Emerging Therapies for Patients With Difficult-to-Treat Migraine.
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ABSTRACT:
SUBMITTER: Kish T
PROVIDER: S-EPMC6152700 | biostudies-other | 2018 Oct
REPOSITORIES: biostudies-other
Publications
Emerging Therapies for Patients With Difficult-to-Treat Migraine.
P & T : a peer-reviewed journal for formulary management 20181001 10
The landscape of migraine therapy is set to change with the introduction of new classes of medications aimed at providing options for patients who have not responded to previous therapies. However, the pricing of the new agents will likely be a key determinant in the extent of their use in clinical practice. ...[more]
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Project description:BackgroundFremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings.MethodsThis retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway-targeted mAb [CGRP mAb]).ResultsData were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were - 7.7 (77.0%) in EM patients, - 10.1 (68.7%) in CM patients, - 10.8 (80.6%) in the MO subgroup, - 9.9 (68.3%) in the MDD subgroup, - 9.5 (66.4%) in the GAD subgroup, and - 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively.ConclusionsIn this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb).
| S-EPMC9109352 | biostudies-literature
Project description:Fremanezumab is a fully humanized monoclonal antibody (IgG2Δa) that targets calcitonin gene-related peptide (CGRP), a key neuropeptide involved in the pathophysiology of migraine. Fremanezumab is approved for quarterly and monthly subcutaneous dosing for the preventive treatment of migraine in adults. The phase 3 clinical development program for fremanezumab aimed to evaluate the efficacy of this preventive treatment across different patient populations, including those with difficult-to-treat migraine. Two pivotal 12-week, phase 3, placebo-controlled studies investigated quarterly and monthly dosing of fremanezumab in participants with chronic migraine (HALO CM) and episodic migraine (HALO EM). The efficacy of fremanezumab was further explored in individuals with difficult-to-treat chronic or episodic migraine in the 12-week FOCUS study, which enrolled participants who had previously experienced an inadequate response to 2-4 pharmacological classes of migraine preventive medications. The long-term efficacy of fremanezumab was assessed in a 12-month long-term study (HALO LTS), which enrolled participants completing the 12-week HALO studies and new participants. Across these studies, treatment with fremanezumab dosed quarterly or monthly provided significant reductions in the frequency of migraine days, headache days of at least moderate severity, and migraine- and headache-related disability compared with placebo. Sustained improvements were seen with long-term fremanezumab treatment. Subgroup analyses of participants with difficult-to-treat migraine (those with comorbid depression, overuse of acute headache medications, and concomitant use of other migraine preventive medications) demonstrated the effectiveness of quarterly or monthly fremanezumab in these populations. Ongoing studies are further exploring the potential benefits of fremanezumab in difficult-to-treat migraine and other headache and pain disorders.
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Project description:OBJECTIVE:To understand the efficacy of zolmitriptan applied with Adhesive Dermally Applied Microarray (ADAM) in treating types of migraine (those with severe headache pain, the presence of nausea, treatment ≥2 hours after migraine onset, or migraine present upon awakening) that are historically considered to be less responsive to oral medications. BACKGROUND:ADAM is an investigational system for intracutaneous drug administration. In a pivotal Phase 2b/3 study (ZOTRIP, N = 321 in the modified intention-to-treat population), ADAM zolmitriptan 3.8 mg provided superior pain freedom and freedom from patients' usual most bothersome associated symptom (MBS), compared with placebo at 2 hours post-dose. We undertook a post hoc analysis of data from the ZOTRIP trial to examine these same outcomes in subsets of patients whose migraine characteristics have been associated with poorer outcomes when treated with oral medications. METHODS:The ZOTRIP trial was a multicenter, randomized, double-blind, placebo-controlled, parallel group Phase 2b/3 study conducted at 36 sites in the United States. Presented here are post hoc subgroup analyses of patients with nausea (n = 110) or severe pain (n = 72) at baseline, those whose treatment was delayed 2 or more hours after onset (n = 75), and those who awoke with migraine (n = 80). The Cochran-Mantel-Haenszel test was used to assess whether patients in the ADAM zolmitriptan 3.8 mg group had superior treatment outcomes compared with placebo. RESULTS:In patients with nausea, 2-hour pain freedom was achieved in 44% (26/59) in the ADAM zolmitriptan 3.8 mg group and 14% (7/51) in the placebo group (P = .005) (odds ratio = 5.11, 95% CI: 1.96-13.30), and 2-hour MBS freedom was achieved in 68% (40/59) in the active treatment group and 45% (23/51) of those receiving placebo (P = .009) (odds ratio = 2.86, 95% CI: 1.28-6.43). For those with severe pain, corresponding pain-free values were 26% (10/39) and 15% (5/33) (P = .249) (odds ratio = 2.14, 95% CI: 0.60-7.62), and MBS-free values were 64% (25/39) and 42% (14/33) (P = .038) (odds ratio = 2.86, 95% CI: 1.05-7.79). Among participants who awoke with migraine, 44% (16/36) and 16% (7/44) were pain-free in the ADAM zolmitriptan 3.8 mg and placebo groups, respectively (P = .006) (odds ratio = 4.29, 95% CI: 1.50-12.31), and 72% (26/36) vs 39% (17/44) were MBS-free, respectively (P = .003) (odds ratio = 4.40, 95% CI: 1.61-12.05). In those whose treatment was delayed ≥2 hours, pain freedom in the active treatment group and placebo group were 33% (12/36) and 10% (4/39), respectively (P = .017) (odds ratio = 4.33, 95% CI: 1.24-15.10), and MBS freedom was achieved in 69% (25/36) and 41% (16/39), respectively, in the delayed treatment group (P = .014) (odds ratio = 3.37, 95% CI: 1.27-8.95). No significant effects (overall interaction P = .353) were observed in logistical regression models of treatment by subgroup interaction. CONCLUSION:Severe pain, delayed treatment, awakening with a headache, and the presence of nausea are factors that predict a poorer response to acute migraine treatment. In these post hoc analyses of subgroups of patients with each of these characteristics in the ZOTRIP trial, participants receiving ADAM zolmitriptan 3.8 mg displayed nearly uniformly better headache responses (2-hour headache freedom and 2-hour MBS freedom) compared with those who received placebo.
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Project description:Glioblastoma multiforme (GBM) remains a challenging disease, as it is the most common and deadly brain tumour in adults and has no curative solution and an overall short survival time. This incurability and short survival time means that, despite its rarity (average incidence of 3.2 per 100,000 persons), there has been an increased effort to try to treat this disease. Standard of care in newly diagnosed glioblastoma is maximal tumour resection followed by initial concomitant radiotherapy and temozolomide (TMZ) and then further chemotherapy with TMZ. Imaging techniques are key not only to diagnose the extent of the affected tissue but also for surgery planning and even for intraoperative use. Eligible patients may combine TMZ with tumour treating fields (TTF) therapy, which delivers low-intensity and intermediate-frequency electric fields to arrest tumour growth. Nonetheless, the blood-brain barrier (BBB) and systemic side effects are obstacles to successful chemotherapy in GBM; thus, more targeted, custom therapies such as immunotherapy and nanotechnological drug delivery systems have been undergoing research with varying degrees of success. This review proposes an overview of the pathophysiology, possible treatments, and the most (not all) representative examples of the latest advancements.
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Project description:Psoriatic involvement in areas of the body such as nails, palms and soles (palmoplantar), and scalp is associated with dramatically negative effects on quality of life relative to involvement elsewhere in the body. Although numerous evidence-based studies demonstrate the efficacy of biologics for overall skin clearance in moderate-to-severe plaque psoriasis (including tumor necrosis factor α [TNFα] inhibitors and interleukin [IL]-17A, IL-12/IL-23, IL-23, IL-17F, and IL-17A/F inhibitors), large, randomized, placebo-controlled clinical studies of psoriasis with nail, palmoplantar, and scalp involvement are needed to better inform decision-making in clinical practice. Moreover, biologic failure caused by drug ineffectiveness is a common occurrence in patients who do not respond, lose response, or are intolerant to treatment. Brodalumab is a fully human IL-17 receptor A antagonist that demonstrates high rates of skin clearance among the latest generation of biologic therapies for treatment of moderate-to-severe psoriasis. This review summarizes current literature on the efficacy of brodalumab and other therapies in difficult-to-treat psoriasis including psoriasis in difficult-to-treat locations (such as psoriasis with nail, palmoplantar, or scalp involvement) and psoriasis in patients whose disease did not respond to other biologics.
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Project description:ObjectiveRecently, several academics have recommended that the concept of difficult-to-treat depression (DTD) should be considered in some of the cases where achieving or maintaining remission of depressive symptoms is not possible. In 2020, a consensus statement, not based on a formal process and systematic review defined difficult-to-treat depression as "depression that continues to cause significant burden despite normal treatment efforts". In addition to addressing symptom control, interventions for DTD should also target other factors, including the management of psychiatric and medical comorbidities, psychosocial functioning, self-esteem, and self-management strategies. The purpose of this scoping review is to explore the scientific literature, which is still unclear and vague, regarding the pathophysiology and treatment of difficult-to-treat depression, providing a summary of its current conceptualization. This represents a cultural and scientific shift that offers clinicians and researchers valid and up-to-date study criteria, thus expanding upon the model of treatment-resistant depression (TRD). Consequently contributions, concepts, theories and gaps of the state of the art in the description of difficult-to-treat depression have been summarized here.MethodA research study was conducted using PubMed, Scopus, PsycINFO, Cochrane Library, and Open Grey databases to identify and examine articles reporting key features related to the recent concept of difficult-to-treat depression. The research covered a period of time between January 1, 2013, and March 1, 2023. Based on a formal checklist, two researchers independently assessed the eligibility criteria to determine which studies to include or exclude in this search. Further data evaluations were conducted for the articles that were deemed to have the most comprehensive descriptions.ResultsThe results of the research yielded a body of literature that provides a clear definition of difficult-to-treat depression and insights into its clinical application and research perspective.ConclusionsDTD represents a cultural and scientific shift that provides clinicians and researchers with valid and up-to-date study criteria that allow the extension of the treatment-resistant depression (TRD) model. The main difference lies in the operational process of assessment and intervention in the depressive syndrome in relation to the search for a therapeutic response. The results of this review show that DTD is a theoretically and clinically useful conceptualization for depressive syndromes that are not just simply resistant to treatment. This clinical condition entails a novel clinical therapeutic approach for specific patients and may be used throughout the world to help recognize this clinical condition while optimizing overall care for these patients. However, as we have highlighted, in the absence of RCTs and further observational studies, it is desirable that DTD be further investigated and defined..
| S-EPMC10375274 | biostudies-literature
Project description:To describe factors associated with early treatment of migraine, and to examine reasons patients do not treat early, this cross-sectional observational study email-recruited migraineurs >or= 18-years-old who were currently prescribed acute migraine medication. Within 24 h of migraine resolution, eligible patients completed an online migraine strikes questionnaire which addressed pain severity, associated symptoms, and other variables including reasons for not treating early. Results reported were descriptive. Among 1,044 evaluable patients, early treatment was significantly associated with several factors such as leisure activity at onset (OR 1.32, P=0.010), photophobia (OR 1.39, P=0.013), diagnosis of migraine with aura (OR 1.36, P=0.004), and other factors. Among 840 patients who reported wanting to treat earlier desire to reserve medication for a severe migraine was the most common reason given for not doing so (51.2%). Overcoming these factors may facilitate earlier migraine treatment.
| S-EPMC3451646 | biostudies-literature
Project description:BackgroundMigraine prevalence is age and sex dependent, predominating in women in early and middle adulthood; however, migraine also represents a substantial burden for men and adults of all ages. Thus, understanding this burden and the efficacy of migraine preventive medications in both sexes and across age groups is critical. The randomized, placebo-controlled, double-blind, phase 3b FOCUS study demonstrated the safety and efficacy of fremanezumab, a fully humanized monoclonal antibody (IgG2∆a) that selectively targets calcitonin gene-related peptide as a migraine preventive treatment for individuals with migraine and prior inadequate response to 2 to 4 migraine preventive medication classes. Here, we assessed the efficacy of fremanezumab in participants from FOCUS subgrouped by age (18-45 years and > 45 years) and sex.MethodsIn the FOCUS study, eligible participants were randomized (1:1:1) to 12 weeks of double-blind treatment with quarterly fremanezumab, monthly fremanezumab, or matched monthly placebo. In this post hoc analysis, we evaluated changes from baseline in monthly migraine days (primary endpoint of FOCUS) and other secondary and exploratory efficacy outcomes in prespecified age (18-45 and > 45 years) and sex subgroups.ResultsThe modified intention-to-treat population (received ≥ 1 dose of study drug and had ≥ 10 days of postbaseline efficacy assessments for the primary endpoint) totaled 837 participants (18-45 years, n = 373; > 45 years, n = 464; male, n = 138; female, n = 699). Consistent reductions in monthly average number of migraine days during 12 weeks were observed, regardless of age (18-45 years: quarterly fremanezumab, - 4.1 days; monthly fremanezumab, - 4.7 days; placebo, - 0.9 days; P < 0.001; > 45 years: quarterly fremanezumab, - 3.6 days; monthly fremanezumab, - 3.7 days; placebo, - 0.3 days; P < 0.001) and sex (male: quarterly fremanezumab, - 4.1 days; monthly fremanezumab, - 4.6 days; placebo, - 0.3 days; P < 0.001; female: quarterly fremanezumab, - 3.6 days; monthly fremanezumab, - 3.9 days; placebo, - 0.6 days; P < 0.001). Fremanezumab also reduced monthly headache days of at least moderate severity, monthly days of acute medication use, and improved Migraine Disability Assessment scores across subgroups.ConclusionsThese results demonstrate the efficacy of fremanezumab in patients with difficult-to-treat migraine for reducing migraine and headache days, acute medication use, and disability, regardless of age or sex.Trial registrationClinicalTrials.gov Identifier NCT03308968 (FOCUS), registered October 13, 2017.
| S-EPMC8903667 | biostudies-literature
Project description:IntroductionFor the past 20 years vagus nerve stimulation (VNS) has been an approved invasive treatment option for treatment-resistant depression (TRD) across Europe. In contrast to more common treatments, such as ECT, knowledge about VNS is low both in the general population and among professionals.MethodsIn this narrative review, we provide a clinically and scientifically sound overview of VNS. Hypotheses on the mechanism of action as well as the current evidence base on efficacy are presented. Perioperative management, adverse event profile and follow-up including dose titration are described. A comparison of international guideline recommendations on VNS is also provided. Furthermore, we formulate criteria that are helpful in the selection of appropriate patients.ResultsElectrical impulses are transmitted afferently via the vagus nerve and stimulate a neuromodulatory cerebral network via different pathways. Many studies and case series demonstrated the efficacy of VNS as an adjuvant procedure for TRD. The effect occurs with a latency period of 3-12 months and possibly increases with the duration of VNS. If stimulation recommendations are followed, side effects are tolerable for most patients.ConclusionThe use of VNS is an approved, effective and well-tolerated long-term therapy for chronic and treatment-resistant depression. Further sham-controlled studies over a longer observational period are desirable to improve the evidence.
| S-EPMC9452433 | biostudies-literature