scholarly journals Shift from high-frequency to low-frequency episodic migraine in patients treated with Galcanezumab: results from two global randomized clinical trials

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jakub Jedynak ◽  
Eric Eross ◽  
Astrid Gendolla ◽  
Mallikarjuna Rettiganti ◽  
Virginia L. Stauffer
Keyword(s):  
Quality Of Life ◽  
Migraine Headache ◽  
Disease Burden ◽  
Randomized Clinical Trials ◽  
Low Frequency ◽  
Episodic Migraine ◽  
Double Blind ◽  
Link Type ◽  
Post Hoc

Abstract Background Patients with episodic migraine (EM) with a higher-frequency of migraine headache days (HFEM: 8–14 migraine headache days/month) have a greater disease burden and a higher risk of progressing to chronic migraine (CM) with associated acute treatment overuse versus those with low-frequency EM (LFEM: 4–7 migraine headache days/month). In this post hoc analysis, we assessed the proportions of patients who shifted from HFEM to LFEM and to very low-frequency EM (VLFEM: 0–3 migraine headache days/month) status following treatment with galcanezumab versus placebo. Methods EVOLVE-1 and EVOLVE-2 were double-blind, Phase 3 studies in patients with EM. Patients (18–65 years) were randomized (2:1:1) to subcutaneous monthly injections of placebo, galcanezumab 120 mg (240 mg loading dose) or 240 mg, for up to 6 months. Data were pooled and endpoints were change from baseline in number of migraine headache days/month and patients who shifted from HFEM to LFEM or VLFEM status. Impact of change in HFEM status on migraine headache days/month, quality of life and disability was also assessed. Results A total of 66% (1176/1773) patients from EVOLVE studies had HFEM status at baseline and were included in this analysis; placebo: 592, galcanezumab 120 mg: 294 and galcanezumab 240 mg: 290. At each month, both doses of galcanezumab resulted in a higher proportion of patients who shifted to 0–7 monthly headache days/month (VLFEM or LFEM status). Patients who shifted from HFEM at baseline to VLFEM status at Month 3, a relatively larger proportion of patients on galcanezumab 120 mg versus placebo remained at VLFEM status at Months 4–6; Months 4–5 for galcanezumab 240 mg versus placebo. Among the galcanezumab-treated patients who did-not-shift or shifted to LFEM or VLFEM status for ≥3 consecutive months until the end of the study, patients who shifted from HFEM to VLFEM status experienced the largest reduction in migraine headache days/month and the largest clinically meaningful improvements in daily functioning (MSQ-RFR) and disability (MIDAS). Conclusions In patients with HFEM, treatment with galcanezumab (120 mg and 240 mg) significantly reduced migraine headache days/month, maintained remission status at subsequent months until the end of the study, and improved patients’ quality of life versus placebo. Trial registration ClinicalTrials.gov Identifier: EVOLVE-1, NCT02614183; EVOLVE-2, NCT02614196.

scholarly journals Effect of galcanezumab on severity and symptoms of migraine in phase 3 trials in patients with episodic or chronic migraine

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Michael Ament ◽  
Kathleen Day ◽  
Virginia L Stauffer ◽  
Vladimir Skljarevski ◽  
Mallikarjuna Rettiganti ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Migraine Headache ◽  
Randomized Clinical Trials ◽  
Episodic Migraine ◽  
Double Blind Study ◽  
Double Blind ◽  
Prodromal Symptoms ◽  
Link Type ◽  
Associated Symptoms ◽  
Severe Migraine

Abstract Background Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days compared with placebo. Here, we analyze data from 3 randomized clinical trials (2 episodic trials [EVOLVE-1, EVOLVE-2] and 1 chronic trial [REGAIN]), to examine if galcanezumab also alleviates the severity and symptoms of migraine. Methods The episodic migraine trials were 6-month, double-blind studies in patients with episodic migraine (4–14 monthly migraine headache days). The chronic migraine trial was a 3-month, double-blind study in patients with chronic migraine (≥ 15 headache days per month, where ≥ 8 met criteria for migraine). Patients (18–65 years) were randomized to placebo or galcanezumab 120 mg with a 240-mg loading dose or 240 mg. Patients recorded headache characteristics, duration, severity, and presence of associated symptoms with each headache. The outcomes analyzed were changes from baseline in number of monthly migraine headache days with nausea and/or vomiting, photophobia and phonophobia, aura, and prodromal symptoms other than aura. Additional outcomes analyzed included the number of moderate-to-severe monthly migraine headache days, number of severe migraine headache days, and mean severity of remaining migraine headache days. Change from baseline in the proportion of days with nausea and/or vomiting and the proportion of days with photophobia and phonophobia among the remaining monthly migraine headache days were also analyzed. Results Galcanezumab was superior to placebo in reducing the frequency of migraine headache days with associated symptoms of migraine such as nausea and/or vomiting, photophobia and phonophobia, and prodromal symptoms. Galcanezumab reduced the frequency of migraine headache days with aura in the episodic migraine studies. There was a significant reduction in the proportion of remaining migraine headache days with nausea and/or vomiting for the episodic and chronic migraine studies, and with photophobia and phonophobia for the episodic migraine studies. Galcanezumab was superior to placebo in reducing the number of monthly moderate-to-severe migraine headache days and the overall and monthly severe migraine headache days. Conclusions Galcanezumab reduces the frequency of migraine headache days and can alleviate potentially disabling non-pain symptoms on days when migraine is present in patients with episodic or chronic migraine. Trial registration NCT, NCT02614183 (EVOLVE-1), registered 25 November 2015; NCT, NCT02614196, (EVOLVE-2), registered 25 November 2015; NCT, NCT02614261 (REGAIN), registered 25 November 2015.

Migraine-related disability, impact, and health-related quality of life among patients with episodic migraine receiving preventive treatment with erenumab

Cephalalgia ◽  
2018 ◽  
Vol 38 (10) ◽  
pp. 1622-1631 ◽  
Author(s):  
Dawn C Buse ◽  
Richard B Lipton ◽  
Yngve Hallström ◽  
Uwe Reuter ◽  
Stewart J Tepper ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Impact Test ◽  
Episodic Migraine ◽  
Health Related Quality ◽  
Double Blind ◽  
Related Quality ◽  
Health Related ◽  
Headache Impact ◽  
Assessment Questionnaire

Background We evaluated the effect of erenumab, a fully human monoclonal antibody that inhibits the canonical calcitonin gene-related peptide receptor, on migraine-related disability, impact, and health-related quality of life among patients with episodic migraine. Methods Patients enrolled in a phase 3, 6-month, double-blind, placebo-controlled study of once-monthly erenumab 70 and 140 mg for migraine prevention (STRIVE) used an eDiary during the baseline and double-blind treatment phases to complete validated, specific questionnaires, including the modified (monthly) Migraine Disability Assessment Questionnaire; Headache Impact Test; and Migraine-Specific Quality of Life Questionnaire-role function-restrictive (MSQ-RFR), -role function-preventive (MSQ-RFP), and -emotional function (MSQ-EF). Results A total of 955 patients were randomized to receive erenumab 70 mg (n = 317), erenumab 140 mg (n = 319), or placebo (n = 319). Erenumab versus placebo resulted in significantly greater improvements in all patient-reported outcomes; changes from baseline were numerically higher with 140 mg erenumab. Improvements occurred rapidly and were maintained over 6 months of treatment. Between-group differences from placebo over months 4–6 for the 70- and 140-mg dose groups were, respectively, −2.1 and −2.8 for modified (monthly) Migraine Disability Assessment Questionnaire, −2.1 and −2.3 for Headache Impact Test, 5.1 and 6.5 for MSQ-RFR, 4.2 and 5.4 for MSQ-RFP, and 5.2 and 6.7 for MSQ-EF ( p < 0.001 for all). Erenumab also significantly reduced the proportion of patients with severe and very severe migraine-related disability and increased the proportion of patients with clinically meaningful improvements in migraine-related impact and health-related quality of life. Conclusion Erenumab reduced migraine disability and impact and improved patients’ health-related quality of life, reinforcing its role as a promising new therapy for migraine prevention.

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.

scholarly journals Onset of efficacy and duration of response of galcanezumab for the prevention of episodic migraine: a post-hoc analysis

2019 ◽  
Vol 90 (8) ◽  
pp. 939-944 ◽  
Author(s):  
Peter J Goadsby ◽  
David W Dodick ◽  
James M Martinez ◽  
Margaret B Ferguson ◽  
Tina M Oakes ◽  
...  
Keyword(s):  
Migraine Headache ◽  
Episodic Migraine ◽  
Preventive Effect ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Hoc Analysis ◽  
Duration Of Response ◽  
Registration Number ◽  
Post Hoc ◽  
Sustained Responses

Background and objectiveAs new migraine prevention treatments are developed, the onset of a preventive effect, how long it is maintained and whether patients initially non-responsive develop clinically meaningful responses with continued treatment can be assessed.MethodsAnalyses were conducted post-hoc of a double-blind, placebo-controlled, phase II-a study in patients with episodic migraine receiving galcanezumab 150 mg or placebo biweekly for 12 weeks (Lancet Neurol 13:885, 2014). The number of migraine headache days per week, and onset of efficacy measured as the first week galacanezumab separated from placebo were determined. Patients with ≥50%, ≥75% and 100% reduction in migraine headache days from baseline at months 1, 2 and 3 were calculated and defined as sustained responses. Non-responders (<50% response) at month 1 or 2 who then showed ≥50%, ≥75% and 100% response at later time-points were calculated.ResultsPatients were randomised to galcanezumab (n=107) or placebo (n=110). A significant (p=0.018) change of −0.89±0.11 (galcanezumab) vs −0.53±0.11 (placebo) migraine headache days indicated onset at week 1. Forty-seven per cent of galcanezumab and 25% of placebo patients responding at month 1 maintained response through months 2 and 3. Of non-responders at month 1, 27% on galcanezumab and 20% on placebo responded on months 2 and 3, and 50% of galcanezumab non-responders in months 1 and 2 responded on month 3, vs 24% on placebo.ConclusionsThe onset of efficacy of galcanezumab is within 1 week in a majority of patients, and patients receiving galcanezumab are twice more likely to maintain responses than placebo patients. Early non-responders may respond by month 2 or month 3.Trial registration numberNCT01625988.

scholarly journals Efficacy of galcanezumab in patients with migraine and history of failure to 3–4 preventive medication categories: subgroup analysis from CONQUER study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Rose Okonkwo ◽  
Antje Tockhorn-Heidenreich ◽  
Chad Stroud ◽  
Marie-Ange Paget ◽  
Manjit S. Matharu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Subgroup Analysis ◽  
Migraine Headache ◽  
Response Rate ◽  
Maximum Tolerated Dose ◽  
Episodic Migraine ◽  
Patient Functioning ◽  
Preventive Medication ◽  
History Of

Abstract Background Chronic migraine (CM) and episodic migraine (EM) are associated with substantial headache-related disability, poor quality of life and global societal burden. In this subgroup analysis from the CONQUER study, we report efficacy outcomes from a pre-specified analysis of galcanezumab versus placebo in patients with CM or EM and 3–4 prior preventive medication category failures due to inadequate efficacy (after at least 2 months at maximum tolerated dose), or safety or tolerability reasons. The patient population is of particular interest due to evidence of decreased quality of life and increased economic burden among patients with migraine that is inadequately managed and is of interest to decision-makers globally. Methods Key outcomes included overall mean change from baseline in monthly migraine headache days and proportions of patients achieving ≥30% (CM), ≥50%, and ≥ 75% reduction (response rates) in monthly migraine headache days across Months 1–3. Patient functioning and disability were evaluated at Month 3. Results Of the 462 randomized patients, 186 (40.3%) had a history of 3–4 preventive category failures. Galcanezumab versus placebo resulted in significantly (P ≤ .001) larger overall mean reduction in monthly migraine headache days (total: − 5.49 versus − 1.03; CM: − 6.70 versus − 1.56; EM: − 3.64 versus − 0.65). Similarly, the ≥50% response rate was significantly (P ≤ .001) higher with galcanezumab versus placebo (total: 41.0 versus 12.7; CM: 41.5 versus 8.4; EM: 41.1 versus 16.5). In the CM group, the ≥30% response rate was significantly higher in the galcanezumab group than the placebo group (CM, 57.5 versus 19.8, P ≤ .0001) as was the ≥75% response rate (13.3 versus 2.6, P ≤ .05). Galcanezumab also resulted in significant (P < .0001) improvements in patient functioning and reductions in disability. Conclusions Galcanezumab was effective in a difficult-to-treat population of patients with CM or EM who had failed 3–4 prior preventive medication categories. Trial registration CONQUER. Clinicaltrials.gov identifier: NCT03559257.

Disability, burden, and symptoms related to sensitization in migraine patients associate with headache frequency

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Stefano Di Antonio ◽  
Matteo Castaldo ◽  
Marta Ponzano ◽  
Francesca Bovis ◽  
Paola Torelli ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Migraine ◽  
High Frequency ◽  
Low Frequency ◽  
Episodic Migraine ◽  
Headache Frequency ◽  
Headache Attack ◽  
Burden Of Headache ◽  
The Difference

Abstract Objectives This observational study aimed to assess the difference in disability, burden, and sensitization between migraine patients with low-frequency headache attack (1–8 headache days/month), high-frequency headache attack (9–14 headache days/months), and patients with chronic migraine (>14 headache days/months). Methods Migraine patients with or without aura were divided into three groups according to headache frequency (low-frequency episodic migraine; high-frequency episodic migraine; chronic migraine). Questionnaires were used to assess the burden of headache, quality of life, phycological burden, and symptoms related to sensitization (estimated by the Central Sensitization Inventory). Differences among migraine groups were assessed using Chi-Quadro test, ANOVA, or Kruskal–Wallis as appropriate. Results 136 patients were included (68 low-frequency episodic migraine, 45 high-frequency episodic migraine, 23 chronic migraine). Patients with high frequency episodic migraine and chronic migraine differed from patients with low frequency episodic migraine showing a worse burden of headache (p=0.002; p=0.002), worse level of physical (p=0.001; p<0.001) and mental (p=0.002; p=0.001) quality of life, worse level of depression (p=0.008; p=0.003), and increase presence of symptoms related to sensitization (p<0.001; p=0.003). No differences were found in any variables between patients with high-frequency episodic migraine and patients with chronic migraine (p>0.05). Conclusions Patients with high-frequency episodic migraine and chronic migraine could be considered in the same segment of the migraine population, with similar degrees of disability and sensitization related symptoms.

scholarly journals Chinese phytotherapy to reduce stress, anxiety and improve quality of life: randomized controlled trial

2016 ◽  
Vol 50 (5) ◽  
pp. 853-860 ◽  
Author(s):  
Leonice Fumiko Sato Kurebayashi ◽  
Ruth Natalia Teresa Turrini ◽  
Gisele Kuba ◽  
Miki Hoshi Minamizawa Shimizu ◽  
Raymond Sehiji Takiguch
Keyword(s):  
Quality Of Life ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Improve Quality ◽  
Double Blind ◽  
Randomized Controlled ◽  
Stress Levels ◽  
The Difference ◽  
Post Hoc

Abstract OBJECTIVE To evaluate the effect of Chinese phytotherapyto reduce stress levels, anxiety and improve quality of life. METHOD double-blind randomized controlled trial with 89 volunteers divided into three groups: control (no intervention), Placebo and Phytotherapy. The study was conducted in 2015 with healthy adults treated at the Integrated and Eastern Therapy Institute,in Sao Paulo, Brazil. Participants were evaluated at baseline and after three weeks with the Stress Symptoms List (SSL), Anxiety Inventory-Trait and State and SF12v2 for quality of life. Intervention groups received a placebo or Gan May Zao formula (GMDZ)flaskwith 50 ml. RESULTS According to ANOVA, there were significant differences (p = 0.025) after treatment of stress (SSL2). And the difference was between control and Phytotherapy groups, according to the Tukey post hoc (p = 0.022). There were no differences in the levels of state-anxiety and physical and mental domains in the SF12v2. CONCLUSION The GMDZ formula reduced stress levels, but more studies are needed with greater sample, with reassessment of dosage and a longer period of treatment to confirm and extend the results. Brazilian Registry of Clinical Trials: RBR-28s4hz.

scholarly journals Preventive effect of oral magnesium in postmastectomy pain: protocol for a randomised, double-blind, controlled clinical trial

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e017986 ◽  
Author(s):  
Véronique Morel ◽  
Dominique Joly ◽  
Christine Villatte ◽  
Bruno Pereira ◽  
Gisèle Pickering
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Clinical Trial ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Preventive Effect ◽  
Double Blind ◽  
Link Type ◽  
Oral Magnesium

IntroductionBreast cancer affects 1 in 10 women worldwide, and mastectomy is a cause of chronic pain with neuropathic characteristics.N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine, memantine, dextromethorphan or magnesium are used to treat refractory pain by blocking NMDAR. Oral memantine has been shown to prevent postmastectomy pain and cognitive impact and to maintain quality of life. Likewise, the present study is intended to assess the preventive effect of oral magnesium, administered ahead of mastectomy, on the development of neuropathic pain. As a physiological blocker of NMDAR, magnesium could be an interesting candidate to prevent postoperative pain and associated comorbidities, including cognitive and emotional disorders, multiple analgesic consumption and impaired quality of life.Methods and analysisA randomised double-blind controlled clinical trial (NCT03063931) will include 100 women with breast cancer undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France. Magnesium (100 mg/day; n=50) or placebo (n=50) will be administered for 6 weeks, starting 2 weeks before surgery. Intensity of pain, cognitive and emotional function and quality of life will be assessed by questionnaires. The primary endpoint is pain intensity on a 0–10 numerical rating scale at 1 month postmastectomy. Data analysis will use mixed models; all tests will be two-tailed, with type-I error set at α=0.05.Ethics and disseminationThe study protocol and informed consent form were approved in December 2016 by the French Research Ethics Committee (South East VI Committee). Results will be communicated in various congresses and published in international publications.Trial registration numberNCT03063931.

scholarly journals Study protocol of a randomized, double-blind, placebo-controlled, multi-center trial to treat antipsychotic-induced weight gain: the Metformin-Lifestyle in antipsychotic users (MELIA) trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nini de Boer ◽  
Sinan Guloksuz ◽  
Caroline van Baal ◽  
Leonie Willebrands ◽  
Jeroen Deenik ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Body Weight ◽  
Weight Gain ◽  
Lifestyle Intervention ◽  
Pragmatic Trial ◽  
Secondary Outcome ◽  
Double Blind ◽  
Major Health Problem ◽  
Link Type

Abstract Background Antipsychotic-induced Weight Gain (AiWG) is a debilitating and common adverse effect of antipsychotics. AiWG negatively impacts life expectancy, quality of life, treatment adherence, likelihood of developing type-2 diabetes and readmission. Treatment of AiWG is currently challenging, and there is no consensus on the optimal management strategy. In this study, we aim to evaluate the use of metformin for the treatment of AiWG by comparing metformin with placebo in those receiving treatment as usual, which includes a lifestyle intervention. Methods In this randomized, double-blind, multicenter, placebo-controlled, pragmatic trial with a follow-up of 52 weeks, we aim to include 256 overweight participants (Body Mass Index (BMI) > 25 kg/m2) of at least 16 years of age. Patients are eligible if they have been diagnosed with schizophrenia spectrum disorder and if they have been using an antipsychotic for at least three months. Participants will be randomized with a 1:1 allocation to placebo or metformin, and will be treated for a total of 26 weeks. Metformin will be started at 500 mg b.i.d. and escalated to 1000 mg b.i.d. 2 weeks thereafter (up to a maximum of 2000 mg daily). In addition, all participants will undergo a lifestyle intervention as part of the usual treatment consisting of a combination of an exercise program and dietary consultations. The primary outcome measure is difference in body weight as a continuous trait between the two arms from treatment inception until 26 weeks of treatment, compared to baseline. Secondary outcome measures include: 1) Any element of metabolic syndrome (MetS); 2) Response, defined as ≥5% body weight loss at 26 weeks relative to treatment inception; 3) Quality of life; 4) General mental and physical health; and 5) Cost-effectiveness. Finally, we aim to assess whether genetic liability to BMI and MetS may help estimate the amount of weight reduction following initiation of metformin treatment. Discussion The pragmatic design of the current trial allows for a comparison of the efficacy and safety of metformin in combination with a lifestyle intervention in the treatment of AiWG, facilitating the development of guidelines on the interventions for this major health problem. Trial registration This trial was registered in the Netherlands Trial Register (NTR) at https://www.trialregister.nl/trial/8440 as NTR NL8840 on March 8, 2020.

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