Ahuja, Dhruv

ABSTRACT We conducted a USA claims‐based cohort study in 20,705 patients with inflammatory bowel diseases (IBD) on advanced therapies to estimate the overall and comparative risk of tuberculosis between advanced therapies using inverse probability of treatment weighted Cox proportional hazards model. The incidence rate (IR, per 100,000 person‐years) of tuberculosis with TNF antagonists ( n = 9378) and non‐TNF‐targeting biologics (anti‐integrins [ n = 5877], anti‐interleukins [ n = 5450]) was similar (38 [95% CI, 8–69] vs. 33[7–59]). Adjusting for covariates, risk of tuberculosis was similar (HR, 1.16 [0.41–3.31]). In low incidence regions like USA, the incidence of tuberculosis after starting advanced therapies for IBD is very low, and comparable across advanced therapies.

INTRODUCTION: We conducted a retrospective cohort study comparing the safety of advanced therapies in patients with ulcerative colitis (UC). METHODS: Using an administrative claims database (OptumLabs Data Warehouse), we identified patients with UC who initiated treatment with tumor necrosis factor-α (TNF) antagonists, anti-integrin agents, anti-interleukin, Janus kinase inhibitors (JAK), or sphingosine-1 phosphate receptor modulators between 2016 and 2022 and had followed up for at least 1 year before and after treatment initiation. We compared the risk of serious infections, venous thromboembolism, and major adverse cardiovascular events through multinomial propensity score-based inverse probability weighting, with propensity scores estimated through generalized boosted models that accounted for disease characteristics, healthcare utilization, comorbidities, and previous and concomitant medications, and the competing risk of mortality. We calculated cause-specific hazard ratios (HR) and 95% confidence intervals for multiple treatment comparisons. RESULTS: We included 9,430 patients with UC treated with TNF antagonists (n = 4,111), anti-integrins (n = 3,165), anti-ILs (n = 1,342), JAK inhibitors (n = 701), or sphingosine-1 phosphate receptor modulators (n = 111), followed over median 27 months. After adjusting for confounding variables, anti-ILs were associated with a lower risk of serious infections compared with TNF antagonists (HR, 0.66 [95% confidence interval, 0.51–0.87]) and anti-integrins (HR, 0.75 [0.57–0.98]). JAK inhibitors were associated with a lower risk of serious infections compared with TNF antagonists (HR, 0.66 [0.46–0.94]). The incidence of venous thromboembolism (incidence rate, 1.4–2.0 per 100 py) and major adverse cardiovascular event (0.5–1.0 per 100 py) was very low, without any significant differences across agents. DISCUSSION: In a real-world cohort of patients with UC, anti-ILs and JAK inhibitors were associated with a lower risk of serious infections and may offer net benefit, especially in patients with previous TNF antagonist exposure.

ABSTRACT Background Advanced therapies increase the risk of shingles in inflammatory bowel diseases (IBD). Aim To compare the risk of shingles with different advanced therapies in patients with IBD. Methods We identified patients with IBD who initiated treatment with tumour necrosis factor (TNF) antagonists, anti‐integrins, anti‐interleukins, Janus kinase (JAK) inhibitors, or sphingosine‐1 phosphate receptor (S1PR) modulators between 2016 and 2022 and had follow‐up for at least 1 year before and after treatment initiation. We estimated the incidence rate (IR per 100 person‐year [PY]) of shingles (overall and complicated) and compared the risk with different advanced therapies through multinomial propensity score‐based inverse probability of treatment weighting (IPTW), with propensity scores estimated through generalised boosted models, accounting for disease characteristics, healthcare utilisation, comorbidities and prior and concomitant medications. Weighted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for multiple treatment comparisons. Results We included 21,675 patients followed over 27 months. IRs per 100 PY of shingles and complicated shingles were: TNF antagonists 1.0/0.3, anti‐integrin agents 1.4/0.4, anti‐interleukins 1.2/0.5, JAK inhibitors 3.3/0.9 and S1PR modulators 2.0/1.0. After adjusting for confounding variables, JAK inhibitors were associated with higher risks of shingles than TNF antagonists (HR 2.19; 1.28–3.75), anti‐integrins (HR 1.87; 1.12–3.14) and anti‐interleukins (HR 1.70; 0.98–2.96). Conclusions JAK inhibitors were associated with 1.7–2.2‐fold higher risk of shingles than other advanced therapies.