Hair loss due to use of CGRP monoclonal antibodies

CGRP monoclonal antibodies for Migraine Headache Treatment May Cause Hair Loss in a Small Proportion of Users

CGRP and Its Role in Migraine

Migraine is a highly prevalent and disabling disorder, with an estimated 1 in 5 women and 1 in 15 men in the United States affected by migraines.

In the current model for migraine pathogenesis, neurons on dural blood vessels trigger the release of plasma proteins and vasoactive substances, including calcitonin gene-related peptide (CGRP), substance P, and neurokinin A. The release of vasoactive factors triggers vasodilation and dural plasma extravasation, resulting in neurogenic inflammation and thereby producing pain.

Calcitonin gene-related peptide (CGRP) is now thought to play a key role in migraines. CGRP levels are elevated in serum between attacks of episodic and chronic migraine and this increase is then reversed upon treatment with standard  first-line treatments like triptans. It is well known that injection of the CGRP peptide triggers moderate to severe headaches similar to typical migraine.

CGRP Targeting Drugs

Calcitonin gene-related peptide (CGRP) inhibitors block the effect of CGRP. Calcitonin gene-related peptide-targeted drugs have proven safe and effective for migraine prevention in large randomized-controlled, double-blind trials with an average duration of six months.

There are two types of CGRP inhibitors – monoclonal antibodies and CGRP receptor antagonists (gepants).

The monoclonal antibodies include:

•       Aimovig (erenumab): Approved May 17, 2018

•       Ajovy (fremanezumab): Approved Sept 14, 2018

•       Emgality (galcanezumab): Approved Sept 27, 2018

•       Vyepti (eptinezumab): Approved Feb 21, 2020.

The “gepants” include:

•       Ubrelvy (ubrogepant): Approved Dec 23, 2019

•       Nurtec ODT (rimegepant sulfate): Approved Feb 27, 2020.

•       Qulipta (atogepant):  Approved Sept 28, 2021

•       Zavegepant (Zavzpret): Aapproved March 10, 2023)

Hair Loss with CGRP Inhibiting Drugs

Although hair loss was reported in some clinical trial studies of these drugs, the duration of the double blind studies has generally been short and so the world really relies on phase IV post marketing type studies to get a sense of how common alopecia truly is. Before these drugs came to market, hair loss was not an issue that was discucssed all that often.

Sessa et al 2021: The First Signficiant Report of Possible Hair Loss with CGRP Antibodies

In 2021, Sessa evaluated reports to FDA Adverse Event Reporting System (FAERS) database. There were 23,312 cases were reported during the study period. 67.0% of these were by consumers.  Cases in the age range 18-64 years. A total of 1303 unlabeled adverse events were reported. 49 had statistically significant disproportionality of reporting in comparison with other drugs used for acute or preventative treatment of migraine. The top 5 adverse events were: blood pressure problems, alopecia, anxiety, influenza like illness and depression.

Ruiz et al, 2023

In a new report, authors described two patients that reported temporary hair loss with CGRP antibodies. In the second part of their paper, they provide a review of the reports in the FDA Adverse Event Reporting System (FAERS) database

Patient 1

The first patient, a 69 year old female,  experienced alopecia within three months of starting erenumab. The hair loss did not improve with ongoing use or transition to fremanezumab.

Patient 2

The second patient, a 33 year old female,  reported alopecia within two weeks of starting erenumab. The hair loss continued after transition to galcanezumab. Then, months later, there was also recurrent hair loss within one month of starting fremanezumab.

In the FDA Adverse Event Reporting System (FAERS) database, Ruiz et al point out that alopecia has been reported so far with

erenumab (1158)

galcanezumab (554)

fremanezumab (175)

eptinezumab (23)

rimegepant (26)

ubrogepant (4)

atogepant (3)

Conclusion

Taken together, this data supports a notion that hair loss can occur from use of this new class of medications. Fortunately, it still seems to be occurrirng in only a small minority of patients. In some studies, including the study by Evers et al, a switch to another CGRP monoclonal antibody lead to a cessation of hair loss and shedding. So sometimes it may be possible to stop shedding simply by switching the drug and other times this has no effect.

More studies are needed of hair loss in users of CGRP monoclonal antibodies.

REFERENCE

Donovan J. Hair loss from CGRP Monoclonal Antibodies

Ruiz M et al. Alopecia as an emerging adverse event to CGRP monoclonal antibodies: Cases Series, evaluation of FAERS, and literature review. Cephalalgia. 2023 Feb;43(2):3331024221143538.