Relationship Between Patient Sex and Serum Tumor Necrosis Factor Antagonist Drug and Anti-drug Antibody Concentrations in Inflammatory Bowel Disease; A Nationwide Cohort Study.

Mohammad Shehab,Ahmad Alfadhli,Israa Abdullah,Ghadeer Alhendi,Anwar Alhadab,Hajer Alasfour,Ali H Ziyab,Robert Battat

doi:10.3389/fmed.2021.801532

Abstract

Background: Anti-drug antibodies to infliximab (ATI) and adalimumab (ATA) are associated with loss of response to tumor necrosis factor antagonist (anti-TNF) therapy in inflammatory bowel disease (IBD). We evaluated the relationship between patient sex and serum TNF antagonist drug and antibody concentrations in inflammatory bowel disease.Methods: A nationwide multicenter retrospective cohort study was conducted by evaluating patients' charts from July 2018 until September 2021. The effect of patient sex on anti-drug antibodies and serum drug concentration in patients with IBD across seven hospitals was investigated. A subgroup analysis also investigated the effect of anti-TNF combination therapy. Geometric means were calculated, and multiple linear regression was used to estimate the adjusted ratio of geometric means (RoGM) and their 95% confidence intervals (CI).Results: In the total study sample (n = 1093), males receiving infliximab had higher anti-drug antibody concentrations (38.3 vs. 22.3 AU/ml; aRoGM = 1.72, 95% CI: 1.30–2.27, p < 0.001) compared to females. Additionally, infliximab serum drug concentrations among males were lower compared to females (2.6 vs. 4.1 ug/ml; aRoGM = 0.62, 95% CI: 0.44–0.88, p = 0.007). In the subgroup analysis (n = 359), male compared to female patients on combination therapy with infliximab and immunomodulators had similar anti-drug antibody concentrations (30.2 vs. 21.9 AU/ml; aRoGM = 1.38, 95% CI: 0.79–2.40, p = 0.254). There was no difference in the anti-drug antibody and serum drug concentrations among males and females on adalimumab.Conclusion: In patients receiving infliximab, anti-drug antibodies were higher in males than females. Consistent with this, serum drug concentrations were lower in males than females on infliximab. There was no difference in anti-drug antibody and serum drug concentrations among males and females on adalimumab. In addition, no difference in anti-drug antibodies between males and females receiving anti-TNF combination therapy was observed.

Highlights

Tumor necrosis factor antagonist therapies are commonly used for the management of moderate to severe inflammatory bowel disease (IBD) [1,2,3,4]
Infliximab serum drug concentrations among males were lower compared to females (2.6 vs. 4.1 ug/ml; adjusted ratio of geometric means (aRoGM) = 0.62, 95% confidence intervals (CI): 0.44–0.88, p = 0.007)
In the subgroup analysis (n = 359), male compared to female patients on combination therapy with infliximab and immunomodulators had similar anti-drug antibody concentrations (30.2 vs. 21.9 AU/ml; aRoGM = 1.38, 95% CI: 0.79–2.40, p = 0.254)

Summary

Introduction

Tumor necrosis factor antagonist (anti-TNF) therapies are commonly used for the management of moderate to severe inflammatory bowel disease (IBD) [1,2,3,4]. Combination therapy, the concurrent administration of an immunomodulator with an anti-TNF, has been associated with improvement in pharmacokinetics by decreasing immunogenicity and increasing serum drug concentrations [1,2,3,4]. When considering anti-TNF therapy for pediatric patients with IBD, the ECCO-ESPGHAN guidelines recommend the use of infliximab combination therapy, with an immunomodulator, to reduce the risk of developing anti-drug antibodies to infliximab (ATI). Anti-drug antibodies to infliximab (ATI) and adalimumab (ATA) are associated with loss of response to tumor necrosis factor antagonist (anti-TNF) therapy in inflammatory bowel disease (IBD). We evaluated the relationship between patient sex and serum TNF antagonist drug and antibody concentrations in inflammatory bowel disease

Methods

Results

Discussion

Conclusion