Reviews/Anti CGRP Antibodies/Monthly migraine days in episodic migraine
Episodic Migraine · CGRP-EMR-01 · v2
Across several large, independent, blinded trials, each of four different anti-CGRP antibodies cut the number of migraine days per month more than a dummy injection did in people with episodic migraine. Erenumab trials showed reductions of 3.2 to 3.7 days versus 1.8 for placebo [1] and a 2.9 versus 1.8 difference [2]; galcanezumab cut 4.7 and 4.6 days versus 2.8 [4]; fremanezumab and eptinezumab showed the same direction [28][29]. The extra benefit over placebo is small in absolute terms, roughly one to two days, because the placebo response itself is large. But the claim only says the drugs reduce migraine days, and every trial points the same way across different molecules, companies and countries. Real-world patient cohorts show the same pattern [9][16]. The panel treated the direction of effect as firmly supported even though the size of the effect is modest.
Four distinct antibodies each beat placebo on the pre-specified primary endpoint of monthly migraine days in episodic migraine: erenumab reduced days by 3.2 and 3.7 versus 1.8 for placebo from a baseline of 8.3 [1], with a treatment difference of -1.0 (95% CI -1.6, -0.5) in ARISE [2]; galcanezumab reduced days by 4.7 and 4.6 versus 2.8 [4] and 4.3 and 4.2 versus 2.3 [5]; fremanezumab showed differences of -2.81 and -2.64 (p<0.0001) [28]; and eptinezumab showed a -1.0 difference [29]. A Japanese phase 3 trial found a -1.67 difference (95% CI -2.56, -0.78) in episodic migraine [13], and a phase 2 dose-ranging study found -1.25, -2.31 and -1.89 across doses [17]. Real-world cohorts corroborate, with erenumab cutting 4.5 monthly migraine days in high-frequency episodic patients [9]. Direction and statistical significance are uniform across every included trial. The contested point: The division is over magnitude rather than direction: the placebo-subtracted effect is modest (around one day for erenumab [2], around two for galcanezumab and fremanezumab [5][28]) against a large placebo response, and the eptinezumab phase-2 estimate [29] had a confidence interval (-2.0 to 0.1) crossing zero and only a one-sided p=0.0306, so it does not independently establish the effect. The Sceptic flagged these points but recorded that none undercut the directional claim the panel assessed.
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The eptinezumab phase-2 primary endpoint [29] was borderline: between-group difference -1.0 with 95% CI -2.0 to 0.1 crossing zero and only one-sided p=0.0306; it does not independently establish the effect.
Placebo-subtracted effect sizes are modest (~1 MMD for erenumab [2], ~2 MMD for galcanezumab/fremanezumab [4][5][28]) against a large placebo response; the reduction is real and significant but small in absolute terms. The claim asserts only direction, which is supported.
Where it remains uncertain. The placebo-subtracted effect is modest, roughly 1 to 2 days [2][5][28], and the eptinezumab phase-2 interval crosses zero (-2.0 to 0.1, one-sided p=0.0306) [29].
Aleatory
Placebo arms themselves reduced monthly migraine days by 1.8 to 2.8 [1][4][5], so the between-patient variability in spontaneous improvement is substantial and narrows the net drug effect.
The load-bearing papers from a corpus of 43, each classified by what it does to the claim. Every DOI is taken from the corpus the claim was graded on.
Pivotal phase 3 RCT: erenumab significantly reduces MMD in EM.
“by months 4 through 6, the number of days was reduced by 3.2 in the 70-mg erenumab group and by 3.7 in the 140-mg erenumab group, as compared with 1.8 days in the placebo group (P<0.001 for each dose vs. placebo)”
Panel auditInternal validity: high · scope of inference: Adults with episodic migraine over 6 months.Key limitations: industry funded · long-term durability unknown per abstract
Second erenumab phase 3 RCT confirms significant MMD reduction in EM.
“Patients receiving erenumab experienced -2.9 days change in monthly migraine days, compared with -1.8 days for placebo, least-squares mean (95% CI) treatment difference of -1.0 (-1.6, -0.5) ( p < 0.001)”
Panel auditInternal validity: high · scope of inference: Adults with episodic migraine at month 3.Key limitations: industry funded · single 70 mg dose
Galcanezumab phase 3 (EVOLVE-1): significant MMD reduction in EM.
“treatment with galcanezumab significantly reduced monthly migraine headache days (both P < .001) by 4.7 days (120 mg) and 4.6 days (240 mg) compared with placebo (2.8 days)”
Panel auditInternal validity: high · scope of inference: Adults with episodic migraine over 6 months.Key limitations: industry funded
In HFEM patients MMD was reduced by 4.3 days at weeks 45-48, though uncontrolled.
Panel auditInternal validity: low · scope of inference: HFEM and CM patients with ≥3 prior preventive failures.Key limitations: no control · observational · refractory selection
4 of 43 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.
Converging significant primary-endpoint RCT evidence across four independent antibodies establishes the MMD-reduction effect in episodic migraine despite modest effect magnitude.
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.
Eptinezumab episodic phase-3 numeric results. The eptinezumab episodic case rests on one borderline phase-2 estimate [29]; the phase-3 PROMISE-1 abstracts [31][32] carry no extractable figures. The panel rates this the highest-importance open gap for the claim, and names the study design that would close it: Report full numeric primary-endpoint results from a phase-3 placebo-controlled eptinezumab trial in episodic migraine.
Open question: What is the phase-3 primary-endpoint reduction in monthly migraine days for eptinezumab in episodic migraine? Why it is still open: The corpus holds only a borderline phase-2 estimate [29] and numberless phase-3 abstracts [31][32].
Priors is a sceptical first reader, not peer review, and not medical advice.
Release 2026-q4 · graded 21 Oct 2026 · protocol v0.19