High-dose frequency beta-interferons increase the risk of liver test abnormalities in multiple sclerosis: A longitudinal study

  • Chan S
  • Kingwell E
  • Oger J
 et al. 
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Abstract

BACKGROUND: Post-marketing studies and case reports have linked beta-interferon (IFNβ) treatment with liver enzyme abnormalities and liver injuries in patients with multiple sclerosis (MS). Few predictors of risk exist.

OBJECTIVE: We investigated the effect of IFNβ and other patient characteristics on levels of the liver enzyme, alanine aminotransferase (ALT).

METHOD: Repeated ALT test results were reviewed retrospectively for 1064 MS patients prescribed an IFNβ as their first immunomodulatory drug. Liver enzyme abnormality was defined as an ALT elevation twice the upper limit of normal (≥ 2 ULN). The Generalized Estimating Equation (GEE) was used to analyze the effect of age (≤ 35, >35-40, >40-45, >45 years), gender, disease duration, IFNβ product, and duration of treatment (≤ 5, >5-15, >15-40, >40 months) on de novo liver enzyme abnormality.

RESULTS: Over a mean treatment period of 38.7 months (SD=34.9), 12.4% (95/766) of MS patients developed de novo liver enzyme abnormality. Multivariable GEE results showed a dose frequency response effect of IFNβs on liver enzyme abnormality: OR=3.8(95% CI: 1.6-9.2) for IFNβ-1a 44 µg SC, and OR=3.4 (95% CI: 1.5-7.9) for IFNβ-1b 250 µg SC compared with the lower frequency IFNβ-1a 30 µg IM. Younger age (≤ 40 years), male gender, and ≤ 15 months of IFNβ exposure were also independent predictors.

CONCLUSION: A dose frequency response effect was observed, with high-frequency IFNβs having the greatest risk. The first 15 months of treatment, men, and younger patients were also associated with elevated risk. Regular ALT monitoring in MS patients appears prudent; long-term consequences of ALT elevations should be further investigated.

Author-supplied keywords

  • alanine aminotransferase
  • beta-interferon
  • hepatic injury
  • liver injury
  • liver test abnormality
  • multiple sclerosis
  • serum liver biochemistry

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Authors

  • S. Chan

  • E. Kingwell

  • J. Oger

  • E. Yoshida

  • H. Tremlett

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