Erenumab Dosage for Migraine Prevention

An Evidence-Based Narrative Review With Recommendations

Stewart J. Tepper MD; Huma U. Sheikh MD; Carrie O. Dougherty MD; Stephanie J. Nahas MD MSEd; Paul K. Winner DO; Ananda Krishna Karanam PhD; Andrew M. Blumenfeld MD; Ahmad Abdrabboh PharmD MPH; Soeren Rasmussen MD; Jamie L. Weiss PhD; Jessica Ailani MD

Disclosures

Headache. 2022;62(4):420-435. 

In This Article

Safety Data: EM and CM

Results from the regulatory clinical studies have shown a favorable safety and tolerability profile for erenumab (Table 9). The safety of erenumab was further established over 4.5 years[23] in the Phase 2 EM study and 1-year OLE[29] of the pivotal Phase 2 CM study. The findings from the interim analysis[23] at the end of 4+ years in participants with EM showed exposure-adjusted incidence rates of 124.9/100-person-years for adverse events (AEs) and 3.8/100-person-years for serious AEs. The most frequent AEs reported during the study were nasopharyngitis (10.9/100-person-years), upper respiratory tract infection (6.8/100-person-years), and influenza (4.7/100-person-years). Data during 4+ years of the EM study follow-up showed that the incidence rates of constipation did not increase with either of the erenumab doses (1.3/100-person-years [n/N:9/383] and 2.6/100-person-years [n/N:15/250] for erenumab 70 and 140 mg, respectively). The incidence of AEs reported during the OLE[29] of the Phase 2 CM study was similar to that observed during the Phase 2 CM DBTP, with no new safety signals. The results showed the exposure-adjusted incidence rate for all AEs was 148.5/100-person-years with erenumab 140 mg (3.7 with >Grade 3) and 132/100-person-years with erenumab 70 mg (6.6 with >Grade 3), and an exposure-adjusted incidence rate for serious AEs of 4.7/100-person-years with erenumab 140 mg and 3.3/100-person-years with erenumab 70 mg.

The findings from the pooled safety analysis (2375 participants) showed a favorable and stable AE profile over time for erenumab with >3 years of exposure.[33] The exposure-adjusted rates of constipation with erenumab during the short-term DBTP were 10.7 (140 mg) and 4.6 (70 mg) per 100 person-years, and 2.1 (140 mg) and 1.4 (70 mg) per 100 person-years during the long-term extensions. However, a further pooled analysis (2443 participants),[34] focusing on vascular safety, showed hypertension was reported in 0.2% (n = 1) of those receiving erenumab 140 mg and 0.8% (n = 7) receiving 70 mg.

In terms of immunogenicity, data from a pooled analysis[34] of clinical studies of erenumab for migraine prevention showed that the incidence of anti-erenumab antibody production by those in the DBTP was low. In participants receiving a 70 mg dose of erenumab, 6.3% (56/884) developed anti-erenumab antibodies (3 were neutralizing antibody-positive) and in those receiving a 140 mg dose, 2.6% (13/504) developed these antibodies (none was neutralizing antibody-positive). The efficacy and safety of erenumab were not affected by the development of anti-erenumab antibodies.

The Food and Drug Administration label changes for erenumab, since it was introduced to the market, do include warnings of the potential for severe constipation and the development or worsening of hypertension, as well as rash, alopecia, and oral mucosal ulceration.[7] It is therefore prudent for the provider to closely monitor patients treated with erenumab for these adverse effects. Of note, long-term data do not show a clearly higher likelihood of AEs, including constipation and hypertension, for erenumab 140 mg than 70 mg.

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