Safety and Efficacy of Ustekinumab and Vedolizumab Among Older Adults With Inflammatory Bowel Disease

Introduction: There is a lack of safety and efficacy data for newer biologic agents among adults 60 years old with inflammatory bowel disease (IBD) given their limited inclusion in clinical trials. We conducted a retrospective cohort study comparing the therapeutic efficacy and adverse events associated with ustekinumab (UST) or vedolizumab (VDZ) use in older adults as compared to younger adults with IBD. Methods: This single-center retrospective study compared adults 18 to 60 years old to individuals ≥60 years old with a confirmed diagnosis of IBD who began VDZ or UST treatment between 2014-2021. Endoscopic remission was the primary efficacy outcome, with endoscopic response and clinical remission secondary outcomes. The primary safety outcome was infection-related hospitalization, with secondary outcomes including non-severe side-effects. Chi-square, Fisher’s exact tests were used to compare outcomes by age, and multivariate regression to compare all predictors associated with safety and efficacy. Results: Of 953 participants: 783 (82%) were < 60 years old, 170 (18%) were ≥60 years old, 367 (39%) had ulcerative colitis and 552 (58%) had Crohn’s disease, 405 initiated VDZ whereas 548 initiated UST. Baseline characteristics were similar across age; however, prior treatment with an anti-TNF biologic and/or immunomodulator was more common in younger participants (P< 0.01). When assessing efficacy, younger and older participants had comparable rates of endoscopic remission (25.9% vs 27.7%, P=0.64) and clinical remission (26.6% vs 26.5%, P=0.98) (Figure 1). When assessing safety across age, infection-related hospitalization rates were comparable (8.9% vs 8.8%, P=0.96) and younger participants were more likely than older participants to have non-severe adverse events (19.8% vs 12.8%, P=0.04). Biologic dose escalation was more frequent in younger patients on VDZ than older patients (39% vs 25%; p≤0.05); there was no association between age and other secondary outcomes (Figure 1). In multivariate analysis, measures of disease severity (prior biologic use, prior steroid use, severe baseline disease) but not age, were associated with decreased clinical and endoscopic remission and increased infection risk (P< 0.05) (Table 1). Conclusion: The use of UST and VDZ had similar efficacy and safety outcomes in older adults as compared to younger individuals with IBD. Decisions to utilize these biologics should be driven by overall disease burden, and not be deferred due to advanced chronological age alone.Figure 1.: Frequency of Efficacy and Safety Outcomes Across Participant Age (N=953) *P-values calculated via Pearson’s chi-square analysis. Intention to treat (ITT) analysis was used to address missing data. 1: Endoscopic remission defined as clinician documentation of “inactive” colitis on follow-up endoscopy during trial. Partial endoscopic response defined as clinician documentation of improvement in endoscopic score from “moderate-severe or severe” colitis on baseline endoscopy to “mild” or “moderate” colitis on follow-up endoscopy during trial. Endoscopic remission defined as clinician documentation of “inactive” colitis on follow-up endoscopy during trial. 2: Clinical remission defined as clinician report of no IBD-related symptoms in participant. Partial clinical response defined as clinician report of improvement in at least one IBD-related symptom in participant. 3: Non-severe safety outcomes reported by clinicians as secondary to the biologic treatment, including infection or abscess not requiring hospitalization, joint pain or nausea attributed to biologic use, and infusion or injection site reaction. Table 1. - Multivariable Analysis Assessing Predictors of Biologic Efficacy and Safety Among Adults with IBD Variable Primary Efficacy Outcomes Primary Safety Outcomes Endoscopic Remission1 OR (95%CI) Clinical Remission2 OR (95%CI) Infection-Related HospitalizationOR (95%CI) Non-Severe Adverse Events3 OR (95%CI) Age: < 60 years Ref. Ref. Ref. Ref. ≥ 60 years 1.06 (0.68, 1.66) 0.93 (0.61, 1.42) 0.99 (0.53, 1.87) 0.62 (0.37, 1.05) Sex: Male Ref. Ref. Ref. Ref. Female 1.20 (0.88, 1.64) 1.00 (0.74, 1.35) 1.10 (0.69, 1.73) 1.17 (0.84, 1.64) Body Mass Index (BMI) 1.01 (0.97, 1.04) 1.02 (0.99, 1.05) 0.99 (0.95, 1.04) 1.00 (0.97, 1.04) Tobacco use: Never Ref. Ref. Ref. Ref. Ever 0.92 (0.62, 1.34) 1.14 (0.81, 1.61) 1.30 (0.78, 2.15) 0.92 (0.62, 1.36) Diagnosis: Crohn's Disease Ref. Ref. Ref. Ref. Ulcerative Colitis 1.15 (0.81, 1.64) 1.96 (1.43, 2.56)* 1.19 (0.73, 1.93) 0.50 (0.34, 0.73)* Indeterminant 0.21 (0.06, 0.76)* 0.91 (0.38, 2.19) 1.73 (0.63, 4.79) 1.07 (0.47, 2.47) Disease Duration (in years) 1.01 (0.99, 1.03) 1.00 (0.99, 1.02) 0.99 (0.97, 1.02) 1.00 (0.98, 1.02) Prior Steroid Use: Never Ref. Ref. Ref. Ref. Ever 0.88 (0.54, 1.43) 0.48 (0.32, 0.74)* 2.77 (0.98, 7.83) 1.08 (0.64, 1.82) Disease Severity: Mild Ref. Ref. Ref. Ref. Moderate 0.61 (0.26, 1.42) 1.88 (0.82, 4.32) 3.32 (0.44, 25.26) 0.74 (0.32, 1.74) Severe 0.41 (0.18, 0.96) 0.97 (0.41, 2.27) 3.28 (0.43, 25.00) 0.89 (0.38, 2.10) Abbreviations: Inflammatory Bowel Disease (IBD), Odds Ratio (OR), Confidence Interval (CI), Standard Deviation (SD), N (sample size).*Statistical significance (P<0.05) in multivariate logistic regression analysis adjusted for baseline demographic variables. Imputation via Chained Equations (MICE) under assumption of missingness at random. Data were imputed 40 times with 5 iterations, and results of the imputed datasets were combined (pooled) using Rubin's rules.1: Endoscopic remission defined as “inactive” colitis on follow-up endoscopy during trial or endoscopic remission as documented by clinician.2: Clinical remission defined as clinician report of no disease-related symptoms in participant.3: Non-severe adverse events reported by clinicians as secondary to the biologic treatment, including infection or abscess not requiring hospitalization, joint pain or nausea attributed to biologic use, and infusion or injection site reaction.