Chronic Cluster Headache Research Articles

Anti-CGRP monoclonal antibodies in chronic cluster headache

Commentary

Phenotype of Cluster Headache: Clinical Variability, Persisting Pain Between Attacks, and Comorbidities-An Observational Cohort Study in 825 Patients.

IntroductionCluster headaches can occur with considerable clinical variability. The inter- and intra-individual variability could contribute to the fact that the clinical headache phenotype is not captured by too strict diagnostic criteria, and that the diagnosis and the effective therapy are thereby delayed. The aim of the study was to analyze the severity and extent of the clinical symptoms of episodic and chronic cluster headaches with regard to their variability and to compare them with the requirements of the International Classification of Headache Disorders 3rd edition (ICHD-3) diagnostic criteria.MethodsThe study was carried out as a cross-sectional analysis of 825 patients who had been diagnosed with cluster headaches by their physician. Using an online questionnaire, standardized questions on sociodemographic variables, clinical features of the cluster headache according to ICHD-3, and accompanying clinical symptoms were recorded.ResultsThe majority of patients with cluster headaches have clinical features that are mapped by the diagnostic criteria of ICHD-3. However, due to the variability of the symptoms, there is a significant proportion of clinical phenotypes that are not captured by the ICHD-3 criteria for cluster headaches. In addition, change in the side of the pain between the cluster episodes, pain location, as well as persisting pain between the attacks is not addressed in the ICHD-3 criteria. In the foreground of the comorbidities are psychological consequences in the form of depression, sleep disorders, and anxiety.ConclusionsThe variability of the phenotype of cluster headaches can preclude some patients from receiving an appropriate diagnosis and effective therapy if the diagnostic criteria applied are too strict. The occurrence of persisting pain between attacks should also be diagnostically evaluated due to its high prevalence and severity as well as psychological strain. When treating patients with cluster headaches, accompanying psychological illnesses should carefully be taken into account.

Effectiveness of medication in cluster headache

BackgroundThe aim of this work is to analyze the reports on cluster headache attacks collected online in the citizen science project CLUE with respect to the effectiveness of drugs taken during the attacks. The collection of data within the framework of citizen science projects opens up the possibility of investigating the effectiveness of acute medication on the basis of a large number of individual attacks instead of a simple survey of patients.MethodsData from 8369 cluster headache attacks, containing information about acute medication taken and the assessment of its effect, were collected from 133 participants using an online platform and a smartphone app. Chi-square tests were used to investigate whether the effect of the three recommended acute drugs differs when distinguishing between participants with chronic or episodic cluster headache. Furthermore, it was investigated whether there are differences between smokers and non-smokers in the assessment of the effect of the acute medication.ResultsOur participants rated the effectiveness of sumatriptan 6 mg s.c. as significantly better than oxygen and zolmitriptan nasal spray. Oxygen is considered to be significantly better in episodic versus chronic cluster headache, and sumatriptan is considered to be significantly better in chronic versus episodic cluster headache. Smokers rate the effect of oxygen as significantly better than non-smokers.ConclusionsDespite some methodological limitations, web-based data collection is able to support findings from clinical trials in a real world setting about effectiveness of acute cluster headache treatment in several situations.

Episodic and Chronic Cluster Headache: Evaluation of Health-Related Quality of Life Impact and Estimation of Health-state Utilities (1267)

Episodic and Chronic Cluster Headache: Evaluation of Health-Related Quality of Life Impact and Estimation of Health-state Utilities (1267)

Clinical Features of Cluster Headache: A Hospital-Based Study in Taiwan.

Most previous studies on cluster headache (CH) focus on Western populations. This study aimed to investigate the clinical characteristics of CH in a neurology outpatient population in Taiwan. A cross-sectional survey was conducted from July 2015 to June 2019 in a medical college affiliated with a tertiary care hospital (Tri-Service General Hospital) in Taiwan. All consecutive patients reporting headache as their chief complaint were asked to participate in a face-to-face interview with a qualified headache specialist and to complete a detailed self-administered questionnaire. The diagnosis of CH was made according to the Third edition of the International Classification of Headache Disorders. The subjects comprised 80 consecutive new CH patients (13 women and 67 men; ratio, 1:5). The mean age at presentation was 36.0 ± 10.8 years (range, 16–64 years), mean age at onset was 27.2 ± 12.1 years (range, 5–65 years), and mean time lag before diagnosis was 9.3 ± 10.5 years (range, 0–46.4 years). Of the total CH patients, 25.3% reported feelings of restlessness during headache episodes. A seasonal predilection was reported by 18% of the CH patients. The use of tobacco was the most common (44/80 patients). Chronic CH was only observed in 5% of the patients and only one patient (1.3%) reported both a positive family history for CH and aura. Features of CH in Taiwanese patients differed from that of Caucasian patients; a lower prevalence of chronic CH, positive family history of CH, and occurrence of aura may be less common in the former than in the latter.

OUTCOME OF OCCIPITAL NERVE BLOCK IN PATIENTS WITH CHRONIC HEADACHES

Background: Chronic headaches are very prevalent affecting a sizable number of global populations. Occipital nerve block (OCN) can help them relieve their pain and get back to their normal life. Conditions that are treated with occipital nerve blocks include: Chronic migraine, Episodic migraine, Chronic cluster headaches, Episodic cluster headaches, Tension-type headaches, Occipital neuralgia. These may include types of pain that start at the back of the head near the neck, and then radiate outward throughout the skull. Occipital nerve block is a minimally invasive intervention, inhibits or blocks the disproportionate or chronic signals that are sent to the brain, processed and perceived as headache pain, resulting in pain relief lasting up to several months. It is our humble approach to see the effectiveness of this mode of minimal intervention. Objectives: The aim was to see the effectiveness of Occipital Nerve Block in patients of Chronic headaches. Place of study: Dept of PMR, IPGME & R and SSKM Hospital, Kolkata Period of study: 1 st. September, 2017 to 31 st. August, 2018. (12 months) Study pattern: Prospective Longitudinal Outcome Study Methods: After getting Institutional Ethical Committee clearance a total number of 98 patients with Chronic headaches who did not respond with conservative management were included. Patients with other causes of headache, patients with diabetes, severe hypertension, otherwise th th th contraindicated for injections, are excluded. Occipital nerve blocks performed to patients and were evaluated initially and at the 4 , 8 , and 12 week followed up using Numeric Pain Rating Scale (NPRS). Adverse events and patient satisfaction were recorded, number of attacks pre 4wks and after intervention. Results: Statistically signicant improvement is seen in these patients treated with Occipital Nerve Block Conclusions: Occipital Nerve Block effective mode of management in patients with Chronic headaches and may be recommended to patients with moderate to severe chronic pain that has not responded to conventional treatment such as oral painkillers or lifestyle interventions.

New Management of Cluster Headache

Galcanezumab, a CGRP monoclonal antibody drug, has been approved by the U.S. Food and Drug Administration (FDA) for the prevention of recurrent cluster headaches. This was done after a randomized, double-blind, placebo-controlled trial found it to be effective and safe. Similarly sphenopalatine ganglion stimulation has been found to be effective and safe in a randomized, controlled trial as an acute treatment for chronic cluster headache. This article reviews the mechanisms of action of these therapies and their clinical trial results, clinical uses, and prospects in Japan.

Comprehensive clinical phenotyping of nitroglycerin infusion induced cluster headache attacks.

BackgroundNitroglycerin administration allows the study of cluster headache attacks in their entirety in a standardised way.MethodsA single-blind, placebo-controlled, cross-over study using weight-calculated intravenous nitroglycerin administration at 0.5 µg/kg/min over 20 minutes to study cluster headache attacks, including accompanying non-headache symptoms and cranial autonomic symptoms.ResultsThirty-three subjects with cluster headache were included in the study; 24 completed all three study visits. Nitroglycerin-induced attacks developed in 26 out of 33 subjects (79%) receiving unblinded nitroglycerin infusion, and in 19 out of 25 subjects (76%) receiving single-blinded nitroglycerin infusion, compared with one out of 24 subjects (4%) receiving single-blinded placebo infusion. Episodic cluster headache subjects had a shorter latency period to a nitroglycerin-induced attack compared to the chronic cluster headache (CCH) subjects (U = 15, z = −2.399, p = 0.016). Sixteen of nineteen episodic cluster headache (mean, 84%; 95% confidence interval, 66–100%) and 11 of 14 chronic cluster headache subjects developed a nitroglycerin-induced attack (79%, 54–100%) following the unblinded nitroglycerin infusion. Following the single-blinded nitroglycerin infusion, eight out of 13 episodic cluster headache (62%, 31–92%) and 11 out of 12 chronic cluster headache (92%, 73–100%) subjects developed nitroglycerin-induced attacks. Nitroglycerin induced non-headache symptoms in the majority of subjects receiving it: 91% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visits, compared with 33% in the single-blinded placebo visit. Cranial autonomic symptoms were induced by nitroglycerin infusion, 94% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visit, compared with 17% in the single-blinded placebo visit.ConclusionIntravenous weight-adjusted nitroglycerin administration in both episodic cluster headache in bout and chronic cluster headache is effective and reliable in inducing cluster headache attacks, cranial autonomic symptoms and non-headache symptoms.

Occipital Nerve Stimulation for Pain Modulation in Drug-Resistant Chronic Cluster Headache.

Occipital nerve stimulation (ONS) is a surgical treatment proposed for drug-resistant chronic cluster headache (drCCH). Long-term series assessing its efficacy are scarce. We designed a retrospective observational study with consecutive sampling, evaluating the follow-up of 17 drCCH patients who underwent ONS. Our main endpoint was the reduction the rate of attacks per week. We also evaluated the pain intensity through the Visual Analogue Scale (VAS), patient overall perceived improvement and decrease in oral medication intake. After a median follow-up of 6.0 years (4.5–9.0), patients decreased from a median of 30 weekly attacks to 22.5 (5.6–37.5, p = 0.012), 7.5 at 1 year (p = 0.006) and 15.0 at the end of follow-up (p = 0.041). The VAS decreased from a median of 10.0 to 8.0 (p = 0.011) at three months, to 7.0 (p = 0.008) at twelve months and 7.0 (p = 0.003) at the end of the follow-up. A total of 23.5% had an overall perceived improvement of ≥70% at 3 months, 41.2% at 1 year and 27.8% at the end of follow-up. Reducing prophylactic oral medication was possible in 76.5% and it was stopped in 17.7%. Triptan use decreased in all the responder patients and 17.7% stopped its intake. A total of 41.2% presented mild adverse events. In conclusion, our long-term experience suggests that ONS could be an interesting option for drCCH-selected patients, as it is a beneficial and minimally invasive procedure with no serious adverse events.

A retrospective observation on 105 patients with chronic cluster headache receiving indomethacin.

Indomethacin (IMC) as a prophylactic treatment is considered to be ineffective in cluster headache (CH). However, small series suggested the interest of IMC in CH. Some authors support that an IMC test is useful in all trigeminal autonomic cephalalgias. We described clinical features of IMC responders in a retrospective cohort of chronic cluster headache (CCH). This single-center and retrospective study was conducted in a tertiary care specialist headache center in France. Patients were selected between January 2007 and December 2008. We included all patients fulfilling CCH criteria (ICHD-3-beta). Data were collected from medical records. We recorded all the prescriptions of IMC as a prophylactic treatment. Responders were defined by 50% reduction in attack frequency; complete response was defined by disappearance of the attacks. The non-responders must have received at least 100 mg daily during 7 days. The study consisted of 324 CCH, 121 female (37%) and 203 males (63%) with an average age at onset of 33.93 (± 14.71) years. Of the patients, 105 were treated with IMC. Thirty patients (29%) were responders. Thirty-four patients (32%) were non-responders. Responding status was undefined for 41 patients (39%). Twelve patients (11%) had a complete response. Responders were composed by 18 women (60%) and 12 men (40%) and had on average 44.89 (± 12.88) years. The minimal effective dose was 86.11 mg daily (± 48.72). This study shows the interest of IMC in CCH patients. We recommend an IMC test as a third-line treatment in CCH.

Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache.

Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series. To evaluate ONS long-term efficacy in rCCH. We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption. At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P<.001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%). Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.

Noninvasive Neuromodulation in Headache: An Update.

Migraine is a common disabling primary headache condition. Although strives have been made in treatment, there remains an unmet need for safe, effective acute, and preventative treatments. The promising concept of neuromodulation of relevant neuronal targets in a noninvasive fashion for the treatment of primary headache disorders has led to the trial of numerous devices over the years. We aimed to review the evidence on current neuromodulation treatments available for the management of primary headache disorders. Randomized controlled trial as well as open-label and real-world studies on central and peripheral cephalic and noncephalic neuromodulation modalities in primary headaches were critically reviewed. The current evidence suggests a role of single-pulse transcranial magnetic stimulation, supraorbital nerve stimulation, and remote noncephalic electrical stimulation as migraine abortive treatments, with stronger evidence in episodic rather than in chronic migraine. Single-pulse transcranial magnetic stimulation and supraorbital nerve stimulation also hold promising evidence in episodic migraine prevention and initial positive evidence in chronic migraine prevention. More evidence should clarify the therapeutic role of the external vagus nerve stimulation and transcranial direct current stimulation in migraine. However, external vagus nerve stimulation may be effective in the acute treatment of episodic but not chronic cluster headache, in the prevention of hemicrania continua and paroxysmal hemicrania but not of short-lasting neuralgiform headache attacks. The difficulty in setting up sham-controlled studies has thus far prevented the publication of robust trials. This limitation along with the cost of these therapies has meant that their use is limited in most countries. Neuromodulation is a promising nonpharmacological treatment approach for primary headaches. More studies with appropriate blinding strategies and reduction of device cost may allow more widespread approval of these treatments and in turn increase clinician's experience in neuromodulation.

Drug profile: galcanezumab for prevention of cluster headache

ABSTRACT Introduction: Cluster headache [CH] is a severely disabling trigeminal autonomic cephalalgia [TAC]. Approximately 1 in 1,000 adults are affected by CH. Calcitonin gene-related peptide [CGRP] is an important mediator in the pathophysiology of CH. Galcanezumab is a monoclonal antibody with an affinity for the CGRP peptide, FDA approved for the prevention of episodic CH. Areas covered: Search words queried were ‘cluster headache,’ ‘cluster headache, and CGRP,’ ‘cluster headache, and galcanezumab.’ Over 99 articles in Pubmed and prescribing information for galcanezumab were reviewed. Some of the data pertaining to CH trials with fremanezumab were reviewed using clinical trials.org. Expert opinion: Galcanezumab has shown benefit in decreasing the weekly frequency of CH attacks across week 1 through week 3 in patients with CH; 8.7 attacks in the galcanezumab group, as compared with 5.2 in the placebo group (95% confidence interval, 0.2 to 6.7; P = 0.04). It has a favorable risk-benefit ratio. The prevention of CH with CGRP inhibition represents a novel advance for a condition with a significant unmet need. The negative trial results of galcanezumab for chronic cluster headache [CCH] may be due to the refractory nature and sheds light on the critical need to investigate the underlying biology and therapeutic options.

‘A cry in the dark’: a qualitative exploration of living with cluster headache

Cluster headache is a rare primary headache disorder said to be one of the most painful conditions in existence. Limited evidence demonstrates cluster headache patients have difficulties securing a diagnosis and poor access to services. There is a gap in research around psychosocial needs, meaning there are no evidence-based guidelines to inform optimal management of this patient group in primary care. The aim of this study is to explore the perspectives of cluster headache patients in the United Kingdom in order to suggest ways their care can be improved. It is an in-depth qualitative study involving telephone interviews with 15 participants with either chronic or episodic cluster headache. Semi-structured interviews (43-58 minutes) were conducted, recorded and transcribed verbatim. Two researchers conducted thematic analysis to identify themes. Participants described the impact cluster headache has on their quality of life. They also felt the legitimacy of their disorder was questioned. This situation was often exacerbated by a reported lack of awareness among General Practitioners (GPs), which negatively impacted their care in terms of diagnosis and access to treatments and specialists. They attempted to control the pain through treatments and avoiding triggers, often with detrimental consequences for their social contact and mental health. Findings indicate the need to improve the lived experience of cluster headache patients in two key areas: (1) raising awareness of the disorder and its impact among GPs, and (2) extending care beyond clinical treatment provision, supporting patients in self-management and addressing its psychosocial impact, with implications for the management of this group in primary care.

Ketamine-Magnesium for Refractory Chronic Cluster Headache: A Case Series.

To evaluate the safety and efficacy of ketamine-magnesium combination to reduce attacks in a series of patients with refractory chronic cluster headache (rCCH). Refractory chronic cluster headache (CCH) is a rare but highly debilitating condition that needs new treatment options. A previous publication reported that a single infusion of ketamine-magnesium combination was effective in 2 patients with rCCH. The treatment was proposed to consecutive patients with rCCH seen in 2 French hospitals between November 2015 and February 2020 and who were resistant to at least 3 preventive treatments. They received a single ketamine infusion (0.5mg/kg over 2hours) combined with magnesium sulfate (3000mg). The main outcome was a comparison of the number of daily attacks 2weeks prior to the ketamine-magnesium infusion and 1week after (on days 7 and 8). The second outcome was the percentage of responders (patients with ≥50% reduction in the frequency of daily attacks). Safety was assessed by the recording of adverse events during infusion. Descriptive statistics are presented as mean±standard deviation. Seventeen patients (14 men), with an age of 35.2±8.1years, were included. They presented with CCH for 6.6±4.3years. The number of daily attacks decreased from 4.3±2.4 before treatment to 1.3±1.0 after treatment (difference: -3.1 (95% CI: -4.5 to -1.6), P<.001). Seventy six percent (13/17) were responders. Transient and mild sedation was reported by 7/17 patients (41.2%). The ketamine-magnesium combination seems an effective and well-tolerated therapy for rCCH. Placebo-controlled studies should be conducted to further confirm these findings.

The effect of pituitary adenylate cyclase-activating peptide-38 and vasoactive intestinal peptide in cluster headache.

Previously reported increases in serum levels of vasodilating neuropeptides pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) during attacks of cluster headache could indicate their involvement in cluster headache attack initiation. We investigated the attack-inducing effects of PACAP38 and vasoactive intestinal peptide in cluster headache, hypothesising that PACAP38, but not vasoactive intestinal peptide, would induce cluster-like attacks in episodic active phase and chronic cluster headache patients. In a double-blind crossover study, 14 episodic cluster headache patients in active phase, 15 episodic cluster headache patients in remission phase and 15 chronic cluster headache patients were randomly allocated to receive intravenous infusion of PACAP38 (10 pmol/kg/min) or vasoactive intestinal peptide (8 pmol/kg/min) over 20 min on two study days separated by at least 7 days. We recorded headache intensity, incidence of cluster-like attacks, cranial autonomic symptoms and vital signs using a questionnaire (0-90 min). In episodic cluster headache active phase, PACAP38 induced cluster-like attacks in 6/14 patients and vasoactive intestinal peptide induced cluster-like attacks in 5/14 patients (p = 1.000). In chronic cluster headache, PACAP38 and vasoactive intestinal peptide both induced cluster-like attacks in 7/15 patients (p = 0.765). In episodic cluster headache remission phase, neither PACAP38 nor vasoactive intestinal peptide induced cluster-like attacks. Contrary to our hypothesis, attack induction was lower than expected and roughly equal by PACAP38 and vasoactive intestinal peptide in episodic active phase and chronic cluster headache patients, which contradicts the PAC1-receptor as being solely responsible for attack induction.Trial registration: clinicaltrials.gov (identifier NCT03814226).

Deep Brain Stimulation for Chronic Cluster Headache: Meta‐Analysis of Individual Patient Data

Deep brain stimulation (DBS) is a treatment option for refractory chronic cluster headache (CCH). Despite several recent prospective case series reporting a good outcome, the effectiveness and the optimal stimulation target of DBS for CCH remain unclear. We aimed to obtain precise estimates and predictors of long-term pain relief in an individual patient data meta-analysis. Furthermore, we aimed to construct a probabilistic stimulation map of effective DBS. We invited investigators of published cohorts of patients undergoing DBS for CCH, identified by a systematic review of MEDLINE from inception to Febuary 15, 2019, to provide individual patient data on baseline covariates, pre- and postoperative headache scores at median (12-month) and long-term follow-up, in addition to individual imaging data to obtain individual electrode positions. We calculated a stimulation map using voxel-wise statistical analysis. We used multiple regression analysis to estimate predictors of pain relief. Among 40 patients from four different cohorts representing ~50% of all previously published cases, we found a significant 77% mean reduction in headache attack frequency over a mean follow-up of 44 months, with an overall response rate of 75%. Positive outcome was not associated with baseline covariates. We identified 2 hotspots of stimulation covering the midbrain ventral and retrorubral tegmentum. This study supports the hypothesis that DBS provides long-term pain relief for the majority of CCH patients. Our stimulation map of the region of influence of therapeutic DBS identified an optimal anatomical target site that can help surgeons to guide their surgical planning in the future. ANN NEUROL 2020;88:956-969.

Baseline tear fluid CGRP is elevated in active cluster headache patients as long as they have not taken attack abortive medication.

Calcitonin gene-related peptide plays a key role in cluster headache pathophysiology. It is released from the trigeminal nerve, which also innervates the eye. In this study, we tested if tear fluid calcitonin gene-related peptide measurement detects elevated calcitonin gene-related peptide levels in cluster headache patients compared to controls. Calcitonin gene-related peptide concentration in tear fluid and plasma of 16 active episodic and 11 chronic cluster headache patients (all outside acute attacks) and 60 controls were assessed using ELISA. Cluster headache patients without use of attack abortive medication in the last 48 h showed significantly elevated tear fluid calcitonin gene-related peptide levels (1.78 ± 1.57 ng/ml, n = 17) compared to healthy controls (0.79 ± 0.74 ng/ml, p = 0.003) and compared to cluster headache patients who had used attack abortive medication in the last 48 h (0.84 ± 1.40 ng/ml, n = 10, p = 0.022). High calcitonin gene-related peptide levels in cluster headache patients were independent of the occurrence of a cluster headache attack in the last 48 hours (no attack: 1.95 ± 1.65 ng/ml, n = 8; attack: 1.63 ± 1.59 ng/ml, n = 9, p = 0.82) as long as no acute medication was used. No significant difference in tear fluid calcitonin gene-related peptide levels between episodic (1.48 ± 1.34 ng/ml) and chronic cluster headache patients (2.21 ± 1.88 ng/ml, p = 0.364) was detected. In contrast to these results in tear fluid, there were no significant group differences in plasma calcitonin gene-related peptide levels. This study shows that active cluster headache patients have increased calcitonin gene-related peptide levels in tear fluid compared to healthy subjects, which are reduced to control levels after intake of attack abortive medication. Calcitonin gene-related peptide measurement in tear fluid is non-invasive, and has the advantage of allowing direct access to calcitonin gene-related peptide released from the trigeminal nerve.

Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache: Results from a retrospective case series support individual treatment attempts.

ObjectiveTo assess the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor in chronic cluster headache (CCH) treatment under real world conditions.BackgroundCalcitonin gene-related peptide has an important pathophysiological role in cluster headache. Although the randomised controlled trial with the calcitonin gene-related peptide antibody galcanezumab was negative, chronic cluster headache patients with insufficient response to other preventive treatments have been receiving individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies.MethodsData from 22 chronic cluster headache patients who received at least one dose of a calcitonin gene-related peptide(-receptor) antibody and recorded attack frequency in a headache diary were retrospectively collected at eight headache centres.ResultsThe number of previous preventive therapies was 6.5 ± 2.4 (mean ± standard deviation, range: 2–11). The average number of attacks per week was 23.3 ± 16.4 at baseline and significantly decreased by −9.2 ± 9.7 in the first month of treatment with a calcitonin gene-related peptide(-receptor) antibody (p < 0.001). Fifty-five percent of the patients were 50% responders and 36% were 75% responders with respect to attack frequency. Significant reduction of attack frequency started at week 1 (−6.8 ± 2.8 attacks, p < 0.01). Results were corroborated by significant decreases in weekly uses of acute headache medication (−9.8 ± 7.6, p < 0.001) and pain intensity during attacks (−1.2 ± 2.0, numerical rating scale (NRS) [0–10], p < 0.01) in the first month. In months 2 (n = 14) and 3 (n = 10), reduction of attack frequency from baseline was −8.0 ± 8.4 (p = 0.004) and −9.1 ± 10.0 (p = 0.024), respectively.ConclusionUnder real-world conditions, individual treatment with calcitonin gene-related peptide(-receptor) antibodies was effective in 55% of our chronic cluster headache patients. This finding supports individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies in chronic cluster headache patients insufficiently responding to other therapies.

Galcanezumab for the prevention of cluster headache

ABSTRACT Introduction Cluster headache (CH) is among the worst painful conditions. The available therapies are scarce and not specific, leaving many patients unsatisfied because of poor efficacy and/or tolerability. Patients not responding to common treatments are offered semi-invasive and invasive procedures with uncertain results. Based on the current understanding of CH pathophysiology, new possible therapeutic approaches come from drugs interfering with Calcitonin Gene Related Peptide (CGRP). Areas covered After summarizing the evidence for CGRP involvement in CH pathophysiology, we review the published literature (PubMed) and information (clinicaltrials.gov, EudraCT, EMA and FDA websites) regarding a novel anti-CGRP monoclonal antibody, Galcanezumab, its pharmacological properties, development, and evidence for the treatment of CH. Publications regarding other indications (migraine) are considered for completeness and safety/tolerability profile. Expert opinion In one randomized clinical trial, Galcanezumab has proven to be effective and safe as a preventive treatment in episodic CH, with a favorable tolerability profile offering a potential new option in the therapeutic arsenal. Inefficacy of galcanezumab in chronic CH as well as the inefficacy of another monoclonal antibody against CGRP (fremanezumab) in both episodic and chronic CH question the scalability of the drug in CH management. Further, studies comparing galcanezumab to the current standard treatments are highly desirable.