Trial of Galcanezumab in Prevention of Episodic Cluster Headache

Goadsby, PJ; Dodick, David W.; Leone, Massimo; Bardos, Jennifer; Oakes, Tina M.; Millen, Brian A.; Zhou, Chunmei; Dowsett, Sherie A.; Aurora, Sheena K.; Ahn, Andrew H.; Yang, Jyun Yan; Conley, Robert R.; Martinez, J. Michael

doi:10.1056/nejmoa1813440

Cited by 187 publications

(221 citation statements)

References 39 publications

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“…Among these, 7 studies were found to be directly related to our study, but one ongoing clinical trial on chronic cluster headache (NCT02438826) was excluded because the trial did not reach its primary endpoint. Lastly, 3889 patients from 6 multi-centered double blinded trials [14][15][16][17][18][19], one open-labeled clinical trial [20] were pooled. Among them, 6 trails focused on chronic and/or episodic migraine, and one trial on episodic cluster headache.…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

“…Three of the seven studies are at high risk of attrition bias [15,18,20] which can be explained by a relatively high discontinue rate related to prolonged experiment period [15,20] and high proportion of discontinue in placebo group due to lack of efficacy [18]. One study is at high risk of selection bias [20].…”

Section: Quality Assessmentmentioning

confidence: 99%

“…For decades, CGRP is considered a promising target for treatment of migraine and cluster headache. Previous clinical trials have supported the use of CGRP monoclonal antibodies as a preventive treatment for migraine and episodic cluster headache [14][15][16][17][18][19][20]. The development of drugs that targets to CGRP has become a successful translation from bench to clinic [10].…”

Section: Introductionmentioning

confidence: 99%

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Different doses of galcanezumab versus placebo in patients with migraine and cluster headache: a meta-analysis of randomized controlled trials

et al. 2020

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Background: Galcanezumab is a novel monoclonal antibody that target to calcitonin gene-related peptide (CGRP). It has been tested for the preventive treatment of migraine and episodic cluster headache by multiple randomized clinical trials (RCTs) and have been found to reduce headache frequency. Methods:We systematically searched PubMed and Embase on Cochrane Central Register of Controlled Trials (CENTRAL) from the earliest date to August 1, 2019. Relative risk (RR) and weighted mean difference (WMD) were used to evaluate clinical outcomes.Results: Seven studies were pooled with 3889 patients. Subcutaneous injection of Galcanezumab at 120 mg, 240 mg leads to a statistically significant response rate for the treatment of migraine compared with placebo (120 mg: RR = 1.51; 95% CI, 1.33 to 1.70; P < 0.001; 240 mg: RR = 1.58; 95% CI, 1.43 to 1.76; P < 0.001). Among them, 120 mg group has the same treatment efficacy with 240 mg group (50% response: RR = 1.06; 95% CI, 0.92 to 1.22; P = 0.425; 75% response: RR = 1.07; 95% CI, 0.94 to 1.23; P = 0.301; 100% response; RR = 1.06; 95% CI, 0.81 to 1.37; P = 0.682; MHD: RR = − 0.08; 95% CI, − 0.55 to − 0.40; P = 0.748) while related to a lower risk for adverse events for the treatment of migraine (120 mg RR = 1.06; 95% CI, 0.99 to 1.14; P = 0.084; 240 mg: RR = 1.17; 95% CI, 1.09 to 1.25; P < 0.001). 300 mg per month galcanezumab is effective for the prevention of episodic cluster headache measured by at least 50% reduction of cluster headache frequency at week 3 (RR = 1.36; 95% CI, 1.00-1.84; P = 0.048).Conclusions: Use of galcanezumab is related to a significantly reduced monthly headache frequency compared with placebo for the treatment of migraine and episodic cluster headache, 120 mg has the same treatment efficacy with 240 mg group while related to a lower risk for adverse effects for the treatment of migraine. 300 mg per month galcanezumab is effective for the prevention of episodic cluster headache with no significantly increased adverse events.

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Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Section: Quality Assessmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Different doses of galcanezumab versus placebo in patients with migraine and cluster headache: a meta-analysis of randomized controlled trials

et al. 2020

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“…19 Given that for cluster headache, the central origin of the attack is even more evident than for migraine, 20 these clinical findings further confute the peripheral theory. Very recent evidence demonstrates that the antibody dosed once monthly at 300 mg reduces cluster headache attack frequency without evidence that only the pain component is prevented.…”

mentioning

confidence: 97%

“…Reportedly, the BBB evolved to keep large circulating proteins from entering the brain and is therefore impermeable to antibodies. To answer this question, we may take advantage of a recent contribution 31 evaluating the pharmacokinetics of galcanezumab in different tissues of rats receiving a dose of 4 mg/kg that corresponds to the loading dose adopted in migraine 31 or cluster headache 19 patients. 23 However, the BBB impermeability to antibodies is not absolute, and systemically delivered antibodies can prompt functionally relevant pharmacodynamic effects in the brain.…”

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confidence: 99%

A Popperian View on Anti‐CGRP Biologics in Migraine

Chiarugi

2019

Headache

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Diagnosis and Management of Headache

Robbins

2021

JAMA

118

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IMPORTANCE Approximately 90% of people in the US experience headache during their lifetime. Migraine is the second leading cause of years lived with disability worldwide.OBSERVATIONS Primary headache disorders are defined as headaches that are unrelated to an underlying medical condition and are categorized into 4 groups: migraine, tension-type headache, trigeminal autonomic cephalalgias, and other primary headache disorders. Studies evaluating prevalence in more than 100 000 people reported that tension-type headache affected 38% of the population, while migraine affected 12% and was the most disabling. Secondary headache disorders are defined as headaches due to an underlying medical condition and are classified according to whether they are due to vascular, neoplastic, infectious, or intracranial pressure/volume causes. Patients presenting with headache should be evaluated to determine whether their headache is most likely a primary or a secondary headache disorder. They should be evaluated for symptoms or signs that suggest an urgent medical problem such as an abrupt onset, neurologic signs, age 50 years and older, presence of cancer or immunosuppression, and provocation by physical activities or postural changes. Acute migraine treatment includes acetaminophen, nonsteroidal anti-inflammatory drugs, and combination products that include caffeine. Patients not responsive to these treatments may require migraine-specific treatments including triptans (5-HT 1B/D agonists), which eliminate pain in 20% to 30% of patients by 2 hours, but are accompanied by adverse effects such as transient flushing, tightness, or tingling in the upper body in 25% of patients. Patients with or at high risk for cardiovascular disease should avoid triptans because of vasoconstrictive properties. Acute treatments with gepants, antagonists to receptors for the inflammatory neuropeptide calcitonin gene-related peptide, such as rimegepant or ubrogepant, can eliminate headache symptoms for 2 hours in 20% of patients but have adverse effects of nausea and dry mouth in 1% to 4% of patients. A 5-HT 1F agonist, lasmiditan, is also available for acute migraine treatment and appears safe in patients with cardiovascular risk factors. Preventive treatments include antihypertensives, antiepileptics, antidepressants, calcitonin gene-related peptide monoclonal antibodies, and onabotulinumtoxinA, which reduce migraine by 1 to 3 days per month relative to placebo.CONCLUSIONS AND RELEVANCE Headache disorders affect approximately 90% of people during their lifetime. Among primary headache disorders, migraine is most debilitating and can be treated acutely with analgesics, nonsteroidal anti-inflammatory drugs, triptans, gepants, and lasmiditan.

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Trial of Galcanezumab in Prevention of Episodic Cluster Headache

Cited by 187 publications

References 39 publications

Different doses of galcanezumab versus placebo in patients with migraine and cluster headache: a meta-analysis of randomized controlled trials

Different doses of galcanezumab versus placebo in patients with migraine and cluster headache: a meta-analysis of randomized controlled trials

A Popperian View on Anti‐CGRP Biologics in Migraine

Diagnosis and Management of Headache

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