LOWER MORTALITY RISK WITH COMBINATION THERAPY WITH ANTI-TNF THERAPY AND THRIOPURINE COMPARED TO THIOPURINE ALONE IN ELDERLY PATIENTS WITH UC
Authors: Chaaban Lara , Kobeissi Lynn , Paul Nicole , Melia Joanna 
Published: January 2024

Abstract

INTRODUCTION
Despite increasing incidence rates of ulcerative colitis (UC) in the elderly, efficacy and safety data for medical management in this cohort is lacking due to underrepresentation in clinical trials and registries. Selection of medical therapy is often complex, taking into consideration a multitude of factors, including real and perceived risks of infection and malignancy. In the past, immunomodulators, such as thiopurines, were commonly used as monotherapy for maintenance, offering the added advantages of affordability and oral administration. Indeed, there are elderly patients who have been maintained for decades on thiopurine monotherapy. Further, thiopurines can be used in combination with anti-TNF therapy for improved efficacy and reduced immunogenicity compared to monotherapy with either agent in ulcerative colitis (UC). Whether the use of combination therapy imposes an additive risk compared to thiopurine monotherapy is still unclear. This study aimed to investigate outcomes of thiopurine monotherapy versus combination therapy with anti-TNF agents in elderly patients (age ≥65 years) with UC.

METHODS
The TriNetX Research Network was accessed on October 15th, 2023, to compare outcomes in elderly patients 65 years or older with UC who are receiving thiopurine monotherapy and patients who are receiving combination therapy with an anti-TNF (adalimumab, certolizumab pegol, golimumab, or infliximab). The outcomes examined were 1-year rate of corticosteroid and colectomy as well as 10-year rate of mortality, colon cancer, skin cancer, and respiratory and urinary tract infections. Statistical risk analysis was performed using the TriNetX analytical platform.

RESULTS
A total of 2,597 patients (2,245 thiopurines monotherapy and 352 AZA plus anti-TNF combination therapy) were included in the study (Table 1). Among the monotherapy and combination therapy cohorts, mean age was 71 years old and approximately 56% male. Ten-year mortality was higher in the thiopurine monotherapy group (OR 1.67, p=0.002). The combination therapy cohort had higher rates of steroid use (32.4% vs. 24.3%, p=0.001) and colectomy at 1 year compared to the monotherapy cohort (4.5% vs. 1.2%, p&lt;0.001). There was no significant difference in 10-year risk of colon cancer (OR 1.05, p=0.88), skin cancer (OR 1.51, p=0.06), incidence of respiratory (OR 1.48, p=0.07) and urinary tract infections (OR 1.18, p=0.23).

CONCLUSION
The study findings highlight the risks of thiopurine use in patients over the age of 65 given the significantly higher 10-year mortality risk in thiopurine monotherapy-treated patients. The results also suggest that combination therapy with thiopurine and anti-TNF therapies - despite utilization in patients with more active disease indicators - is not associated with an additive risk in terms of infection and mortality in elderly patients.

Table 1 Characteristics and Outcomes of Elderly Patients with UC either on Thiopurine Monotherapy or Combination Therapy with anti-TNF agents