Skip to main content

Advertisement

Log in

Elevated liver enzymes in patients with ankylosing spondylitis treated with etanercept

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

TNF-alpha blocking agents are very effective in patients with ankylosing spondylitis (AS), but several cases of liver problems have been published. We systematically studied the frequency of this potential side effect in our AS patients treated with etanercept. Consecutive AS patients treated with etanercept for at least 3 months were included. Liver disease was defined as elevated liver enzymes more than 1.5 times the upper normal limit (UNL) and was categorised as probably, possibly, probably not or not related to etanercept treatment. Patients with and without raised liver enzymes were compared for prognostic factors. A total of 105 patients were included. Fifteen patients had elevated liver enzymes more than once. In nine cases, the liver disease was probably (five) or possibly (four) related to etanercept treatment. The liver enzyme elevations were serious (>3× UNL) in six cases and resulted in permanent cessation of etanercept in two cases. The nine patients with liver disease were compared with patients without elevated liver enzymes. No differences were found in age or use of alcohol; however, in patients with liver disease, a higher body mass index and a trend for a higher atherogenic index were observed. Hepatic steatosis was observed in five of six patients with elevated liver enzymes. Elevated serum aminotransferases, probably or possibly related to etanercept treatment, were observed in 9 % of the AS patients. An increased risk for the elevation of liver enzymes was found in patients with a higher body mass index. We recommend regular testing of liver enzymes in patients treated with etanercept.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Zochling J, Van der Heyde D, Burgos-Vargas R, Collantes E, Davis JC Jr, Dijkmans B et al (2006) ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 65:442–452

    Article  PubMed  CAS  Google Scholar 

  2. European Medicines Agency: EPAR product information etanercept (2012) http://www.emea.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000262/human_med_000764.jsp&mid=WC0b01ac058001d124. Accessed Aug 2012

  3. Gorman JD, Sack KE, Davis JC Jr (2002) Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med 346:1349–1356

    Article  PubMed  CAS  Google Scholar 

  4. Ozorio G, McGarity B, Bak H, Jordan AS, Lau H, Marshall C (2007) Autoimmune hepatitis. following infliximab therapy for ankylosing spondylitis. Med J Aust 187:524–526

    PubMed  Google Scholar 

  5. Farah M, Al Rashidi A, Owen DA, Yoshida EM, Reid GD (2008) Granulomatous hepatitis associated with etanercept therapy. J Rheumatol 35:349–351

    PubMed  Google Scholar 

  6. Carlsen KM, Riis L, Madsen OR (2009) Toxic hepatitis induced by infliximab in a patient with rheumatoid arthritis with no relapse after switching to etanercept. Clin Rheumatol 28:1001–1003

    Article  PubMed  CAS  Google Scholar 

  7. Tobon GJ, Cañas C, Jaller JJ, Restrepo JC, Anaya JM (2007) Serious liver disease induced by infliximab. Clin Rheumatol 26:578–581

    Article  PubMed  Google Scholar 

  8. Braun J, Pham T, Sieper J, Davis J, Van der Linden S, Dougados M et al (2003) International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 62:817–824

    Article  PubMed  CAS  Google Scholar 

  9. The Uppsala Monitoring Centre: The use of the WHO-UMC system for standardised care causality assessment, undated. http://who-umc.org/Graphics/24734.pdf. Accessed Aug 2012

  10. Ioannou GN, Weiss NS, Boyko EJ, Mozaffarian D, Lee SP (2006) Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States. Hepatology 43:1145–1151

    Article  PubMed  CAS  Google Scholar 

  11. Calin A, Dijkmans BAC, Emery P, Hakala M, Kalden J, Leirisalo-Repo M et al (2004) Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis. Ann Rheum Dis 63:1594–1600

    Article  PubMed  CAS  Google Scholar 

  12. Van der Heijde D, Da Silva JC, Dougados M, Geher P, Van der Horst-Bruinsma IE, Juanola X et al (2006) Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis. Ann Rheum Dis 65:1572–1577

    Article  PubMed  Google Scholar 

  13. Van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J et al (2006) Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 54:2136–2146

    Article  PubMed  Google Scholar 

  14. Inman RD, Davis JC Jr, Van der Heijde D, Diekman L, Sieper J, Kim SI et al (2008) Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum 58:3402–3412

    Article  PubMed  CAS  Google Scholar 

  15. Sokolove J, Strand V, Greenberg JD, Curtis JR, Kavanaugh A, Kremer JM et al (2010) Risk of elevated liver enzymes associated with TNF inhibitor utilisation in patients with rheumatoid arthritis. Ann Rheum Dis 69:1612–1617

    Article  PubMed  CAS  Google Scholar 

  16. Massarotti M, Marasini B (2009) Successful treatment with etanercept of a patient with psoriatic arthritis after adalimumab-related hepatotoxicity. Int J Immunopathol Pharmacol 22:547–549

    PubMed  CAS  Google Scholar 

  17. European Medicines Agency: EPAR product information infliximab (2012) http://www.emea.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000240/human_med_001023.jsp&mid=WC0b01ac058001d124; table 2. Accessed Aug 2012

  18. Cansu DU, Kalifoglu T, Korkmaz C (2008) Short-term course of chronic hepatitis B and C under treatment with etanercept associated with different disease modifying antirheumatic drugs without antiviral prophylaxis. J Rheumatol 35:421–424

    PubMed  CAS  Google Scholar 

  19. Peterson JR, Hsu FC, Simkin PA, Wener MH (2003) Effect of tumour necrosis factor alpha antagonists on serum transaminases and viraemia in patients with rheumatoid arthritis and chronic hepatitis C infection. Ann Rheum Dis 62:1078–1082

    Article  PubMed  CAS  Google Scholar 

  20. Oniankitan O, Duvoux C, Challine D, Mallat A, Chevalier X, Pawlotsky JM et al (2004) Infliximab therapy for rheumatic diseases in patients with chronic hepatitis B or C. J Rheumatol 31:107–109

    PubMed  CAS  Google Scholar 

  21. Parke FA, Reveille JD (2004) Anti-tumor necrosis factor agents for rheumatoid arthritis in the setting of chronic hepatitis C infection. Arthritis Rheum 51:800–804

    Article  PubMed  CAS  Google Scholar 

  22. Roux CH, Brocq O, Breuil V, Albert C, Euller-Ziegler L (2006) Safety of anti-TNF-alpha therapy in rheumatoid arthritis and spondylarthropathies with concurrent B or C chronic hepatitis. Rheumatology 45:1294–1297

    Article  PubMed  CAS  Google Scholar 

  23. Marotte H, Fontanges E, Bailly F, Zoulim F, Trepo C, Miossec P (2007) Etanercept treatment for three months is safe in patients with rheumatological manifestations associated with hepatitis C virus. Rheumatology 46:97–99

    Article  PubMed  CAS  Google Scholar 

  24. Daïen CI, Monnier A, Claudepierre P, Constantin A, Eschard JP, Houvenagel E et al (2009) Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases. Rheumatology 48:883–886

    Article  PubMed  Google Scholar 

  25. Tubach F, Salmon D, Ravaud P, Allanore Y, Goupille P, Bréban M et al (2009) Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: the three-year prospective French research axed on tolerance of biotherapies registry. Arthritis Rheum 60:1884–1894

    Article  PubMed  CAS  Google Scholar 

  26. Menghini VV, Arora AS (2001) Infliximab-associated reversible cholestatic liver disease. Mayo Clin Proc 76:84–86

    Article  PubMed  CAS  Google Scholar 

  27. Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E et al (2002) Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 137:1–10

    PubMed  CAS  Google Scholar 

  28. Ekstedt M, Franzén LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G et al (2006) Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44:865–873

    Article  PubMed  CAS  Google Scholar 

  29. Chu CJ, Lu RH, Wang SS, Chang FY, Wu SL, Lu CL et al (2007) Risk factors associated with non-alcoholic fatty liver disease in Chinese patients and the role of tumor necrosis factor-alpha. Hepatogastroenterology 54:2099–2102

    PubMed  CAS  Google Scholar 

  30. Jamnitski A, Visman IM, Peters MJ, Dijkmans BA, Voskuyl AE, Nurmohamed MT (2010) Beneficial effect of 1-year etanercept treatment on the lipid profile in responding patients with rheumatoid arthritis: the ETRA study. Ann Rheum Dis 69:1929–1933

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The clinical part of this study was partially supported by Wyeth/Pfizer. We thank I. Visman for the statistical analysis.

Disclosures

MT Nurmohamed has received consultancy fees from Abbott, Roche, Pfizer, MSD, UCB, SOBI and BMS and payment for lectures from Abbott, Roche and Pfizer.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. C. van Denderen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Denderen, J.C., Blom, G.J., van der Horst-Bruinsma, I.E. et al. Elevated liver enzymes in patients with ankylosing spondylitis treated with etanercept. Clin Rheumatol 31, 1677–1682 (2012). https://doi.org/10.1007/s10067-012-2072-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-012-2072-7

Keywords

Navigation