Monthly Migraine Headache Research Articles

Galcanezumab in chronic migraine

ObjectiveTo evaluate the efficacy and safety of galcanezumab, a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide, in the preventive treatment of chronic migraine.MethodsA phase 3, randomized, double-blind, placebo-controlled study of LY2951742 in patients with chronic migraine (Evaluation of Galcanezumab in the Prevention of Chronic Migraine [REGAIN]) was a phase 3 study with a 3-month double-blind, placebo-controlled treatment phase and a 9-month open-label extension. Eligible patients 18 to 65 years of age with chronic migraine were randomized 2:1:1 to monthly subcutaneous injections of placebo (n = 558), galcanezumab 120 mg (with a 240-mg loading dose, n = 278), or galcanezumab 240 mg (n = 277). The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days (MHDs) during the 3-month double-blind treatment phase.ResultsMean number of monthly MHDs at baseline was 19.4 for the total sample. Both galcanezumab dose groups demonstrated greater overall mean reduction in the number of monthly MHDs compared to placebo (placebo −2.7, galcanezumab 120 mg −4.8, galcanezumab 240 mg −4.6) (p < 0.001 for each dose compared to placebo). There were no clinically meaningful differences between galcanezumab doses and placebo on any safety or tolerability outcome except for a higher incidence of treatment-emergent injection-site reaction (p < 0.01), injection-site erythema (p < 0.001), injection-site pruritus (p < 0.01), and sinusitis (p < 0.05) in the galcanezumab 240-mg group relative to placebo.ConclusionsBoth doses of galcanezumab were superior to placebo in reducing the number of monthly MHDs. Galcanezumab appears efficacious, safe, and well tolerated for the preventive treatment of chronic migraine.ClinicalTrials.gov identifierNCT02614261.Classification of evidenceThis interventional study provides Class I evidence that galcanezumab is superior to placebo in the reduction of the number of monthly MHDs.

A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine

BackgroundGalcanezumab, a humanized monoclonal antibody that selectively binds to the calcitonin gene-related peptide, has demonstrated in previous Phase 2 and Phase 3 clinical studies (≤6-month of treatment) a reduction in the number of migraine headache days and improved patients’ functioning. This study evaluated the safety and tolerability, as well as the effectiveness of galcanezumab for up to 12 months of treatment in patients with migraine.MethodsPatients diagnosed with episodic or chronic migraine, 18 to 65 years old, that were not exposed previously to galcanezumab, were randomized to receive galcanezumab 120 mg or 240 mg, administered subcutaneously once monthly for a year. Safety and tolerability were evaluated by frequency of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to study discontinuation. Laboratory values, vital signs, electrocardiograms, and suicidality were also analyzed. Additionally, overall change from baseline in the number of monthly migraine headache days, functioning, and disability were assessed.ResultsOne hundred thirty five patients were randomized to each galcanezumab dose group. The majority of patients were female (> 80%) and on average were 42 years old with 10.6 migraine headache days per month at baseline. 77.8% of the patients completed the open-label treatment phase, 3.7% of patients experienced an SAE, and 4.8% discontinued due to AEs. TEAEs with a frequency ≥ 10% of patients in either dose group were injection site pain, nasopharyngitis, upper respiratory tract infection, injection site reaction, back pain, and sinusitis. Laboratory values, vital signs, or electrocardiograms did not show anyclinically meaningful differences between galcanezumab dosesOverall mean reduction in monthly migraine headache days over 12 months for the galcanezumab dose groups were 5.6 (120 mg) and 6.5 (240 mg). Level of functioning was improved and headache-related disability was reduced in both dose groups.ConclusionTwelve months of treatment with self-administered injections of galcanezumab was safe and associated with a reduction in the number of monthly migraine headache days. Safety and tolerability of the 2 galcanezumab dosing regimens were comparable.Trial registrationClinicalTrials.gov as NCT02614287, posted November 15, 2015. These data were previously presented as a poster at the International Headache Congress 2017: PO-01-184, Late-Breaking s of the 2017 International Headache Congress. (2017). Cephalalgia, 37(1_suppl), 319–374.

Evaluation of Galcanezumab for the Prevention of Episodic Migraine

Migraine is a disabling neurological disease characterized by severe headache attacks. Treatment options reduce migraine frequency for many patients, but adverse effects lead to discontinuation in many patients. To demonstrate that galcanezumab is superior to placebo in the prevention of episodic migraine with or without aura. The EVOLVE-1 (Evaluation of LY2951742 in the Prevention of Episodic Migraine 1) trial was a double-blind, randomized, placebo-controlled (January 11, 2016, to March 22, 2017) trial comparing galcanezumab (120 mg and 240 mg) vs placebo. Patients received treatments once monthly for 6 months (subcutaneous injection via prefilled syringe) and were followed up for 5 months after their last injection. It was a multicenter, clinic-based study involving 90 sites in North America. Participants in the study were adults (aged 18 to 65 years) with at least a 1-year history of migraine, 4 to 14 migraine headache days per month and a mean of at least 2 migraine attacks per month within the past 3 months, and were diagnosed prior to age 50 years. During the study, no other preventive medications were allowed. A total of 1671 patients were assessed; 809 did not meet study entry or baseline criteria, and 858 were included in the intent-to-treat population. Patients were randomized (2:1:1) to monthly placebo, galcanezumab, 120 mg, and galcanezumab, 240 mg. The primary outcome was overall mean change from baseline in the number of monthly migraine headache days during the treatment period. Secondary measures included at least 50%, at least 75%, and 100% reduction in monthly migraine headache days, migraine headache days with acute medication use, and scores from the Migraine-Specific Quality of Life questionnaire, Patient Global Impression of Severity, and Migraine Disability Assessment. Treatment-emergent adverse events and serious adverse events were reported. Of the 1671 patients assessed, 858 (mean age, 40.7 years; 718 women [83.7%]) met study entry criteria and received at least 1 dose of investigational product. The primary objective was met for both galcanezumab doses; treatment with galcanezumab significantly reduced monthly migraine headache days (both P < .001) by 4.7 days (120 mg) and 4.6 days (240 mg) compared with placebo (2.8 days). All key secondary objectives were also significant after multiplicity adjustment. There were no meaningful differences between 120-mg and 240-mg doses of galcanezumab on measures of efficacy. Completion rate during treatment was high (81.9%; n = 718), and the incidence of discontinuation owing to adverse events was less than 5% across all treatment groups. Galcanezumab 120-mg and 240-mg monthly injections provided clinical benefits and improved functioning. The incidence rate of adverse events was low, demonstrating the favorable tolerability profile of galcanezumab. ClinicalTrials.gov Identifier: NCT02614183.

P010. OnabotulinumtoxinA for treatment of chronic migraine: results after 1 year of treatment.

OnabotulinumtoxinA (OnabotA) was approved for treatment of chronic migraine (CM) following the PREEMPT trials[1, 2], and was licensed in Italy in February 2013. Thus, in December 2013 we began to offer OnabotA to patients with CM who did not respond to other preventive therapy (mostly topiramate, beta blockers, amitriptyline and calcium channel antagonists). Demographic and migraine characteristics of patients were recorded, and changes in monthly migraine days and headache intensity (the latter variable was evaluated only after the first session of treatment), as well as, the number of symptomatic medications intake, were assessed. From December 2013, 40 patients (9 males, 31 females) were treated with at least four therapeutic sessions. Their mean age (± SD) at treatment onset was 51.3±12.6 years (range: 27-80). All the patients fulfilled the ICHD-III criteria for CM[3] and 28 (70%) were receiving other preventive therapy. In 34 of these patients (85%) overuse of symptomatic medications was observed at the onset of treatment. After obtaining an informed consent, we administered OnabotA according to the PREEMPT protocol (155 UI for a total of 31 injections divided across 7 head/neck muscles), performing no additional injections in the first session (from the second session we also adopted “follow the pain” protocol), and we gave the patients a paper diary to register the headache evolution. After one year of treatment we analyzed the data related to the 40 patients, observing positive results in all the variables considered. In particular, following 1-year treatment there was a reduction from 25.1±6.1 to 19.8±9.1 in the mean (± SD) number of monthly migraine days (reduction of 21%, p < 0.0001). The intake of symptomatic medications was reduced of about 12%, but the difference was not statistically significant. Most (78%) of the patients (n = 23) who had accurately registered the data reported that the greatest clinical benefit of OnabotA was the reduction in the headache intensity. Finally, no severe adverse event was observed, and mild pain in the injection site was the most reported experience. No patient discontinued the treatment because of side effects. We can conclude that the use of OnabotA according to the PREEMPT paradigm is an effective and well-tolerated treatment in patients with chronic migraine in a real-life setting. Written informed consent to publication was obtained from the patient(s).

Migraine preventive therapy with topiramate reduces the number of migraine auras: results from PROMPT, a randomised, placebo-controlled trial

Rationale: To evaluate topiramate efficacy for prevention of migraine aura's in addition to migraine headaches. Methods: After a 4–8-week baseline period, patients entered a 26-week open-label phase (OL); topiramate was titrated from 25 to 100mg/day in weekly 25-mg steps, and could be further adjusted (range: 50–200mg/day). Dosing was kept stable for the last 4 weeks, and patients were randomised to continue this dose (n=254) or switch to placebo (n=258) for 26 weeks in the double-blind phase (DB). Trial subjects recorded the occurrence of migraine auras with or without subsequent migraine headache in a diary. The number of monthly aura days was asssessed for subjects reporting an aura at least once troughout the study, and the change in monthly aura days versus baseline was calculated for the various visits. Results: 6-month treatment with topiramate was completed by 571/818 entered subjects (70%) who experienced a significant reduction in mean monthly migraine days from 8.86at start to 4.78at month-6 (mean change: -4.08 days; p<0.001)[1]. Migraine auras were reported by 269/818 entered subjects (33%) who experienced a significant reduction in mean monthly aura days from 3.01at start to 1.66at month-6 (mean change: -1.36 days; p<0.001). Topiramate was well tolerated and adverse events were consistent with those previously observed. Conclusion: Migraine preventive treatment with topiramate resulted in a reduction in monthly aura days similar to the reduction in monthly migraine headache days. Reference: Diener HC, et al. Lancet Neurology 2007;6:1054–62.