Trajectory of blood pressure after initiating anti-calcitonin gene-related peptide treatment of migraine: a target trial emulation from the veterans health administration.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is involved in migraine pathophysiology and blood pressure regulation. Although clinical trials have established the cardio-cerebrovascular safety profile of anti-CGRP treatment, limited high-quality real-world evidence exists on its long-term effects on blood pressure (BP). To address this gap, we examined the safety of anti-CGRP treatment on BP in patients with migraine headache in the Veterans Health Administration (VHA). METHODS: We emulated a target trial of patients who initiated anti-CGRP treatment or topiramate for migraine prevention between May 17th, 2018 and February 28th, 2023. We calculated stabilized inverse probability weights to balance between groups and then used weighted linear mixed-effect models to estimate the systolic and diastolic BP changes over the study period. For patients without hypertension at baseline, we estimated the cumulative incidence of hypertension using Kaplan-Meier curve. We also used weight mixed-effect Poisson model to estimate the number of antihypertension medications for patients with hypertension at baseline. RESULTS: This analysis included 69,589 patients and 554,437 blood pressure readings. of these, 18,880 patients received anti-CGRP treatment, and they were more likely to be women, have a chronic migraine diagnosis and higher healthcare utilization than those received topiramate. Among patients without hypertension at baseline, we found no significant differences in systolic BP changes over the four-year follow-up between anti-CGRP (slope [standard error, SE] = 0.48[0.06]) and topiramate treated patients (slope[SE] = 0.39[0.04]). The incidence of hypertension was similar for anti-CGRP and topiramate group (4.4 vs 4.3 per 100 person-years). Among patients with hypertension at baseline who initiated anti-CGRP treatment, we found a small but persistent effect on exacerbating hypertension during the first four years of treatment, as evidenced by a significant annual 3.7% increase in the number of antihypertensive medications prescribed (RR = 1.037, 95%CI 1.025-1.048). CONCLUSIONS: Our findings suggest that anti-CGRP treatment is safe regarding blood pressure in patients without hypertension. However, for those with baseline hypertension, anti-CGRP treatment resulted in a small but persistent increase in the number of antihypertensives, indicating an exacerbation of hypertension. Future studies are needed to evaluate the cardio-cerebrovascular safety of anti-CGRP treatment beyond the first four years.

Calcitonin Gene-Related Peptide Monoclonal Antibodies and Risk of SARS-CoV-2 Infection and Severe COVID-19 Outcomes Among Veterans With Migraine Disorder.

Importance: Calcitonin gene-related peptide (CGRP), a neuropeptide involved in migraine pathophysiology, is also a key neuroimmune modulator. CGRP antagonists may help mitigate the hyperinflammatory response observed in patients with COVID-19; however, findings from the literature are contradictory, and to date, no study has investigated the safety and effectiveness of CGRP antagonists against COVID-19. Objective: To evaluate the association between CGRP monoclonal antibody (mAb) treatment and risk of SARS-CoV-2 infection and sequela hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death. Design, Setting, and Participants: This retrospective cohort study analyzed the electronic health records of US veterans aged 18 to 65 years who were diagnosed with migraine disorder and were at risk of COVID-19 between January 20, 2020, and May 19, 2022. Exposure: Initiation of CGRP mAbs. Main Outcomes and Measures: The main outcome was cumulative incidence of SARS-CoV-2 infection. Odds of 30-day hospitalization, requiring supplemental oxygen, use of mechanical ventilation, or death were secondary outcomes. Results: Among 8 178 652 eligible person-trials (354 294 veterans), 9992 (mean [SD] age, 46.0 [9.5] years; 53.9% male) initiated CGRP mAbs and 8 168 660 (mean [SD] age, 46.6 [10.2] years; 65.7% male) did not initiate CGRP mAbs. Over a 28-month follow-up period, 1247 initiators (12.5%) and 780 575 noninitiators (9.6%) tested positive for SARS-CoV-2. After censoring persons who deviated from treatment, the incidence was 7.4 cases per 1000 person-months among initiators and 6.9 per 1000 person-months among noninitiators. The inverse probability-weighted observational analogs of intention-to-treat and per-protocol hazard ratios were 0.95 (95% CI, 0.89-1.01) and 0.93 (95% CI, 0.86-1.02), respectively. No significant differences in the likelihood of hospitalization (odds ratio [OR], 0.93; 95% CI, 0.62-1.41), requiring supplemental oxygen (OR, 0.77; 95% CI, 0.45-1.30), use of mechanical ventilation (OR, 0.85; 95% CI, 0.26-2.84), or death (OR, 0.67; 95% CI, 0.09-5.23) were observed between CGRP mAb initiators and noninitiators who tested positive for SARS-CoV-2. Conclusions and Relevance: In this cohort study, CGRP mAb treatment was not associated with positive SARS-CoV-2 test results or risk of severe COVID-19 outcomes, suggesting that CGRP mAbs may be used for migraine prevention during the COVID-19 pandemic. Given the few events of requiring supplemental oxygen, use of mechanical ventilation, and death, replication analysis in a larger sample of patients later in the course of disease is warranted.