Can Emgality (galcanezumab) cause transaminitis (elevated liver enzymes)?

Emgality (Galcanezumab) and Transaminitis: Risk Assessment

Emgality (galcanezumab) has not been documented to cause transaminitis or elevated liver enzymes as a known adverse effect, and routine liver function monitoring is not required during treatment.

Background on Emgality

Galcanezumab (Emgality) is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP), used for the preventive treatment of migraine in adults 1. Unlike many other medications, monoclonal antibodies like galcanezumab undergo proteolytic degradation rather than hepatic metabolism, which generally makes them less likely to cause liver toxicity.

Evidence on Liver Safety with Emgality

The safety profile of galcanezumab has been well-documented in clinical trials:

• In the CONQUER trial, which included patients who had failed multiple previous preventive medications, treatment-emergent adverse events were similar between galcanezumab and placebo groups (51% vs 53%), with no specific mention of liver enzyme elevations 2.

• The most commonly reported adverse effects of galcanezumab are injection site reactions (erythema, pruritus, and swelling) 3.

• Unlike other medications such as tolvaptan, which has a documented 5% risk of elevated transaminases (compared to 1% with placebo) 4, there is no similar evidence for galcanezumab causing liver enzyme elevations.

Medications Known to Cause Transaminitis

For comparison, several medications are well-documented to cause transaminitis:

• Tolvaptan: Associated with idiosyncratic drug-induced liver injury in approximately 5% of patients, with most cases occurring within the first 18 months of treatment 4.

• Remdesivir: In a case series, 23% of patients experienced elevated hepatic enzymes 4.

• Statins: Elevated hepatic transaminases generally occur in 0.5% to 2.0% of cases and are dose-dependent 4.

• Rifabutin: Asymptomatic elevation of liver enzymes has been reported at a frequency similar to rifampin, with clinical hepatitis occurring in less than 1% of patients 4.

Management Approach for Patients on Emgality

While specific monitoring for liver enzymes is not required for galcanezumab based on current evidence, general principles for managing patients with elevated transaminases include:

1. Baseline Assessment:

   • Consider obtaining baseline liver function tests before initiating any new medication, especially in patients with pre-existing liver disease or on other potentially hepatotoxic medications.

2. Monitoring:

   • Routine liver enzyme monitoring is not required specifically for galcanezumab.
   • For patients with pre-existing liver disease or on multiple medications, periodic monitoring may be reasonable as part of general care.

3. Management of Elevated Transaminases:

   • If transaminase elevations are detected during treatment:
     • Rule out other common causes (alcohol use, fatty liver disease, viral hepatitis, other medications)
     • Consider the timing of elevation in relation to medication initiation
     • Evaluate the severity of elevation (mild elevations <3× ULN may be monitored, while elevations >3× ULN warrant closer attention) 4

Conclusion

Based on available evidence, galcanezumab (Emgality) has not been associated with transaminitis or liver enzyme elevations. The medication undergoes minimal hepatic processing, making it a relatively safe option from a liver perspective. If transaminase elevations are observed in a patient taking galcanezumab, other more common causes should be investigated before attributing the elevation to the medication.

For patients with pre-existing liver disease, galcanezumab may represent a safer option compared to other preventive migraine treatments that have documented hepatotoxicity.