Jerry S Wolinsky1, T Erik Borresen2, Dennis W Dietrich3, Daniel Wynn4, Yulia Sidi5, Joshua R Steinerman6, Volker Knappertz7, Scott Kolodny8. 1. University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: Jerry.S.Wolinsky@uth.tmc.edu. 2. Mecklenburg Neurological Associates, Charlotte, NC, USA. 3. Advanced Neurological Specialists, Great Falls, MT, USA. 4. Consultants in Neurology, Northbrook, IL, USA. 5. Teva Pharmaceuticals, Netanya, Israel. 6. Global Clinical Development, Teva Pharmaceuticals, Frazer, PA, USA. 7. Global Clinical Development, Teva Pharmaceuticals, Frazer, PA, USA; Heinrich-Heine Universität Düsseldorf, Düsseldorf, Germany. 8. Teva Pharmaceuticals, Cleveland, OH, USA.
Abstract
BACKGROUND: The efficacy and safety of glatiramer acetate (GA) 20 mg/mL once-daily subcutaneous injections (GA20) in relapsing-remitting multiple sclerosis (RRMS) is well-established. However, injection-related adverse events (IRAEs) may impede treatment adherence and tolerability. GA 40 mg/mL three-times weekly (GA40) also has a favorable efficacy and safety profile. OBJECTIVE: To evaluate the safety, tolerability, and patient experience when converting from GA20 to GA40. METHODS/TRIAL DESIGN:GLACIER was an open-label, randomized, parallel-group trial conducted at 31 sites in the US between June 2013 and December 2013. Stable RRMS patients on GA20 were randomized in a 1:1 ratio to continue with GA20 or convert to GA40. The adjusted mean annualized rate of IRAEs was the primary endpoint for this study. Additionally, the severity of IRAEs, rate of injection-site reactions (ISRs), and patient-reported MS impact and treatment satisfaction were compared for the two treatment groups over the 4-month core study. RESULTS: A total of 209 patients were randomized to convert to GA40 (n=108) or continue with GA20 (n=101). The adjusted mean annualized rate of IRAEs was reduced by 50% with GA40 (35.3 events per year; n=108) versus GA20 (70.4 events per year; n=101) (risk ratio (RR)=0.50; 95% confidence interval [CI]=0.34-0.74; p=0.0006). There was a 60% reduction in the rate of moderate/severe events (GA40 (n=108): 0.9 events per year versus GA20 (n=101): 2.2 events per year; RR=0.40; p=0.0021). Perception of treatment convenience improved for GA40-treated patients soon after converting and was sustained. CONCLUSIONS: The GLACIER study demonstrates a favorable IRAE and convenience profile of GA40 for RRMS patients. TRIAL REGISTRATION: NCT01874145 available at clinicaltrial.gov.
RCT Entities:
BACKGROUND: The efficacy and safety of glatiramer acetate (GA) 20 mg/mL once-daily subcutaneous injections (GA20) in relapsing-remitting multiple sclerosis (RRMS) is well-established. However, injection-related adverse events (IRAEs) may impede treatment adherence and tolerability. GA 40 mg/mL three-times weekly (GA40) also has a favorable efficacy and safety profile. OBJECTIVE: To evaluate the safety, tolerability, and patient experience when converting from GA20 to GA40. METHODS/TRIAL DESIGN: GLACIER was an open-label, randomized, parallel-group trial conducted at 31 sites in the US between June 2013 and December 2013. Stable RRMS patients on GA20 were randomized in a 1:1 ratio to continue with GA20 or convert to GA40. The adjusted mean annualized rate of IRAEs was the primary endpoint for this study. Additionally, the severity of IRAEs, rate of injection-site reactions (ISRs), and patient-reported MS impact and treatment satisfaction were compared for the two treatment groups over the 4-month core study. RESULTS: A total of 209 patients were randomized to convert to GA40 (n=108) or continue with GA20 (n=101). The adjusted mean annualized rate of IRAEs was reduced by 50% with GA40 (35.3 events per year; n=108) versus GA20 (70.4 events per year; n=101) (risk ratio (RR)=0.50; 95% confidence interval [CI]=0.34-0.74; p=0.0006). There was a 60% reduction in the rate of moderate/severe events (GA40 (n=108): 0.9 events per year versus GA20 (n=101): 2.2 events per year; RR=0.40; p=0.0021). Perception of treatment convenience improved for GA40-treated patients soon after converting and was sustained. CONCLUSIONS: The GLACIER study demonstrates a favorable IRAE and convenience profile of GA40 for RRMS patients. TRIAL REGISTRATION: NCT01874145 available at clinicaltrial.gov.
Authors: Chiara Zecca; G Bellavia; L Brambilla; L P Gutierrez; C Gerardi; A M Fiori; L R Bernardini; G Camera; G Disanto; L Petrini; J Perugini; C G Antozzi; V Torri Clerici; A Bellino; P A Confalonieri; C Gobbi; R E Mantegazza; S Rossi Journal: CNS Drugs Date: 2018-07 Impact factor: 5.749
Authors: Lisa H Tostanoski; Haleigh B Eppler; Boyan Xia; Xiangbin Zeng; Christopher M Jewell Journal: Biomater Sci Date: 2019-02-26 Impact factor: 6.843