Earlier discontinuation of TNF-α inhibitor therapy in female patients with inflammatory bowel disease is related to a greater risk of side effects

Aliment Pharmacol Ther. 2019 Aug;50(4):386-396. doi: 10.1111/apt.15380. Epub 2019 Jul 16.

Abstract

Background: In rheumatoid arthritis and psoriasis female sex has been shown to be associated with discontinuation of anti-tumour necrosis factor-α (TNF-α) therapy.

Aim: To retrospectively assess the association between sex and TNF-α drug persistence in patients with inflammatory bowel disease (IBD).

Methods: All IBD patients on anti-TNF-α therapy with a minimum follow-up of 12 months in a single tertiary centre were identified. Patient and treatment characteristics and reasons for anti-TNF-α discontinuation were recorded. Overall and cause-specific drug persistence was analysed with Kaplan-Meier followed by Cox proportional hazards regression models.

Results: We included 529 patients (49.9% male) with 631 treatment episodes (2280 anti-TNF-α treatment years) and 289 discontinuations of therapy. Female sex (adjusted hazard ratio [aHR] 1.42, 95% confidence interval [CI] 1.16-1.74), greater age at start of therapy per decade (aHR 1.15, 95% CI 1.04-1.27] and dose escalation (aHR 3.74, 95% CI 2.78-5.02) were associated with TNF-α inhibitor discontinuation. Total cohort cause-specific analysis identified female sex to be associated with side effects (aHR 4.05, 95% CI 2.36-6.98) but not to other discontinuation reasons. Adalimumab (aHR 1.70, 95% CI 1.11-2.60) and golimumab (aHR 4.97, 95% CI 2.30-10.74) use and dose-escalation (aHR 7.71, 95% CI 5.28-11.26) were associated with secondary loss of response.

Conclusion: Drug persistence of anti-TNF-α therapy is lower in females as compared to males, mainly because of higher rates of side effects in females. Understanding the sex specific differences in effectiveness and safety of anti-TNF-α compounds can aid physicians in clinical decision-making.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Adolescent
  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology
  • Assessment of Medication Adherence
  • Cohort Studies
  • Drug Administration Schedule
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Female
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunologic Factors / adverse effects*
  • Immunotherapy / adverse effects
  • Inflammatory Bowel Diseases / drug therapy
  • Male
  • Psoriasis / drug therapy*
  • Psoriasis / epidemiology
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Withholding Treatment* / statistics & numerical data
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha
  • golimumab
  • Adalimumab