Dataset Information

CGRP monoclonal antibodies in migraine: an efficacy and tolerability comparison with standard prophylactic drugs.

ABSTRACT:

Background

Several drugs are available for the preventive treatment of both episodic and chronic migraine. The choice of which therapy to initiate first, second, or third is not straightforward and is based on multiple factors, including general efficacy, tolerability, potential for serious adverse events, comorbid conditions, and costs. Recently, a new class of migraine preventive drugs was introduced, i.e. monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor.

Methods

The present article summarizes the evidence gathered with this new migraine preventive drug class from randomized placebo-controlled clinical trials. It further puts this into perspective next to the evidence gained by the most widely used agents for the prevention of episodic and chronic migraine with an emphasis on efficacy and the robustness with which this efficacy signal was obtained.

Results

Although being a relatively new class of migraine preventive drugs, monoclonal antibodies blocking the CGRP pathway have an efficacy which is at least comparable if not higher than those of the currently used preventive drugs. Moreover, the robustness of this efficacy signal is substantiated by several randomized clinical trials each including large numbers of patients. In addition, because of their excellent tolerability and with long-term safety data emerging, they seem to have an unprecedented efficacy over adverse effect profile, clearly resulting in an added value for migraine prevention.

Conclusions

Balancing the data presented in the current manuscript with additional data concerning long term safety on the one hand and cost issues on the other hand, can be of particular use to health policy makers to implement this new drug class in the prevention of migraine.

SUBMITTER: Vandervorst F

PROVIDER: S-EPMC8547103 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

CGRP monoclonal antibodies in migraine: an efficacy and tolerability comparison with standard prophylactic drugs.

Vandervorst Fenne F Van Deun Laura L Van Dycke Annelies A Paemeleire Koen K Reuter Uwe U Schoenen Jean J Versijpt Jan J

The journal of headache and pain 20211025 1

<h4>Background</h4>Several drugs are available for the preventive treatment of both episodic and chronic migraine. The choice of which therapy to initiate first, second, or third is not straightforward and is based on multiple factors, including general efficacy, tolerability, potential for serious adverse events, comorbid conditions, and costs. Recently, a new class of migraine preventive drugs was introduced, i.e. monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its rece ...[more]

PMID: 34696711

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Project description:OBJECTIVE:Evaluate the safety and tolerability of oral rimegepant when used for acute treatment concomitantly with a monoclonal antibody (mAb) targeting the calcitonin gene-related peptide (CGRP) ligand or receptor (CGRP mAb) for the preventive treatment of migraine. BACKGROUND:The efficacy of CGRP mAbs for the preventive treatment of migraine and the small molecule CGRP receptor antagonist rimegepant for acute treatment has been demonstrated in randomized controlled clinical trials. Over the past few years, the US Food and Drug Administration has approved 4 CGRP mAbs for the preventive treatment of migraine and 2 small molecule CGRP receptor antagonists for the acute treatment of migraine. A previous case report of 2 patients receiving concomitant treatment with rimegepant and erenumab suggested that rimegepant may be safely used as acute treatment in patients who are also receiving a preventive regimen involving CGRP mAbs. We report here 13 additional patients with migraine who simultaneously used rimegepant and either erenumab, fremanezumab, or galcanezumab and assess the rate of on-treatment adverse events (AEs). METHODS:This was a substudy nested within a multicenter, open-label, long-term safety study in adults with 2-14 monthly migraine attacks of moderate to severe pain intensity. A subgroup experiencing 2-8 monthly attacks and taking a stable dose of a CGRP mAb also took rimegepant 75 mg as needed up to once daily for acute treatment for 12 weeks. RESULTS:The 13 patients (11 women [85%]; mean age 49.9 years) enrolled in the substudy were being treated with CGRP mAbs (erenumab [n = 7], fremanezumab [n = 4], or galcanezumab [n = 2]). Mean (SD) time in the rimegepant treatment period was 9.6 (4.6) weeks. Mean (SD) 4-week rimegepant exposure was 7.8 (5.5) doses; a total of 224 doses were taken. Five (38%) patients reported ?1 on-treatment AE. Of these, 2 (15%) patients had mild or moderate nasopharyngitis; no other AEs occurred in ?2 patients. Three patients had AEs of mild or moderate severity that were considered potentially treatment-related. No patients had serious AEs, AEs leading to discontinuation, or aminotransferase levels >3× the upper limit of normal. CONCLUSION:Rimegepant, when used as an oral acute treatment in patients receiving CGRP mAbs as preventive treatment, was well tolerated; no safety issues were identified. Studies involving larger patient populations are needed to confirm these findings.

Project description:BackgroundTo date, real-world evidence on persistence to anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA have excluded eptinezumab. This retrospective cohort study was performed to compare treatment persistency among patients with migraine on anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA.MethodsThis retrospective study used IQVIA PharmMetrics data. Adult patients with migraine treated with an anti-CGRP mAb or onabotulinumtoxinA who had 12 months of continuous insurance enrollment before starting treatment were included. A "most recent treatment episode" analysis was used in which the most recent episode was defined as the latest treatment period with the same drug (anti-CGRP mAb or onabotulinumtoxinA) without a ≥ 15-day gap in medication supply on/after June 25, 2020, to December 31, 2021. Patients were indexed at the start of their most recent episode. Patients were considered non-persistent and discontinued the therapy associated with their most recent episode if there was ≥ 15-day gap in medication supply. A Cox proportional-hazards model estimated the discontinuation hazard between treatments. The gap periods and cohort definition were varied in sensitivity analyses.ResultsThe study included 66,576 patients (median age 46 years, 88.6% female). More eptinezumab-treated patients had chronic migraine (727/1074), ≥ 3 previous acute (323/1074) or preventive (333/1074) therapies, and more prior treatment episodes (3) than other treatment groups. Based on a 15-day treatment gap, patients on subcutaneous anti-CGRP mAbs had a 32% (95% CI: 1.19, 1.49; erenumab), 42% (95% CI: 1.27, 1.61; galcanezumab), and 58% (95% CI: 1.42, 1.80; fremanezumab) higher discontinuation hazard than those receiving eptinezumab, with this relationship attenuated, but still statistically significant based on 30-day and 60-day treatment gaps. There was no significant difference in the discontinuation hazard between eptinezumab and onabotulinumtoxinA. Based on a 15-day treatment gap among patients who newly initiated therapy, the discontinuation hazard of subcutaneous anti-CGRP mAbs remained significantly higher compared to eptinezumab and onabotulinumtoxinA.ConclusionPatients treated with eptinezumab demonstrated persistency that was higher than subcutaneous anti-CGRP mAbs and similar to onabotulinumtoxinA.

Project description:New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection.Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1).These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1 influenza.

Project description:BackgroundHead-to-head comparator trials between first-line oral migraine preventatives and the new monoclonal antibodies (mAbs) blocking the calcitonin gene-related peptide (CGRP) pathway have not been published to date.ObjectivesThis study aimed to indirectly compare the clinical efficacy and safety of mAbs against CGRP or its receptor (CGRPR) and topiramate in episodic migraine prophylaxis using meta-analysis.MethodsWe included controlled trials testing efficacy and safety of erenumab, galcanezumab, fremanezumab, eptinezumab, and topiramate in adults diagnosed with episodic migraine. We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from January 2000 to November 2020. We used the Risk of Bias 2 (RoB2) tool to assess the risk of bias and report pooled mean effects (mean difference and risk ratio) as estimated in a random effect model. For efficacy analysis, we determined the reduction of monthly migraine days (MMDs), reduction of days with acute medication (AMDs), and 50% responder rates (50% RR). For safety, we determined adverse events (AEs) occurring in ≥ 2% of study participants and the number of patients who discontinue treatment due to AEs (DAEs). The number needed to treat (NNT) and to harm (NNH) were estimated as well as the likelihood to help or harm (LLH).ResultsWe included 13 trials involving 7557 patients: three trials with erenumab, two trials with galcanezumab, two trials with fremanezumab, one trial with eptinezumab, and five trials with topiramate, for the prophylaxis of episodic migraine in adults. The placebo-subtracted reduction (pooled mean difference) of MMDs were - 1.55 (95% CI - 1.86 to - 1.24; active drug n = 3326 vs placebo n = 2219, 8 studies) for the CGRP(R) mAb and - 1.11 (95% CI - 1.62 to - 0.59; active drug n = 1032 vs placebo n = 543, 4 studies) for topiramate (p for subgroup difference = 0.15). 'Cognitive' and 'sensory & pain'-related adverse events occurred more often in patients treated with topiramate compared with those treated with a CGRP(R) mAb (p for subgroup difference 0.03 and < 0.001, respectively). Based on the 50% RR and DAE, the NNT, NNH, and LHH for the CGRP(R) mAbs were 6, 130, and 24.3:1, respectively. For topiramate, these values were 7, 9, and 1.8:1, respectively.ConclusionThe efficacy of CGRP(R) mAbs to reduce migraine days does not differ from topiramate. However, the safety profile is in favor of the CGRP(R) mAbs, with a higher likelihood to help than to harm compared with topiramate. The diversity of endpoint determination and the heterogeneity between studies for some endpoints cause some limitations for this study.

Dataset Information

CGRP monoclonal antibodies in migraine: an efficacy and tolerability comparison with standard prophylactic drugs.

Background

Methods

Results

Conclusions

Publications

CGRP monoclonal antibodies in migraine: an efficacy and tolerability comparison with standard prophylactic drugs.

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