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 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 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.

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)

scholarly journals Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4

2017 ◽  
Vol 76 (12) ◽  
pp. 1986-1991 ◽  
Author(s):  
Paul Emery ◽  
Jiří Vencovský ◽  
Anna Sylwestrzak ◽  
Piotr Leszczyński ◽  
Wieslawa Porawska ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Response Rates ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Term Efficacy ◽  
Open Label Extension ◽  
Extension Period

ObjectivesSB4 (Benepali, Brenzys) is a biosimilar of reference etanercept (ETN). In a randomised, double-blind, 52-week study, SB4 demonstrated comparable efficacy and safety to ETN in patients with rheumatoid arthritis (RA). The open-label extension period evaluated long-term efficacy, safety and immunogenicity when continuing SB4 versus switching from ETN to SB4.MethodsIn the randomised, double-blind phase, patients received weekly subcutaneous administration of 50 mg SB4 or ETN with background methotrexate for up to 52 weeks. Patients in the Czech Republic and Poland who completed the 52-week visit were enrolled in the open-label extension period and received SB4 for 48 additional weeks. Efficacy, safety and immunogenicity were assessed up to week 100.ResultsOf 245 patients entering the extension period, 126 continued to receive SB4 (SB4/SB4) and 119 switched to SB4 (ETN/SB4). American College of Rheumatology (ACR) response rates were sustained and comparable between SB4/SB4 and ETN/SB4 with ACR20 response rates at week 100 of 77.9% and 79.1%, respectively. Other efficacy results, including radiographic progression, were also comparable between the groups. After week 52, rates of treatment-emergent adverse events were 47.6% (SB4/SB4) and 48.7% (ETN/SB4); one patient/group developed non-neutralising antidrug antibodies. No cases of active tuberculosis or injection-site reactions were reported during the extension period. One patient (SB4/SB4) died of hepatic cancer.ConclusionsSB4 was effective and well tolerated over 2 years in patients with RA. Efficacy, safety and immunogenicity were comparable between the SB4/SB4 and ETN/SB4 groups, showing no risk associated with switching patients from ETN to SB4.Trial registration numberNCT01895309; 2012-005026-30

scholarly journals A Randomized, Double-Blind, Placebo-Controlled Phase III Trial On The Efficacy and Safety of Tocilizumab in Patients With Colchicine-Resistant or -Intolerant Familial Mediterranean Fever

2021 ◽  
Author(s):  
Tomohiro Koga ◽  
Shuntaro Sato ◽  
Naoko Hagimori ◽  
Hiroshi Yamamoto ◽  
Masataka Ishimura ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
Mediterranean Fever ◽  
Accompanying Symptoms ◽  
Fever Attacks ◽  
Serum Crp

Abstract Objective To evaluate the efficacy and safety of tocilizumab (TCZ), an interleukin 6 receptor monoclonal antibody, in patients with familial Mediterranean fever (FMF). Methods We performed a double-blind, randomized, parallel-group trial, followed by an open-label extension trial, in patients with colchicine-resistant or -intolerant FMF (crFMF). Patients were randomly assigned (1:1) to receive TCZ (162 mg every week) or placebo, administered subcutaneously, for 24 weeks. Rescue treatment was allowed if the rescue criteria were met. The primary endpoint was the number of fever attacks over the 24 weeks of treatment. Secondary endpoints included the frequency of accompanying symptoms during attacks, serum CRP and SAA values, and adverse events (AEs). The open-label extension study evaluated the long-term safety and efficacy of TCZ in patients who had completed the preceding study. Results We randomly assigned 23 patients to either TCZ (n = 11) or placebo (n = 12). The TCZ–placebo rate ratios were 0.691 (95% confidence intervals (CI), 0.189–2.531; P = 0.577) for the fever attacks, based on the group rates per week. The recurrence of attacks was significantly lower in the TCZ group (hazard ratio = 0.457; 95% CI, 0.240–0.869). Fever attacks, accompanying symptoms, serum CRP and SAA values were controlled in most of the patients who received long-term TCZ. In these trials, the numbers and severity of AEs did not differ between groups. Conclusion Although a primary endpoint was not met in the preceding trial, long-term administration of TCZ showed stable efficacy and safety for patients with crFMF.

scholarly journals Reversion from chronic migraine to episodic migraine following treatment with erenumab: Results of a post-hoc analysis of a randomized, 12-week, double-blind study and a 52-week, open-label extension

Cephalalgia ◽  
2020 ◽  
pp. 033310242097399
Author(s):  
Richard B Lipton ◽  
Stewart J Tepper ◽  
Stephen D Silberstein ◽  
David Kudrow ◽  
Messoud Ashina ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Chronic Migraine ◽  
Controlled Trial ◽  
Treatment Phase ◽  
Episodic Migraine ◽  
Double Blind Study ◽  
Open Label ◽  
Double Blind ◽  
Clinical Trial Registration

Objective To determine reversion rates from chronic migraine to episodic migraine during long-term erenumab treatment. Methods A daily headache diary was completed during the 12-week, double-blind treatment phase of a placebo-controlled trial comparing erenumab 70 mg, 140 mg, and placebo, and weeks 1–12, 21–24, 37–40, and 49–52 of the open-label treatment phase. Chronic migraine to episodic migraine reversion rates were assessed over the double-blind treatment phase; persistent reversion to episodic migraine over 24 weeks (double-blind treatment phase through the first 12 weeks in the open-label treatment phase), long-term persistent reversion to episodic migraine over 64 weeks (double-blind treatment phase plus open-label treatment phase); delayed reversion to episodic migraine through the first 12 weeks of the open-label treatment phase among patients remaining in chronic migraine during the double-blind treatment phase. Results In the double-blind treatment phase, 53.1% (95% confidence interval: 47.8–58.3) of 358 erenumab-treated completers had reversion to episodic migraine; monthly reversion rates to episodic migraine were typically higher among patients receiving 140 mg versus 70 mg. Among 181 completers (receiving erenumab for 64 weeks), 98 (54.1% [95% confidence interval: 46.6–61.6]) had reversion to episodic migraine during the double-blind treatment phase; of those, 96.9% (95% confidence interval: 91.3–99.4) had persistent reversion to episodic migraine, 96.8% (95% confidence interval: 91.1–99.3) of whom had long-term persistent reversion to episodic migraine. Delayed reversion to episodic migraine occurred in 36/83 (43.4% [95% confidence interval: 32.5–54.7]) patients; of these, 77.8% (95% confidence interval: 60.9–89.9) persisted in reversion through week 64. Conclusions Patients with reversion to episodic migraine at week 12 will likely persist as episodic migraine with longer-term erenumab; others may achieve delayed reversion to episodic migraine. Clinical trial registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02066415

scholarly journals Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine

Cephalalgia ◽  
2019 ◽  
Vol 39 (11) ◽  
pp. 1455-1464 ◽  
Author(s):  
Messoud Ashina ◽  
Peter J Goadsby ◽  
Uwe Reuter ◽  
Stephen Silberstein ◽  
David Dodick ◽  
...  
Keyword(s):  
Adverse Events ◽  
Vital Signs ◽  
Clinical Trial Data ◽  
Treatment Phase ◽  
Episodic Migraine ◽  
Upper Respiratory Tract ◽  
Open Label ◽  
Long Term Study ◽  
Open Label Extension

Background Previously published three-month placebo-controlled and one-year open-label clinical trial data have provided information on the efficacy and safety of erenumab. Methods Interim analysis was undertaken from an ongoing five-year open-label treatment phase after all patients completed three years in the open-label treatment phase or discontinued the study. Adult patients with episodic migraine enrolled in the open-label treatment phase initially received 70 mg erenumab monthly. A protocol amendment increased the dosage to 140 mg monthly to assess long-term safety of the higher dose. Safety and tolerability were assessed by monitoring adverse events, electrocardiograms, laboratory assessments, and vital signs. Results Of 383 patients enrolled in the open-label treatment phase, at data cutoff 235 (61.3%) remained in the study, all received 140 mg for ≥1 year. Median (Q1, Q3) exposure (70 or 140 mg) for all patients enrolled was 3.2 (1.3, 3.4) years. The most frequent adverse events (≥4.0/100 patient-years) were reported as viral upper respiratory tract infection, sinusitis, influenza, and back pain. Exposure-adjusted serious adverse event rates were 4.2/100 patient-years. There was no increase in cardiovascular events over time. Conclusions In this long-term study of a CGRP-receptor antibody, erenumab was found to be safe and well-tolerated with a spectrum and rate of adverse events consistent with shorter-term placebo-controlled studies. Trial registration ClinicalTrials.gov NCT01952574

scholarly journals Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001649
Author(s):  
John B Buse ◽  
Bruce W Bode ◽  
Ann Mertens ◽  
Young Min Cho ◽  
Erik Christiansen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Dose Adjustment ◽  
Main Phase ◽  
Open Label ◽  
Open Label Extension ◽  
Registration Number ◽  
Flexible Dose

IntroductionThe PIONEER 7 trial demonstrated superior glycemic control and weight loss with once-daily oral semaglutide with flexible dose adjustment versus sitagliptin 100 mg in type 2 diabetes. This 52-week extension evaluated long-term oral semaglutide treatment and switching from sitagliptin to oral semaglutide.Research design and methodsA 52-week, open-label extension commenced after the 52-week main phase. Patients on oral semaglutide in the main phase continued treatment (n=184; durability part); those on sitagliptin were rerandomized to continued sitagliptin (n=98) or oral semaglutide (n=100; initiated at 3 mg) (switch part). Oral semaglutide was dose-adjusted (3, 7, or 14 mg) every 8 weeks based on glycated hemoglobin (HbA1c) (target <7.0% (<53 mmol/mol)) and tolerability. Secondary endpoints (no primary) included changes in HbA1c and body weight.ResultsIn the durability part, mean (SD) changes in HbA1c and body weight from week 0 were –1.5% (0.8) and –1.3% (1.0) and –2.8 kg (3.8) and –3.7 kg (5.2) at weeks 52 and 104, respectively. In the switch part, mean changes in HbA1c from week 52 to week 104 were –0.2% for oral semaglutide and 0.1% for sitagliptin (difference –0.3% (95% CI –0.6 to 0.0); p=0.0791 (superiority not confirmed)). More patients achieved HbA1c <7.0% with oral semaglutide (52.6%) than sitagliptin (28.6%; p=0.0011) and fewer received rescue medication (9% vs 23.5%). Respective mean changes in body weight were –2.4 kg and –0.9 kg (difference –1.5 kg (95% CI –2.8 to –0.1); p=0.0321). Gastrointestinal adverse events were the most commonly reported with oral semaglutide.ConclusionsLong-term oral semaglutide with flexible dose adjustment maintained HbA1c reductions, with additional body weight reductions, and was well tolerated. Switching from sitagliptin to flexibly dosed oral semaglutide maintained HbA1c reductions, helped more patients achieve HbA1c targets with less use of additional glucose-lowering medication, and offers the potential for additional reductions in body weight.Trial registration numberNCT02849080.

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