Migraine patients treated with anti-CGRP receptor antibodies at risk of developing high BP

Netherlands: A study published in Neurology has concluded that migraine patients are at risk of developing high blood pressure when treated with anti-CGRP (receptor) antibodies. The researchers recommended that this be added to the international and national guidelines. This is because some patients have blood pressure within the normal range, but anti-hypertensive treatment may be required in some patients. The study has provided Class III evidence for this research.

Migraine is characterized by recurrent episodes of headache, ranging from moderate to severe. This is accompanied by photo- and phonophobia and bouts of nausea and vomiting. The pathophysiology remains uncovered, but it has been previously identified that calcitonin gene-related peptide (CGRP) plays an important role.

The new treatments which have been proposed to prevent migraine target CGRP. Eptinezumab, Fremanezumab, and Galcanezumab are the three monoclonal antibodies that target the CGRP ligand, while Erenumab targets the CGRP receptor.

CGRP is a potent vasodilator; therefore, its role is related to BP in migraine.These may lead to hypertension. None of the RCTs conducted previously have reported hypertension and cardiovascular risk. But the concern arose when hypertension cases surfaced after postmarketing with Erenumab.

FDA reported Sixty-one cases of hypertension after erenumab treatment. Migraine is related to an increased risk for cardiovascular and cerebrovascular events, so anti-CGRP treatment should not be related to this risk.

Based on the above considerations, a prospective follow-up study was conducted to assess whether preventive drugs like erenumab and fremanezumab increased BP or not in migraine patients during 1-year follow-up. Dr Simone de Vries Lentsch led the team from the Department of Neurology at Leiden University Medical Centre and the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus University Medical Center.

The key points of the study are:

• The study included those migraine patients who had a history of erenumab and fremanezumab treatment at the Leiden Headache Center ( January 2019 - 2021 ).
• A total of 109 patients started erenumab while 87 started fremanezumab.
• In erenumab treated patients, 85% were female with  average age was 42 years while 51% patients had history of chronic migraine.
• Among  fremanezumab treated patients, 74 were women of  45 years were there. Nearly 55% had history of chronic migraine. 
• The readings of BP measurements were collected at baseline (T0) till follow-up (12 months), with a 3-month interval (T1–T4).
• The readings of both systolic and diastolic BP were increased at all time points with a p-value of < 0.001compared to the baseline.
• The mean systolic BP was increased by 5.2 mm Hg (maximum).
• The mean diastolic BP was increased by 3.5 mm Hg.
• In the erenumab group (n = 109), BP (both systolic and diastolic) measurements were increased at all time points with all p values < 0.001) compared to T0.
• For fremanezumab (n = 87), systolic BP was increased compared with T0 at T1 with p-value of 0.006 and T2 with p-value of 0.004.
• 3.7% of patients had normal BP at T0. These patients required treatment after initiation with erenumab treatment.

The researchers said, "We observed an increase in systolic BP at all time points at T1, T2, T3 and T4 with a rise of 5.0 mm Hg, 4.9 mm Hg, 4.7 mm Hg and 5.2 mm Hg, respectively. The p values were < 0.001."

Erenumab had a more significant effect than fremanezumab in systolic BP, with a p-value of 0.03.

They wrote the diastolic BP increased at T1, T2, T3 and T4 with an increase of 3.3 mm Hg, 3.2 mm Hg,2.5 mm Hg and 3.5 mm Hg. The confidence interval was 95% and p < 0.001.

Erenumab had a more considerable estimated value for an increase in diastolic BP than fremanezumab, with p = 0.03.

We collected BP measurements and found that mean systolic and diastolic BP increased after three months of treatment. It was a long-lasting effect and was observed for 12 months. Nearly 38% had a relevant increase in BP at any time, while others had normal BP.

We found that most patients did not require BP treatment, but we did report a modest effect on the mean BP.

They explained that BP and cardiovascular events have a continuous relationship and the treatment benefits outweigh the anti-hypertensive treatment risk.

Our results demonstrated a more significant and more consistent BP effect in patients treated with erenumab.

We cannot conclude the reason for these differences. Some possibilities, like erenumab may have a more significant inhibiting effect on the CGRP pathway than fremanezumab, and these affect the CGRP pathway in different ways, which may lead to clinical differences. There may be a lack of statistical power in the analyses for the fremanezumab subgroup, and also, fremanezumab has limited data.

Further research is warranted to confirm additional details and possible explanations.

We reported that increasing the dosage from 70 to 140 mg would increase BP in such cases. We want to conclude that 3.7% of erenumab-treated patients had new-onset hypertension in our study, which required treatment, but it is not sufficient to identify patient-specific risk factors. We strongly believe that monitoring BP in patients treated with CGRP-targeting drugs is of utmost importance, as timely detection makes adequate intervention possible.

Physicians should be aware of this, and caution regarding anti-CGRP (receptor) antibodies should be added to clinical treatment guidelines for migraine.

Further reading:

Blood Pressure in Patients With Migraine Treated With Monoclonal Anti-CGRP (Receptor) Antibodies A Prospective Follow-up Study Simone de Vries Lentsch et al. Neurology Oct 2022, 99 (17)