Publications by authors named "Dubinsky M"
Background And Aims: Treating ulcerative colitis (UC) in patients with prior advanced therapy (AT) exposure may be challenging. We report the efficacy and safety of risankizumab, a monoclonal interleukin 23p19 antibody, in patients with UC and prior inadequate response or intolerance to AT (AT-IR).
Methods: In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo.
Background And Aims: We evaluated the association between endoscopic outcomes following risankizumab induction and subsequent rates of hospitalization and surgery through 52 weeks of risankizumab (both doses) maintenance therapy in patients with Crohn's disease (CD).
Methods: Patients with moderately to severely active CD and clinical response to 12-week risankizumab induction were rerandomized to continued therapy or drug withdrawal in the phase 3 FORTIFY maintenance trial. Incidence rates (events/100 person-years) of CD-related hospitalization and surgery, and the composite of both, through 52 weeks of maintenance were compared between patients achieving vs not achieving predefined endoscopic outcomes following induction.
Objective: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P receptor expression on cardiac cells is involved in cardiac conduction. We report cardiovascular treatment-emergent adverse events (TEAEs) associated with S1P receptor modulators and other cardiovascular events in the etrasimod UC clinical programme.
View Article and Find Full Text PDFBackground/aims: Active inflammatory bowel disease (IBD) increases the risk of pregnancy complications and contraceptive side effects, and contraceptive use may impact the clinical course of IBD. Although young people are at elevated risk for unintended pregnancy, those with IBD receive minimal disease-specific contraceptive guidance. We characterized perspectives and preferences on contraception and reproductive health counseling from young women with IBD.
View Article and Find Full Text PDFIntroduction: Bowel urgency has recently been recognized as a Crohn's disease (CD) symptom that substantially impacts patients' quality of life. The Urgency NRS is a single-item patient-reported outcome measure assessing bowel urgency severity in the past 24 h (0-10 scale). We aimed to evaluate the psychometric properties of the Urgency Numeric Rating Scale (NRS) in adults with moderately to severely active CD and to estimate thresholds for meaningful improvement and bowel urgency remission.
View Article and Find Full Text PDFArticle Synopsis
- Therapeutic drug monitoring (TDM) for biologic therapies in inflammatory bowel disease (IBD) focuses on optimizing medication doses but faces challenges like identifying ideal drug levels and dealing with variability in drug response.
- Recent advancements, including population pharmacokinetic/pharmacodynamic (PK/PD) modeling and model-informed precision dosing (MIPD) tools, as well as point-of-care testing and new software, present promising solutions to these challenges.
- Implementing these innovations could lead to personalized dosing strategies, moving away from the current one-size-fits-all approach that doesn't meet the diverse needs of IBD patients.
Despite the fundamental role of bacterial strain variation in gut microbiota function, the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments.
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- Etrasimod is a selective oral drug that has been linked to a potential increased risk of macular edema, a condition affecting the eye.
- In a clinical study focusing on patients with conditions like ulcerative colitis and Crohn's disease, the rate of macular edema associated with etrasimod was similar to that of a placebo, with very few cases reported.
- Overall, macular edema and other eye-related issues were rare among patients taking etrasimod, and most related side effects were not serious.
Background: Bowel urgency, the sudden and immediate need to have a bowel movement, is common in patients with ulcerative colitis (UC) and Crohn's disease (CD). While its impact in UC is well established, less is known about its importance in CD. Further, what level of bowel urgency control patients with UC or CD would consider to be acceptable or in remission has not been established.
View Article and Find Full Text PDFBackground: Small bowel obstructions (SBOs) are a common complication following staged IPAA. Our goal was to compare early post-operative SBO outcomes between different staged ileal pouch-anal anastomosis (IPAA) and to further analyze the type of procedures required in patients who needed operative management of SBO.
Methods: In this retrospective cohort study, we selected all patients who presented to our tertiary care center between 2008 and 2017, with ulcerative colitis or IBD-Unspecified colitis and who underwent a primary total proctocolectomy with IPAA for medically refractory disease or dysplasia (n = 623).
Background: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152.
Methods: Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance.
Background: Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response.
Methods: We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms.
Background: Treatment of inflammatory bowel disease-Crohn's disease (CD) and ulcerative colitis (UC)-is dependent on healthcare providers' (HCPs') clinical assessment of patient symptoms. We therefore evaluated which CD and UC symptoms impact HCPs' treatment choices and assessed the impact of those symptoms on treatment decision-making. We also examined the role of complete control (mucosal/histologic healing, clinical remission, no bowel urgency) in treatment decision-making, considerations for dose escalation or switching treatments, and HCPs' willingness to use the Urgency Numeric Rating Scale (NRS) to assess bowel urgency severity.
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- Etrasimod is an oral medication aimed at treating moderately to severely active ulcerative colitis (UC), and this study focused on its impact on patients' health-related quality of life (HRQoL).
- The analysis used data from two Phase 3 clinical trials and assessed HRQoL using various questionnaires at different time points.
- Results showed that patients taking etrasimod experienced significantly greater improvements in HRQoL measures compared to those on a placebo, especially among certain patient groups, indicating the medication's effectiveness.
Background: Psychiatric disorders in patients with inflammatory bowel disease (IBD) represent a significant but uncertain facet of the disease, with unsolved questions regarding their overall magnitude, their impact on intestinal disease, and the whole burden of psychiatric manifestations.
Aim: This systematic review summarizes the evidence on the prevalence and impact of psychiatric disorders, including depression, anxiety, bipolar disorder (BD), and schizophrenia, among patients with IBD.
Methods: A systematic search across PubMed/MEDLINE, Embase, and Scopus databases from January 2010 to January 2023 was performed to identify relevant studies.
Introduction: The aim of this study was to report the frequency and impact of endoscopic response and remission on the risk of subsequent pouchitis in patients with Crohn's disease-like pouch inflammation (CDLPI) on therapy.
Methods: This was a single-center retrospective study of patients older than 18 years with CDLPI on therapy.
Results: Among 110 included patients with CDLPI in clinical remission, endoscopic remission was not significantly associated with a reduced risk of subsequent pouchitis when compared with endoscopic response.
Objective: IBD is characterised by dysbiosis, but it remains unclear to what extent dysbiosis develops in unaffected at-risk individuals. To address this, we investigated age-related patterns of faecal and serum markers of dysbiosis in high-risk multiplex IBD families (two or more affected first-degree relatives).
Design: Faecal and serum samples were collected from multiplex IBD and control families (95 IBD, 292 unaffected, 51 controls).
Background: Risankizumab is efficacious and well tolerated in adults with moderately to severely active Crohn's disease (CD).
Aim: To evaluate the corticosteroid-sparing effect of risankizumab in CD.
Methods: During the 12-week induction period, patients maintained stable baseline corticosteroid doses, up to 20 mg/day prednisone or equivalent.
Article Synopsis
- A phase 3b clinical trial was conducted to compare the effectiveness and safety of risankizumab and ustekinumab in patients with moderate-to-severe Crohn's disease who didn't respond to anti-TNF therapy.
- The study evaluated two primary outcomes: clinical remission at week 24 and endoscopic remission at week 48, with risankizumab being tested for noninferiority and superiority, respectively.
- Results showed that risankizumab was not only noninferior to ustekinumab for clinical remission but also superior for endoscopic remission, with significant improvements reported in patients receiving risankizumab.
Introduction: The impact of pregnancy on the development of pouchitis in women who have undergone total proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis is poorly understood.
Methods: This was a retrospective study of women with ulcerative colitis who underwent total proctocolectomy with ileal pouch anal anastomosis and subsequently became pregnant at Mount Sinai Hospital. The primary outcome was acute pouchitis during pregnancy or the postpartum period defined as symptoms of increased stool frequency and urgency treated with antibiotics.
Article Synopsis
- Recruiting patients with inflammatory bowel disease (IBD) for clinical trials has become increasingly difficult, prompting the need for more inclusive eligibility guidelines.
- The study utilized the RAND/UCLA Appropriateness Method to gather insights from IBD specialists through a two-round voting process, resulting in 26 actionable recommendations for broadening trial participation.
- Key recommendations include being more inclusive of complex disease types, flexible with safety criteria, recognizing non-invasive imaging, reducing mandatory washout periods, and easing age restrictions, all of which were deemed feasible and appropriate by experts.
Article Synopsis
- - Etrasimod is a daily oral medication aimed at treating moderately to severely active ulcerative colitis, and this study compares its effectiveness against placebo in patients with prior biological or Janus kinase inhibitor treatment.
- - The analysis showed that both biologic/JAK inhibitor naïve and experienced patients who took etrasimod had significantly higher rates of clinical remission compared to those taking placebo, particularly highlighted in weeks 12 and 52 of the treatment.
- - Overall, both groups of patients benefited from etrasimod in terms of treatment response, indicating its potential as an effective option for managing ulcerative colitis symptoms.
Background: Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC.
Methods: This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally.