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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Certolizumab Pegol

, MD.

Author Information and Affiliations

Last Update: February 14, 2026.

OVERVIEW

Introduction

Certolizumab pegol is a Fab fragment of a monoclonal antibody to human tumor necrosis factor alpha (TNFα) conjugated with polyethylene glycol (pegol) which has potent antiinflammatory activity and is used in the therapy of severe rheumatoid arthritis and inflammatory bowel disease. Certolizumab pegol has had limited use and has yet to be specifically linked to instances of idiosyncratic acute liver injury or reactivation of hepatitis B, but is likely to cause similar hepatic injury to what has been described for other TNFα antagonists such as infliximab and adalimumab.

Background

Certolizumab (ser" toe liz' ue mab) pegol is a Fab fragment of a humanized recombinant monoclonal antibody to TNFα conjugated to polyethylene glycol (pegol). The monoclonal antibody fragment binds avidly to serum and tissue bound TNFα causing its inactivation and degradation. Inhibition of TNFα activity leads to modulation of the inflammatory and pain pathways activated by this cytokine. The polyethylene glycol alters its pharmacokinetics, prolonging its half-life, and allowing for every 4 week administration. Certolizumab pegol was approved in the United States in 2008 for use in Crohn disease and its indications were subsequently extended to rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis and plaque psoriasis. Certolizumab is considered a disease modifying antirheumatic drug (DMARD) and has been shown to improve symptoms as well as joint and cartilage damage in the inflammatory arthritidies. Certolizumab pegol is available as lyophilized powder for reconstitution or in prefilled syringes as 200 mg/1.0 mL under the brand name of Cimzia. The typical dose of certolizumab pegol for Crohn disease is 200 to 400 mg subcutaneously initially and at weeks 2 and 4, followed by 400 mg every 4 weeks or 200 mg every two weeks. Recommendations vary by indication and age. Common side effects include injection site reactions, headache, nausea, abdominal discomfort, diarrhea, skin rash and fever. Uncommon, but potentially severe adverse reactions include bone marrow suppression, severe and opportunistic infections, neurological reactions, heart failure, malignancies including lymphoma, and hypersensitivity reactions. TNF antagonists are also capable of causing immune suppression, which can result in reactivation of microbial infections including tuberculosis and hepatitis B.

Hepatotoxicity

Certolizumab pegol has been associated with a low rate of serum aminotransferase elevations during therapy, similar to the rate found with placebo therapy. The ALT elevations have been transient, mild and asymptomatic, and have rarely required dose modification. Despite having been available for more than a decade, certolizumab pegol has been linked to only a few cases of clinically apparent liver injury all of which have been mild and self-limited in course. Nevertheless, it is likely that certolizumab pegol, like infliximab and adalimumab, is capable of inducing clinically apparent liver injury that resembles autoimmune hepatitis, which generally arises after at least 3 months of use and is associated with a hepatocellular pattern of serum enzyme elevation and autoantibody formation. Autoimmune hepatitis induced by anti-TNFα blocking agents can be severe and self-sustained and require corticosteroid therapy. Most severe cases of autoimmune-like hepatitis have been linked to infliximab therapy.

Certolizumab, like other TNFα antagonists, can also be expected to cause reactivation of chronic hepatitis B. Reactivation typically occurs in patients who are inactive HBsAg carriers, with normal serum aminotransferase levels and no or only low levels of HBV DNA in serum. The immune suppression caused by the immunomodulatory agent leads to an increase in HBV replication and rise in serum HBV DNA levels. With stopping the immunosuppression (or between cycles of therapy), restoration of immune function leads to an acute immunological response to the heightened viral replication and a flare of hepatitis, that can be severe and can result in hepatic failure and death. Reactivation in patients with anti-HBc without HBsAg (serologic pattern of previous HBV infection) has been reported only rarely in patients treated with anti-TNF antagonists, and is more common after therapy with rituximab and bone marrow transplantation. The anti-TNF inhibitors have little or no effect on hepatitis C virus levels and have been used safely in patients with chronic hepatitis C.

Likelihood score: D (possible rare cause of clinically apparent liver injury as well as reactivation of hepatitis B).

Mechanism of Injury

The mechanism of liver injury due to certolizumab pegol and other TNFα antagonists is not known, but is likely caused by immune modulation and induction of autoimmunity.

Outcome and Management

Most published cases of hepatotoxicity due to anti-TNFα agents have been mild and self-limited. Patients who are to start certolizumab pegol therapy should be screened for evidence of hepatitis B, and those with preexisting HBsAg should be offered prophylaxis with an oral antiviral agent such as lamivudine, tenofovir or entecavir. Patients who develop an autoimmune hepatitis-like syndrome during certolizumab therapy may not recover promptly with stopping the TNFα antagonist and may require corticosteroid therapy. In this event, the corticosteroid dose should be kept to a minimum to control the disease and, ultimately, attempts should be made to withdraw immunosuppression (or decrease to levels used before administration of certolizumab). Rechallenge with another TNFα antagonist after hepatotoxicity from certolizumab pegol has not been reported. Although there appears to be little cross reactivity in hepatic injury among the various TNF antagonists, switching agents after clinically apparent liver injury should be done with caution and only with careful monitoring.

Drug Class: Antirheumatic Agents; Gastrointestinal Agents, Inflammatory Bowel Disease Agents

Other Drugs in the Subclass, Tumor Necrosis Factor Antagonists: Adalimumab, Etanercept, Golimumab, Infliximab

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Certolizumab – Cimzia®

DRUG CLASS

Antirheumatic Agents; Gastrointestinal Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

DRUGCAS REGISTRY NUMBERMOLECULAR FORMULASTRUCTURE
Certolizumab Pegol 428863-50-7 Monoclonal antibody image 135347437 in the ncbi pubchem database

ANNOTATED BIBLIOGRAPHY

References updated: 14 February 2026

Abbreviations Used: TNF, tumor necrosis factor alpha; anti-TNF, antibody to TNF; ANA, anti-nuclear antigen; dsDNA, double stranded DNA; HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; anti-HBs, antibody to HBsAg; anti-HBc, antibody to hepatitis B core antigen; HBeAg, hepatitis B e antigen; anti-HBe, antibody to HBeAg; HCV, hepatitis C virus, anti-HCV, antibody to HCV.

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  • Björnsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, Weber S, et al. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023;43:115-126. [PMC free article: PMC7614006] [PubMed: 35899490]
    (Initial results from the prospective European multi-national drug-induced liver injury registry [UK, Spain, Germany, Switzerland, Portugal, Iceland] describes 246 cases, the most frequent implicated agents being amoxicillin-clavulanate [12%], flucloxacillin [11%] atorvastatin [8%], nivolumab/ipilimumab [8%], infliximab [5%], nitrofurantoin [4.5%], disulfiram [2%], ibuprofen [2%], and HDS products [7.3%]; jaundice in 60% and fatal outcome in 4%; no mention of adalimumab or other TNF antagonists).
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    (Concise review of the mechanism of action, efficacy, safety, and costs of drugs for ulcerative colitis and Crohn disease, mentions that the monoclonal antibodies to TNF are effective in induction and maintenance of remissions, infliximab and adalimumab being approved for both forms, certolizumab for ulcerative colitis only and golimumab for Crohn disease only; discussion of adverse events mentions reactivation of hepatitis B and induction of autoimmune conditions but without mention of hepatotoxicity).
  • Drugs for plaque psoriasis. Med Lett Drugs Ther. 2024;66(1712):153-160. [PubMed: 39302348]
    (Concise review of the mechanism of action, efficacy, safety, and costs of drugs for psoriasis, mentions that four TNF antagonists are approved for moderate-to-severe plaque psoriasis and that adverse events include reactivation of hepatitis B but does not mention hepatotoxicity).
  • Bensaghir I, Tahiri L, Farih S, Rkain H, Allali F. Certolizumab-induced liver injury in ankylosing spondylitis: a case report and causality assessment. Cureus. 2024;16:e66569. [PMC free article: PMC11385431] [PubMed: 39258044]
    (34 year old man with ankylosing spondylitis refractory to infliximab therapy developed evidence of mild liver injury 6 months after starting certolizumab [ALT 151 U/L; no mention of bilirubin or Alk P] which resolved within a month after stopping certolizumab).
  • Björnsson HK, Sigmundsson HK, Björnsson ES. Severe liver injury due to infliximab therapy and adalimumab. Scand J Gastroenterol. 2025;60:1238-1246. [PubMed: 41086316]
    (Review of the literature on cases of severe liver injury attributed to TNF antagonists identified 12 reports of severe acute liver injury due to infliximab but only one due to adalimumab [Hagel 2011] and none due to golimumab or certolizumab pegol).
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  • Peggie E, Shetty S, Johnston M, May C, Oien K, Kohnen G. Certolizumab-associated autoimmune-like hepatitis. BMJ Case Rep. 2025;18:e266955.. [PubMed: 41423287]
    (30ish year old woman with psoriasis had a rapid clinical response certolizumab but developed enzyme elevations 10 weeks of therapy with worsening for a month after stopping [bilirubin 0.5 rising to 1.2 mg/dL, ALT 230 to 1788 U/L, Alk P 81 to 237 U/L, ANA 1:640, IgG 11.7 mg/dL] but ultimately resolving without corticosteroid therapy by 20 weeks).
  • Chen H, Jiang S, Wang J, Zhang A, Zhu L. Hepatobiliary disorders associated with TNF-α inhibitors: a pharmacovigilance analysis of FAERS and JADER. Front Immunol. 2026;16:1739631. [PMC free article: PMC12832726] [PubMed: 41601665]
    (Analysis of the US FDA adverse event reporting system [FAERS] between 2004 and 2025 for TNF antagonists found 19,083 reports of hepatobiliary events, 9501 for adalimumab, 3979 infliximab, 3949 etanercept, 1012 certolizumab pegol, and 642 golimumab).
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Bookshelf ID: NBK548466PMID: 31643785
Drug Records

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