PMID- 34322853 OWN - NLM STAT- MEDLINE DCOM- 20220208 LR - 20220218 IS - 1179-1934 (Electronic) IS - 1172-7047 (Print) IS - 1172-7047 (Linking) VI - 35 IP - 9 DP - 2021 Sep TI - Safety, Patient-Reported Well-Being, and Physician-Reported Assessment of Walking Ability in Patients with Multiple Sclerosis for Prolonged-Release Fampridine Treatment in Routine Clinical Practice: Results of the LIBERATE Study. PG - 1009-1022 LID - 10.1007/s40263-021-00840-x [doi] AB - BACKGROUND: Prolonged-release fampridine (PR-FAM) 10-mg tablet twice daily is the only approved pharmacological treatment for improvement of walking ability in adults with multiple sclerosis (MS). LIBERATE assessed the safety/effectiveness of PR-FAM in the real-world. OBJECTIVES: The aim of this study was to collect additional safety data, including the incidence rate of seizures and other adverse events (AEs) of interest, from patients with MS taking PR-FAM in routine clinical practice (including patients aged >/= 65 years and those with pre-existing cardiovascular risk factors). Other objectives included change over time in patient-reported evaluation of physical and psychological impact of MS while taking PR-FAM, and change over time in physician-reported assessment of walking ability in MS patients taking PR-FAM. METHODS: Patients with MS newly prescribed PR-FAM were recruited (201 sites, 13 countries). Demographic/safety data were collected at enrolment through 12 months. Physician-rated Clinical Global Impression of Improvement (CGI-I) scores for walking ability, and Multiple Sclerosis Impact Scale-29 (MSIS-29) were assessed. RESULTS: Safety analysis included 4646 patients with 3534.8 patient-years of exposure; median (range) age, 52.6 (21-85) years, 87.3% < 65 years, and 65.7% women. Treatment-emergent AEs (TEAEs) were reported in 2448 (52.7%) patients, and serious TEAEs were reported in 279 (6.0%) patients, of whom 37 (< 1%) experienced treatment-emergent serious AEs (TESAEs) considered related to PR-FAM. AEs of special interest (AESI) occurred in 1799 (38.7%) patients, and serious AESI in 128 (2.8%) patients. Seventeen (< 1%) patients experienced actual events of seizure. Overall, 1158 (24.9%) patients discontinued treatment due to lack of efficacy. At 12 months, a greater proportion of patients on-treatment had improvement from baseline in CGI-I for walking ability versus those who discontinued (61% vs. 11%; p < 0.001). MSIS-29 physical impact score improved significantly for patients on-treatment for 12 months versus those who discontinued (mean change, baseline to 12 months: - 9.99 vs. - 0.34 points; p < 0.001). Results were similar for MSIS-29 psychological impact. CONCLUSION: No new safety concerns were identified in this real-world study, suggesting that routine risk-minimization measures are effective. CGI-I and MSIS-29 scores after 12 months treatment with PR-FAM treatment show clinical benefits consistent with those previously reported. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01480063. CI - (c) 2021. The Author(s). FAU - Castelnovo, Giovanni AU - Castelnovo G AD - Service de Neurologie, CHU Caremeau, Nimes, France. FAU - Gerlach, Oliver AU - Gerlach O AD - Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands. AD - Academic MS Center Limburg, School for Mental Health and Neuroscience, Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands. FAU - Freedman, Mark S AU - Freedman MS AD - Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada. FAU - Bergmann, Arnfin AU - Bergmann A AD - NeuroTransData GmbH, Neuburg an der Donau, Germany. FAU - Sinay, Vladimiro AU - Sinay V AD - Institute of Translational and Cognitive Neuroscience (INCyT) INECO Foundation, Favaloro University, Buenos Aires, Argentina. FAU - Castillo-Trivino, Tamara AU - Castillo-Trivino T AD - Donostia University Hospital, San Sebastian, Spain. FAU - Kong, George AU - Kong G AD - Biogen, Cambridge, MA, USA. FAU - Koster, Thijs AU - Koster T AD - Biogen, Cambridge, MA, USA. thijs.koster@biogen.com. FAU - Williams, Heather AU - Williams H AD - Biogen, Maidenhead, Berkshire, UK. FAU - Gafson, Arie R AU - Gafson AR AD - Biogen, Cambridge, MA, USA. FAU - Killestein, Joep AU - Killestein J AD - Department of Neurology, MS Center Amsterdam, Amsterdam UMC, VU Medical Center, Amsterdam, The Netherlands. LA - eng SI - ClinicalTrials.gov/NCT01480063 PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Pragmatic Clinical Trial PT - Research Support, Non-U.S. Gov't DEP - 20210728 PL - New Zealand TA - CNS Drugs JT - CNS drugs JID - 9431220 RN - 0 (Delayed-Action Preparations) RN - 0 (Potassium Channel Blockers) RN - BH3B64OKL9 (4-Aminopyridine) SB - IM MH - 4-Aminopyridine/*administration & dosage MH - Adult MH - Aged MH - Aged, 80 and over MH - Delayed-Action Preparations/administration & dosage MH - Female MH - Humans MH - Male MH - Middle Aged MH - Multiple Sclerosis/diagnosis/*drug therapy/physiopathology MH - *Patient Reported Outcome Measures MH - *Physicians MH - Potassium Channel Blockers/*administration & dosage MH - Prospective Studies MH - Treatment Outcome MH - Walking/*physiology MH - Young Adult PMC - PMC8408054 COIS- Giovanni Castelnovo has received research/educational grants from Allergan, Biogen, Merz, and Novartis, and speaking/consulting fees from Allergan, Biogen, Ipsen, Merck, Merz, Novartis, and Sanofi-Genzyme. Mark S. Freedman has received research/educational grants from EMD (Canada), Roche, and Sanofi-Genzyme (Canada); consulting fees from Actelion (Janssen/J&J), Alexion, Biogen, Celgene (BMS), EMD, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva Canada Innovation; advisory board/board of directors/similar group for Actelion (Janssen/J&J), Alexion, Atara Biotherapeutics, Bayer, Biogen, Celgene (BMS), Clene Nanomedicine, GRI Bio, Magenta Therapeutics, Merck Serono, MedDay, Novartis, Roche, Sanofi-Genzyme, and Teva Canada Innovation; and speaker bureaus for EMD Serono and Sanofi-Genzyme. Vladimiro Sinay has received reimbursement for developing educational presentations, educational/research grants, and consultation fees/travel stipends from Bayer, Biogen, Biosidus, Gador, Genzyme, Merck, Novartis, Raffo/Asofarma, and Roche. Tamara Castillo-Trivino has received speaking/consulting fees and/or travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. Joep Killestein has received speaking/consulting fees from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. George Kong, Thijs Koster, Heather Williams and Arie R. Gafson are employees of, and hold stock/stock options in, Biogen. Oliver Gerlach and Arnfin Bergmann have no disclosures to declare. EDAT- 2021/07/30 06:00 MHDA- 2022/02/09 06:00 PMCR- 2021/07/28 CRDT- 2021/07/29 07:01 PHST- 2021/06/22 00:00 [accepted] PHST- 2021/07/30 06:00 [pubmed] PHST- 2022/02/09 06:00 [medline] PHST- 2021/07/29 07:01 [entrez] PHST- 2021/07/28 00:00 [pmc-release] AID - 10.1007/s40263-021-00840-x [pii] AID - 840 [pii] AID - 10.1007/s40263-021-00840-x [doi] PST - ppublish SO - CNS Drugs. 2021 Sep;35(9):1009-1022. doi: 10.1007/s40263-021-00840-x. Epub 2021 Jul 28.