Adverse Events Reported with Therapies Targeting the CGRP Pathway During the First 6 Months Post-launch: A Retrospective Analysis Using the FDA Adverse Events Reporting System

Silberstein, Stephen D; Reshef, Shoshana; Cohen, Joshua M.; Gandhi, Sanjay; Seminerio, Michael J.; Campos, Verena Ramirez; Kessler, Yoel; Thompson, Stephen; Blumenfeld, Andrew

doi:10.1007/s12325-022-02346-4

Cited by 22 publications

(13 citation statements)

References 40 publications

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“…Erenumab was generally well tolerated, and all adverse effects subsided after stopping treatment. However, mild to moderate constipation (affecting 33% of our population) and bloating (affecting 10% of our population) were common adverse effects, which is consistent with previous trials in participants with headache as well as empirical data . Of note, patients with rosacea are more likely to have gastrointestinal diseases such as irritable bowel syndrome and inflammatory bowel disorders, which could have affected our data .…”

Section: Discussionsupporting

confidence: 89%

Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea

Wienholtz,

Christensen,

et al. 2024

JAMA Dermatol

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ImportanceTreatment of erythema and flushing in rosacea is challenging. Calcitonin gene-related peptide (CGRP) has been associated with the pathogenesis of rosacea, raising the possibility that inhibition of the CGRP pathway might improve certain features of the disease.ObjectiveTo examine the effectiveness, tolerability, and safety of erenumab, an anti–CGRP-receptor monoclonal antibody, for the treatment of rosacea-associated erythema and flushing.Design, Setting, and ParticipantsThis single-center, open-label, single-group, nonrandomized controlled trial was conducted between June 9, 2020, and May 11, 2021. Eligible participants included adults with rosacea with at least 15 days of either moderate to severe erythema and/or moderate to extreme flushing. No concomitant rosacea treatment was allowed throughout the study period. Visits took place at the Danish Headache Center, Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark. Participants received 140 mg of erenumab subcutaneously every 4 weeks for 12 weeks. A safety follow-up visit was performed at week 20. Data analysis occurred from January 2023 to January 2024.Intervention140 mg of erenumab every 4 weeks for 12 weeks.Main Outcomes and MeasuresThe primary outcome was mean change in the number of days with moderate to extreme flushing during weeks 9 through 12, compared with the 4-week run-in period (baseline). The mean change in number of days with moderate to severe erythema was a secondary outcome. Adverse events were recorded for participants who received at least 1 dose of erenumab. Differences in means were calculated with a paired t test.ResultsA total of 30 participants (mean [SD] age, 38.8 [13.1] years; 23 female [77%]; 7 male [23%]) were included, of whom 27 completed the 12-week study. The mean (SD) number of days with moderate to extreme flushing was reduced by −6.9 days (95% CI, −10.4 to −3.4 days; P &lt; .001) from 23.6 (5.8) days at baseline. The mean (SD) number of days with moderate to severe erythema was reduced by −8.1 days (95% CI, −12.5 to −3.7 days; P &lt; .001) from 15.2 (9.1) days at baseline. Adverse events included transient mild to moderate constipation (10 participants [33%]), transient worsening of flushing (4 participants [13%]), bloating (3 participants [10%]), and upper respiratory tract infections (3 participants [10%]), consistent with previous data. One participant discontinued the study due to a serious adverse event (hospital admission due to gallstones deemed unrelated to the study), and 2 participants withdrew consent due to lack of time.Conclusions and RelevanceThese findings suggest that erenumab might be effective in reducing rosacea-associated flushing and chronic erythema (participants generally tolerated the treatment well, which was consistent with previous data), and that CGRP-receptor inhibition holds potential in the treatment of erythema and flushing associated with rosacea. Larger randomized clinical trials are needed to confirm this finding.Trial RegistrationClinicalTrials.gov Identifier: NCT04419259

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Section: Discussionsupporting

confidence: 89%

Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea

Wienholtz,

Christensen,

et al. 2024

JAMA Dermatol

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“…Although the evidence provided by these studies is not considered to be of the same quality as RCTs, they are very useful in that they generally confirm the results of the RCTs regarding efficacy, tolerability, and safety, and they do so within a wide variety of international cohorts, often over longer time periods. 40 Although not consistently identified as significant issues within the clinical trials, 35,41 safety issues that have been identified based on "real-world" experience include constipation and hypertension (both primarily for erenumab) and Raynaud's phenomenon; [42][43][44][45][46] however, it appears very uncommon for these or other adverse events to necessitate discontinuation of therapy. Given the active surveillance for adverse events internationally, there is a high level of confidence that any adverse events that emerge with long-term use will be identified rapidly.…”

Section: "Real-world" Studiesmentioning

confidence: 99%

Calcitonin gene‐related peptide‐targeting therapies are a first‐line option for the prevention of migraine: An American Headache Society position statement update

Charles,

Digre,

Goadsby

et al. 2024

Headache

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ObjectiveTo provide a position statement update from The American Headache Society specifically regarding therapies targeting calcitonin gene‐related peptide (CGRP) for the prevention of migraine.BackgroundAll migraine preventive therapies previously considered to be first‐line treatments were developed for other indications and adopted later for migraine. Adherence to these therapies is often poor due to issues with efficacy and tolerability. Multiple new migraine‐specific therapies have been developed based on a broad foundation of pre‐clinical and clinical evidence showing that CGRP plays a key role in the pathogenesis of migraine. These CGRP‐targeting therapies have had a transformational impact on the management of migraine but are still not widely considered to be first‐line approaches.MethodsEvidence regarding migraine preventive therapies including primary and secondary endpoints from randomized placebo‐controlled clinical trials, post hoc analyses and open‐label extensions of these trials, and prospective and retrospective observational studies were collected from a variety of sources including PubMed, Google Scholar, and ClinicalTrials.gov. The results and conclusions based upon these results were reviewed and discussed by the Board of Directors of The American Headache Society to confirm consistency with clinical experience and to achieve consensus.ResultsThe evidence for the efficacy, tolerability, and safety of CGRP‐targeting migraine preventive therapies (the monoclonal antibodies: erenumab, fremanezumab, galcanezumab, and eptinezumab, and the gepants: rimegepant and atogepant) is substantial, and vastly exceeds that for any other preventive treatment approach. The evidence remains consistent across different individual CGRP‐targeting treatments and is corroborated by extensive “real‐world” clinical experience. The data indicates that the efficacy and tolerability of CGRP‐targeting therapies are equal to or greater than those of previous first‐line therapies and that serious adverse events associated with CGRP‐targeting therapies are rare.ConclusionThe CGRP‐targeting therapies should be considered as a first‐line approach for migraine prevention along with previous first‐line treatments without a requirement for prior failure of other classes of migraine preventive treatment.

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“…-Se recomienda individualizar su uso en menores de 18 años, pacientes con patología cerebrovascular o cardiovascular grave en el último año o con factores de riesgo vascular no controlados, y pacientes con enfermedad de Raynaud (sobre todo secundaria), así como evitar el erenumab en pacientes con estreñimiento grave mal controlado. En estudios de la vida real no han aparecido eventos cardiovasculares de relevancia, más allá de la advertencia sobre el efecto en la presión arterial 85,86 , que en general no supera las cifras de normalidad. Es recomendable vigilar las cifras de presión arterial, en especial con el uso de erenumab en pacientes con predisposición, los primeros 7 días tras la infiltración.…”

Section: Conclusiones Y Resumen De Las Recomendacionesunclassified

Consenso sobre anticuerpos monoclonales en migraña del Grupo de Estudio de Cefaleas de la Asociación Madrileña de Neurología

González¹,

García²,

Miguel³

et al. 2024

KRANION

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Introducción: A finales de 2018 fue autorizado en España el uso de los primeros anticuerpos monoclonales contra el péptido relacionado con el gen de la calcitonina (CGRP) o su receptor como tratamiento preventivo de la migraña. Su posología y mecanismo de acción los diferencian de los fármacos orales actuales. El acceso a estos tratamientos requiere el cumplimiento de unas condiciones especiales para su financiación en nuestro medio. En este documento se revisan los aspectos fundamentales de estos fármacos. Además, se han elaborado una serie de recomendaciones prácticas sobre su manejo basadas en los principales consensos internacionales y en nuestra experiencia actual en la práctica clínica.

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Adverse Events Reported with Therapies Targeting the CGRP Pathway During the First 6 Months Post-launch: A Retrospective Analysis Using the FDA Adverse Events Reporting System

Cited by 22 publications

References 40 publications

Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea

Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea

Calcitonin gene‐related peptide‐targeting therapies are a first‐line option for the prevention of migraine: An American Headache Society position statement update

Consenso sobre anticuerpos monoclonales en migraña del Grupo de Estudio de Cefaleas de la Asociación Madrileña de Neurología

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