Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials.

BACKGROUND AND AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. We aimed to demonstrate superiority of CT-P13 SC versus placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately-to-severely active CD or UC and inadequate response/intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks (W) 0, 2, and 6. At W10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until W54 (maintenance phase) using pre-filled syringes. (Co-)primary endpoints were clinical remission and endoscopic response (CD) and clinical remission (UC) at W54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At W54 in the CD study, statistically significant higher proportions of CT-P13 SC- versus placebo-treated patients achieved clinical remission (62.3% versus 32.1%; P < 0.0001) and endoscopic response (51.1% versus 17.9%; P < 0.0001). In the UC study, clinical remission rates at W54 were statistically significantly higher with CT-P13 SC versus placebo (43.2% versus 20.8%; P < 0.0001). Achievement of key secondary endpoints was significantly higher with CT-P13 SC versus placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSION: CT-P13 SC was more effective than placebo as maintenance therapy and well tolerated in patients with moderately-to-severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, NCT03945019 (CD) and NCT04205643 (UC).

Tissue-specific reprogramming leads to angiogenic neutrophil specialization and tumor vascularization in colorectal cancer.

Neutrophil (PMN) tissue accumulation is an established feature of ulcerative colitis (UC) lesions and colorectal cancer (CRC). To assess the PMN phenotypic and functional diversification during the transition from inflammatory ulceration to CRC we analyzed the transcriptomic landscape of blood and tissue PMNs. Transcriptional programs effectively separated PMNs based on their proximity to peripheral blood, inflamed colon, and tumors. In silico pathway overrepresentation analysis, protein-network mapping, gene signature identification, and gene-ontology scoring revealed unique enrichment of angiogenic and vasculature development pathways in tumor-associated neutrophils (TANs). Functional studies utilizing ex vivo cultures, colitis-induced murine CRC, and patient-derived xenograft models demonstrated a critical role for TANs in promoting tumor vascularization. Spp1 (OPN) and Mmp14 (MT1-MMP) were identified by unbiased -omics and mechanistic studies to be highly induced in TANs, acting to critically regulate endothelial cell chemotaxis and branching. TCGA data set and clinical specimens confirmed enrichment of SPP1 and MMP14 in high-grade CRC but not in patients with UC. Pharmacological inhibition of TAN trafficking or MMP14 activity effectively reduced tumor vascular density, leading to CRC regression. Our findings demonstrate a niche-directed PMN functional specialization and identify TAN contributions to tumor vascularization, delineating what we believe to be a new therapeutic framework for CRC treatment focused on TAN angiogenic properties.

Evolution of Symptoms After Ustekinumab Induction Therapy in Patients With Crohn's Disease.

BACKGROUND & AIMS: Ustekinumab is an effective treatment of Crohn's disease (CD). Of interest to patients is knowing how soon symptoms may improve. We analyzed ustekinumab response dynamics from the ustekinumab CD trials. METHODS: Patients with CD received intravenous induction with ustekinumab ∼6 mg/kg (n = 458) or placebo (n = 457). Week 8 ustekinumab responders received subcutaneous ustekinumab 90 mg as the first maintenance dose or as an extended induction dose for nonresponders. Patient-reported symptom changes (stool frequency, abdominal pain, general well-being) within the first 14 days and clinical outcomes through week 44 were evaluated using the CD Activity Index. RESULTS: After ustekinumab infusion, stool frequency improvement was significantly (P < .05) greater than placebo on day 1 and for all patient-reported symptoms by day 10. In patients with no history of biologic failure or intolerance, cumulative clinical remission rates increased from 23.0% at week 3 to 55.5% at week 16 after the subcutaneous dose at week 8. Corresponding cumulative rates for patients with a history of biologic failure or intolerance increased from 12.9% to 24.1%. Neither change from baseline in CD Activity Index score nor week 8 ustekinumab pharmacokinetics were associated with week 16 response. Among all patients who received subcutaneous ustekinumab 90 mg q8w, up to 66.7% were in clinical response at week 44. CONCLUSIONS: Ustekinumab induction provided symptom relief by day 1 post-infusion. Following ustekinumab infusion and a subcutaneous 90 mg injection, clinical outcomes continued to increase through week 16 and up to week 44. Regardless of week 8 clinical status or ustekinumab pharmacokinetics, patients should receive additional treatment at week 8. CLINICALTRIALS: gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Post-traumatic stress disorder symptoms are frequent among inflammatory bowel disease patients of South Asian descent-A case-control study.

BACKGROUND: Post-traumatic stress (PTS) is the psycho-physiological response to a traumatic or life-threatening event and is implicated in inflammatory bowel disease (IBD). IBD-PTS is present in up to 30% of white, non-Hispanic patients. The rates of IBD in Asian populations are expanding, making the exploration of IBD-PTS in this population imperative. METHODS: Adult patients of South/Southeast (S/SE) Asian decent with IBD for more than 6 months were recruited online via social media and patient-support groups. Participants completed the post-traumatic stress disorder (PTSD) Checklist-5 (PCL-5), the United States National Institutes of Health's Patient-Reported Outcomes Measurement Information System (NIH-PROMIS) -43 profile and demographics. S/SE Asian participants were age and sex matched (1:2) with randomly selected white, non-Hispanic controls. Statistical analyses evaluated differences in IBD-PTS symptoms between groups, the relationship between disease severity and health-related quality of life (HRQoL) and predictors of IBD-PTS severity. RESULTS: Forty-seven per cent of the 51 S/SE Asian participants met the diagnostic cut-off for PTSD on the PCL-5 compared to 13.6% of 110 IBD controls. The mean global score on the PCL-5 was three times higher in S/SE Asians. Patients of S/SE Asian decent were over five times more likely to have PTSD due to their IBD experiences than controls, nearly doubling when controlling for disease activity. More severe IBD-PTS was present in S/SE Asian patients with active disease and those with extraintestinal manifestations. Higher global levels of IBD-PTS were associated with poorer HRQoL in S/SE Asians where increased hyperarousal from IBD-PTS predicted more sleep disturbance. CONCLUSIONS: S/SE Asian patients are five times more likely to experience IBD-PTS than their white, non-Hispanic counterparts. Several cultural factors lead to IBD-PTS in S/SE Asian patients that must be considered by IBD providers. Preventing, screening for and treating IBD-PTS in this population appears warranted.

Review of Adalimumab Biosimilar SB5 in Immune-Mediated Inflammatory Diseases.

SB5 is an approved biosimilar of adalimumab, a recombinant monoclonal anti-tumor necrosis factor (TNF) antibody. The approval of SB5 was based on the comparison with reference adalimumab in analytical studies, pharmacokinetic (PK) and immunogenicity assessments, and randomized controlled trials. Efficacy data was primarily obtained in patients with rheumatoid arthritis, and extended to include additional indications such as psoriasis, Crohn's disease, or ulcerative colitis by extrapolation. Following its approval, additional post-marketing data have been collected comparing SB5 with reference adalimumab. This review summarizes the clinical data on SB5 from randomized controlled trials and provides a comprehensive overview of the available post-approval data. In "real-world" settings, SB5 was as effective as its reference product across different indications and countries, treatment persistence was well maintained throughout studies, and no new safety concerns were identified. In both controlled and "real-world" settings, switching from reference adalimumab to SB5 was not associated with altered efficacy or clinical complications. In post-approval studies, the quality of SB5 was consistent over time, independent of the batch and process changes, and the SB5 autoinjector was preferred over other autoinjectors by both healthcare professionals and patients. Taken together, these data support the use of SB5 whenever reference adalimumab is appropriate and demonstrate that switching from reference adalimumab to SB5 is feasible.

The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease.

BACKGROUND: The disease severity index (DSI) for inflammatory bowel disease (IBD) combines measures of disease phenotype, inflammatory activity, and patient-reported outcomes. We aimed to validate the DSI and assess its utility in predicting a complicated IBD course. METHODS: A multicenter cohort of adults with IBD was recruited. Intraclass correlation coefficients (ICCs) and weighted Kappa assessed inter-rater reliability. Cronbach's alpha measured internal consistency of DSI items. Spearman's rank correlations compared the DSI with endoscopic indices, symptom indices, quality of life, and disability. A subgroup was followed for 24 months to assess for a complicated IBD course. Area under the receiver operating characteristics curve (AUROC) and multivariable logistic regression assessed the utility of the DSI in predicting disease progression. RESULTS: Three hundred and sixty-nine participants were included (Crohn's disease [CD], n = 230; female, n = 194; mean age, 46 years [SD, 15]; median disease duration, 11 years [interquartile range, 5-21]), of which 171 (CD, n = 99; ulcerative colitis [UC], n = 72) were followed prospectively. The DSI showed inter-rater reliability for CD (ICC 0.93, n = 65) and UC (ICC 0.97, n = 33). The DSI items demonstrated inter-rater agreement (Kappa > 0.4) and internal consistency (CD, α > 0.59; UC, α > 0.75). The DSI was significantly associated with endoscopic activity (CDn=141, r = 0.65, P < .001; UCn=105, r = 0.80, P < .001), symptoms (CDn=159, r = 0.69, P < .001; UCn=132, r = 0.58, P < .001), quality of life (CDn=198, r = -0.59, P < .001; UCn=128, r = -0.68, P < .001), and disability (CDn=83, r = -0.67, P < .001; UCn=52, r = -0.74, P < .001). A DSI of 23 best predicted a complicated IBD course (AUROC = 0.82, P < .001) and was associated with this end point on multivariable analyses (aOR, 9.20; 95% confidence interval, 3.32-25.49). CONCLUSIONS: The DSI reliably encapsulates factors contributing to disease severity and accurately prognosticates the longitudinal IBD course.

This study shows that the disease severity index (DSI) for inflammatory bowel disease (IBD) is a valid and reliable instrument encapsulating the disease phenotype, disease activity, and impact of the disease on the patient; and it accurately predicts for incident disease complications.

Persistent perineal sinus following proctocolectomy in the inflammatory bowel disease patient.

Prolonged perineal wound healing following proctocolectomy in patients with inflammatory bowel disease (IBD) is a frustrating result for the medical team and patients who were hoping for improved quality of life. Prolonged healing, which lasts more than 6 months following proctocolectomy, is termed persistent perineal sinus (PPS) and typically necessitates further surgical management. Healing of the PPS is difficult due to the resulting "dead space" following proctocolectomy, necessitating the need to fill the void with viable tissue in an area with anatomic constraints. Here we provide a narrative review and comprehensively address the incidence, pathogenesis, and clinical and operative management of a PPS in patients with IBD following proctocolectomy. Operative methods discussed include surgical debridement, flap closure of the perineum, omental flap closure, and gracilis muscle transposition. It is necessary to further investigate and establish a gold standard of care for these patients.

Baseline TREM-1 Whole Blood Gene Expression Does Not Predict Response to Adalimumab Treatment in Patients with Ulcerative Colitis or Crohn's Disease in the SERENE Studies.

BACKGROUND AND AIMS: This study assessed whether baseline triggering receptor expressed on myeloid cells [TREM-1] whole blood gene expression predicts response to anti-TNF therapy in patients with UC or CD. METHODS: TREM-1 whole blood gene expression was analysed by RNA sequencing [RNA-seq] in patients with moderately to severely active UC or CD treated with adalimumab in the Phase 3 SERENE-UC and SERENE-CD clinical trials. The predictive value of baseline TREM-1 expression was evaluated and compared according to endoscopic and clinical response vs non-response, and remission vs non-remission, at Weeks 8 and 52 [SERENE-UC], and Weeks 12 and 56 [SERENE-CD]. RESULTS: TREM-1 expression was analysed in 95 and 106 patients with UC and CD, respectively, receiving standard-dose adalimumab induction treatment. In SERENE-UC, baseline TREM-1 expression was not predictive of endoscopic response [p=0.48], endoscopic remission [p=0.53], clinical response [p=0.58] or clinical remission [p=0.79] at Week 8, or clinical response [p=0.60] at Week 52. However, an association was observed with endoscopic response [p=0.01], endoscopic remission [p=0.048], and clinical remission [p=0.04997] at Week 52. For SERENE-CD, baseline TREM-1 expression was not predictive of endoscopic response [p=0.56], endoscopic remission [p=0.33], clinical response [p=0.07], clinical remission [p=0.65] at Week 12, or endoscopic response [p=0.61], endoscopic remission [p=0.51], clinical response [p=0.62] or clinical remission [p=0.97] at Week 56. CONCLUSIONS: Baseline TREM-1 gene expression did not uniformly predict adalimumab response in SERENE clinical trials. Further research is needed to identify potential blood-based biomarkers predictive of response to anti-TNF therapy in patients with IBD.

Neuroimmune Modulation Through Vagus Nerve Stimulation Reduces Inflammatory Activity in Crohn's Disease Patients: A Prospective Open-label Study.

BACKGROUND AND AIMS: Crohn's disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the 'inflammatory reflex', has been established in patients with rheumatoid arthritis and biologic-naive CD. The aim of this study was to explore the safety and efficacy of vagus nerve stimulation in patients with treatment-refractory CD, in a 16-week, open-label, multicentre, clinical trial. METHODS: A vagus nerve stimulator was implanted in 17 biologic drug-refractory patients with moderately to severely active CD. One patient exited the study pre-treatment, and 16 patients were treated with vagus nerve stimulation [4/16 receiving concomitant biologics] during 16 weeks of induction and 24 months of maintenance treatment. Endpoints included clinical improvement, patient-reported outcomes, objective measures of inflammation [endoscopic/molecular], and safety. RESULTS: There was a statistically significant and clinically meaningful decrease in CD Activity Index at Week 16 [mean ±â€…SD: -86.2 ±â€…92.8, p = 0.003], a significant decrease in faecal calprotectin [-2923 ±â€…4104, p = 0.015], a decrease in mucosal inflammation in 11/15 patients with paired endoscopies [-2.1 ±â€…1.7, p = 0.23], and a decrease in serum tumour necrosis factor and interferon-γ [46-52%]. Two quality-of-life indices improved in 7/11 patients treated without biologics. There was one study-related severe adverse event: a postoperative infection requiring device explantation. CONCLUSIONS: Neuroimmune modulation via vagus nerve stimulation was generally safe and well tolerated, with a clinically meaningful reduction in clinical disease activity associated with endoscopic improvement, reduced levels of faecal calprotectin and serum cytokines, and improved quality of life.

The importance of predicting patient responses to monoclonal antibodies for Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a chronic immune-mediated inflammatory bowel disease that results in relapsing and remitting symptoms but progressive transmural bowel damage leading to significant morbidity. CD results from dysregulation of the immune system related to genetic and environmental factors. While the use of monoclonal antibodies targeting cytokines and adhesion molecules has been shown to improve outcomes in CD patients, their widespread use has been limited due to high costs as well as variable access. Here, we summarize the factors that have been shown to correlate with responsiveness to biologic agents for use in practice. AREAS COVERED: We summarize the current literature regarding factors that have been shown to influence patient response to various biologic agents including: patient-related factors (e.g. age, gender, weight smoking history); disease-specific factors (e.g. disease duration, location/extension, behavior/phenotype, severity); genetic markers; transcription factors, and the gut microbiome. Finally, we review the utility of prediction models and present data supporting the use of recently developed decision support tools. EXPERT OPINION: Clinical decision support tools developed by machine learning are currently available for the selection of biologic agents in CD patients. We expect these models to become an integral tool for clinicians in the treatment of CD in the coming years.

COVID-19 and Inflammatory Bowel Disease.

The COVID-19 pandemic caused by the SARS-CoV-2 virus represents an unprecedented global health crisis. Safe and effective vaccines were rapidly developed and deployed that reduced COVID-19-related severe disease, hospitalization, and death. Patients with inflammatory bowel disease are not at increased risk of severe disease or death from COVID-19, and data from large cohorts of patients with inflammatory bowel disease demonstrate that COVID-19 vaccination is safe and effective. Ongoing research is clarifying the long-term impact of SARS-CoV-2 infection on patients with inflammatory bowel disease, long-term immune responses to COVID-19 vaccination, and optimal timing for repeated COVID-19 vaccination doses.

Hospitalization Experiences and Post-traumatic Stress in Inflammatory Bowel Disease: Opportunities for Change.

INTRODUCTION: Medical trauma related to IBD (IBD-PTS) affects approximately 25% of patients and is associated with poor outcomes. Prior studies identify common hospitalization experiences as potentially traumatic but have not measured risk relationships for the development of IBD-PTS. We aim to investigate what aspects of hospitalizations may increase the chance of medical trauma and IBD-PTS development. METHODS: Adult patients with IBD enrolled in the IBD Partners database were recruited. Study specific questionnaires included PTSD checklist, 5th edition (PCL-5), patient experience questionnaire, and items about the patient's most stressful hospitalization and nonhospital sources of medical trauma. Established criteria for the PCL-5 identified significant IBD-PTS symptoms (re-experiencing, avoidance, mood change, hyperarousal, global diagnosis). Select disease and treatment information was obtained from the main IBD Partners dataset. Univariate and multivariate statistics evaluated the relationships between hospitalization data and IBD-PTS. RESULTS: There were 639 participants with at least 1 hospitalization for IBD included. Approximately two-thirds had Crohn's disease; most were White, non-Hispanic, female, middle-aged, and reported their IBD as being in remission. Forty percent of patients stated a hospitalization was a source of IBD-PTS. Frequent anxiety while hospitalized increased the odds of IBD-PTS 2 to 4 times; similar relationships existed for pain/pain control. Higher quality communication, information, and listening skills reduced the odds of IBD-PTS, albeit marginally. CONCLUSIONS: Patients with IBD consistently cite hospitalizations as potential sources of medical trauma. Poorly managed anxiety and pain demonstrate the greatest chance for IBD-PTS development. Gender and racial/ethnic differences emerged for these risks. Positive interactions with the medical team may help mitigate in-hospital IBD-PTS development.

This study finds IBD patients with the poorest hospital experiences and those with poor pain and anxiety control are at the highest risk of developing post-traumatic stress disorder symptoms due to medical trauma. Medical staff behavior is an important consideration.

Atovaquone attenuates experimental colitis by reducing neutrophil infiltration of colonic mucosa.

Ulcerative colitis (UC) is a chronic relapsing disease featuring aberrant accumulation of neutrophils in colonic mucosa and the luminal space. Although significant advances in UC therapy have been made with the development of novel biologics and small molecules targeting immune responses, success of most current therapies is still limited, with significant safety concerns. Thus, there is a need to develop additional safe and effective therapies for the treatment of UC. Antimalarial drugs have been safely used for many years to resolve tissue inflammation and the associated pathologies. Atovaquone is a recent FDA-approved antimalarial drug that has shown anti-viral and tumor-suppressive properties in vitro however, its role in mucosal inflammation has not been evaluated. Using pre-clinical murine DSS-induced colitis model combined with complementary in vivo peritonitis and ex vivo human neutrophil activation and chemotaxis assays we investigated functional and mechanistic impacts of atovaquone on disease resolution and neutrophil trafficking. We demonstrate that atovaquone promotes resolution of DSS-induced murine colitis by reducing neutrophil accumulation in the inflamed colonic mucosa. Mechanistically, we show that atovaquone suppressed induction of CD11b expression in neutrophils, reducing their polarization and migratory ability. Thus, our findings identify a new role of atovaquone in promoting resolution of mucosal inflammation, supporting the idea of potential repurposing of this FDA-approved drug as UC therapeutic.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease.

BACKGROUND & AIMS: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease. METHODS: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews. An iterative Delphi process was conducted to establish consensus: panelists anonymously voted on items using a 9-point Likert scale, and feedback was incorporated between rounds to refine statements. Consensus meetings were held to ratify the outcome domains and core outcome measures. Stakeholders were recruited internationally, and included gastroenterologists, colorectal surgeons, methodologists, and clinical trialists. RESULTS: A total of 235 patients and 53 experts participated. Patient-reported outcomes, quality of life, endoscopy, biomarkers, and safety were considered core domains; histopathology was an additional domain for UC. In CD, there was consensus to use the 2-item patient-reported outcome (ie, abdominal pain and stool frequency), Crohn's Disease Activity Index, Simple Endoscopic Score for Crohn's Disease, C-reactive protein, fecal calprotectin, and co-primary end points of symptomatic remission and endoscopic response. In UC, there was consensus to use the 9-point Mayo Clinic Score, fecal urgency, Robarts Histopathology Index or Geboes Score, fecal calprotectin, and a composite primary end point including both symptomatic and endoscopic remission. Safety outcomes should be reported using the Medical Dictionary for Regulatory Activities. CONCLUSIONS: This multidisciplinary collaboration involving patients and clinical experts has produced the first core outcome set that can be applied to randomized controlled trials of CD and UC.

Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn's disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial.

BACKGROUND: Active-comparator trials are important to inform patient and physician choice. We aimed to evaluate the efficacy and safety of monotherapy with either ustekinumab or adalimumab in biologic-naive patients with moderately to severely active Crohn's disease. METHODS: We conducted a randomised, double-blind, parallel-group, active-comparator, phase 3b trial (SEAVUE) at 121 hospitals or private practices in 18 countries. We included biologic-naive patients aged 18 years or older with moderately to severely active Crohn's disease and a Crohn's Disease Activity Index (CDAI) score of 220-450, who had not responded to or were intolerant to conventional therapy (or were corticosteroid dependent) and had at least one ulcer of any size at baseline endoscopic evaluation. Eligible patients were randomly assigned (1:1; via an interactive web response system) to receive ustekinumab (approximately 6 mg/kg intravenously on day 0, then 90 mg subcutaneously once every 8 weeks) or adalimumab (160 mg on day 0, 80 mg at 2 weeks, then 40 mg once every 2 weeks, subcutaneously) through week 56. Study treatments were administered as monotherapy and without dose modifications. Patients, investigators, and study site personnel were masked to treatment group assignment. The primary endpoint was the proportion of patients who were in clinical remission (CDAI score <150) at week 52 in the intention-to-treat population (ie, all patients who were randomly assigned to a treatment group). This trial is registered with ClinicalTrials.gov, NCT03464136, and EudraCT, 2017-004209-41. FINDINGS: Between June 28, 2018, and Dec 12, 2019, 633 patients were assessed for eligibility and 386 were enrolled and randomly assigned to receive ustekinumab (n=191) or adalimumab (n=195). 29 (15%) of 191 patients in the ustekinumab group and 46 (24%) of 195 in the adalimumab group discontinued study treatment before week 52. There was no significant difference between the ustekinumab and adalimumab groups in the occurrence of the primary endpoint; at week 52, 124 (65%) of 191 patients in the ustekinumab group versus 119 (61%) of 195 in the adalimumab group were in clinical remission (between-group difference 4%, 95% CI -6 to 14; p=0·42). Safety for both groups was consistent with previous reports. Serious infections were reported in four (2%) of 191 patients in the ustekinumab group and five (3%) of 195 in the adalimumab group. No deaths occurred through week 52 of the study. INTERPRETATION: Both ustekinumab and adalimumab monotherapies were highly effective in this population of biologic-naive patients, with no difference in the primary outcome between the drugs. FUNDING: Janssen Scientific Affairs.

Recommendations on the Appropriate Management of Steroids and Discharge Planning During and After Hospital Admission for Moderate-Severe Ulcerative Colitis: Results of a RAND Appropriateness Panel.

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40-60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0-1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4-6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.

Normal Sperm DNA Integrity in Patients With Inflammatory Bowel Disease on Ustekinumab Maintenance Therapy.

We demonstrate that ustekinumab does not adversely affect semen quality or sex hormones in male patients. Ustekinumab is not detectable in semen and poses no risk to partners. Our observations support a recommendation to continue ustekinumab therapy in patients wishing to conceive.