of ≥4
(64% and 71%), ≥6 (83% and 86%) or ≥7 (98% and 97%). The IRs for any AE or SAE were higher in the HADC vs CC: IRR (95% CI) for AEs was 1.37 (1.23; 1.53) and SAEs was 1.26 (1.02; 1.54).
Conclusions: For patients remaining on long-term fingolimod treatment, those with HAD after an exposure to previous DMTs showed benefits in terms of low ARR, delayed EDSS progression and no new safety concerns. The intrinsic limitation of the open-label extension study cannot be excluded.
Disclosure:
1Cohen JA, et al. J Neurol. 2013;260:2023-2032.
Funding source: This study is supported by Novartis Pharma AG, Basel, Switzerland.
Galina Vorobeychik reports personal compensation for consulting and research support for Biogen Idec, Genzyme, Novartis, Roche, Serono Merck, and Teva Neuroscience
Virginia Devonshire has received honoraria for Advisory meetings and speaking from EMD Serono, Biogen Idec, Teva Neurosciences, Novartis, and Sanofi-Genzyme
Mark Freedman has received honoraria or consultation fees from Actelion, Bayer Healthcare, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Hoffman La-Roche, Sanofi-Aventis, and Teva Canada Innovation. He is a member of a company advisory board, board of directors/other similar groups for Actelion, Bayer Healthcare, Biogen Idec, Hoffman La-Roche, Merck Serono, Novartis, Opexa, and Sanofi-Aventis. He has participated in Genzyme's company-sponsored speaker bureau
Francois Grand'Maison has received research funding from Chugai, Novartis, Biogen, Genzyme, and Actelion
Daniel Selchen has received honoraria for speaking and ad boards from Bayer, Biogen, Novartis, Merck Serono, Roche, Sanofi Genzyme, and Teva
Ludwig Kappos' institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva); license fees for Neurostatus products; and grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and Swiss National Research Foundation)
Jeffrey Cohen reports personal compensation for consulting for Adamas, Merck, Mallinckrodt, Novartis, and Receptos and as a Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical
Robyn Schecter, Paola Haddad, Nadia Tenenbaum, Alit Bhatt and Ron Pimentel are employees of Novartis
Abstract: EP1695
Type: ePoster
Abstract Category: Therapy - disease modifying - 28 Long-term treatment monitoring
Background: Fingolimod treatment improved the clinical and MRI outcomes over 12 months in relapsing-remitting MS (RRMS) patients with highly active disease (HAD) after an exposure to previous disease-modifying therapies (DMTs)1.
Objective: To evaluate the long-term effectiveness and safety of fingolimod in RRMS patients with HAD after an exposure to previous DMTs.
Methods: LONGTERMS is a single-arm, open-label extension study of phase 2/3/3b trials of fingolimod in relapsing MS. Two cohorts of patients who received fingolimod 0.5 mg as the only dose in the core phase of three phase 3 trials were analysed: Highly active disease cohort (HADC, N=463) and overall core cohort (CC, N=1212). HADC included patients who received any DMT during the year before study entry and either (1) had as many or more relapses in the year before study entry than 2 years before study entry or (2) had ≥1 relapse in the previous year and ≥1 Gd+ T1 lesion or ≥9 T2 lesions at baseline (BL). Effectiveness evaluations included relapse (annualised relapse rate [ARR], estimated by negative binomial regression) and disability outcomes (Kaplan-Meier [KM] estimates for patients not reaching Expanded Disability Status Scale (EDSS) of ≥4, ≥6, or ≥7). Incidence rate ratios (IRRs; IR for HADC/CC) were reported for any adverse events (AEs) and serious AEs (SAEs).
Results: BL demographics and disease characteristics of patients in the HADC and CC cohorts were: women, 74% and 70%; mean age (years), 38.6 and 37.9; mean number of relapses in the year prior to enrolment in the core studies, 1.5 and 1.5; mean EDSS, 2.5 and 2.3. The median (range) exposure to fingolimod was: HADC, 1361 (2-3546) days and CC, 1545 (2-3619) days. From BL to Month (M)120, 46% and 53% of patients remained relapse free in the HADC and CC, respectively. The ARR (95% CI) remained low during M0-6 to M0-120 (HADC, 0.46 [0.38; 0.56] to 0.27 [0.24; 0.31]; CC, 0.36 [0.32; 0.41] to 0.21 [0.19; 0.23]). At M96, most patients in both HADC and CC did not reach an EDSS score of ≥4
(64% and 71%), ≥6 (83% and 86%) or ≥7 (98% and 97%). The IRs for any AE or SAE were higher in the HADC vs CC: IRR (95% CI) for AEs was 1.37 (1.23; 1.53) and SAEs was 1.26 (1.02; 1.54).
Conclusions: For patients remaining on long-term fingolimod treatment, those with HAD after an exposure to previous DMTs showed benefits in terms of low ARR, delayed EDSS progression and no new safety concerns. The intrinsic limitation of the open-label extension study cannot be excluded.
Disclosure:
1Cohen JA, et al. J Neurol. 2013;260:2023-2032.
Funding source: This study is supported by Novartis Pharma AG, Basel, Switzerland.
Galina Vorobeychik reports personal compensation for consulting and research support for Biogen Idec, Genzyme, Novartis, Roche, Serono Merck, and Teva Neuroscience
Virginia Devonshire has received honoraria for Advisory meetings and speaking from EMD Serono, Biogen Idec, Teva Neurosciences, Novartis, and Sanofi-Genzyme
Mark Freedman has received honoraria or consultation fees from Actelion, Bayer Healthcare, Biogen Idec, Chugai, EMD Canada, Genzyme, Merck Serono, Novartis, Hoffman La-Roche, Sanofi-Aventis, and Teva Canada Innovation. He is a member of a company advisory board, board of directors/other similar groups for Actelion, Bayer Healthcare, Biogen Idec, Hoffman La-Roche, Merck Serono, Novartis, Opexa, and Sanofi-Aventis. He has participated in Genzyme's company-sponsored speaker bureau
Francois Grand'Maison has received research funding from Chugai, Novartis, Biogen, Genzyme, and Actelion
Daniel Selchen has received honoraria for speaking and ad boards from Bayer, Biogen, Novartis, Merck Serono, Roche, Sanofi Genzyme, and Teva
Ludwig Kappos' institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva); support of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva); license fees for Neurostatus products; and grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and Swiss National Research Foundation)
Jeffrey Cohen reports personal compensation for consulting for Adamas, Merck, Mallinckrodt, Novartis, and Receptos and as a Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical
Robyn Schecter, Paola Haddad, Nadia Tenenbaum, Alit Bhatt and Ron Pimentel are employees of Novartis