Risk of Venous Thromboembolism and CV Events during Targeted Treatment of Nonspecific Bowel Inflammations

Introduction

Tofacitinib is the first small molecule immunosuppressive drug approved for the treatment of ulcerative colitis (UC). However, its administration is associated with the occurrence of thromboembolic events. Accumulating safety data for tofacitinib indicate a low incidence of adverse events, but IBD and concomitant anti-inflammatory therapy (e.g., corticosteroids) are in themselves associated with an increased risk of thromboses and cardiovascular diseases. Therefore, it is important to compare the occurrence of these events during treatment with tofacitinib with an active comparator.

The aim of this study was to use data from a large health insurance database in the USA to compare the incidence of VTE and CV events in IBD patients treated with tofacitinib or TNF-α inhibitors.

Analyzed Data and Assessed Population

This was a cohort retrospective study that utilized health data from nearly 90 million individuals from the period 2008–2019. Patients diagnosed with IBD (according to ICD codes) who were first prescribed tofacitinib or TNF-α inhibitors were included in the analysis. The primary endpoint was the incidence of VTE and major CV events (MACE) defined as acute illnesses requiring hospitalization (according to ICD codes). The authors used Cox proportional hazards models for the analysis. They also evaluated the time to onset of the event and separately analyzed the group of patients over 50 years of age.

A total of 305 IBD patients initiated on tofacitinib and 19,096 patients initiated on TNF-α inhibitors were identified. Tofacitinib patients were older (mean age 44 vs. 39 years), had more comorbid conditions, a longer disease duration, more prior hospitalizations, and more frequent previous treatments with corticosteroids, immunomodulatory drugs, and TNF-α inhibitors.

By using the propensity score, balance between therapeutic groups was achieved in the statistical analysis in terms of all demographic parameters, except for more frequent prior use of TNF-α inhibitors in the tofacitinib group.

Findings

VTE was identified in 5% of patients treated with tofacitinib and in 4% of patients with TNF-α inhibitors. Weighted comparison showed that tofacitinib treatment was not associated with a significantly higher risk of VTE than TNF-α inhibitors (hazard ratio [HR] 1.72; 95% confidence interval [CI] 0.74–3.01; p = 0.14). The incidence of hospitalizations due to VTE was comparable between groups (1% vs. 1%; HR 1.49; 95% CI 0.00–4.48; p = 0.92).

MACE were identified in 2% of patients on tofacitinib and 1% of patients treated with TNF-α inhibitors. Neither was the administration of tofacitinib associated with a significantly higher risk for this endpoint (HR 2.50; 95% CI 0.37–6.18; p = 0.52).

Higher VTE and MACE risks were observed in individuals with a Charlson Comorbidity Index (CCI) ≥ 2. However, this difference was not statistically significant (p = 0.53 for VTE and p = 0.15 for MACE).

Similar results were found in the subgroup of patients older than 50 years: for the incidence of VTE HR 2.95 (95% CI 0.45–5.59), for the incidence of MACE HR 4.89 (95% CI 0.32–11.12).

Conclusion

In this large study with an active comparator, tofacitinib was not associated with an increased risk of VTE or MACE in IBD patients. The incidence of VTE was low, and the results were similar even in patients over 50 years of age.

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Source: Kochar B. D., Cheng D., Cai T., Ananthakrishnan A. N. Comparative risk of thrombotic and cardiovascular events with tofacitinib and anti-TNF agents in patients with inflammatory bowel diseases. Dig Dis Sci 2022 Feb 3, doi: 10.1007/s10620-022-07404-z [Epub ahead of print].