Efficacy of galcanezumab in patients with migraine and history of failure to 3-4 preventive medication categories: subgroup analysis from CONQUER study

Background: Chronic migraine (CM) and episodic migraine (EM) are associated with substantial headache-related disability, poor quality of life and global societal burden. In this subgroup analysis from the CONQUER study, we report efficacy outcomes from a pre-specified analysis of galcanezumab versus placebo in patients with CM or EM and 3–4 prior preventive medication category failures due to inadequate efficacy (after at least 2 months at maximum tolerated dose), or safety or tolerability reasons. The patient population is of particular interest due to evidence of decreased quality of life and increased economic burden among patients with migraine that is inadequately managed and is of interest to decision-makers globally. Methods: Key outcomes included overall mean change from baseline in monthly migraine headache days and proportions of patients achieving ≥30% (CM), ≥50%, and ≥ 75% reduction (response rates) in monthly migraine headache days across Months 1–3. Patient functioning and disability were evaluated at Month 3. Results: Of the 462 randomized patients, 186 (40.3%) had a history of 3–4 preventive category failures. Galcanezumab versus placebo resulted in significantly (P ≤ .001) larger overall mean reduction in monthly migraine headache days (total: − 5.49 versus − 1.03; CM: − 6.70 versus − 1.56; EM: − 3.64 versus − 0.65). Similarly, the ≥50% response rate was significantly (P ≤ .001) higher with galcanezumab versus placebo (total: 41.0 versus 12.7; CM: 41.5 versus 8.4; EM: 41.1 versus 16.5). In the CM group, the ≥30% response rate was significantly higher in the galcanezumab group than the placebo group (CM, 57.5 versus 19.8, P ≤ .0001) as was the ≥75% response rate (13.3 versus 2.6, P ≤ .05). Galcanezumab also resulted in significant (P < .0001) improvements in patient functioning and reductions in disability. Conclusions: Galcanezumab was effective in a difficult-to-treat population of patients with CM or EM who had failed 3–4 prior preventive medication categories

Patient Perspectives and Experiences of Preventive Treatments and Self-Injectable Devices for Migraine:A Focus Group Study

BACKGROUND: Although several self-injectable preventive treatments for migraine have become available, they are not yet widely used. Thus, understanding patients’ perceptions towards them is limited. OBJECTIVE: This study aimed to inform the design of a preference-elicitation instrument, which is being developed to quantify preventive treatment preferences of people with migraine. METHODS: We conducted a qualitative study involving nine in-person focus groups (three per country) in the United States, the United Kingdom, and Germany. Participants were adults (n = 47) with episodic or chronic migraine who were currently using or had used a prescription preventive treatment for migraine within the previous 5 years. During the focus groups, participants described their experiences of migraine and preventive treatments; handled and simulated self-injection using five different unbranded, fired demonstration auto-injectors and prefilled syringes; and ranked different aspects of preventive treatments by importance. Focus groups were analyzed with a focus on themes that would be feasible or meaningful to include in a subsequent preference-elicitation instrument. RESULTS: Reducing the frequency and severity of migraine attacks was consistently ranked as the most important aspect of preventive treatment. Participants expressed dissatisfaction with available daily oral preventive treatments for migraine they had previously used because they were ineffective or caused intolerable adverse events. Many participants were willing to self-inject a treatment that was effective and tolerable. When presented with devices for self-injecting a preventive treatment for migraine, participants generally preferred autoinjectors over prefilled syringes. Participants especially valued safety features such as the unlocking step and automated needle insertion, and audible and visual dose confirmation increased confidence in autoinjector use. Autoinjector needle protection mechanisms were also appreciated, especially by participants averse to needles, as the needles are not visible. CONCLUSIONS: This study highlights the fact that many people with migraine still lack access to a preventive treatment that is effective and tolerable. In addition to efficacy and safety considerations, treatment decisions may be guided by the mode of administration. In the case of self-injectable preventive treatments, key device characteristics affecting these decisions may be ease of use, comfort, and confidence in self-injection. Insights gained from this study were used to help develop a preliminary set of attributes and levels for a preference-elicitation instrument. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40271-021-00525-z

Systematic literature review of methodologies and data sources of existing economic models across the full spectrum of Alzheimer’s disease and dementia from apparently healthy through disease progression to end of life care: a systematic review protocol

Introduction Dementia is one of the greatest health challenges the world will face in the coming decades, as it is one of the principal causes of disability and dependency among older people. Economic modelling is used widely across many health conditions to inform decisions on health and social care policy and practice. The aim of this literature review is to systematically identify, review and critically evaluate existing health economics models in dementia. We included the full spectrum of dementia, including Alzheimer’s disease (AD), from preclinical stages through to severe dementia and end of life. This review forms part of the Real world Outcomes across the Alzheimer’s Disease spectrum for better care: multimodal data Access Platform (ROADMAP) project. Methods and analysis Electronic searches were conducted in Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Economic Literature Database, NHS Economic Evaluation Database, Cochrane Central Register of Controlled Trials, Cost-Effectiveness Analysis Registry, Research Papers in Economics, Database of Abstracts of Reviews of Effectiveness, Science Citation Index, Turning Research Into Practice and Open Grey for studies published between January 2000 and the end of June 2017. Two reviewers will independently assess each study against predefined eligibility criteria. A third reviewer will resolve any disagreement. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed using the Phillips checklist for decision analytic modelling. A narrative synthesis will be used. Ethics and dissemination The results will be made available in a scientific peer-reviewed journal paper, will be presented at relevant conferences and will also be made available through the ROADMAP project

Measuring quality of life of people with predementia and dementia and their caregivers: a systematic review protocol

Introduction Dementia is the fastest growing major cause of disability globally and may have a profound impact on the health-related quality of life (HRQoL) of both the patient with dementia and those who care for them. This review aims to systematically identify and synthesise the measurements of HRQoL for people with, and their caregivers across the full spectrum of, dementia from its preceding stage of predementia to end of life. Methods and analysis A systematic literature review was conducted in Medical Literature Analysis and Retrieval System Online , ExcerptaMedicadataBASE, Cochrane Database of Systematic Reviews , Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effect, National Health Service Economic Evaluation Database and PsycINFO between January 1990 and the end of April 2017. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed with the Effective Public Health Practice Project quality assessment tool. HRQoL measurements will be presented separately for people with dementia and caregivers by instrument used and, when possible, HRQoL will be reported by disease type and stage of the disease. Descriptive statistics of the results will be provided. A narrative synthesis of studies will also be provided discussing differences in HRQoL measurements by instrument used to estimate it, type of dementia and disease severity. Ethics and dissemination This systematic literature review is exempt from ethics approval because the work is carried out on published documents. The findings of the review will be disseminated in a related peer-reviewed journal and presented at conferences. They will also contribute to the work developed in the Real World Outcomes across the Alzheimer’s disease spectrum for better care: multimodal data access platform (ROADMAP)

Challenges for Optimizing Real-World Evidence in Alzheimer’s Disease: The ROADMAP Project

ROADMAP is a public-private advisory partnership to evaluate the usability of multiple data sources, including real-world evidence, in the decision-making process for new treatments in Alzheimer’s disease, and to advance key concepts in disease and pharmacoeconomic modeling. ROADMAP identified key disease and patient outcomes for stakeholders to make informed funding and treatment decisions, provided advice on data integration methods and standards, and developed conceptual cost-effectiveness and disease models designed in part to assess whether early treatment provides long-term benefit

Efficacy of galcanezumab in patients with migraine and history of failure to 3–4 preventive medication categories: subgroup analysis from CONQUER study

Background: Chronic migraine (CM) and episodic migraine (EM) are associated with substantial headache-related disability, poor quality of life and global societal burden. In this subgroup analysis from the CONQUER study, we report efficacy outcomes from a pre-specified analysis of galcanezumab versus placebo in patients with CM or EM and 3–4 prior preventive medication category failures due to inadequate efficacy (after at least 2 months at maximum tolerated dose), or safety or tolerability reasons. The patient population is of particular interest due to evidence of decreased quality of life and increased economic burden among patients with migraine that is inadequately managed and is of interest to decision-makers globally. Methods: Key outcomes included overall mean change from baseline in monthly migraine headache days and proportions of patients achieving ≥30% (CM), ≥50%, and ≥ 75% reduction (response rates) in monthly migraine headache days across Months 1–3. Patient functioning and disability were evaluated at Month 3. Results: Of the 462 randomized patients, 186 (40.3%) had a history of 3–4 preventive category failures. Galcanezumab versus placebo resulted in significantly (P ≤.001) larger overall mean reduction in monthly migraine headache days (total: − 5.49 versus − 1.03; CM: − 6.70 versus − 1.56; EM: − 3.64 versus − 0.65). Similarly, the ≥50% response rate was significantly (P ≤.001) higher with galcanezumab versus placebo (total: 41.0 versus 12.7; CM: 41.5 versus 8.4; EM: 41.1 versus 16.5). In the CM group, the ≥30% response rate was significantly higher in the galcanezumab group than the placebo group (CM, 57.5 versus 19.8, P ≤.0001) as was the ≥75% response rate (13.3 versus 2.6, P ≤.05). Galcanezumab also resulted in significant (P <.0001) improvements in patient functioning and reductions in disability. Conclusions: Galcanezumab was effective in a difficult-to-treat population of patients with CM or EM who had failed 3–4 prior preventive medication categories. Trial registration: CONQUER. Clinicaltrials.gov identifier: NCT03559257

Response to 'Do different treatment strategies of galcanezumab have similar effect on migraine?'

Paroxysmal Cerebral Disorder

Benefit-Risk Assessment of Galcanezumab Versus Placebo for the Treatment of Episodic and Chronic Migraine Using the Metrics of Number Needed to Treat and Number Needed to Harm

INTRODUCTION: Subcutaneous galcanezumab was an effective, well-tolerated preventive treatment for adults with episodic (EM) or chronic migraine (CM) in 4 phase 3 randomized controlled trials: EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER. Number needed to treat (NNT) and to harm (NNH) are metrics of effect size used to evaluate benefit-risk profiles. This study evaluated NNT, NNH, and benefit-risk profiles (measured as likelihood to be helped or harmed, LHH) of galcanezumab 120 mg versus placebo in patients with EM or CM. METHODS: Primary efficacy outcomes were responses defined as ≥ 30%, ≥ 50%, and ≥ 75% reductions from baseline in number of monthly migraine headache days in patients with EM (EVOLVE-1; EVOLVE-2; CONQUER) and CM (REGAIN; CONQUER); corresponding NNTs to achieve respective responses; and corresponding NNHs for discontinuations due to adverse events (DCAEs) among the safety population. Secondary efficacy outcomes were responses for patients with ≥ 2 failed prior preventive treatments due to lack of efficacy and/or for tolerability reasons. All LHHs were based on ≥ 50% response and DCAEs. RESULTS: During double-blind treatment periods with galcanezumab 120 mg, NNT to achieve ≥ 30% and ≥ 50% responses ranged from 4 to 10 and NNT to achieve ≥ 75% responses ranged from 5 to 23 in individual trials. NNH ranged from 93 to 1000, while LHH ranged from 18.6 to 104.6. NNTs were generally more robust among patients with EM than with CM; however, in patients with failure of ≥ 2 prior preventive treatments, NNTs to achieve ≥ 30% and ≥ 50% responses were similar between patients with CM and EM. NNHs were imputed as 1000 for both migraine types. Resulting LHHs were 178.8 (EM) and 127 (CM). CONCLUSION: Across 4 trials, galcanezumab 120 mg demonstrated a favorable benefit-risk profile versus placebo, based on low NNTs to achieve response and high NNHs associated with DCAEs. LHH values consistently far exceeded 1. TRIAL REGISTRATION NUMBERS: EVOLVE-1: ClinicalTrials.gov identifier, NCT02614183; EVOLVE-2: ClinicalTrials.gov identifier, NCT02614196; REGAIN: ClinicalTrials.gov identifier, NCT02614261; CONQUER: ClinicalTrials.gov identifier, NCT03559257