Egilius L. H. Spierings

Precipitating and Aggravating Factors of Migraine Versus Tension-type Headache

Objective.—We conducted the present study to determine whether there are headache precipitating and aggravating factors that differentiate migraine from tension‐type headache and headache precipitating and aggravating factors that differentiate tension‐type headache from migraine.

“Hemicrania Continua”: Another Headache Absolutely Responsive to Indomethacin:

Two cases suffering from a headache apparently at variance with well recognized headaches are described. It is characterized by a steady, non-paroxysmal, probably severe to moderately severe hemicrania localized anteriorly or anteroposteriorly and is not associated with nausea. Indomethacin exerts an absolute, persistent and clearly dose-dependent effect on this headache, which differs from unilateral headache syndromes such as cluster headache and cervicogenic headache in its temporal pattern and indomethacin response. It differs from chronic paroxysmal hemicrania in its temporal pattern and in the lack of accompanying symptoms.

Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study

BACKGROUND Migraine remains poorly treated, with few effective preventive drugs available. We assessed the safety and efficacy of LY2951742, a fully humanised monoclonal antibody to calcitonin gene-related peptide, for migraine prevention. METHODS We did a randomised, double-blind, placebo-controlled, phase 2 proof-of-concept study at 35 centres in the USA. Patients aged 18-65 years with four to 14 migraine headache days per month were randomly assigned (1:1) to LY2951742 or placebo by a computerised randomisation scheme. LY2951742 (150 mg) or placebo were given as a subcutaneous injection once every 2 weeks for 12 weeks. The primary endpoint was the mean change in number of migraine headache days per 28-day period assessed at 9-12 weeks. Safety was assessed over 24 weeks, including the 12-week treatment period and the subsequent 12 weeks after study drug administration. Patients and treating investigators were masked to treatment allocation. Analyses were by intention to treat. A mixed-effects model of repeated measures was used, including patient baseline value, treatment, visit, and treatment-by-visit interaction as fixed effects, and patients as random effects. Safety measures were analysed according to the treatment received. This study has been completed and is registered with ClinicalTrials.gov, NCT01625988. FINDINGS Between July 31, 2012, and Sept 18, 2013, 218 patients were randomly assigned to LY2951742 (n=108, but one patient withdrew before treatment) or placebo (n=110). The mean change from baseline to week 12 in the number of migraine headache days was -4·2 (SD 3·1; 62·5% decrease) in the LY2951742 group compared with -3·0 (SD 3·0; 42·3% decrease) in the placebo group (least-squares mean difference -1·2, 90% CI -1·9 to -0·6; p=0·0030). Adverse events that occurred more frequently with LY2951742 than with placebo included injection site pain, erythema, or both (21 [20%] of 107 vs seven [6%] of 110), upper respiratory tract infections (18 [17%] vs ten [9%]), and abdominal pain (six [6%] vs three [3%]). There were two serious adverse events reported in the treatment arm and four in the placebo arm, none of which were deemed to be related to the study drug. INTERPRETATION These results provide preliminary evidence that LY2951742 might be beneficial in migraine prevention and provide support for the role of calcitonin gene-related peptide in the pathogenesis of migraine. Further controlled studies are needed to assess the safety and efficacy of monoclonal calcitonin gene-related peptide antibodies for the preventive treatment of migraine. FUNDING Arteaus Therapeutics.

OnabotulinumtoxinA for Treatment of Chronic Migraine: Pooled Analyses of the 56-Week PREEMPT Clinical Program

Objective.— To evaluate safety and efficacy of onabotulinumtoxinA (BOTOX®) as headache prophylaxis in adults with chronic migraine.

tDCS-Induced Analgesia and Electrical Fields in Pain-Related Neural Networks in Chronic Migraine

Objective.— We investigated in a sham‐controlled trial the analgesic effects of a 4‐week treatment of transcranial direct current stimulation (tDCS) over the primary motor cortex in chronic migraine. In addition, using a high‐resolution tDCS computational model, we analyzed the current flow (electric field) through brain regions associated with pain perception and modulation.

Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study

BACKGROUND Benefits of calcitonin-gene related peptide (CGRP) inhibition have not been established in chronic migraine. Here we assess the safety, tolerability, and efficacy of two doses of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of chronic migraine. METHODS In this multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel-group phase 2b study, we enrolled men and women (aged 18-65 years) from 62 sites in the USA who had chronic migraine. Using a randomisation list generated by a central computerised system and an interactive web response system, we randomly assigned patients (1:1:1, stratified by sex and use of concomitant preventive drugs) to three 28-day treatment cycles of subcutaneous TEV-48125 675/225 mg (675 mg in the first treatment cycle and 225 mg in the second and third treatment cycles), TEV-48125 900 mg (900 mg in all three treatment cycles), or placebo. Investigators, patients, and the funder were blinded to treatment allocation. Daily headache information was captured using an electronic diary. Primary endpoints were change from baseline in the number of headache-hours during the third treatment cycle (weeks 9-12) and safety and tolerability during the study. Secondary endpoint was change in the number of moderate or severe headache-days in weeks 9-12 relative to baseline. Efficacy endpoints were analysed for the intention-to-treat population. Safety and tolerability were analysed using descriptive statistics. This trial is registered with ClinicalTrials.gov, number, NCT02021773. FINDINGS Between Jan 8, 2014, and Aug 27, 2014, we enrolled 264 participants: 89 were randomly assigned to receive placebo, 88 to receive 675/225 mg TEV-48125, and 87 to receive 900 mg TEV-48125. The mean change from baseline in number of headache-hours during weeks 9-12 was -59.84 h (SD 80.38) in the 675/225 mg group and -67.51 h (79.37) in the 900 mg group, compared with -37.10 h (79.44) in the placebo group. The least square mean difference in the reduction of headache-hours between the placebo and 675/225 mg dose groups was -22.74 h (95% CI -44.28 to -1.21; p=0.0386), whereas the difference between placebo and 900 mg dose groups was -30.41 h (-51.88 to -8.95; p=0.0057). Adverse events were reported by 36 (40%) patients in the placebo group, 47 (53%) patients in the 675/225 mg dose group, and 41 (47%) patients in the 900 mg dose group, whereas treatment-related adverse events were recorded in 15 (17%) patients, 25 (29%) patients, and 28 (32%) patients, respectively. The most common adverse events were mild injection-site pain and pruritus. Four (1%) patients had serious non-treatment-related adverse events (one patient in the placebo group, one patient in the 675/225 mg group, and two patients in the 900 mg group); no treatment-related adverse events were serious and there were no relevant changes in blood pressure or other vital signs. INTERPRETATION TEV-48125 given by subcutaneous injection every 28 days seems to be tolerable and effective, thus supporting the further development of TEV-48125 for the preventive treatment of chronic migraine in a phase 3 trial. FUNDING Teva Pharmaceuticals.

Prophylactic treatment of cluster headache with verapamil

SYNOPSIS

Eletriptan in acute migraine: A double-blind, placebo-controlled comparison to sumatriptan

Objective: To compare the efficacy, safety, and tolerability of oral eletriptan (20 mg, 40 mg, and 80 mg) with that of oral sumatriptan (100 mg) and placebo for the acute treatment of migraine. Background: Eletriptan is a potent and selective agonist at human recombinant 5HT 1B/1D receptors, with efficacy in animal models that predict antimigraine activity. In healthy volunteers, the pharmacokinetics of eletriptan are characterized by linear and rapid oral absorption. Methods: Randomized, double-blind, parallel-group study conducted in 857 outpatients with a diagnosis of migraine according to the International Headache Society (IHS) criteria. Of these, 692 took study medication for one acute migraine attack and provided on-drug efficacy data. Subjects received either placebo, 100 mg of sumatriptan or 20 mg, 40 mg, or 80 mg of eletriptan for the treatment of an acute migraine attack. The primary endpoint was the percentage of patients with a headache response (improvement in pain intensity from moderate or severe to mild or none) at 2 hours after treatment. Results: At the primary endpoint (2 hours after dosing), headache response rates were 24% (30/126) for placebo; 55% (63/115) for sumatriptan, 100 mg; 54% (70/129) for eletriptan, 20 mg; 65% (76/117) for eletriptan, 40 mg; and 77% (91/118) for eletriptan, 80 mg. There was a difference compared with placebo ( p p p p Conclusion: In this placebo-controlled trial, eletriptan, at selected doses, demonstrated superior efficacy, onset of action and patient acceptability in the acute treatment of migraine when compared with oral sumatriptan and placebo.

Naratriptan efficacy in migraineurs who respond poorly to oral sumatriptan.

Objectives.—To determine whether 347 patients would respond to a 50‐mg oral dose of sumatriptan, even though they considered themselves poor responders to this acute therapy for migraine, and to investigate whether oral naratriptan can be an effective acute therapy for migraine in the subset of patients who did not respond to sumatriptan under double‐blind, well‐controlled conditions.

A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee

Summary Tanezumab is efficacious in a phase III clinical trial of patients with moderate to severe osteoarthritis pain of the hip or knee. ABSTRACT Tanezumab is a humanized monoclonal antinerve growth factor antibody in development for treatment of chronic pain. In a phase III, placebo‐ and active‐controlled study, we investigated the efficacy and safety of tanezumab for osteoarthritis (OA) hip or knee pain. Patients (N = 610) received up to 2 doses of intravenous tanezumab (5 or 10 mg in 8‐week intervals), controlled‐release oral oxycodone (10 to 40 mg every 12 hours), or placebo. The primary endpoint was mean change from baseline to week 8 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain score for tanezumab versus placebo and oxycodone. Secondary endpoints included change from baseline in WOMAC Physical Function and Stiffness scores, Patients Global Assessment (PGA) of OA, and patient response, defined as ≥30%, ≥50%, ≥70%, and ≥90% improvement from baseline in WOMAC Pain score. Tolerability and safety also were assessed. Both tanezumab groups demonstrated significant improvements in WOMAC Pain score versus placebo (P < .001) and oxycodone (P ≤ .018). Tanezumab also provided significant improvements versus placebo and oxycodone for WOMAC Physical Function and Stiffness scores and PGA of OA (P ≤ .002 for all) at week 8. For all analyses, oxycodone did not differ from placebo. Adverse event frequency was higher with oxycodone (63.3%) than tanezumab (40.7% to 44.7%) or placebo (35.5%); serious adverse event frequency was similar among treatments. The adverse event profile for tanezumab was similar to previous tanezumab studies. Results indicate that tanezumab is efficacious in the treatment of OA pain; no new safety signals were identified.