scholarly journals Long-Term Efficacy and Safety of Erenumab

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012029
Author(s):  
Peter J. Goadsby ◽  
Uwe Reuter ◽  
Michel Lanteri-Minet ◽  
Gabriel Paiva da Silva Lima ◽  
Peggy Hours-Zesiger ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Episodic Migraine ◽  
Responder Rate ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Sustained Efficacy ◽  
Link Type ◽  
Sustained Effects ◽  
Open Label Extension

ObjectiveTo report the efficacy and safety of erenumab among episodic migraine (EM) patients who were unsuccessful on 2–4 preventive treatments observed at week 64 of Open-Label Extension Phase (OLEP) of the LIBERTY study (ClinicalTrials.govNCT03096834).MethodsThe OLEP evaluating monthly erenumab 140 mg for 3 years, enrolled 240 patients who completed the double-blind treatment phase (DBTP) of 12 weeks during which they received placebo or erenumab 140 mg subcutaneous injections every 4 weeks as monotherapy. Efficacy outcomes were evaluated through the initial 52 weeks of OLEP (from DBTP baseline to total 64 weeks) in the overall population, patients receiving erenumab in DBTP, and patients from DBTP placebo arm who switched to erenumab in OLEP. Endpoints included reduction of ≥50% in monthly migraine days (MMD) from DBTP baseline and change in MMD from DBTP baseline, Headache Impact Test, and Migraine Physical Function Impact Diary (Physical Impairment and Everyday Activities) scores.ResultsAltogether, the week 52 visit of the OLEP was completed by 204/240 (85.0%) patients. Among patients continuing erenumab, the 50% responder rate increase from 29.9% at weeks 9%–12% to 44.3% at week 61–64. The 50% responder rate in patients who initiated erenumab in the OLEP remained higher in the OLEP (50.0% at week 61–64) than during DBTP (14.2% at weeks 9–12) compared to patients in continuous erenumab arm. In the OLEP, the 50% responder rate for the overall population increased from weeks 13–16 until weeks 37–40 and then remained stable through weeks 61–64. Patients treated with erenumab in DBTP showed sustained effects on all efficacy outcomes; those initiating erenumab in the OLEP demonstrated continued improvement from week 13 onward. Adverse events (AEs) were reported, considering both treatment groups, by ∼80.8% (serious AEs [SAEs] by 6.7%); 76.3% (5.9%) in the continuing erenumab arm; and 85.2% (7.4%) in those starting erenumab in OLEP. No deaths were reported.ConclusionsIn patients with EM who were unsuccessful on 2–4 prior preventive treatments, the LIBERTY study demonstrated sustained efficacy on erenumab monotherapy treatment through 64 weeks in both treatment arms. Safety of erenumab was consistent with that observed in previous clinical trials.Classification of evidenceThe current study provides Class IV evidence on data from patients with episodic migraine, that erenumab is safe and provides sustained efficacy at 52 weeks.Clinicaltrials.gov identifierNCT03096834.

scholarly journals Two-year efficacy and safety of erenumab in participants with episodic migraine and 2–4 prior preventive treatment failures: results from the LIBERTY study

2021 ◽  
pp. jnnp-2021-327480
Author(s):  
Michel Dominique Ferrari ◽  
Uwe Reuter ◽  
Peter J Goadsby ◽  
Gabriel Paiva da Silva Lima ◽  
Subhayan Mondal ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Responder Rate ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Registration Number

ObjectiveTo evaluate individual and group long-term efficacy and safety of erenumab in individuals with episodic migraine (EM) for whom 2–4 prior preventatives had failed.MethodsParticipants completing the 12-week double-blind treatment phase (DBTP) of the LIBERTY study could continue into an open-label extension phase (OLEP) receiving erenumab 140 mg monthly for up to 3 years. Main outcomes assessed at week 112 were: ≥50%, ≥75% and 100% reduction in monthly migraine days (MMD) as group responder rate and individual responder rates, MMD change from baseline, safety and tolerability.ResultsOverall 240/246 (97.6%) entered the OLEP (118 continuing erenumab, 122 switching from placebo). In total 181/240 (75.4%) reached 112 weeks, 24.6% discontinued, mainly due to lack of efficacy (44.0%), participant decision (37.0%) and adverse events (AEs; 12.0%). The ≥50% responder rate was 57.2% (99/173) at 112 weeks. Of ≥50% responders at the end of the DBTP, 36/52 (69.2%) remained responders at ≥50% and 22/52 (42.3%) at >80% of visits. Of the non-responders at the end of the DBTP, 60/185 (32.4%) converted to ≥50% responders in at least half the visits and 24/185 (13.0%) converted to ≥50% responders in >80% of visits. Change from baseline at 112 weeks in mean (SD) MMD was −4.2 (5.0) days. Common AEs (≥10%) were nasopharyngitis, influenza and back pain.ConclusionsEfficacy was sustained over 112 weeks in individuals with difficult-to-treat EM for whom 2–4 prior migraine preventives had failed. Erenumab treatment was safe and well tolerated, in-line with previous studies.Trial registration numberNCT03096834

scholarly journals 096 Assessment of the efficacy of erenumab during the open-label treatment (13–24 weeks) of subjects with episodic migraine who failed 2–4 prior preventive treatments: results of the LIBERTY study

2019 ◽  
Vol 90 (e7) ◽  
pp. A31.1-A31
Author(s):  
Lauren Giles ◽  
Uwe Reuter ◽  
Peter Goadsby ◽  
Michel Lanteri-Minet ◽  
Peggy Hours-Zesiger ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Specific Medication ◽  
Continuous Use ◽  
To Receive ◽  
Headache Impact

IntroductionTo assess efficacy of erenumab in the first three months of the open-label extension phase (OLEP; 13–24 weeks) of the LIBERTY study.MethodsIn the double-blind treatment phase (DBTP), 246 patients were randomized to placebo and erenumab 140 mg for 12 weeks, following which, patients completing that phase (N=240) were enrolled in OLEP, to receive monthly erenumab 140 mg. Outcomes measured monthly throughout to week 24 were achievement of at least 50%/75%/100% reduction in monthly migraine days (MMD), change from DBTP baseline in MMD, monthly acute migraine-specific medication days (MSMD), Headache Impact Test (HIT-6TM) total score, everyday activities (EA) and physical impairment (PI) as measured by the Migraine Physical Function Impact Diary (MPFID).ResultsOverall, 228/240(95.0%) patients completed the 24 week visit of the OLEP. In the overall population at Week 24, 39.2%, 15.9% and 7.0% patients achieved ≥50%/≥75%/100% reduction in MMD. The mean (standard deviation) change from DBTP baseline in MMD was −2.7(4.4) and −1.4(3.0) in MSMD; and −7.6(8.0), −2.5(9.2) and −4.0(9.0) in HIT-6TM, MPFID-PI and MPFID-EA scores respectively. Patients with continuous use of erenumab showed sustained efficacy in all outcomes assessed. Patients who switched from placebo to erenumab in the OLEP showed improvement from the first measurement at Week 16 on all outcomes assessed.ConclusionsEfficacy of erenumab was sustained throughout 24 weeks in a hard to treat patient population with multiple prior preventive treatment failures. Overall, efficacy data over 24 weeks (assessed over weeks 13–16,17–20 and 21–24) was generally in line with prior erenumab trials.

scholarly journals Efficacy and safety of fremanezumab in patients with episodic and chronic migraine with documented inadequate response to 2 to 4 classes of migraine preventive medications over 6 months of treatment in the phase 3b FOCUS study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Messoud Ashina ◽  
Joshua M. Cohen ◽  
Maja Galic ◽  
Verena Ramirez Campos ◽  
Steve Barash ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Medication Use ◽  
Episodic Migraine ◽  
Inadequate Response ◽  
Open Label ◽  
Double Blind ◽  
Moderate Severity ◽  
Preventive Medication ◽  
Open Label Extension ◽  
Acute Headache

Abstract Background Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab. Methods Episodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or  ≥75% reduction in monthly migraine days were evaluated. Results Of the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: − 4.7 [5.4]; − 5.1 [4.7]; − 5.5 [5.0]), monthly headache days of at least moderate severity (− 4.5 [5.0]; − 4.8 [4.5]; − 5.2 [4.9]), days per month of acute headache medication use (− 4.3 [5.2]; − 4.9 [4.6]; − 4.8 [4.9]), days with photophobia/phonophobia (− 3.1 [5.3]; − 3.4 [5.3]; − 4.0 [5.2]), and days with nausea or vomiting (− 2.3 [4.6]; − 3.1 [4.5]; − 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%). Conclusion Fremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes. Trial registration ClinicalTrials.gov NCT03308968 (FOCUS).

Etanercept in the Longterm Treatment of Patients With Ankylosing Spondylitis

2009 ◽  
Vol 36 (6) ◽  
pp. 1256-1264 ◽  
Author(s):  
BEN DIJKMANS ◽  
PAUL EMERY ◽  
MARKKU HAKALA ◽  
MARJATTA LEIRISALO-REPO ◽  
EMILIO MARTIN MOLA ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Safety Data ◽  
Blind Study ◽  
Double Blind Study ◽  
Upper Respiratory Tract ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Tract Infections

Objective.To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis (AS).Methods.A 96-week open-label extension study, which followed a 12-week double-blind placebo-controlled trial, was designed to provide longterm efficacy and safety data, including radiographic outcomes, for patients treated with etanercept 25 mg twice weekly (NCT00421980). In all, 81 patients were enrolled (96% of the participants from the double-blind study). Key efficacy measures included improvement using the Assessment in Ankylosing Spondylitis 20% (ASAS20) criteria, the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) method. Paired t tests were used to test within-group changes from baseline.Results.The percentage of responders, by ASAS20 criteria, remained relatively constant in patients who received etanercept during the 12-week double-blind study (60% at Week 0 and 83% at Week 96 of the open-label extension); more patients from the placebo group became responders after being switched to etanercept (23% and 74%, respectively). A similar trend was also observed using the ASAS40 and ASAS5/6 criteria, the BASFI, and the BASDAI. Most patients had no change from baseline in mSASSS values. Etanercept was well tolerated; the most frequent adverse events were injection site reactions (n = 30; 37.0%) and headache (n = 18; 22.2%), and the most frequent infections were upper respiratory tract infections (n = 43; 53.1%) and flu syndrome (n = 22; 27.2%).Conclusion.For 2 years, etanercept was clinically effective and well tolerated, with no unexpected safety findings.

056 Perampanel and secondarily generalised seizures in a pooled analysis of phase III studies and their open-label extension: effect of enzyme-inducing antiepileptic drugs

2018 ◽  
Vol 89 (6) ◽  
pp. A23.2-A23
Author(s):  
David Ko ◽  
Betsy Williams ◽  
Anna Patten ◽  
Antonio Laurenza
Keyword(s):  
Antiepileptic Drugs ◽  
Phase Iii ◽  
Adjunctive Treatment ◽  
Seizure Freedom ◽  
Partial Seizures ◽  
Open Label ◽  
Double Blind ◽  
Link Type ◽  
Open Label Extension ◽  
Phase Iii Studies

IntroductionPerampanel is approved for adjunctive treatment of partial seizures, with or without secondarily generalised seizures (SGS), and primary generalised tonic-clonic seizures in epilepsy patients aged ≥12 years. Approval of perampanel for partial seizures was based on three randomised, double-blind, placebo-controlled, Phase III Studies 304 (NCT00699972), 305 (NCT00699582) and 306 (NCT00700310); patients completing these could enter open-label extension (OLEx) Study 307 (NCT00735397). Here, we report efficacy of perampanel as adjunctive treatment of SGS by co-administration of enzyme-inducing antiepileptic drugs (EIAEDs) versus non-EIAEDs in both the Phase III and OLEx studies.MethodsIn the double-blind studies, patients (≥12 years) with partial seizures, with or without SGS, receiving 1–3 AEDs at Baseline were randomised to placebo or 2–12 mg/day perampanel for 19 weeks. In the OLEx, patients received ≤12 mg/day perampanel for ≤272 weeks. Efficacy assessments included median percent change in SGS frequency/28 days, SGS 50% and 75% responder and seizure-freedom rates.ResultsFor patients with SGS at pre-perampanel Baseline, 564 were in the double-blind studies and 388 received perampanel for ≥1 year in the OLEx. In the double-blind studies, perampanel co-administered with an EIAED (carbamazepine, eslicarbazepine, oxcarbazepine, phenytoin) had reduced efficacy compared with non-EIAEDs due to increased clearance; this was particularly evident at higher doses, although these differences were still greater than placebo. In the OLEx, concomitant administration of both non-EIAEDs and EIAEDs was associated with sustained efficacy, with slightly better efficacy during the first, second and third years of perampanel exposure for non-EIAEDs compared with EIAEDs.ConclusionPerampanel demonstrated good and sustained long-term efficacy against SGS. With the recent FDA approval of perampanel for monotherapy use for partial seizures, non-EIAED data may be more relevant for consideration if perampanel is used as a single agent (no other AED) while real-world data and experience are accumulated.Study supportEisai Inc.

Erenumab (AMG 334) in episodic migraine

Neurology ◽  
2017 ◽  
Vol 89 (12) ◽  
pp. 1237-1243 ◽  
Author(s):  
Messoud Ashina ◽  
David Dodick ◽  
Peter J. Goadsby ◽  
Uwe Reuter ◽  
Stephen Silberstein ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Safety Data ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension

Objective:To assess long-term safety and efficacy of anti–calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM).Methods:Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without imputation for missing data.Results:Of 472 patients enrolled in the parent study, 383 continued in the OLE with a median exposure to erenumab of 575 days (range 28–822 days). Mean (SD) MMD were 8.8 (2.6) at parent study baseline, 6.3 (4.2) at week 12 (beginning of OLE), and 3.7 (4.0) at week 64 (mean change from baseline [reduction] of 5.0 days). At week 64, 65%, 42%, and 26% achieved ≥50%, ≥75%, and 100% reduction in MMD, respectively. Mean HIT-6 scores were 60.2 (6.3) at baseline and 51.7 (9.2) at week 64. MSQ and MIDAS improvements from baseline were maintained through week 64. Safety profiles during the OLE were similar to those in the double-blind phase, which overall were similar to placebo.Conclusions:One-year efficacy, supported by functional improvements and favorable safety and tolerability profiles, supports further investigation of erenumab as a preventive treatment in patients with EM.Clinicaltrials.gov identifier:NCT01952574.Classification of evidence:This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life.

Long-term safety and efficacy of erenumab in patients with chronic migraine: Results from a 52-week, open-label extension study

Cephalalgia ◽  
2020 ◽  
Vol 40 (6) ◽  
pp. 543-553 ◽  
Author(s):  
Stewart J Tepper ◽  
Messoud Ashina ◽  
Uwe Reuter ◽  
Jan Lewis Brandes ◽  
David Doležil ◽  
...  
Keyword(s):  
Adverse Event ◽  
Chronic Migraine ◽  
Treatment Phase ◽  
Extension Study ◽  
Open Label ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
Event Rates

Background This study reports the long-term safety and efficacy of erenumab in chronic migraine patients. Methods This was a 52-week open-label extension study of a 12-week double-blind treatment phase study. During the double-blind treatment phase, patients received placebo or once-monthly erenumab 70 mg or 140 mg. During the open-label treatment phase, the initial monthly dose was erenumab 70 mg. Following protocol amendment, patients continued to receive erenumab 70 mg if they had already completed their Week 28 visit, otherwise, patients switched from 70 mg to 140 mg; if enrolled after the amendment, patients received 140 mg monthly throughout. Results In all, 451/609 (74.1%) enrolled patients completed the study. The exposure-adjusted patient incidence rate for any adverse event was 126.3/100 patient-years for the overall erenumab group. Overall, the adverse event profile was similar to that observed in the double-blind treatment phase. Adverse event incidence rates did not increase with long-term erenumab treatment compared with the double-blind treatment phase, and no new serious or treatment-emergent events were seen. Efficacy was sustained throughout the 52 weeks. Clinically significant reductions from double-blind treatment phase baseline (about half) were observed for monthly migraine days and migraine-specific medication days. Achievement of ≥50%, ≥75% and 100% reductions from the double-blind treatment phase baseline in monthly migraine days at Week 52 were reported by 59.0%, 33.2% and 8.9% of patients, respectively, for the combined dose group. A numerically greater benefit was observed with 140 mg compared with 70 mg at Weeks 40 and 52. Conclusions Sustained efficacy of long-term erenumab treatment in patients with chronic migraine is demonstrated, with safety results consistent with the known safety profile of erenumab and adverse event rates comparable to placebo adverse event rates in the double-blind treatment phase. Trial registration: This study is registered at ClinicalTrials.gov (NCT02174861)

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