Can certolizumab pegol (Cimzia) cause elevated alanine aminotransferase (ALT) and thrombocytosis?

Can Cimzia Cause Elevated ALT and High Platelets?

Yes, Cimzia (certolizumab pegol) can cause elevated ALT, but it does not typically cause thrombocytosis (high platelets). 1

Elevated ALT (Liver Enzyme Abnormalities)

Certolizumab pegol is a recognized cause of drug-induced liver injury, though this adverse effect is rare. The FDA label does not list specific hepatotoxicity rates, but post-marketing surveillance and case reports have documented hepatocellular liver injury with certolizumab 1.

Evidence for Hepatotoxicity:

• Case reports using the Roussel Uclaf Causality Assessment Method (RUCAM) have confirmed probable causality between certolizumab and hepatocellular liver injury, with scores of 7 indicating "probable" drug-induced liver injury 2, 3

• The hepatotoxicity pattern is typically hepatocellular (elevated ALT/AST) rather than cholestatic 3

• Liver enzyme elevations can occur at any point during treatment, though onset timing varies 2

• Discontinuation of certolizumab typically leads to normalization of liver enzymes without recurrence 2, 3

Clinical Monitoring Recommendations:

While the FDA label for Cimzia does not mandate routine liver function monitoring (unlike some other biologics), vigilant monitoring for hepatotoxicity is prudent given documented cases 2. This is particularly important because:

• TNF inhibitors as a class can cause liver injury 4
• Patients often receive concomitant medications (like methotrexate) that also affect the liver 3

If ALT elevation occurs:

• Exclude other causes (viral hepatitis, autoimmune liver disease, other hepatotoxic drugs) 3
• Consider discontinuation if ALT is ≥3× upper limit of normal with symptoms, or ≥5× upper limit of normal without symptoms 5
• Liver enzymes typically normalize after drug cessation 2, 3

Thrombocytosis (High Platelets)

Cimzia does NOT cause elevated platelet counts. In fact, the opposite may occur:

• The FDA label does not list thrombocytosis as an adverse effect 1
• TNF inhibitors like certolizumab are used to treat inflammatory conditions where thrombocytosis is often a reactive phenomenon due to underlying inflammation 6
• Successful treatment with certolizumab would be expected to reduce inflammatory markers and normalize elevated platelet counts that were elevated due to disease activity

Important Caveat:

If a patient on Cimzia develops high platelets, consider:

• Reactive thrombocytosis from inadequately controlled underlying inflammatory disease (RA, Crohn's disease, etc.)
• Concurrent infection or other inflammatory process
• Unrelated hematologic disorder

The platelet elevation is almost certainly NOT caused by the Cimzia itself.

Laboratory Test Interference:

Note that Cimzia can cause falsely elevated aPTT (activated partial thromboplastin time) assay results without actual coagulation abnormalities 1. However, this is a laboratory artifact, not true thrombocytosis, and does not affect platelet counts 1.

Summary Algorithm:

If elevated ALT occurs on Cimzia:

1. Exclude viral hepatitis (HBV, HCV), autoimmune hepatitis, and other hepatotoxic drugs
2. If ALT ≥3× ULN with symptoms OR ≥5× ULN without symptoms → discontinue Cimzia
3. Monitor for normalization after cessation
4. Consider alternative biologic if needed

If high platelets occur on Cimzia:

1. This is NOT from Cimzia
2. Evaluate for inadequate disease control (check inflammatory markers)
3. Rule out infection or other inflammatory process
4. Consider primary hematologic disorder if persistent and unexplained