You are here

  • Home
  • Archive
  • Volume 14, Issue 3
  • Efficacy of migraine prophylaxis treatments for treatment-naïve patients and those with prior treatment failure: a protocol for systematic review and network meta-analysis of randomised controlled trials

Article Text

Article menu

Download PDFPDF

Neurology
Protocol
Efficacy of migraine prophylaxis treatments for treatment-naïve patients and those with prior treatment failure: a protocol for systematic review and network meta-analysis of randomised controlled trials
  1. Pawin Numthavaj1,
  2. Thunyarat Anothaisintawee1,
  3. John Attia2,
  4. Gareth McKay3,
  5. Ammarin Thakkinstian1
  1. 1 Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  2. 2 School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia
  3. 3 Centre for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK
  1. Correspondence to Dr Thunyarat Anothaisintawee; thunyarata{at}gmail.com

Abstract

Introduction Migraine headache is a significant health problem affecting patients’ psychological well-being and quality of life. Several network meta-analyses (NMAs) have compared the efficacy of migraine prophylaxis medications. However, some have focused exclusively on oral medications, while others were limited to injectable medications. Moreover, none of these NMAs conducted a stratified analysis between treatment-naïve patients and those with prior treatment failure. Therefore, this systematic review and NMA will compare the efficacy among all treatments for migraine prophylaxis, stratified by the treatment status of patients (ie, treatment-naïve and previous treatment failure).

Methods and analysis Randomised-controlled trials that included patients with chronic or episodic migraine, assessed the efficacy of oral or injectable treatments for migraine prophylaxis and measured the outcomes as monthly migraine day, monthly headache day, migraine-related disability, health-related quality of life or adverse drug events will be eligible for inclusion in this review. Relevant studies will be searched from Medline, Scopus, the US National Institutes of Health Register, and the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) databases since inception through 15 August 2023. Risk of bias assessment will be performed using a revised tool for assessing the risk of bias in randomised trials. Two-stage NMA will be applied to compare relative treatment effects among all treatments of migraine prophylaxis. Surface under the cumulative ranking curve will be applied to estimate and rank the probability to be the best treatment. Consistency assumption will be assessed using a design-by-treatment interaction model. Publication bias will be assessed by comparison-adjusted funnel plot. All analyses will be stratified according to patients’ status (ie, treatment-naïve and prior treatment failure).

Ethics and dissemination This study is a systematic review protocol collecting data from published literature and does not require approval from an institutional review board. Results from this systematic review will be published in a peer-reviewed journal.

PROSPERO registration number CRD42020171843.

  • Migraine
  • Systematic Review
  • Quality of Life
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi-org.ezproxy.u-pec.fr/10.1136/bmjopen-2023-077916

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    STRENGTHS AND LIMITATIONS OF THIS STUDY

    • Both published and unpublished studies will be searched to minimise the publication bias.

    • The analysis will be stratified according to patient treatment status (ie, treatment-naïve or prior treatment failure).

    • Short-term and long-term treatment efficacy will be assessed.

    • Heterogeneity between studies may be presented due to differences in patient characteristics, research methodology, definitions of prior treatment failure and study time periods.

    • The definition of prior treatment failure may vary depending on the specific criteria used in each study.

    Background and rationale

    Migraine is a chronic neurological disease that affects both sexes; one year prevalence of migraine is estimated at 20.7% and 9.7% in women and men, respectively.1 Migraine is defined as a moderate to severe intensity throbbing headache that is usually unilateral; it is aggravated by physical activity and can be associated with photophobia, phonophobia, nausea and vomiting. Frequent migraine attacks can worsen a person’s performance2 and also affect psychological well-being and health-related quality of life.3 Moreover, risks of analgesic medication overuse and associated psychological disorders such as anxiety and depression were significantly higher in patients who had frequent migraine attacks.4 Therefore, prevention of migraine is important in order to improve patient outcomes and decrease the risk of medication overuse, headache-related stress and psychological problems.

    Indications for preventive treatment usually depend on the frequency of migraine attacks, impairment of the patient’s functionality, risk of analgesic medication overuse and patient preference. Normally, migraine prophylaxis is prescribed for patients with chronic migraine, defined as having headaches at least 15 days per month (of which at least 8 days are migraine attacks) or episodic migraine, defined as having attacks >4 days but <15 days per month.5

    Several conventional treatments are prescribed for migraine prevention including antiepileptic drugs, beta-blockers, calcium channel blockers, antidepressants and angiotensin receptor blockers. However, only antiepileptic drugs, beta-blockers and angiotensin receptor blockers provide evidence of migraine prophylaxis according to the American Headache Society (AHS) consensus statement.5 Although the efficacy of these oral drugs is favourable in terms of decreasing the frequency of migraine attacks and reducing the severity of symptoms, long-term compliance is suboptimal. Results from previous studies found that approximately 40% of patients with chronic migraine did not adhere to oral preventive treatments because of suboptimal efficacy, adverse events or poor tolerability.6–8 Moreover, previous studies indicated that up to 78% of patients with migraine encountered treatment failure.9 10 This failure could be attributed to the fact that conventional treatments were originally developed for other conditions and do not directly address migraine pathophysiology. In addition, most previous trials excluded individuals who had experienced treatment failures, resulting in a significant gap in evidence specifically tailored for this group of patients.

    Currently, there are also some injectable preventive treatments available for migraine prophylaxis such as onabotulinumtoxinA and calcitonin gene-related peptide (CGRP) antagonists (eg, fremanezumab, galcanezumab and erenumab). The primary pathogenesis of migraine symptoms is vasodilatation and neurogenic inflammation that result from the binding of CGRP, an important neurotransmitter in the development and progression of migraine,11 to its receptor. Thus, blocking this interaction, via the inhibition of CGRP receptors, can rapidly terminate and prevent migraine symptoms.12–14 Therefore, CGRP receptor antagonists are the first mechanism-based and disease-specific class of preventive treatment for migraine prophylaxis.

    The efficacy of these treatments is demonstrated from both systematic review (SR)15 16 and randomised controlled trials (RCTs).17 18 Moreover, these injectable preventive treatments have additional advantages such as no requirement for dose titration, rapid onset and low incidence of adverse drug reactions, making the tolerability of these treatments high.19–21

    Although these preventive treatments have been available for many years, there is a scarcity of head-to-head RCTs directly comparing their efficacy and tolerability in patients with naive treatment or prior response to preventive treatment22–24 and patients with previous preventive treatment failure.17 25–28 Consequently, to help guide clinical practice, it is necessary to conduct a comprehensive review and network meta-analysis (NMA). Previous SR and NMAs have been limited by focusing exclusively on oral medications29 30 or anti-CGRP monoclonal antibodies.31–33 Furthermore, none of these NMAs conducted a stratified analysis between treatment-naïve patients and those with prior treatment failure. The AHS recommends that migraine prophylaxis agents should be selected based on patient characteristics such as prior treatment response, disease severity and duration.5 Patients who have experienced failure with two or more available preventive treatments (due to reasons such as inadequate efficacy, tolerability issues, comorbidities or poor compliance) should be prioritised for anti-CGRP monoclonal antibody.34 Combining data from patients with various disease severities and treatment response in a single pooled analysis may not be appropriate for guiding clinical practice.

    Therefore, we aim to perform an SR and NMA comparing the efficacy and risk of adverse events among all oral and injectable treatments used for migraine prophylaxis, stratified by two distinct patient groups: those who are treatment-naïve and those with previous treatment failure. Additionally, this study will identify the most effective drugs for both short-term and long-term prevention of migraine symptoms. The findings from our SR and NMA will offer valuable evidence to inform recommendations for migraine prophylaxis in treatment-naïve individuals and those who have previously not responded to conventional preventive treatments.

    Methods

    This SR and NMA will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the PRISMA Network Meta-Analysis Extension statement.35 36

    Type of studies

    Parallel or cross-over RCTs that directly compared any pairs of both oral and injectable preventive active treatments, placebo or no intervention will be eligible. Cross-over RCTs will be included if the results of the first administration are reported separately. RCTs that compared different doses of the same drugs will be excluded.

    Type of participants

    Studies that included participants with chronic or episodic migraine with or without aura will be included. Episodic migraine is defined as headache on at least 5 days (but <15 days) per month that fulfils the International Classification of Headache Disorders (ICHD)-3 criteria (ie, duration of headache is 4–72 hours, if untreated, and characteristics of headache have at least two of the following: (1) unilateral location, (2) pulsating quality, (3) moderate to severe pain intensity, (4) aggravation by routine physical activity and during headache has at least one of the following: (1) nausea and/or vomiting, (2) photophobia and phonophobia). Chronic headache is defined as headache at least 15 days per month with at least 8 days fulfilling the ICHD-3 criteria.37

    Prior preventive treatment failure is defined as a history of at least one previously failed preventive treatment or is defined according to the definition specified in each included study. Preventive treatment failure can be an efficacy failure (inadequate reduction in headache frequency after receiving an appropriate therapeutic dose within a sufficient treatment duration) or tolerability failure with drug discontinuation due to adverse events.

    Type of interventions and comparators

    Oral or injectable treatments for migraine prophylaxis are interventions of interest. Only medications with established efficacy according to the AHS consensus statement will be eligible.5 This will include (1) antiepileptic drugs (ie, divalproex sodium, valproate sodium and topiramate), (2) beta-blockers (ie, metoprolol, propranolol and timolol), (3) candesartan, (4) triptans (ie, frovatriptan), (5) onabotulinumtoxinA and (6) monoclonal antibodies targeting CGRP or CGRP receptors (ie, fremanezumab, galcanezumab, eptinezumaband erenumab). Studies that directly compared any of these active treatments or compared the active drugs with placebo will be eligible.

    Outcomes of interest

    The primary outcome will be the frequency of headache, expressed as the monthly average number of migraine days, where a day is defined by:

    • A headache that lasts at least 4 hours; meets ICHD-III criteria C and D for migraine without aura (1.1), B and C for migraine with aura (1.2) or ICHD-III criteria for probable migraine (1.6).

    • A day with a headache that is successfully treated with a triptan, ergotamine or other migraine-specific acute medication.

    Secondary outcomes will be as follows:

    • The monthly average number of moderate to severe headache days is defined as a day with moderate or severe pain that lasts at least 4 hours or a day with a headache that is successfully treated by an acute headache medication.

    • The proportion of participants who responded to treatment is defined as a 50% reduction in the number of migraine days or number of moderate or severe headache days from baseline.

    • Migraine-related disability is measured by the Headache Impact Test or the Migraine Disability Assessment questionnaire or other measurements specified in the studies.

    • Health-related quality of life is measured by the Short Form 36-Item Health Survey or other measurements specified in the studies.

    • Adverse drug events.

    Search strategy

    Search terms and search strategies will be constructed to identify relevant studies based on population (ie, episodic or chronic migraine) and prophylaxis intervention (ie, divalproex sodium, valproate sodium, topiramate, metoprolol, propranolol, timolol, frovatriptan, onabotulinumtoxinA and monoclonal antibodies targeting CGRP or CGRP receptors such as fremanezumab, galcanezumab and erenumab). Medical Subject Heading in Medline will also be supplemented with free text terms. Search terms and search strategies are presented as follows.

    (((“Migraine Disorders”[Mesh]) OR migraine)) AND (((((((((((((((((((((“Valproic Acid”[Mesh]) OR “Topiramate”[Mesh]) OR “Metoprolol”[Mesh]) OR “Propranolol”[Mesh]) OR “Timolol”[Mesh]) OR frovatriptan) OR “Botulinum Toxins, Type A”[Mesh]) OR “Calcitonin Gene-Related Peptide Receptor Antagonists”[Mesh]) OR divalproex) OR valproate) OR topiramate) OR metoprolol) OR propranolol) OR timolol) OR onabotulinumtoxina) OR fremanezumab) OR galcanezumab) OR erenumab) OR “Calcitonin Gene-Related Peptide Receptor Antagonists”) OR Eptinezumab) OR Gepant)) AND ((Prophylaxis OR prevention)).

    Databases

    Medline, Scopus and WHO International Clinical Trials Registry Platform databases will be searched since inception through 15 August 2023. The US National Institutes of Health Register (www.clinicaltrials.gov) will be searched to identify ongoing RCTs. Reference lists of all included studies will also be explored where appropriate to identify additional relevant studies.

    Study selection

    Citations of all studies identified from searching will be exported into EndNote, and duplicate studies will be removed. First, two reviewers will independently select the studies based on titles and abstracts. Full articles will be reviewed according to the inclusion and exclusion criteria after screening titles and abstracts. Disagreement between both reviewers will be resolved by consensus with a third party. Number of included and excluded studies, along with reasons for study exclusion will be recorded to construct a flow chart of study selection according to PRISMA guidelines.

    Data extraction

    The following data from included studies will be extracted independently and in duplicate using a standardised data record form:

    • Characteristics of included study: first author name, year of publication, study design (ie, parallel or cross-over RCT), study setting and type of migraine (ie, chronic or episodic migraine).

    • Baseline characteristics of study participants: mean age and body mass index, percent male, duration of migraine headache, monthly number of migraine days at baseline and mean migraine-related disability score at baseline.

    • Interventions and controls: type of intervention, dosage, duration of treatment and drug administration.

    • Primary and secondary outcomes: method of outcome measurement, time of measurement, number of participants, mean and SD of each continuous outcome and number of participants who did or did not have dichotomous outcomes by treatment groups.

    Disagreement between both reviewers will be resolved by consensus with a third party. Corresponding authors of the included studies will be contacted if there is insufficient data.

    Risk of bias assessment

    Risk of bias of the included studies will be assessed using a revised tool for assessing risk of bias in randomised trials (RoB 2).38 The revised tool for assessing risk of bias in randomised trials consists of five domains as follows:

    • Bias arising from the randomisation process.

    • Bias due to deviations from intended interventions.

    • Bias due to missing outcome data.

    • Bias in the measurement of the outcome.

    • Bias in the selection of the reported result.

    Each domain has a series of questions where possible response options are ‘yes’, ‘probably yes’, ‘probably no’, ‘no’ and ‘no information’. A ‘yes’ answer might suggest either lower or higher risk of bias, depending on the framing of the questions. Risk of bias for each domain will be classified as ‘low risk of bias’, ‘some concern’ or ‘high risk of bias’, determined by an algorithm that maps responses to questions. Overall risk of bias will also be classified as ‘low risk of bias’, ‘some concern’ or ‘high risk of bias’. ‘Low risk of bias’ will be considered if all domains are ‘low risk of bias’, otherwise studies will be classified as ‘high risk of bias’ if at least one domain is ‘high risk of bias’ or multiple domains are ‘some concerns’ that might significantly lower confidence in the results.

    Two reviewers will perform risk of bias assessments independently. Disagreement between both reviewers will be resolved by consensus through a third party.

    Statistical analysis plan

    Characteristics of the included studies and baseline characteristics of study participants will be described by mean (or median where appropriate) for continuous outcomes, and frequency and percentage for dichotomous outcomes. Pairwise and network meta-analyses will be performed and will be stratified by two patient groups: (1) those who were treatment-naïve and (2) those who had experienced previous preventive treatment failures, irrespective of the number of prior failures.

    Pairwise meta-analysis

    Pairwise meta-analysis will be performed if more than two RCTs had similar population, interventions, comparator and outcomes available. For continuous outcomes, mean difference between intervention and control groups will be estimated and pooled using unstandardised mean difference (USMD) if all studies used similar methods for outcome measurement, otherwise, standardised mean difference (SMD) will be applied. For dichotomous outcomes, risk ratio (RR) will be estimated and pooled using the inverse variance method; a random effect model will be applied instead, if heterogeneity is present.

    Heterogeneity between studies will be estimated using Q-test and I2 statistic. Heterogeneity between studies will be considered, if the Q-test p value is <0.10 or I2 statistic is >25%. Relative treatment effects will be pooled using a fixed effect model, if there is no heterogeneity between studies, otherwise a random effect model will be applied.

    Sources of heterogeneity will be explored by meta-regression analysis. Factors that might be the cause of heterogeneity such as mean age, monthly migraine days at baseline, migraine duration, mean migraine-related disability score at baseline and duration of treatment will be fitted in a meta-regression model one by one. Subgroup analyses according to short-term and long-term prevention regimens, and the factors that can decrease tau2 or I2 from meta-regression will be further performed. Short-term prevention is defined as 4 weeks after initiation of treatment, while long-term prevention is defined as 6–12 months or beyond after initiation of treatment.

    Network meta-analysis

    We will apply an NMA to compare relative treatment effects among all treatments of migraine prophylaxis using a two-stage NMA39 40 as follows. First, relative treatment effect (ie, SMD/USMD or the natural logarithm of the RR) and its variance–covariance will be estimated for each individual study, using placebo as the reference. Second, these relative treatment effects will be pooled across studies by a multivariate meta-analysis with consistency model, and then multiple treatment comparisons will be performed. Surface under the cumulative ranking curve (SUCRA) will be applied to estimate and rank the probability that a treatment will have the highest efficacy and safety. A cluster ranking plot will be constructed to demonstrate the benefit and risk of all treatments by plotting SUCRA for lowest mean monthly migraine days versus lowest adverse events.

    Consistency assumption estimates of the agreement between direct and indirect comparisons will be assessed using a design-by-treatment interaction model that incorporates both loop and design inconsistencies.41 42 If inconsistency is suggested from the model, characteristics of the studies in the loops with an inconsistency factor higher than 2 will be explored. Sensitivity analysis with exclusion of these studies will be further performed.

    Publication bias will be assessed by comparison-adjusted funnel plot.43 The horizontal axis of the comparison-adjusted funnel plot will present the difference between the study-specific effect sizes from the corresponding comparison-specific summary effect and the vertical axis will present the inverse variance of treatment effect. Publication bias is suggested if there is asymmetrical comparison-adjusted funnel plot around the zero line.

    Statistical analyses will be performed using STATA V.18. A p value <0.05 will be applied to establish a level of statistical significance, except for the heterogeneity test as previously indicated.

    The certainty of evidence for NMA of primary outcomes considered in cluster ranking plots will be assessed using the Confidence in Network Meta-Analysis (CINeMA) tool.44 The CINeMA tool consists of six domains: (1) within-study bias, (2) reporting bias, (3) indirectness, (4) imprecision, (5) heterogeneity and (6) incoherence. The confidence of each domain will be graded as no concerns, some concerns or major concerns.

    Ethics and dissemination

    This study is SR protocol collecting data from published literature and therefore does not require institutional review board approval. Results from this SR and NMA will be published in a peer-reviewed journal.

    Patient and public involvement

    There was no patient or public involvement in this review protocol.

    Discussion

    Chronic and episodic migraine headaches represent significant health problems that have a profound impact on patients’ daily functioning and overall quality of life. Although there are currently several medications available for the prevention of migraine attacks, the majority of patients with chronic and episodic migraines have experienced treatment failure (77.9%), which greatly affects their personal, social and professional lives.45 Consequently, the recommended treatment options for patients who have previously failed preventive treatments may differ from those patients who have yet initiated prophylaxis. Unfortunately, previous studies and evidence, including NMAs, have often overlooked this issue by combining both patients with chronic migraine and episodic migraine, irrespective of their prior treatment failure status. Therefore, this study represents the first SR and NMA with the aim of identifying the most suitable migraine prophylaxis treatments for both distinct patient groups: those who are treatment-naïve and those who have experienced previous treatment failure. We expect the findings from this NMA to provide valuable guidance to clinicians and patients in selecting the most appropriate migraine prophylaxis treatment that aligns with the patient’s individual needs. This evidence-based approach will assist in making informed decisions for personalised medicine to optimise treatment outcomes for individuals suffering from migraines.

    Ethics statements

    Patient consent for publication

    References

    1. ↵
      2. Rossi MF ,
      3. Tumminello A ,
      4. Marconi M , et al
      . Sex and gender differences in Migraines: a narrative review. Neurol Sci 2022;43:5729–34. doi:10.1007/s10072-022-06178-6
      OpenUrl
    2. ↵
      2. Dueland AN ,
      3. Leira R ,
      4. Burke TA , et al
      . The impact of migraine on work, family, and leisure among young women -- a multinational study. Curr Med Res Opin 2004;20:1595–604. doi:10.1185/030079904X3357
      OpenUrlCrossRefPubMedWeb of Science
    3. ↵
      2. Dueland AN ,
      3. Leira R ,
      4. Cabelli ST
      . The impact of migraine on psychological well-being of young women and their communication with physicians about migraine: a multinational study. Curr Med Res Opin 2005;21:1297–305. doi:10.1185/030079905X56394
      OpenUrlCrossRefPubMedWeb of Science
    4. ↵
      2. Buse D ,
      3. Manack A ,
      4. Serrano D , et al
      . Headache impact of chronic and episodic migraine: results from the American migraine prevalence and prevention study. Headache 2012;52:3–17. doi:10.1111/j.1526-4610.2011.02046.x
      OpenUrlPubMed
    5. ↵
      2. Ailani J ,
      3. Burch RC ,
      4. Robbins MS , et al
      . The American headache society consensus statement: update on integrating new migraine treatments into clinical practice. Headache 2021;61:1021–39. doi:10.1111/head.14153 Available: https://headachejournal-onlinelibrary-wiley-com.ezproxy.u-pec.fr/toc/15264610/61/7
      OpenUrlCrossRefPubMed
    6. ↵
      2. Hepp Z ,
      3. Dodick DW ,
      4. Varon SF , et al
      . Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia 2015;35:478–88. doi:10.1177/0333102414547138
      OpenUrlCrossRefPubMed
    7. ↵
      2. Blumenfeld AM ,
      3. Bloudek LM ,
      4. Becker WJ , et al
      . Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second International burden of migraine study (IBMS-II) . Headache 2013;53:644–55. doi:10.1111/head.12055 Available: https://headachejournal-onlinelibrary-wiley-com.ezproxy.u-pec.fr/toc/15264610/53/4
      OpenUrlCrossRefPubMedWeb of Science
    8. ↵
      2. Blumenfeld AM ,
      3. Bloudek LM ,
      4. Becker WJ , et al
      . Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second International burden of migraine study (IBMS-II). Headache 2013;53:644–55. doi:10.1111/head.12055
      OpenUrlCrossRefPubMedWeb of Science
    9. ↵
      2. Ford JH ,
      3. Jackson J ,
      4. Milligan G , et al
      . A real-world analysis of migraine: A cross-sectional study of disease burden and treatment patterns. Headache 2017;57:1532–44. doi:10.1111/head.13202
      OpenUrl
    10. ↵
      2. Berger A ,
      3. Bloudek LM ,
      4. Varon SF , et al
      . Adherence with migraine prophylaxis in clinical practice. Pain Pract 2012;12:541–9. doi:10.1111/j.1533-2500.2012.00530.x
      OpenUrlCrossRefPubMedWeb of Science
    11. ↵
      2. Villalón CM ,
      3. Olesen J
      . The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute Antimigraine drugs. Pharmacol Ther 2009;124:309–23. doi:10.1016/j.pharmthera.2009.09.003
      OpenUrlCrossRefPubMedWeb of Science
    12. ↵
      2. de Vries T ,
      3. Villalón CM ,
      4. MaassenVanDenBrink A
      . Pharmacological treatment of migraine: CGRP and 5-HT beyond the Triptans. Pharmacol Ther 2020;211:107528. doi:10.1016/j.pharmthera.2020.107528
      OpenUrl
    13. ↵
      2. Tepper SJ
      . History and review of anti-calcitonin gene-related peptide (CGRP) therapies: from Translational research to treatment. Headache 2018:238–75. doi:10.1111/head.13379
    14. ↵
      2. Salvatore CA ,
      3. Kane SA
      . CGRP receptor antagonists: toward a novel migraine therapy. Curr Pharm Biotechnol 2011;12:1671–80. doi:10.2174/138920111798357401
      OpenUrlCrossRefPubMed
    15. ↵
      2. Lattanzi S ,
      3. Brigo F ,
      4. Trinka E , et al
      . Erenumab for preventive treatment of migraine: A systematic review and meta-analysis of efficacy and safety. Drugs 2019;79:417–31. doi:10.1007/s40265-019-01069-1
      OpenUrlCrossRefPubMed
    16. ↵
      2. Bruloy E ,
      3. Sinna R ,
      4. Grolleau J-L , et al
      . Botulinum toxin versus placebo: A meta-analysis of prophylactic treatment for migraine. Plast Reconstr Surg 2019;143:239–50. doi:10.1097/PRS.0000000000005111
      OpenUrlPubMed
    17. ↵
      2. Ferrari MD ,
      3. Diener HC ,
      4. Ning X , et al
      . Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3B trial. The Lancet 2019;394:1030–40. doi:10.1016/S0140-6736(19)31946-4
      OpenUrl
    18. ↵
      2. Detke HC ,
      3. Goadsby PJ ,
      4. Wang S , et al
      . Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology 2018;91:e2211–21. doi:10.1212/WNL.0000000000006640
      OpenUrlPubMed
    19. ↵
      2. Goadsby PJ ,
      3. Reuter U ,
      4. Hallström Y , et al
      . A controlled trial of Erenumab for episodic migraine. N Engl J Med 2017;377:2123–32. doi:10.1056/NEJMoa1705848
      OpenUrlCrossRefPubMed
    20. ↵
      2. Bigal ME ,
      3. Dodick DW ,
      4. Rapoport AM , et al
      . Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a Multicentre, randomised, double-blind, placebo-controlled, phase 2B study. Lancet Neurol 2015;14:1081–90. doi:10.1016/S1474-4422(15)00249-5
      OpenUrlCrossRefPubMed
    21. ↵
      2. Skljarevski V ,
      3. Oakes TM ,
      4. Zhang Q , et al
      . Effect of different doses of Galcanezumab vs placebo for episodic migraine prevention: A randomized clinical trial. JAMA Neurol 2018;75:187–93. doi:10.1001/jamaneurol.2017.3859
      OpenUrl
    22. ↵
      2. Blumenfeld AM ,
      3. Schim JD ,
      4. Chippendale TJ
      . Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine. Headache 2008;48:210–20. doi:10.1111/j.1526-4610.2007.00949.x
      OpenUrlPubMedWeb of Science
    23. ↵
      2. Cady RK ,
      3. Schreiber CP ,
      4. Porter JAH , et al
      . A multi-center double-blind pilot comparison of onabotulinumtoxinA and Topiramate for the prophylactic treatment of chronic migraine. Headache 2011;51:21–32. doi:10.1111/j.1526-4610.2010.01796.x
      OpenUrlCrossRefPubMed
    24. ↵
      2. Kaniecki RG
      . A comparison of divalproex with propranolol and placebo for the prophylaxis of migraine without aura. Arch Neurol 1997;54:1141–5. doi:10.1001/archneur.1997.00550210071015
      OpenUrlCrossRefPubMedWeb of Science
    25. ↵
      2. Ailani J ,
      3. Pearlman E ,
      4. Zhang Q , et al
      . Positive response to Galcanezumab following treatment failure to onabotulinumtoxinA in patients with migraine: post hoc analyses of three randomized double-blind studies. Eur J Neurol 2020;27:542–9. doi:10.1111/ene.14102
      OpenUrl
    26. ↵
      2. Ashina M ,
      3. Lanteri-Minet M ,
      4. Pozo-Rosich P , et al
      . Safety and efficacy of Eptinezumab for migraine prevention in patients with two-to-four previous preventive treatment failures (DELIVER): a multi-arm, randomised, double-blind, placebo-controlled, phase 3B trial. Lancet Neurol 2022;21:597–607. doi:10.1016/S1474-4422(22)00185-5
      OpenUrl
    27. ↵
      2. Ashina M ,
      3. Tepper S ,
      4. Brandes JL , et al
      . Efficacy and safety of Erenumab (Amg334) in chronic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia 2018;38:1611–21. doi:10.1177/0333102418788347
      OpenUrlPubMed
    28. ↵
      2. Cady R ,
      3. Schreiber C
      . Botulinum toxin type A as migraine preventive treatment in patients previously failing oral prophylactic treatment due to compliance issues. Headache 2008;48:900–13. doi:10.1111/j.1526-4610.2007.00953.x Available: https://headachejournal-onlinelibrary-wiley-com.ezproxy.u-pec.fr/toc/15264610/48/6
      OpenUrlCrossRefPubMedWeb of Science
    29. ↵
      2. Jackson JL ,
      3. Cogbill E ,
      4. Santana-Davila R , et al
      . A comparative effectiveness meta-analysis of drugs for the prophylaxis of migraine headache. PLoS One 2015;10:e0130733. doi:10.1371/journal.pone.0130733
    30. ↵
      2. He A ,
      3. Song D ,
      4. Zhang L , et al
      . Unveiling the relative efficacy, safety and tolerability of prophylactic medications for migraine: Pairwise and network-meta analysis. J Headache Pain 2017;18:26. doi:10.1186/s10194-017-0720-7
    31. ↵
      2. Messina R ,
      3. Huessler E-M ,
      4. Puledda F , et al
      . Safety and tolerability of Monoclonal Antibodies targeting the CGRP pathway and Gepants in migraine prevention: a systematic review and network meta-analysis. Cephalalgia 2023;43. doi:10.1177/03331024231152169
    32. ↵
      2. Yang C-P ,
      3. Zeng B-Y ,
      4. Chang C-M , et al
      . Comparative effectiveness and tolerability of the pharmacology of Monoclonal antibodies targeting the calcitonin gene-related peptide and its receptor for the prevention of chronic migraine: a network meta-analysis of randomized controlled trials. Neurotherapeutics 2021;18:2639–50. doi:10.1007/s13311-021-01128-0
      OpenUrl
    33. ↵
      2. Shi M ,
      3. Guo J ,
      4. Li Z , et al
      . Network meta-analysis on efficacy and safety of different anti-CGRP Monoclonal antibody regimens for prophylaxis and treatment of episodic migraine. Neurol Res 2021;43:932–49. doi:10.1080/01616412.2021.1940672
      OpenUrl
    34. ↵
      The American headache society position statement on integrating new migraine treatments into clinical practice. Headache 2019;59:1–18. doi:10.1111/head.13456
      OpenUrlCrossRef
    35. ↵
      2. Moher D ,
      3. Liberati A ,
      4. Tetzlaff J , et al
      . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009;151:264–9. doi:10.7326/0003-4819-151-4-200908180-00135
      OpenUrlCrossRefPubMedWeb of Science
    36. ↵
      2. Hutton B ,
      3. Salanti G ,
      4. Caldwell DM , et al
      . The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 2015;162:777–84. doi:10.7326/M14-2385
      OpenUrlCrossRefPubMed
    37. ↵
      Headache classification committee of the International headache society (IHS) the International classification of headache disorders. Cephalalgia 2018;38:1–211. doi:10.1177/0333102417738202
      OpenUrlCrossRefPubMed
    38. ↵
      2. Sterne JAC ,
      3. Savović J ,
      4. Page MJ , et al
      . n.d. Rob 2: a revised tool for assessing risk of bias in randomised trials [BMJ (Clinical research ed) 2019;366:l4898]. BMJ:l4898. doi:10.1136/bmj.l4898
    39. ↵
      2. White IR
      . Multivariate random-effects meta-analysis. The Stata Journal 2009;9:40–56. doi:10.1177/1536867X0900900103
      OpenUrl
    40. ↵
      2. White IR
      . Network meta-analysis. The Stata Journal 2015;15:951–85. doi:10.1177/1536867X1501500403
      OpenUrl
    41. ↵
      2. Higgins JPT ,
      3. Jackson D ,
      4. Barrett JK , et al
      . Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Methods 2012;3:98–110. doi:10.1002/jrsm.1044
      OpenUrlCrossRefPubMed
    42. ↵
      2. Jackson D ,
      3. Boddington P ,
      4. White IR
      . The design-by-treatment interaction model: a unifying framework for Modelling loop inconsistency in network meta-analysis. Res Synth Methods 2016;7:329–32. doi:10.1002/jrsm.1188
      OpenUrl
    43. ↵
      2. Chaimani A ,
      3. Higgins JPT ,
      4. Mavridis D , et al
      . Graphical tools for network meta-analysis in STATA. PLoS One 2013;8:e76654. doi:10.1371/journal.pone.0076654
    44. ↵
      2. Nikolakopoulou A ,
      3. Higgins JPT ,
      4. Papakonstantinou T , et al
      . Cinema: an approach for assessing confidence in the results of a network meta-analysis. PLOS Med 2020;17:e1003082. doi:10.1371/journal.pmed.1003082
    45. ↵
      2. Martelletti P ,
      3. Schwedt TJ ,
      4. Lanteri-Minet M , et al
      . My migraine voice survey: a global study of disease burden among individuals with migraine for whom preventive treatments have failed. J Headache Pain 2018;19. doi:10.1186/s10194-018-0946-z

    Footnotes

    • Contributors PN and TA are the principal investigators. PN, TA, GM, JA and AT designed the study. PN and TA drafted the manuscript. PN, TA, GM, JA and AT critically revised the study protocol and the manuscript. The entire project will be supervised by TA and AT.

    • Funding This study was funded by the National Research Council of Thailand (NRCT) (N42A640323). The study funder had no role in the design or conduct of the study.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.