Immune-mediated Diarrhea Research Articles

S132 Focused Expertise of IOTox GI Service Can Improve Quality of Clinical Care and Outcome of Immune Mediated Diarrhea/Colitis Among Inpatients: A Retrospective Review and Quality Improvement Project

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized management of advanced malignancies, but predispose to toxicities such as immune-mediated diarrhea and colitis (IMDC). Systematic management strategy including early evaluation, diagnosis, treatment and close follow up of IMDC ensures high efficacy of clinical remission and reduces the delay and interruption of cancer treatment. We evaluate the quality outcomes of cancer patients in regards to IMDC and cancer after implementation of an institutional practice change following a standardized algorithm by a dedicated toxicity GI service among inpatients in a tertiary cancer hospital. Methods: This is a retrospective quality improvement study comparing outcomes of inpatients admitted with IMDC among years 2017 and 2019. IMDC practice algorithm was implemented in 10/2017. Results: Our sample includes 59 and 67 patients admitted for IMDC in 2017 and 2019 respectively. Genitourinary cancer is the most frequent cancer type (36%) followed by melanoma (23%). Baseline IMDC characteristics are shown in Table-1. We found no significant differences in duration, number of ICI treatments or time from ICI exposure to IMDC as well as clinical severity of IMDC in both groups. Patients admitted in 2019 had significantly higher rates of GI consultation (82% vs 53%, p< 0.001), endoscopic evaluation (70% vs 49%, P=0.01) and acceptance of GI medical management recommendations (55% vs 34%, P=0.015). Same group of patients more frequently received SIT as opposed to 2017 during their index hospital admission (41% vs 21%, P=0.039) which notably translated into significantly lower days to clinical remission (4 vs 10, P=0.046), hospital re-admissions (25% vs 51%, P=0.002) and recurrence of IMDC (24% vs 49%, P=0.002). Patients in 2019 had higher portion of close post discharge GI follow up compared to 2017 (50% vs 32%, P=0.038), and the dedicated IMDC GI specialist follow up contributed to better overall survival (P=0.003, Figure-1). Conclusion: Early evaluation, aggressive treatment and close post hospital follow up by a dedicated toxicity GI service is associated with earlier clinical remission, lower re-admissions, lower recurrence and better overall survival among inpateints with IMDC through a systematic management algorithm. We speculate the substantial improvement in quality of care and outcome of these complex cancer patients with the early involvement of an expert service specialized in this field.Figure 1:: GI follow up vs not Hazard ratio: 0.473 (0.285 - 0.783) P = 0.003Table 1:: IMDC related characteristics in patients treated for colitis in 2017 and 2019 (N=126). ICI: immune checkpoint inhibitor, IMDC: immune mediated diarrhea and colitis; IQR: interquartile range; IV: intravenous

S757 Mesalamine and Cholestyramine for Immune-Mediated Diarrhea and Colitis

S757 Mesalamine and Cholestyramine for Immune-Mediated Diarrhea and Colitis

Outcomes of Immune Checkpoint Inhibitor-related Diarrhea or Colitis in Cancer Patients With Superimposed Gastrointestinal Infections.

Immune-mediated diarrhea and colitis (IMDC) is a common adverse event in cancer patients receiving immune checkpoint inhibitors (ICIs). Gastrointestinal (GI) infections can co-occur with IMDC, and its impact on the course and outcome of IMDC remains unclear. We retrospectively reviewed cancer patients who received ICIs and developed IMDC between January 2015 and September 2019. GI multiplex panel is used to assess GI infection. The study group included patients with positive infection except those who are only positive for Clostridioides difficile or cytomegalovirus. The control group is IMDC patients with negative infection using frequency matching. Patients' disease course and outcome were compared between groups. A total of 72 patients with IMDC were included: 22 in the study group and 50 as control. Escherichia coli of different pathotypes was observed in 17 patients. Five patients had viral infections, for example, adenovirus, norovirus, and sapovirus. Patients with GI infections more frequently had grade 3 or 4 colitis (43% vs. 18%, P=0.041). Overall, GI infections were not associated with different risks of IMDC recurrence or overall survival. Antibiotics treatment did not affect the requirement for infliximab or vedolizumab but relate to a higher risk of IMDC recurrence (50.0% vs. 0.0%, P=0.015). In our study, concomitant GI infections are associated with more severe symptoms in IMDC patients. Antimicrobial treatment did not circumvent the need for immunosuppressive therapy for IMDC or improve the clinical outcome. Concomitant GI infection was not associated with a higher risk of IMDC recurrence or poor overall survival.

Association of Chronic Immune-Mediated Diarrhea and Colitis With Favorable Cancer Response.

Immune-mediated diarrhea and colitis (IMDC) is a common immune-related adverse effect related to immune checkpoint inhibitors. We aimed to identify risk factors for chronic IMDC and its prognostic value in cancer outcomes. We retrospectively collected data on patients with a diagnosis of IMDC between January 2018 and October 2019 and grouped them based on disease duration into acute (≤3 months) and chronic (>3 months) categories. A logistic regression model and the Kaplan-Meier method with log-rank tests were used for biostatistical analysis. In our sample of 88 patients, 43 were in the chronic group and 45 were in the acute group. Genitourinary cancer and melanoma accounted for 70% of malignancies. PD-1/L1 monotherapy (52%) was the more frequently used regimen. We showed that chronic IMDC was associated with proton pump inhibitor use (odds ratio [OR], 3.96; P=.026), long duration of IMDC symptoms (OR, 1.05; P<.001) and hospitalization (OR, 1.07; P=.043), a histologic feature of chronic active colitis (OR, 4.8; P=.025) or microscopic colitis (OR, 5.0; P=.045), and delayed introduction of selective immunosuppressive therapy (infliximab/vedolizumab; OR, 1.06; P=.047). Chronic IMDC also reflected a better cancer response to immune checkpoint inhibitors (30% vs 51%; P=.002) and was accompanied by improved overall survival (P=.035). Similarly, higher doses of selective immunosuppressive therapy were associated with better overall survival (P=.018). Chronic IMDC can develop among patients with a more aggressive disease course and chronic features on colon histology. It likely reflects a prolonged immune checkpoint inhibitor effect and is associated with better cancer outcome and overall survival.

Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study

Background and aimsThe risk of use of immune-mediated diarrhea and colitis (imDC) in patients with preexisting inflammatory bowel disease (IBD) is not fully understood. We report the incidence of imDC...

Correction: Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis.

Correction: Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis.

Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis

BackgroundImmune-mediated diarrhea and colitis (IMDC) is currently diagnosed and monitored by evaluating clinical symptoms. Deep remission is determined by endoscopic and histologic evaluation of the disease process. However, repeating these...

Efficacy and Safety of Vedolizumab and Infliximab Treatment for Immune-Mediated Diarrhea and Colitis in Cancer Patients: A Multi-Center Study

Background: Current treatment guidelines for IMDC recommend steroids as first-line therapy, followed by SITs (infliximab or vedolizumab) for refractory cases. We aimed to compare the efficacy of these two SITs and their impact on cancer outcomes. Methods: We performed a multicenter, retrospective observational cohort study of patients with IMDC who received SITs following steroids from 2016 to 2020. Patients’ demographic, clinical, and overall survival data were collected and analyzed. Findings: A total of 184 patients (62 vedolizumab, 94 infliximab, 28 both) were included. The efficacy of achieving clinical remission of IMDC was similar (89% vs 88%, P =0.79) between the two groups. Compared with infliximab group, vedolizumab group had a shorter steroid exposure (35 vs. 50 days, P <0·001), less hospitalizations (16% vs. 28%, P =0·005), and a shorter hospital stay (median 10·5 vs. 13·5 days, P =0·043), but a longer time to clinical response (17.5 vs. 13 days, P =0·012). Longer durations of immune checkpoint inhibitors (ICIs) treatment (OR 1·01, P =0·004) and steroid use (OR 1·02, P =0·043), and infliximab use alone (OR 2·51, P =0·039) were associated with higher IMDC recurrence. Furthermore, vedolizumab alone ( P =0·027), ≥3 doses of SIT ( P =0·011), and fewer steroid tapering attempts ( P =0·012) were associated with favorable overall survival. Interpretation: Treatment with vedolizumab as compared to infliximab for IMDC led to comparable IMDC response rates, shorter duration of steroid use and fewer hospitalizations, though with slightly longer time to IMDC response. Vedolizumab treatment also associated with lower rates of cancer progression and better overall survival. Funding: None to declare Declaration of Interest: None to declare Ethical Approval: The ethics approval of this study was granted by the IRB committee at the University of Texas MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center. The consent was waived for this study. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

S0185 Chronic Immune-Mediated Diarrhea and Colitis Is Associated With Favorable Cancer Outcomes

INTRODUCTION: Background Immune-mediated diarrhea and colitis (IMDC) is the second most common immune-related adverse effect related to immune checkpoint inhibitor (ICI) therapy. In this study, we aimed to identify risk factors for chronic IMDC and the prognostic value of chronic IMDC in terms of cancer outcome. METHODS: We retrospectively reviewed the charts of all patients with an established diagnosis of IMDC over a study period from January, 2018, through October, 2019, and grouped them, based on duration of disease, into acute (≤3 months) and chronic ( >3 months) IMDC categories. Patient demographics, clinical variables, and overall survival (OS) data were collected. A logistic regression model was used to assess the factors associated with chronic IMDC. The Kaplan-Meier and log-rank tests were used to estimate and compare OS differences between the two groups. RESULTS: Our sample was comprised of 88 patients, with 43 in the chronic IMDC, and 45 in the acute IMDC group. Median age was 65.5 years at the time of IMDC. Genitourinary cancer and melanoma accounted for 70% of malignancies in our cohort. PD-1/L1 monotherapy (52%) was more frequently used than CTLA-4 monotherapy (17%) or combination therapy (31%). Our analysis demonstrated that chronic IMDC was associated with PPI use (OR = 3.96, P = 0.026), long duration of IMDC symptoms (OR = 1.05, P < 0.001) and hospitalization (OR = 1.065, P = 0.043), histological feature of chronic active colitis (OR = 4.8, P = 0.025) or microscopic colitis (OR = 5.0, P = 0.045) and delayed introduction of SIT for IMDC (OR = 1.06, P = 0.047). Our results also demonstrated that chronic IMDC reflected a better cancer response to ICIs (30% vs. 51%, P = 0.002) and is accompanied by improved OS (P = 0.035). Similarly, we observed that high doses of SIT were associated with better OS (P = 0.018). CONCLUSION: Chronic IMDC can develop among patients with more aggressive IMDC disease course and chronic features on colon histology. It likely reflects a prolonged ICI effect, therefore is associated with a better cancer outcome and overall survival. Optimization of IMDC treatment target should be considered to improve treatment outcome in the future.Figure 1Figure 2.: Kaplan-Meier OS curve, stratified by patient. (A) OS duration between the chronic IMDC (>3 months) and acute IMDC groups (≤3 months). (B) OS duration in cases with 1–2 doses of SIT (infliximab or vedolizumab) vs. ≥3 doses of SIT.Table 1

S0137 Comparative Study of Vedolizumab and Infliximab Treatment in Patients With Immune-Mediated Diarrhea and Colitis

S0137 Comparative Study of Vedolizumab and Infliximab Treatment in Patients With Immune-Mediated Diarrhea and Colitis

Multidisciplinary Approach to Immune-Mediated Diarrhea and Colitis From Immunotherapy for Cancer.

Multidisciplinary Approach to Immune-Mediated Diarrhea and Colitis From Immunotherapy for Cancer.

Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis: A Clinical Review.

Immune-mediated diarrhea and colitis (IMDC) is among the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors (ICIs). Many factors will affect the risk of IMDC, including the type of ICI used, the type of underlying cancer, and patient characteristics. A recent study showed that preexisting inflammatory bowel disease significantly increases the risk of diarrhea and colitis with ICI treatment. In terms of management, early endoscopic evaluation improves clinical outcome by identifying high-risk patients who will benefit from early add-on immunosuppressants. Inflammatory markers, including fecal lactoferrin and calprotectin, are good screening tools to predict which patients are at risk for colitis. Calprotectin especially is associated with colitis outcome and can be used as a surrogate marker to follow treatment response. Corticosteroids remain the first-line medical treatment of IMDC management, and add-on therapy with vedolizumab or infliximab should be considered in selected patients. Fecal microbiota transplantation may be considered in refractory cases. The decision to resume ICI should be decided by balancing the risk of recurrent IMDC and the likelihood of benefiting from further ICI treatment. There is no clear evidence about whether the use of immunosuppressants will result in a worse cancer outcome. With emerging evidence, our understanding and management strategies are likely to evolve in the future.

1658 Colonic Metastatic Disease Masquerading as Immune Checkpoint Inhibitor-Mediated Colitis

INTRODUCTION: The use of immune-checkpoint inhibitors (ICIs) in the treatment of advanced cancer has increased exceptionally since ipilimumab was first approved for melanoma in 2011. As the prevalence of patients being treated with ICIs rises so too have their immune related adverse events (irAEs). Clinicians are now faced with the challenge of accurately and promptly recognizing irAEs. With immune-mediated diarrhea and colitis being two of the most common irAEs, an algorithm for their treatment has already been established; however, it is important for clinicians to maintain a broad differential diagnosis when caring for a patient on an ICI with colitis symptoms. CASE DESCRIPTION/METHODS: A 48-year-old woman with a history of metastatic, refractory, triple negative, BRCA positive breast cancer was started on pembrolizumab four years after being diagnosed with breast cancer. 18 months after initiating treatment with pembrolizumab, she developed loose, watery stools. Cross sectional imaging revealed mild, circumferential wall thickening of the proximal ascending colon. A gastrointestinal pathogen nucleic acid detection test was negative, and she was started on a two-week course of budesonide for presumed immune checkpoint inhibitor-mediated colitis (IMC). Her symptoms progressed with bright red blood per rectum and abdominal cramping. Treatment for IMC was escalated with a prednisone taper followed by infliximab infusion. 6 weeks after being treated for IMC, her hemoglobin was 7.6 and ferritin 4. She was referred to gastroenterology for iron deficiency anemia. Repeat abdominal CT revealed increased colonic wall thickening. Colonoscopy revealed an obstructing, ulcerated mass in the ascending colon. Pathology identified poorly differentiated adenocarcinoma consistent with a breast cancer metastasis. She underwent right hemicolectomy 6 months after the initial CT showed colonic thickening. DISCUSSION: Pembrolizumab is one of many ICIs that have been developed for the treatment of advanced-stage malignancies. The gastrointestinal side effects of this class of medications pose a challenge for physicians as IMC is nearly indistinguishable from many other etiologies of diarrhea clinically, and the onset of gastrointestinal symptoms ranges widely from 1 to 32 weeks after starting the medication. As the use of ICIs becomes more widespread, quick and accurate differentiation of an irAE from other life threatening pathology is of vital importance, and early colonoscopy should be considered to rule out metastatic disease.

Management Considerations for Immune Checkpoint Inhibitor-Induced Enterocolitis Based on Management of Inflammatory Bowel Disease.

Immune checkpoint inhibitor therapy has significantly improved the outcomes of various advanced malignancies that were deemed unruly prior to its invention. Immune-mediated diarrhea and enterocolitis are among the most frequently encountered adverse events of immune checkpoint inhibitor therapy. Given the increasing use of these therapies in the treatment of an ever-growing number of malignancies, providing appropriate treatment for such adverse effects has become crucial. In this review, we summarize the current body of evidence concerning the management of immune-mediated diarrhea and enterocolitis. Additionally, management of immune-mediated diarrhea and enterocolitis is likened to that of inflammatory bowel disease, given the resemblance between both entities in pathogenesis and clinical features. Reviewing the literature raised several points regarding this devastating toxicity that still need further investigation by future efforts. Endoscopic and histologic evaluation is pivotal in the assessment of immune-mediated diarrhea and enterocolitis and provides vital information regarding the severity of the disease to guide treatment. Corticosteroids are the main therapy for immune-mediated diarrhea and enterocolitis, with infliximab and vedolizumab as second-line agents. Recently, fecal microbiota transplantation has emerged as a treatment option for immune-mediated diarrhea and enterocolitis that is refractory to corticosteroids. Restarting immune checkpoint inhibitor therapy after resolution of immune-mediated diarrhea and enterocolitis carries a risk of recurrence that is mostly controllable with current immune-suppressive treatment. Lastly, we propose a management algorithm for immune-mediated diarrhea and enterocolitis. Prospective research, preferably as collaborative efforts from oncology and gastroenterology specialists, is needed to refine the management of immune-mediated diarrhea and enterocolitis.

Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis.

PURPOSEImmune checkpoint inhibitor (ICI) therapy often is suspended because of immune-mediated diarrhea and colitis (IMDC). We examined the rate of and risk factors for IMDC recurrence after ICI resumption.METHODSThis retrospective multicenter study examined patients who resumed ICI therapy after improvement of IMDC between January 2010 and November 2018. Univariable and multivariable logistic regression analyses assessed the association of clinical covariates and IMDC recurrence.RESULTSOf the 167 patients in our analysis, 32 resumed an anti–cytotoxic T-cell lymphocyte-4 (CTLA-4) agent, and 135 an anti–programmed cell death 1 or ligand 1 (PD-1/L1) agent. The median age was 60 years (interquartile range [IQR], 50-69 years). The median duration from IMDC to restart of ICI treatment was 49 days (IQR, 23-136 days). IMDC recurred in 57 patients (34%) overall (44% of those receiving an anti–CTLA-4 and 32% of those receiving an anti–PD-1/L1); 47 of these patients (82%) required immunosuppressive therapy for recurrent IMDC, and all required permanent discontinuation of ICI therapy. The median duration from ICI resumption to IMDC recurrence was 53 days (IQR, 22-138 days). On multivariable logistic regression, patients who received anti–PD-1/L1 therapy at initial IMDC had a higher risk of IMDC recurrence (odds ratio [OR], 3.45; 95% CI, 1.59 to 7.69; P = .002). Risk of IMDC recurrence was higher for patients who required immunosuppression for initial IMDC (OR, 3.22; 95% CI, 1.08 to 9.62; P = .019) or had a longer duration of IMDC symptoms in the initial episode (OR, 1.01; 95% CI, 1.00 to 1.03; P = .031). Risk of IMDC recurrence was lower after resumption of anti–PD-1/L1 therapy than after resumption of anti–CTLA-4 therapy (OR, 0.30; 95% CI, 0.11 to 0.81; P = .019).CONCLUSIONOne third of patients who resumed ICI treatment after IMDC experienced recurrent IMDC. Recurrence of IMDC was less frequent after resumption of anti–PD-1/L1 than after resumption of anti–CTLA-4.

Immune-mediated colitis after resumption of immune checkpoint inhibitor therapy.

2577 Background: Immune checkpoint inhibitor (ICI) therapy is often suspended because of immune-mediated diarrhea and colitis (IMDC). We examined the recurrence rate and risk factors for IMDC after ICI resumption. Methods: This retrospective multicenter study examined patients who resumed ICI therapy after improvement of IMDC between 1/2010 and 11/2018. Univariate and multivariate logistic regression analyses assessed the association of clinical covariates and IMDC recurrence. Results: Of the 167 patients in our analysis, 32 resumed an anti-CTLA-4 agent and 135 an anti-PD-1/L1 agent. The median duration from IMDC to restart of ICI treatment was 49 days (IQR, 23-136). IMDC recurred in 57 (34%) patients overall (44% of those resuming an anti–CTLA-4 and 32% resuming an anti–PD-1/L1 agent); 47 of these patients (82%) required immunosuppressive therapy for recurrent IMDC (Table). The median duration from ICI resumption to IMDC recurrence was 53 days (IQR 22-138). On multivariate logistic regression, patients who received anti-PD-1/L1 therapy at initial IMDC had a higher risk of IMDC recurrence (odds ratio [OR], 3.45, 95%CI, 1.59-7.69; P&lt;0.01). Risk of IMDC recurrence was higher for patients who required immunosuppression for initial IMDC (OR, 3.22; 95%CI, 1.08-9.62; P=0.02) or had longer duration of IMDC symptoms in the initial episode (OR, 1.01; 95%CI, 1.00-1.03; P=0.03). Risk of IMDC recurrence was lower for those who resumed anti–PD-1/L1 therapy than for those who resumed anti–CTLA-4 therapy (OR, 0.30; 95%CI, 0.11-0.81; P=0.02). Conclusions: One-third of patients who resumed ICI treatment after IMDC experienced recurrent IMDC. IMDC recurrence was less frequent after resumption of anti–PD-1/L1 than after anti–CTLA-4. Characteristics of recurrent IMDC based on resumed ICI therapy. [Table: see text]

Outcomes of Vedolizumab Treatment in Patients With Immune Checkpoint Inhibitor-Induced Diarrhea and Colitis: A Multi-Center Study

Introduction: Immune mediated diarrhea and colitis (IMDC) can limit immune checkpoint inhibitor (ICPI) treatment, which is an efficacious treatment for advanced malignancies. Given the immune mediated mechanism of this toxicity, steroids and infliximab are commonly used. These agents induce systemic immunosuppression with its associated morbidity. We aimed to assess clinical outcomes of vedolizumab (a gut-targeted anti-integrin agent) as an alternative treatment for IMDC. Methods: This is a retrospective case series of adults who had IMDC and received vedolizumab from 12/2016 to 4/2018 from MD Anderson Cancer Center and Medstar-Georgetown University Center. All patients had IMDC that is refractory to steroids and/or infliximab. Results: Total of 28 patients were included; 20 males (71%), 25 Caucasians (89%) with mean age of 63 years. The most common malignancy was melanoma in 7 patients (25%). According to ICPI regimen, 8 patients (29%) received anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4), 12 (43%) programmed death protein-1 or its ligand (PD-1/L-1) and 8 (29%) combination therapy. Median time from ICPI to IMDC onset was 10 weeks (IQR 1-70). Fifteen patients (54%) had grade 2 and 13 (46%) had grade 3 or 4 IMDC. Diagnostic evaluations for IMDCare shown in Table 1. Mucosal ulceration was present in 8 patients (29%), whereas non-ulcerative inflammation was present 13 (46%). All of our patients had features of active histological inflammation; 14 (50%) had features of chronicity, and 10 (36%) had features of microscopic colitis. The treatment and outcomes of IMDC are shown in Table 2. Mean duration of steroid treatment was 96 days (SD 74). Seven patients received infliximab in addition to steroids and were refractory to it. Median number of vedolizumab infusions was 3 (IQR 1-4) with a dose of 300 mg. Mean duration of follow-up in our study was 15 months. Twenty four patients (86%) achieved and sustained clinical remission. Repeat endoscopic evaluation was performed in 17 patients. Endoscopic remission was attained in 7 (54%) of the 13 patients who had abnormal endoscopic findings initially with 5/17 (29) patients reaching histological remission as well. Table 3 lists the characteristics of patients who had clinical remission. In our cohort, only 1 patient developed skin rash and 1 had joint pain. Conclusion: Vedolizumab can be appropriate for the treatment of steroid refractory IMDC, with favorable outcomes and good safety profile.110_A Figure 1 No Caption available.110_B Figure 2 No Caption available.110_C Figure 3 No Caption available.

Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis

BackgroundImmune checkpoint inhibitors (ICPI) are efficacious treatments for advanced malignancies but can result in immune mediated diarrhea and colitis (IDC). Currently, the guidelines for the treatment of IDC depend only on clinical symptoms. Endoscopic and histologic features of such adverse events are not well studied in a manner that can help to gauge treatment plans. We aimed to characterize endoscopic and histologic features of IDC and to assess their association with clinical outcomes.MethodsOur study included patients who had undergone endoscopy for IDC (1/2010 to 3/2018). Patients with GI infection at time of onset were excluded. High-risk endoscopic features were ulcers deeper than 2 mm, larger than 1 cm, and extensive colonic involvement. Univariate and multivariate logistic regression were performed to assess the association of endoscopic and histological features with clinical outcomes.ResultsA total of 182 patients was included; most were white (92%), males (65%) with a mean age of 60 years. Median time from ICPI initiation to IDC was 7 weeks. Fifty-three percent had grade 3–4 diarrhea, and 32% grade 3–4 colitis. Forty-nine patients had mucosal ulcerations, 66 non-ulcerative inflammation and 67 normal endoscopy. Calprotectin was higher in patients with ulceration (P = 0.04). The sensitivity of lactoferrin to detect histologic and endoscopic inflammation was 90% and 70% respectively. Patients who underwent endoscopy earlier than 7 days after IDC onset had shorter duration of IDC symptoms and duration of steroid treatment than those who underwent endoscopy after 7 days of IDC onset (P = 0.026 and P = 0.053, respectively). Patients who underwent endoscopy > 30 days of symptom onset required longer duration of steroids (P = 0.02), had more recurrent symptoms (P < 0.01) and received later infliximab/vedolizumab add-on therapy than did those who underwent endoscopy ≤30 days (P = 0.03). High-risk features were associated with more frequent (P = 0.03) and longer duration (P = 0.02) hospitalization and infliximab/vedolizumab requirement (P < 0.01). Patients with active histological inflammation had more recurrence (P < 0.01) and repeat endoscopy (P < 0.01). Repeat endoscopy was required in 47 patients. A multivariate logistic regression revealed that longer ICPI treatment was associated with more frequent hospitalizations (OR 1.00; 95%CI 1.00–1.01; P < 0.01) and high-risk endoscopic features were associated with the requirement of infliximab/vedolizumab (OR 3.89; 95%CI 1.68–9.01; P < 0.01).ConclusionHigh risk endoscopic features and active histologic inflammation represent important markers of disease severity with clinical implications and should be used in a timely manner to devise IDC-focused treatment algorithms.