Reviews/Anti CGRP Antibodies/Low discontinuation with CGRP antibodies
Safety · CGRP-SAF-03 · v2
Borderline: within 4 points of the Established/Likely boundary, so a re-grade could land either side.
Across drug-company trials, long-running follow-up studies and independent patient series from several countries, very few people stopped anti-CGRP antibody treatment because of side effects. Where studies gave a figure, it sat below one in twenty, and some real-world series reported about one in fifty or none at all ([3], [16], [37], [13], [27], [33]). A five-year study found no rise in people stopping for side effects over time ([10]). The pattern held for all four marketed antibodies and across different sponsors, which is why the panel treated the finding as well supported. The main cautions are that the word 'low' has no agreed threshold, most pivotal trials were short and funded by the makers, and a small case series recorded new inflammatory problems that short trials are too small to rule out ([31]).
Pivotal randomised trials and long-term/open-label safety studies report adverse-event-driven discontinuation below 5%: galcanezumab 'less than 5% across all treatment groups' [3] and 4.8% over 12 months [16], and erenumab 4.1% of the cohort over 128 weeks [37]. Independent real-world cohorts report lower still: 2.2% stopping for adverse events in central Italy [13], erenumab discontinuation 'rarely caused by AEs (5/49)' [33], and no patients discontinuing CGRP mAbs in a Thai cohort [27]. A five-year open-label erenumab study found no increase in adverse events leading to discontinuation over time [10]. The evidence spans erenumab, galcanezumab, fremanezumab and eptinezumab across multiple countries and sponsors. The contested point: The division is not over direction but over what 'low' means and how tightly the figure is pinned: the claim sets no threshold and the corpus operationalises it as under 5%, so part of the match is semantic. Short, industry-funded pivotal trials ([1], [2], [3], [16]) are underpowered for rare serious harms, and a case series documents new or worsened inflammatory pathology temporally linked to initiation [31].
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One reviewer's only job is to attack the finding. The challenges below were weighed before the grade was set.
The claim's term 'low' is undefined; the corpus operationalises it as <5% discontinuation ([3], [16], [37]), so part of the match is semantic rather than against a pre-specified threshold.
The pivotal RCTs are industry-sponsored ([1] Amgen/Novartis; [2], [12], [21] Teva; [3], [4], [11], [16] Lilly), raising risk of favourable AE-reporting bias in the most-cited discontinuation figures.
Where it remains uncertain. The threshold for 'low' is not pre-specified and most pivotal trials are short and industry-funded, so rare serious harms such as the inflammatory complications in case series [31] could be missed.
Aleatory
Uncommon events such as the new or worsened inflammatory pathology in case series [31] occur unpredictably and are not captured by aggregate discontinuation rates.
Epistemic
The most-cited discontinuation figures come from makers' own pivotal trials ([1], [2], [3], [16]), leaving residual uncertainty about favourable adverse-event reporting.
Inferential
The claim sets no threshold; mapping it to under 5% ([3], [16], [37]) is an inferential step, not a measured match.
The load-bearing papers from a corpus of 37, each classified by what it does to the claim. Every DOI is taken from the corpus the claim was graded on.
Pivotal RCT: explicit <5% AE-discontinuation across arms.
“Completion rate during treatment was high (81.9%; n = 718), and the incidence of discontinuation owing to adverse events was less than 5% across all treatment groups.”
Panel auditInternal validity: high · scope of inference: Galcanezumab discontinuation due to AEs in episodic migraine over 6 months.Key limitations: <5% figure is a ceiling not an exact rate · rate given across all arms including placebo
5-year extension: durability of low AE-discontinuation.
“There were no increases in incidence of AEs, SAEs, or AEs leading to treatment discontinuation over 5 years of exposure.”
Panel auditInternal validity: medium · scope of inference: Long-term erenumab safety in episodic migraine over 5 years.Key limitations: open-label single arm · no discontinuation-due-to-AE rate reported
Real-world cohort: AE-discontinuation only 2.2%, dropouts mainly for inefficacy.
“76 (85.4%) received 6 doses of erenumab, 11 (12.4%) autonomously withdrew the drug due to perceived inefficacy, and 2 (2.2%) due to adverse events.”
Panel auditInternal validity: medium · scope of inference: Erenumab discontinuation due to AEs in a real-life difficult-to-treat migraine population over 6 months.Key limitations: small single-region cohort · uncontrolled
Abstract states AE rates were similar to placebo but reports no discontinuation-due-to-AE rate.
Panel auditInternal validity: high · scope of inference: Erenumab tolerability in episodic migraine over 6 months.Key limitations: no discontinuation-due-to-AE figure · 6-month horizon
4 of 37 papers shown. The full review lists all of them, with the panel’s arbitration →
Claims are graded at each quarterly release, and re-graded between releases only when a pivotal trial lands. Every change is a new version of the claim.
Multiple independent primary studies directly and consistently report low AE-discontinuation, carrying the verdict to the Established band.
Release 2026-q4 re-graded every claim from its corpus under protocol v0.19. An earlier release's grade is shown for the record; it came from an earlier protocol and is not a movement.
Assumptions that carry weight but are not themselves established.
The panel records the gap that would most move the claim, and the study that would close it.
Standardised adverse-event discontinuation definition. Studies pool causes and use different denominators ([13], [15]), so the headline 'under 5%' is not strictly comparable across trials. The panel rates this the highest-importance open gap for the claim, and names the study design that would close it: A pooled analysis using a single pre-specified definition of discontinuation attributable to adverse events across all four antibodies.
Open question: Does adverse-event-driven discontinuation stay below 5% when a single, pre-specified definition is applied uniformly across antibodies and settings? Why it is still open: The corpus figures use varying denominators that pool causes ([13], [15]) and an undefined notion of 'low'.
Priors is a sceptical first reader, not peer review, and not medical advice.
Release 2026-q4 · graded 21 Oct 2026 · protocol v0.19