Pooled Analysis of Real-World Evidence Supports Anti-CGRP mAbs and OnabotulinumtoxinA Combined Trial in Chronic Migraine

Abstract

OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) pathway open a new age for chronic migraine control. However, some 40% patients suffering from chronic migraine is still resistant to treatment. The aim of this work is to answer the following PICOS (participants intervention comparator outcome study design) question: Is there evidence of efficacy and safety of the combined administration of anti-CGRP mAbs and onabotulinumtoxinA in chronic migraine? A systematic review and meta-analysis [Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations] was made up to 19 April 2022. The results are encouraging: the combined treatment proved to afford ≥50% monthly headache days (MHDs)/frequency reduction respect to baseline in up to 58.8% of patients; in comparison, anti-CGRP mAbs reduce MHDs of 1.94 days from baseline and botulinum toxin of 1.86 days. Our study demonstrates for the first time that the combination therapy of onabotulinumtoxinA with anti-CGRP mAbs affords a reduction of 2.67 MHDs with respect to onabotulinumtoxinA alone, with moderate certainty of evidence. Adequately powered, good-quality studies are needed to confirm the response to combination therapy in terms of efficacy and safety. PROSPERO registration: CRD42022313640.

Efficacy and safety of fremanezumab for migraine prophylaxis in patients with at least three previous preventive failures: Prospective, multicenter, real‐world data from a Greek registry

“…In patients failing to achieve at least a 30% reduction in mean MHD after 6 months of fremanezumab treatment, dual targeting with onabotulinumtoxinA add‐on to fremanezumab might be the optimal approach, based on available efficacy results [25, 26], as further exposure to fremanezumab monotherapy is unlikely to produce a delayed clinically meaningful response. An additive effect of onabotulinumtoxinA add‐on to fremanezumab might provide the mechanistic rationale for this dual therapy approach having a distinct mechanism of action when either therapy is given as monotherapy; onabotulinumtoxinA by inhibiting the activation and sensitization of unmyelinated neuronal C‐wide dynamic range afferents [27] and fremanezumab by selectively inhibiting sustained firing of Aδ‐HT fibers in the trigeminal ganglion [7, 28].…”

Bipartite Activation of Sensory Neurons by a TRPA1 Agonist Allyl Isothiocyanate Is Reflected by Complex Ca2+ Influx and CGRP Release Patterns: Enhancement by NGF and Inhibition with VAMP and SNAP-25 Cleaving Botulinum Neurotoxins

“…BoNT/A has been approved and is used clinically with some success for intransigent chronic migraines and off-label for other severe headaches [ 48 ], being recommended as a third-level preventative treatment if first-line (beta-blockers, GABA A -agonists or angiotensin II receptor antagonists) and second-line (amitryptiline [a tricyclic anti-depressant], flunarizine [Ca 2+ antagonist] or sodium valproate [an anti-convulsant]) options prove unsatisfactory [ 51 ]. Interestingly, preliminary clinical evidence suggests that therapies combining BoNT/A injections with antibodies that suppress CGRP signaling are more effective than either treatment alone (reviewed by [ 52 ]). A mechanistic basis is lacking, but these observations seem to indicate that neither BoNT/A nor antibody therapy alone can fully antagonise CGRP signaling in vivo.…”

Efficacy of Essential Oils in Relieving Cancer Pain: A Systematic Review and Meta-Analysis

“…For instance, the study performed by Triana and collaborators [ 82 ] presents a lower weight in the meta-analysis because of its small sample size. The issue of pain assessment is even more important for aged populations with cognitive decline, needing suitable observational tools [ 90 , 91 , 92 ], as well as valid and reliable methods with good psychometric and clinimetric properties in this setting, and deserving consideration for additional sources of pain and their treatment [ 93 , 94 , 95 , 96 , 97 ]. In addition, different cancer types can influence pain, thus making the comparison more difficult.…”