Cluster headache polygenetic risk and known functional variants of <scp><i>CYP3A4</i></scp> are not associated with treatment response

Petersen, Anja Sofie; Barloese, Mads; Lund, Nunu; Pedersen, Adam Friis; Søborg, Mogens; Chalmer, Mona Ameri; Callesen, Ida; Winsvold, Bendik S.; Zwart, John‐Anker; Ostrowski, Sisse Rye; Pedersen, Ole Birger; Sellebjerg, Finn; Søndergaard, Helle Bach; Hansen, Malene Bredahl; Jensen, Rigmor Højland; Hansen, Thomas

doi:10.1111/ene.15736

Cited by 5 publications

(3 citation statements)

References 45 publications

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“…Only 14% reported complete relief of attacks on verapamil [8]. Efficacy does not seem to be associated with high/low dose or sex, but verapamil is more effective in ECH compared to CCH [50,57]. Side effects such as constipation, tiredness and oedema are reported in 12-86% of participants [46,[52][53][54][55].…”

Section: Verapamilmentioning

confidence: 99%

Current treatment options for cluster headache: limitations and the unmet need for better and specific treatments—a consensus article

Lund,

Petersen,

Fronczek

et al. 2023

J Headache Pain

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Aim Treatment for cluster headache is currently based on a trial-and-error approach. The available preventive treatment is unspecific and based on few and small studies not adhering to modern standards. Therefore, the authors collaborated to discuss acute and preventive treatment in cluster headache, addressing the unmet need of safe and tolerable preventive medication from the perspectives of people with cluster headache and society, headache specialist and cardiologist. Findings The impact of cluster headache on personal life is substantial. Mean annual direct and indirect costs of cluster headache are more than 11,000 Euros per patient. For acute treatment, the main problems are treatment response, availability, costs and, for triptans, contraindications and the maximum use allowed. Intermediate treatment with steroids and greater occipital nerve blocks are effective but cannot be used continuously. Preventive treatment is sparsely studied and overall limited by relatively low efficacy and side effects. Neurostimulation is a relevant option for treatment-refractory chronic patients. From a cardiologist’s perspective use of verapamil and triptans may be worrisome and regular follow-up is essential when using verapamil and lithium. Conclusion We find that there is a great and unmet need to pursue novel and targeted preventive modalities to suppress the horrific pain attacks for people with cluster headache. Graphical Abstract

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Section: Verapamilmentioning

confidence: 99%

Current treatment options for cluster headache: limitations and the unmet need for better and specific treatments—a consensus article

Lund,

Petersen,

Fronczek

et al. 2023

J Headache Pain

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show abstract

“…A biomarker need not be restricted to a biochemical compound but could include genes or imaging, but so far none have succeeded in these areas. 59,60 Still, the review has some limitations. First, the literature search identified vastly heterogeneous studies with both variable study designs and highly incomparable outcomes, which is why no meta-analysis was possible.…”

Section: Discussionmentioning

confidence: 99%

“…In a clinical setting, easy access to sample collection is also essential, where both blood, CSF, tear fluid, and saliva are readily available. A biomarker need not be restricted to a biochemical compound but could include genes or imaging, but so far none have succeeded in these areas 59,60 . Thus, a biomarker for CH remains a desirable topic for future research, possibly within omics, which remains unexplored territory.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers in cluster headache: A systematic review

Søborg,

Jensen,

Barloese

et al. 2023

Headache

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ObjectiveTo systematically investigate previously examined biomarkers in blood, urine, cerebrospinal fluid, tear fluid, and saliva of patients with cluster headache.BackgroundCluster headache is a condition with extensive clinical challenges in terms of diagnosis and treatment. Identification of a biomarker with diagnostic implications or as a potential treatment target is highly warranted.MethodsWe conducted a systematic review including peer reviewed full text of studies that measured biochemical compounds in either blood, urine, cerebrospinal fluid, tear fluid, or saliva of patients with cluster headache diagnosed after the implementation of the International Classification of Headache Disorders (1988) written in English, Danish, Swedish, or Norwegian. Inclusion required a minimum of five participants. The search was conducted in PubMed and EMBASE, in September 2022, and extracted data were screened by two authors. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines for reporting systematic reviews were followed. The Newcastle–Ottawa Scale was used to assess the risk of bias in case–controlled studies.ResultsWe included 40 studies involving 832 patients with cluster headache and 872 controls, evaluating 80 potential biomarkers. The risk of bias for case–controlled studies was a median of 6 (range: 3–8) and 20 studies out of 40 (50%) were of fair or good quality. Most studies were identified within three groups: hypothalamic‐regulated hormones, inflammatory markers, and neuropeptides. Among the hypothalamic hormones, cortisol was the most frequently investigated (N = 7) and was elevated in cluster headache in most of the studies. The most frequently examined inflammatory marker was interleukin 1 (N = 3), but findings were divergent. Calcitonin gene–related peptide was the most investigated neuropeptide (N = 9) and all studies found increased levels during attacks.ConclusionBiomarker findings have been inconsistent and widely non‐specific for cluster headache, which explains why none of the previous studies succeeded in identifying a unique biomarker for cluster headache, but instead contributed to substantiating the underlying pathophysiologic mechanisms. Several of the examined biomarkers could hold promise as markers for disease activity but are unfit for a clear distinction from both controls and other headaches.

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Genetic and Phenotypic Profiling of Triptan Users in a Swedish Cluster Headache Cohort

Jennysdotter Olofsgård,

Ran,

Qin

et al. 2024

J Mol Neurosci

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Up to 25% of individuals who live with cluster headache (CH), an extremely painful primary headache disorder, do not adequately respond to the first-line treatment, triptans. Studies have indicated that genetic variants can play a role in treatment response. Likewise, differences in clinical characteristics can give clues to mechanisms underlying triptan non-response. Our aim was to investigate five genetic variants previously implicated in triptan response and their relation to triptan usage in our Swedish CH cohort and to investigate potential distinctions in clinical characteristics. 545 CH patients were screened for the genetic variants rs1024905, rs6724624, rs4795541, rs5443, and rs2651899 with a case control design based on triptan usage. Analysis of clinical characteristics was based on self-reported questionnaire data from 893 patients. One genetic variant, rs1024905, was significantly associated with triptan non-usage in CH (Pc = 0.010). In addition, multi-allele effector analysis showed that individuals with a higher number of effector variants were less likely to use triptans (P = 0.007). Analysis of clinical characteristics showed that triptan users were more likely to have alcohol as a trigger (57.4% vs 43.4%, P = 0.002), have autonomic symptoms (95.1% vs 88.1%, P = 0.002), and be current smokers (27.0% vs 21.9%, P = 0.033) compared to non-users. These results support the hypothesis that genetic variants can play a role in triptan usage in CH and that patients with a typical CH phenotype are more likely to use triptans.

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Cluster headache polygenetic risk and known functional variants of CYP3A4 are not associated with treatment response

Cited by 5 publications

References 45 publications

Current treatment options for cluster headache: limitations and the unmet need for better and specific treatments—a consensus article

Current treatment options for cluster headache: limitations and the unmet need for better and specific treatments—a consensus article

Biomarkers in cluster headache: A systematic review

Genetic and Phenotypic Profiling of Triptan Users in a Swedish Cluster Headache Cohort

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