Serum CGRP in migraine patients using erenumab as preventive treatment

Lentsch, Simone de Vries; Garrelds, Ingrid M.; Danser, A.H. Jan; Terwindt, Gisela M.; MaassenVanDenBrink, Antoinette

doi:10.1186/s10194-022-01483-z

Cited by 13 publications

(11 citation statements)

References 30 publications

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“…In our larger cohort of patients treated with erenumab, free CGRP plasma levels did not differ from those of prophylaxis-naïve patients and remained stable after treatment discontinuation. In line with our results, a recent study on serum CGRP concentrations did not show any difference between before and 2–4 weeks after starting erenumab treatment [ 14 ]. Similarly, a study on salivary CGRP levels detected no significant change during 12 weeks of erenumab therapy [ 19 ].…”

Section: Discussionsupporting

confidence: 93%

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Change of CGRP Plasma Concentrations in Migraine after Discontinuation of CGRP-(Receptor) Monoclonal Antibodies

et al. 2023

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Discontinuation of treatment with monoclonal antibodies (mAb) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway leads to an increase in migraine frequency. We aimed to assess changes in free and total CGRP plasma concentrations after the discontinuation of CGRP(-receptor) mAbs. This prospective analysis included 59 patients with migraine (n = 25 erenumab, n = 25 galcanezumab, n = 9 fremanezumab) who discontinued mAbs after ≥8 months of treatment. Patients were visited at the time of the last mAb injection (V1) and 16 weeks later (V2). For control, 30 migraine patients without preventive drug therapy were included. We measured free CGRP plasma concentrations in the erenumab and fremanezumab group and total CGRP concentrations in the galcanezumab group. Free CGRP plasma concentrations did not change after treatment discontinuation [erenumab: V1 31.2 pg/mL (IQR 25.8–45.6), V2 30.3 pg/mL (IQR 22.9–47.6), p = 0.65; fremanezumab V1 29.4 pg/mL (IQR 16.4–61.9), V2 34.4 (19.2–62.0), p = 0.86]. Controls had similar CGRP values of 32.6 pg/mL (IQR 21.3–44.6). Total CGRP concentrations in the galcanezumab group were 5439.3 pg/mL (2412.7–6338.1) at V1, and decreased to 1853.2 pg/mL (1136.5–3297.0) at V2 (p < 0.001). Cessation of treatment with CGRP(-R) mAbs did not have an impact on the free-circulating CGRP concentrations. Total CGRP decreased significantly after three months of treatment discontinuation.

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Section: Discussionsupporting

confidence: 93%

“…CGRP-targeted treatments in particular are thought to have an impact on CGRP plasma concentrations [ 12 ]. However, a proof-of-concept and a second study on CGRP in peripheral blood in patients on erenumab remained inconclusive [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Change of CGRP Plasma Concentrations in Migraine after Discontinuation of CGRP-(Receptor) Monoclonal Antibodies

et al. 2023

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“…Our novel objective was to describe how the serum levels of CGRP evolve throughout the course of anti‐CGRP/CGRP‐R mAb treatments. A very recently published study has found erenumab numerically decreases the baseline serum CGRP levels at 2 to 4 weeks since the first dose, although the differences were not significant 32 . Here, our results show that these therapies have a lowering effect on the circulating concentrations of alpha‐CGRP not only at 2 weeks since its initiation but also at 3 months since the first dose, identical for both antibodies against the ligand and its receptor.…”

Section: Discussionsupporting

confidence: 58%

“…A very recently published study has found erenumab numerically decreases the baseline serum CGRP levels at 2 to 4 weeks since the first dose, although the differences were not significant. 32 Here, our results show that these therapies have a lowering effect on the circulating concentrations of alpha-CGRP not only at 2 weeks since its initiation but also at 3 months since the first dose, identical for both antibodies against the ligand and its receptor. On top of that, there was a correlation between the amount of circulating alpha-CGRP decreased by the therapies within the first 3 months and the reduction of MMD at the third month of treatment.…”

Section: Discussionsupporting

confidence: 56%

Serum Alpha and Beta‐CGRP Levels in Chronic Migraine Patients Before and After Monoclonal Antibodies Against CGRP or its Receptor

Gárate

González-Quintanilla

González

et al. 2023

Annals of Neurology

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Objective: The objective of this study was to analyze the evolution of alpha and beta-CGRP circulating levels throughout CGRP monoclonal antibodies (mAbs) treatment in patients with chronic migraine (CM). Methods: We recruited patients with CM beginning mAbs along with sex and age paired healthy controls (HCs). Blood was extracted before, 2 weeks (M0.5) and 3 months (M3) after the first dose of mAbs, always in free-migraine periods, and once for HCs. Alpha and beta-CGRP serum levels were measured using enzyme-linked immunosorbent assays (ELISAs) specific for each isoform. Results: Baseline alpha-CGRP levels were significantly elevated in 103 patients with CM (median = 50.3, 95% confidence interval [CI] = 40.5-57.0 pg/ml) compared to 78 HCs (median = 37.5, 95% CI = 33.9-45.0 pg/ml; 95% CI of differences = 2.85-17.08 pg/ml) and significantly decreased (n = 96) over the course of mAb treatment (M0.5: median = 40.4, 95% CI = 35.6-48.2 pg/ml; and M3: median = 40.9, 95% CI = 36.3-45.9 pg/ml). Absolute decrease of alpha-CGRP throughout the treatment positively correlated with the decrease in MMDs. Negative modulation of alpha-CGRP significantly associated with positive scores at the Patient Global Impression of Change scale and with analgesic overuse reversal. Beta-CGRP did not differ at baseline between patients with CM (median = 4.2, 95% CI = 3.0-4.8 pg/ml) and HCs (median = 4.4, 95% CI = 3.4-5.6 pg/ml; À1.09 to 0.60) nor was modulated by mAb treatment (n = 96; M0.5: median = 4.5, 95% CI = 3.5-5.2 pg/ml; and M3: median = 4.6, 95% CI = 3.7-5.2 pg/ml). Interpretation: Treatment with mAbs, regardless of its target, is able to progressively normalize basally increased alpha-CGRP levels in CM and this effect correlates with efficacy measures, which supports a role of this neuropeptide as the first CM biomarker.

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“…A few studies have investigated the prediction of treatment efficacy to mAbs against CGRP signaling using blood-based measurements of CGRP [ 7 , 46 ]. In a recent study of 94 patients with migraine treated with erenumab, baseline serum CGRP levels were not found to predict treatment response, but the treatment period was only 2–4 weeks [ 10 ]. Another recent study found that 96 patients with chronic migraine showed elevated levels of serum CGRP compared to healthy controls, and that these levels subsequently normalized at two weeks and at three months during treatment with erenumab [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

Karlsson¹,

Ashina²,

Cullum³

et al. 2023

J Headache Pain

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Background Erenumab has demonstrated effectiveness for prevention of migraine attacks, but the treatment is costly, and a considerable proportion of patients do not respond to it. The Registry for Migraine study (REFORM) was initiated to discover biomarkers that can predict response to erenumab in patients with migraine. The specific objective was to investigate differences in erenumab efficacy based on clinical information, blood-based biomarkers, structural and functional magnetic resonance imaging (MRI), and response to intravenous infusion of calcitonin gene-related peptide (CGRP). In this first report of the REFORM study, we provide a comprehensive description of the study methodology, and present the baseline characteristics of the study population. Methods The REFORM study was a single-center, prospective, longitudinal cohort study in adults with migraine who were scheduled to receive preventive treatment with erenumab as part of a separate, open-label, single-arm phase IV trial. The study included four periods: a 2-week screening period (Weeks -6 to -5), 4-week baseline period (Week -4 to Day 1), 24-week treatment period (Day 1 to Week 24), and a 24-week follow-up period without treatment (Week 25 to Week 48). Demographic and clinical characteristics were recorded using a semi-structured interview, whilst outcome data were obtained using a headache diary, patient-reported outcomes, blood sampling, brain MRI, and responsiveness to intravenous infusion of CGRP. Results The study enrolled 751 participants, with a mean age ± SD of 43.8 ± 12.2 years, of which 88.8% (n = 667) were female. At enrollment, 64.7% (n = 486) were diagnosed with chronic migraine, and 30.2% (n = 227) had history of aura. The mean monthly migraine days (MMDs) was 14.5 ± 7.0. Concomitant preventive medications were used by 48.5% (n = 364) of the participants, and 39.9% (n = 300) had failed ≥ 4 preventive medications. Conclusion The REFORM study enrolled a population with a high migraine burden and frequent use of concomitant medications. The baseline characteristics were representative of patients with migraine in specialized headache clinics. Future publications will report the results of the investigations presented in this article. Trial registration The study and sub-studies were registered on ClinicalTrials.gov (NCT04592952; NCT04603976; and NCT04674020).

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Serum CGRP in migraine patients using erenumab as preventive treatment

Cited by 13 publications

References 30 publications

Change of CGRP Plasma Concentrations in Migraine after Discontinuation of CGRP-(Receptor) Monoclonal Antibodies

Change of CGRP Plasma Concentrations in Migraine after Discontinuation of CGRP-(Receptor) Monoclonal Antibodies

Serum Alpha and Beta‐CGRP Levels in Chronic Migraine Patients Before and After Monoclonal Antibodies Against CGRP or its Receptor

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

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