Activity of axial spondyloarthritis after one year of anti-tumor necrosis factor therapy among patients with inflammatory bowel diseases.

The disease activity of axSpA after initiating anti-TNF agents for inflammatory bowel diseases (IBD) is poorly understood. We sought to examine the disease activity of axial spondyloarthritis (axSpA) after initiation of anti-tumor necrosis factor (TNF) agents among patients with IBD. This retrospective cohort study included adults with IBD and axSpA who initiated anti-TNF agents between 1/1/2012-10/1/2021 at a large academic center. The primary outcome was symptom resolution (SR) of axSpA at 12 months ("0/10 pain" or "no pain" or "controlled pain" with no morning stiffness and no use of daily NSAIDs). The secondary outcome was clinical remission (CR) of IBD at 12 months (simple clinical colitis activity index <3, Harvey-Bradshaw Index <5, or provider assessment with no use of oral/IV steroids for 30 days). Associations between baseline characteristics and SR of axSpA were examined using logistic regression. 82 patients with axSpA and IBD initiated anti-TNF agents. At 12 months, 52% and 74% achieved SR of axSpA and CR of IBD, respectively. IBD duration <5 years (OR 3.0, 95% CI 1.2-7.5) and adalimumab use (reference: all other anti-TNFs; OR 2.7, 95% CI 1.002-7.1) were associated with SR of axSpA at 12 months. 52% of patients with axSpA and IBD achieved SR of axSpA at 12 months after initiating anti-TNF therapy. Shorter disease duration and adalimumab use may be associated with higher odds of SR. Larger studies are needed to confirm these findings, examine additional clinical predictors of SR, and identify more effective therapeutics for this population.

Risk of Gastrointestinal Infections After Initiating Vedolizumab and Anti-TNFα Agents for Ulcerative Colitis.

GOALS: Characterize and compare the risk of Clostridioides difficile infection (CDI) and cytomegalovirus colitis (CMVC) after initiation of vedolizumab or anti-tumor necrosis factor (TNF)α agents for ulcerative colitis (UC). BACKGROUND: Immunosuppression is a risk factor for gastrointestinal infections including CDI and CMVC among patients with UC; however, the risk according to the biological class is poorly understood. STUDY: A retrospective cohort study of adults with UC involving the initiation of vedolizumab or anti-TNFα agents during June 1, 2014 to December 31, 2020 was conducted at a large academic health system. The primary outcomes for both CDI and CMVC analyses were first CDI or CMVC after biological initiation. The secondary outcome for the CDI analysis was severe CDI (>10,000 white blood cells or serum creatinine >1.5 mg/dL). Independent variables included demographics and UC history/severity factors. Inverse probability of treatment weighted Cox regression was performed to assess the hazard of CDI by biological group. Due to few outcomes, CMVC was reported descriptively. RESULTS: A total of 805 UC patients initiated vedolizumab (n=195) or anti-TNFα agents (n=610). There were 43 CDIs and 11 severe CDIs over 1436 patient-years. The inverse probability of treatment weighted Cox regression demonstrated no association between CDI and vedolizumab versus anti-TNFα (hazard ratio 0.33, 95% confidence interval 0.05-2.03), but identified a significantly lower hazard of severe CDI for vedolizumab versus anti-TNFα (hazard ratio 0.10, 95% confidence interval 0.01-0.76). There were 5 cases of CMVC, all in the anti-TNFα group. CONCLUSIONS: There was a lower adjusted risk of severe CDI but not total CDI associated with vedolizumab. CMVC was not observed after initiating vedolizumab. These findings may provide reassurance regarding the use of vedolizumab when also considering the risk of gastrointestinal infections.

P074 Comparative Risk of Clostridioides Difficile Infection in Vedolizumab vs anti-TNFa Agents in Biologic-Naïve Patients With Ulcerative Colitis.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with adverse outcomes in ulcerative colitis (UC). There is concern that vedolizumab, which inhibits lymphocyte trafficking to the intestines, may increase the risk of gastrointestinal infections such as CDI when compared to other biologics. We conducted a retrospective cohort study to determine if vedolizumab is associated with an increased risk of CDI compared to anti-TNFa agents in UC. METHODS: Retrospective cohort study of adult patients with UC initiating infliximab, adalimumab, or vedolizumab 6/1/14-12/31/20 at a large academic health system. Electronic records were manually reviewed. Patients with Crohn's disease, indeterminate colitis, prior biologic exposures, prior colectomy, and non-UC indications for biologics were excluded. Patients were followed until CDI, colectomy, biologic discontinuation/switch, or last gastroenterology encounter through 8/1/21. The primary outcome was time from biologic initiation to first CDI, defined as positive stool C. difficile toxin or toxigenic C. difficile polymerase chain reaction (PCR) with associated CDI antibiotic prescriptions. Secondary outcomes included CDI-related hospitalization, colectomy, or death within 30 days of CDI. The primary exposure was vedolizumab vs anti-TNFa therapy. Other independent variables included demographics and UC history/severity factors. Propensity scores (PSs) were calculated using logistic regression of vedolizumab vs anti-TNFa on the following covariates: age, sex, Caucasian, body mass index (BMI), disease duration, current systemic corticosteroid use, UC-related hospitalization within prior 12 months, last Mayo endoscopic subscore, Montreal disease extent, albumin, and malignancy history. Inverse probability of treatment weighting (IPTW) was performed using PSs. An univariable Cox proportional hazards model was fit to calculate the unadjusted hazard ratio (HR) of CDI for vedolizumab vs anti-TNFa. A multivariable, IPT-weighted Cox model was then fit with two additional covariates extrinsic to the PS: pre-biologic CDI and immunomodulator exposure (time-varying covariate). Patients were censored at loss of follow-up, biologic discontinuation, or colectomy. RESULTS: 805 UC patients initiated vedolizumab (n = 195) or anti-TNFa agents (n = 610). Vedolizumab patients were older and less commonly received systemic corticosteroids or had UC-related hospitalization within 12 months pre-biologic initiation. There were 43 CDIs over 1,436 patient-years follow-up. CDI and CDI hospitalization occurred less commonly with vedolizumab vs anti-TNFa (CDI: 1.0% vs 6.7%, p = 0.001; CDI hospitalization: 1.0% vs 3.8%, p = 0.042 by log-rank test). There were no differences in colectomies or deaths or exposure to antibiotics/corticosteroids during follow-up or within 30 days preceding CDI. The unadjusted Cox model demonstrated a lower hazard of CDI for vedolizumab vs anti-TNFa (HR 0.17, 95% CI 0.04-0.71). The multivariable IPT-weighted Cox model demonstrated no difference in hazard of CDI for vedolizumab vs anti-TNFa (HR 0.33, 95% CI 0.05-2.03) or immunomodulator exposure (HR 1.01, 95% CI 0.41-2.40). Pre-biologic CDI was associated with an increased hazard of CDI (HR 5.95, 95% CI 2.93-12.09). Among patients who developed CDI, 17/43 (39.5%) had pre-biologic CDI a median of 227 days (IQR 160-550 days) preceding CDI. CONCLUSION: Our study did not identify an increased risk of CDI associated with vedolizumab vs anti-TNFa agents after controlling for UC severity. We hope that these findings will reassure UC providers considering vedolizumab as a first-line biologic agent in the context of gastrointestinal infectious risks.