Real-World Treatment Persistence Among Advanced Therapy-Naïve or -Experienced Patients with Ulcerative Colitis Initiated on Ustekinumab or Adalimumab.

INTRODUCTION: Persistence on advanced therapies in ulcerative colitis (UC) is a useful real-world treatment performance measure. This study compared real-world persistence during the maintenance phase among advanced therapy-naïve and -experienced patients with UC initiated on ustekinumab or adalimumab. METHODS: Claims data from the IQVIA PharMetrics® Plus de-identified database (01/01/2015-06/30/2022) were used to select adult patients with UC treated with ustekinumab or adalimumab based on the agent first initiated (index date) after 10/21/2019. Inverse probability of treatment weighting was used to balance cohorts on baseline characteristics. Persistence on the index agent (no gaps in days of supply of > 120 days for ustekinumab or > 60 days for adalimumab), persistence while corticosteroid-free, while on monotherapy, and persistence on the US labeled dose were described and compared during the 12-month period post-index using Kaplan-Meier analysis and Cox proportional hazards models. Outcomes were analyzed separately among advanced therapy-naïve and advanced therapy-experienced patients. RESULTS: At 12 months post-index, advanced therapy-naïve patients receiving ustekinumab (n = 371) had higher persistence on the index agent [83.8% vs. 57.6%, hazard ratio (95% confidence interval) = 3.09 (2.29-4.16); p < 0.001), persistence while corticosteroid-free [2.00 (1.63-2.45); p < 0.001], persistence while on monotherapy [2.67 (2.07-3.44); p < 0.001], and persistence on the labeled dose [4.21 (2.76-6.44); p < 0.001] versus those receiving adalimumab (n = 1726). At 12 months post-index, advanced therapy-experienced patients receiving ustekinumab (n = 693) had higher persistence on the index agent [78.1% vs. 59.2%, 2.44 (1.82-3.26); p < 0.001], persistence while corticosteroid-free [1.24 (1.01-1.54); p = 0.0447], persistence while on monotherapy [2.53 (2.00-3.21); p < 0.001], and persistence on the labeled dose [4.77 (3.09-7.35); p < 0.001] versus those receiving adalimumab (n = 254). CONCLUSION: This claims-based analysis demonstrated significantly higher treatment persistence, including persistence while corticosteroid-free, persistence while on monotherapy, and persistence on the labeled dose, among both advanced therapy-naïve and advanced therapy-experienced patients with UC initiated on ustekinumab compared to adalimumab.

Real-World Long-Term Persistence and Surgical Procedure-Free Period Among Bio-naïve Patients with Crohn's Disease and Fistula Initiated on Ustekinumab.

INTRODUCTION: Fistula is a common complication of Crohn's disease (CD). Treatment with biologics has been associated with fistula healing. Long-term persistence is an important factor for a chronic inflammatory process such as fistula. This study described 24-month persistence and time-to-surgery endpoints among bio-naïve patients with CD and intestinal fistula who were initiated on ustekinumab. METHODS: Adults with CD and any enteric or perianal fistula initiated on ustekinumab (index date) between September 23, 2016, and March 2, 2022, were selected from the IQVIA PharMetrics® Plus database and followed up to 24 months. Persistence on ustekinumab (no gaps in days of supply of > 120 days) and composite endpoints of being persistent while on monotherapy and persistent while corticosteroid free were also assessed. The date of surgery was defined as the date of first claim for any CD-related surgeries. Persistence and time-to-surgery endpoints were assessed from the index date until the earliest of discontinuation (event), immunomodulator or other biologic use (event), corticosteroid use (event), date of surgery (event), 24-month follow-up or data end (censoring) using Kaplan-Meier analyses. RESULTS: The sample included 445 patients (mean age: 42.8 years; 56.6% female). The most common type of fistula was anal fistula (36.0%). At 24 months after ustekinumab initiation, 64.2% of patients remained persistent (95% confidence interval [CI] 55.8-71.4). Furthermore, 53.3% of patients were persistent while on monotherapy (95% CI 45.1-60.7), and 45.6% of patients were persistent while being corticosteroid free (95% CI 36.9-53.8). At 24 months, 22.8% (95% CI 17.0-30.3) of patients underwent any CD-related surgery. CONCLUSION: This study quantified long-term persistence on ustekinumab among bio-naïve patients with CD and fistula. Over half of patients initiated on ustekinumab were persistent and persistent while on monotherapy 24 months after initiation. Time-to-surgery estimate was comparable to existing evidence. These findings support ustekinumab as a treatment option for long-term management of CD with fistula.

Comparison of real-world healthcare resource utilization among advanced therapy-naïve and advanced therapy-experienced patients with ulcerative colitis initiated on ustekinumab or vedolizumab.

OBJECTIVES: To describe and compare healthcare resource utilization (HRU) among advanced therapy-naïve and advanced therapy-experienced patients with ulcerative colitis (UC) initiating ustekinumab or vedolizumab in the United States. METHODS: Claims data from IQVIA PharMetrics Plus de-identified database (01/01/2015-06/30/2022) were used to identify adult patients with UC initiating ustekinumab or vedolizumab (index date) after 10/21/2019. Baseline characteristics were balanced using inverse probability of treatment weighting. All-cause and UC-related HRU (number of inpatient admissions, inpatient days, emergency department visits, and outpatient visits) were described during the post-index period, and Poisson regression models were used to evaluate associations between index therapy and HRU outcomes. Analyses were performed separately among advanced therapy-naïve or advanced therapy-experienced patients. RESULTS: A total of 444 (ustekinumab) and 1,917 (vedolizumab) advanced therapy-naïve patients, and 647 (ustekinumab) and 1,152 (vedolizumab) advanced therapy-experienced patients were identified. In advanced therapy-naïve patients, higher rates of UC-related inpatient days (rate ratio [95% confidence interval] = 1.84 [1.15, 3.58]; p = 0.004), emergency department visits (1.39 [1.01, 2.17]; p = 0.044), and outpatient visits (1.81 [1.61, 2.04]; p < 0.001) were observed among patients initiating vedolizumab relative to ustekinumab. In advanced therapy-experienced patients, higher rates of UC-related inpatient admissions (1.47 [1.06, 2.12]; p = 0.012), inpatient days (2.18 (1.44, 3.71); p < 0.001), and outpatient visits (1.50 (1.19, 1.82); p < 0.001) were observed among patients initiating vedolizumab relative to ustekinumab. Results were similar when all-cause HRU was examined. CONCLUSIONS: Among patients with UC with and without advanced therapy experience, higher rates of all-cause and UC-related HRU were observed among those treated with vedolizumab relative to ustekinumab.

Real-World Maintenance Phase Persistence on Ustekinumab and Adalimumab in Ulcerative Colitis.

Purpose: To describe real-world persistence in bio-naïve and bio-experienced adults with ulcerative colitis (UC) treated with ustekinumab, a recently approved anti-interleukin 12/23 antibody, or adalimumab, an anti-TNF biologic. Methods: This is a descriptive, retrospective cohort study. Patients initiating ustekinumab or adalimumab (index date, between 10/21/2019 and 08/13/2021) were selected from the Komodo Health comprehensive dataset and stratified into bio-naïve and bio-experienced subgroups based on biologic use 12 months pre-index date. Endpoints evaluated at 12-months after maintenance phase start using Kaplan-Meier analysis included 1) persistence; 2) persistence while being corticosteroid-free (<14 consecutive days of corticosteroid supply after day 90 post-index); and, 3) persistence while on monotherapy (no immunomodulators/non-index biologics/advanced therapies). Results: Ustekinumab cohort included 778 patients (236 bio-naïve, 542 bio-experienced) and adalimumab cohort included 1693 patients (1517 bio-naive, 176 bio-experienced). At 12 months after maintenance phase start, 75.5% and 50.5% of bio-naïve patients persisted on ustekinumab and adalimumab and 72.3% and 56.9% of bio-experienced patients persisted on ustekinumab and adalimumab, respectively. Further, 55.1% and 38.2% of bio-naïve patients were persistent and corticosteroid-free with ustekinumab and adalimumab; 43.7% and 33.4% of bio-experienced patients were persistent and corticosteroid-free with ustekinumab and adalimumab, respectively. Moreover, 68.1% and 44.5% of bio-naïve patients were persistent and on monotherapy with ustekinumab and adalimumab; 61.6% and 47.9% of bio-experienced patients were persistent and on monotherapy with ustekinumab and adalimumab, respectively. Conclusion: At 12 months after maintenance phase start, patients with UC treated with ustekinumab had numerically higher persistence, including persistence while corticosteroid-free and persistence while on monotherapy, than patients treated with adalimumab.

Burden of chronic corticosteroid use among patients with ulcerative colitis initiated on targeted treatment or conventional therapy in the United States.

BACKGROUND: Chronic corticosteroid use is common in ulcerative colitis (UC); however, real-world evidence of its burden to the health care system is limited. OBJECTIVE: To quantify chronic corticosteroid use burden in UC. METHODS: Adults with UC initiated on targeted treatments (ie, biologics and advanced/small molecule therapies) or conventional therapy (index date) were selected from a deidentified US insurance claims database (January 1, 2004, to September 30, 2021). Targeted treatments and conventional therapy initiators were stratified into chronic (>90 days corticosteroid use 12 months post-index [landmark]) and nonchronic corticosteroid users. Patient characteristics 12 months pre-index were balanced with inverse probability of treatment weighting. Health care resource use, costs (US$ 2021), and corticosteroid-related complications were compared in the 12 months post-landmark. RESULTS: Targeted treatment initiators included 1,886 chronic and 1,911 nonchronic corticosteroid users; conventional therapy initiators included 4,980 chronic and 5,199 nonchronic users. Chronic vs nonchronic users had 94% more inpatient days and 16% more outpatient visits among targeted treatment initiators, and 135% more inpatient days and 30% more outpatient visits among conventional therapy initiators (all P < 0.01). Mean all-cause total costs per patient per year were $73,491 for chronic vs $58,884 for nonchronic users ($14,607 higher; P < 0.01) for targeted treatment initiators, and $39,335 for chronic vs $21,271 for nonchronic users ($18,065 higher; P < 0.01) for conventional therapy initiators. Odds of infection and bone loss were 14% and 113% higher, respectively, in chronic vs nonchronic users among targeted treatment initiators and 29% and 47% higher in chronic vs nonchronic users among conventional therapy initiators (all P < .01). CONCLUSIONS: The results of this study suggest that chronic corticosteroid use is associated with substantial clinical and economic burden and may indicate unmet needs in the management of UC progression.

Economic and clinical burden of chronic corticosteroid use in patients with Crohn[apos]s disease initiated on biologic or conventional therapies in the US: A retrospective claims study.

BACKGROUND: Chronic corticosteroid (CS) use is associated with complications, but estimates of the economic and clinical burden in patients with Crohn's disease (CD) are lacking. OBJECTIVE: To estimate the burden of chronic CS use in CD in the United States in terms of health care resource utilization (HRU), health care costs, and CS-related complications. METHODS: This was a retrospective study of adults with CD initiated on biologics or conventional therapies (index date). Patients from a deidentified insurance claims database (2004-2021) were classified as chronic CS users (>90 days of CS use) or nonchronic CS users based on a 12-month landmark period starting on the index date. Patient baseline characteristics were balanced, and outcomes (HRU, costs [2021 US dollars], and CS-related complications) 12 months after the landmark period were compared between CS groups using regressions with nonparametric bootstrap resampling to estimate confidence intervals and P values. RESULTS: Biologic initiators (mean age: 44 years, 55% female) included 3366 chronic and 3401 nonchronic CS users; conventional therapy initiators (mean age: 51 years, 59% female) included 3657 chronic and 3727 nonchronic CS users. Compared with nonchronic users, chronic users had significantly more inpatient days and outpatient visits (biologic initiators: 37% and 24% more, respectively; conventional therapy initiators: 36% and 17%, respectively; all P<0.05). Chronic users also had significantly higher mean all-cause total costs per-patient-per year (biologic: $72,967 vs. $63,100, mean cost difference [MCD] = $9867; conventional therapy: $40,144 vs. $26,426, MCD = $13,718; all P<0.001), as well as higher odds of infection (biologic: 14% higher; conventional therapy: 20% higher) and bone loss (63% and 41%, respectively) (all P<0.05). CONCLUSION: Chronic CS use in patients with CD is associated with a significant economic and clinical burden including higher HRU, health care costs, and prevalence of complications, suggesting unmet needs in the clinical management of this population.

Intestinal Inflammation Does Not Predict Nonalcoholic Fatty Liver Disease Severity in Inflammatory Bowel Disease Patients.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is a common cause of hepatic steatosis in patients with inflammatory bowel disease (IBD). Both metabolic syndrome (MetS) and intestinal inflammation are implicated in NAFLD pathogenesis. METHODS: We performed a retrospective cohort study of patients with IBD and NAFLD seen in our health system from January 1997 to December 2011 to examine associations between IBD severity and phenotype; MetS; and NAFLD fibrosis as estimated by the NAFLD Fibrosis Score (NFS). RESULTS: A total of 84 patients were included in our analysis (24 UC, 60 CD). 23% of patients had MetS. IBD patients with MetS were significantly older at the time of IBD diagnosis (44 vs. 33, p = 0.005) and NAFLD diagnosis (55 vs. 47, p = 0.018). IBD patients with MetS had higher ALT (54 vs. 38 U/L, p = 0.02) and AST (52 vs. 35 U/L, p = 0.004). Comparing MetS patients to non-MetS IBD patients, there was no significant difference between IBD medication use (i.e., steroids, anti-TNFs, and immunomodulators) or NAFLD medication use, other than statins. Both UC and CD patients with concomitant MetS had significantly higher NFS scores than non-MetS patients: UC (-0.4 vs. -2.5, p = 0.02) and CD (-0.8 vs. -2.3, p = 0.03). IBD disease severity, disease location, or IBD medication use was associated with NAFLD severity. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that NAFLD severity in both UC and CD IBD patients is associated with the presence of MetS but not with the severity of IBD.

Inflammatory Bowel Disease Patients' Willingness to Accept Medication Risk to Avoid Future Disease Relapse.

OBJECTIVES: Biomarkers, endoscopy and imaging tests can identify patients at increased risk for early recurrence of symptomatic inflammatory bowel disease (IBD). However, patients may be unwilling to accept additional medical therapy risks related to therapy escalation to avoid a future disease relapse. We sought to quantify IBD patients' willingness to accept medication risk to avoid future disease relapse. METHODS: We conducted a discrete-choice experiment among 202 patients with IBD who were offered choices of therapies with varying risks of lymphoma and infection, and varying time to next IBD relapse. Random parameters logit was used to estimate patients' willingness to accept tradeoffs among treatment features in selecting medication therapy to avoid future disease relapse. RESULTS: To avoid a disease relapse over the next 5 years, IBD patients were willing to accept an average of a 28% chance of a serious infection; and an average of 1.8% chance of developing lymphoma. These results did not significantly change when patients were offered 10 years until their next disease relapse, but were lower (11 and 0.7%, respectively) when offered 1.5 years until the next disease relapse. Patients with active disease symptoms were significantly less willing to accept medication risk for time in remission. CONCLUSIONS: IBD patients are willing to accept high levels of lymphoma and serious infection risk to maintain disease remission. These preferences are congruent with the treatment paradigms emphasizing mucosal healing and early aggressive therapy and highlight patients' strong preferences for therapies resulting in durable remission of at least 5 years.

Impact of JC virus antibody testing in patients with Crohn's disease with loss of response to infliximab: a Markov model.

BACKGROUND: The optimal treatment strategy for patients with Crohn's disease who have loss of response to the anti-tumor necrosis factor α medication infliximab is uncertain. Natalizumab has an alternative mechanism of action, but its use has been limited by the risk of progressive multifocal leukoencephalopathy. In this study, we performed a decision analysis assessing the impact of JC virus (JCV) antibody testing and natalizumab utilization for loss of response to infliximab. METHODS: We constructed a Markov model to assess the difference between unscreened natalizumab use (option 1), JCV antibody testing with natalizumab when appropriate (option 2), and second anti-tumor necrosis factor α use (option 3). The base case was a 35-year-old man with severe Crohn's disease with loss of response to infliximab. The time horizon was 3 years. Results are reported in quality-adjusted life years (QALYs). Deterministic and probabilistic analyses were conducted. Markov analysis using a cohort of 5000 individuals was performed. The impact of JCV antibody status on outcomes in this model was assessed. RESULTS: Option 2 was the preferred strategy (2.0880 QALYs), followed by option 1 (2.0875 QALYs) and option 3 (2.0808 QALYs). Patients in option 2 required fewer surgeries compared with option 3. Previous JCV infection was associated with reduced QALYs with all options that allowed for natalizumab use. CONCLUSIONS: JCV antibody testing and subsequent treatment selection yield improved outcomes over natalizumab without testing or using only a second anti-tumor necrosis factor α in all patients.

Clinical predictors of urgent findings on abdominopelvic CT in emergency department patients with Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) are frequently exposed to diagnostic radiation in emergency departments (EDs). We aimed to examine clinical predictors of urgent abdominopelvic computed tomography (APCT) findings in this population. METHODS: A retrospective cross-sectional study was performed among adults with CD presenting to 2 emergency departments with a gastrointestinal chief complaint. The outcome, APON (abscess, perforation, obstruction, new or worsening non-CD-related findings), included APCTs with new or worsening CD-related or non-CD-related urgent findings. Variables with P < 0.05 in bivariate analyses were included in a multivariable logistic regression model, which was also used to develop a risk score for APON. RESULTS: A total of 481 APCTs were performed and 166 (34.5%) identified APON. Variables retained in the final model were history of intestinal obstruction (odds ratio [OR]: 3.78, 95% confidence interval [CI]: 2.27-6.28), history of intraabdominal abscess (OR: 2.64, 95% CI: 1.43 to 4.88), current hematochezia (OR: 0.38, 95% CI: 0.21 to 0.68), and white blood cell count >12,000/µL (OR: 2.49, 95% CI: 1.63 to 3.84). The c-statistic was 0.72. The risk score subtracts 1 point for hematochezia, and adds 1 point for each of the other variables. Among patients with a risk score of -1, the predicted and observed risk for APON was 9% and 6%, respectively. Any score greater than -1 had a predicted and observed risk of 19.8% and higher. CONCLUSIONS: An APON risk score of -1 is associated with a low risk of urgent APCT findings in patients with CD in the emergency department. Implementation of such a tool may support clinical decision-making in the ED setting.

Use of abdominopelvic computed tomography in emergency departments and rates of urgent diagnoses in Crohn's disease.

BACKGROUND & AIMS: In the United States, the use of abdominopelvic computed tomography (APCT) by emergency departments for patients with abdominal pain has increased, despite stable admission rates and diagnosis requiring urgent intervention. We proposed that trends would be similar for patients with Crohn's disease (CD). METHODS: We conducted a retrospective study of data from 648 adults with CD who presented at 2 emergency departments (2001-2009; 1572 visits). Trends in APCT use were assessed with Spearman correlation coefficient. We compared patient characteristics and APCT findings during 2001-2003 and 2007-2009. RESULTS: APCT use increased from 2001 (used for 47% of encounters) to 2009 (used for 78% of encounters; P = .005), whereas admission rates were relatively stable at 68% in 2001 and 71% in 2009 (P = .06). The overall proportion of APCTs with findings of intestinal perforation, obstruction, or abscess was 29.0%; 34.9% of APCTs were associated with urgent diagnoses, including those unrelated to CD. Between 2001-2003 and 2007-2009, the proportions of APCTs that detected intestinal perforation, obstruction, or abscess were similar (30% vs 29%, P = .92), as were the proportions used to detect any diagnosis requiring urgent intervention, including those unrelated to CD (36% vs 34%, P = .91). CONCLUSIONS: Despite the increased use of APCT by emergency departments for patients with CD, there were no significant changes in admission rates between the periods of 2001-2003 and 2007-2009. The proportion of APCTs that detected intestinal perforation, obstruction, abscess, or other urgent conditions not related to CD remained high.