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1.
N Engl J Med ; 391(12): 1119-1129, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39321363

RESUMEN

BACKGROUND: Tulisokibart is a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response. METHODS: We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. Cohort 1 included patients regardless of status with respect to the test for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response. The primary analysis was performed in cohort 1; the primary end point was clinical remission at week 12. Patients with a positive test for likelihood of response from cohorts 1 and 2 were combined in prespecified analyses. RESULTS: In cohort 1, a total of 135 patients underwent randomization. A significantly higher percentage of patients who received tulisokibart had clinical remission than those who received placebo (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). In cohort 2, a total of 43 patients underwent randomization. A total of 75 patients with a positive test for likelihood of response underwent randomization across both cohorts. Among patients with a positive test for likelihood of response (cohorts 1 and 2 combined), clinical remission occurred in a higher percentage of patients who received tulisokibart than in those who received placebo (32% vs. 11%; difference, 21 percentage points; 95% CI, 2 to 38; P = 0.02). Among all the enrolled patients, the incidence of adverse events was similar in the tulisokibart and placebo groups; most adverse events were mild to moderate in severity. CONCLUSIONS: In this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis. (Funded by Prometheus Biosciences, a subsidiary of Merck; ARTEMIS-UC ClinicalTrials.gov number, NCT04996797.).


Asunto(s)
Anticuerpos Monoclonales , Colitis Ulcerosa , Inducción de Remisión , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Método Doble Ciego , Infusiones Intravenosas , Inducción de Remisión/métodos , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/antagonistas & inhibidores , Resultado del Tratamiento
2.
Artículo en Inglés | MEDLINE | ID: mdl-39461462

RESUMEN

BACKGROUND AND AIMS: Risankizumab is a selective IL23 inhibitor approved for the treatment of Crohn's disease (CD). We report a large long-term real-world experience with risankizumab in CD. METHODS: We performed a prospective monitoring of clinical outcomes in patients in our center who started treatment with risankizumab. Patients with active luminal disease who had at least 12 weeks of follow-up were included in the effectiveness analysis. Harvey-Bradshaw Index (HBI) as well as C-reactive protein (CRP) and fecal calprotectin (FCP) were used to monitor disease activity. Primary outcomes were clinical remission and steroid-free clinical remission rates at weeks 12, 26, and 52. Univariate analysis followed by a multivariate analysis using a logistic regression model was performed to identify predictors of steroid-free clinical remission at one year. All patients who started treatment with risankizumab for any indication were included in the safety analysis. RESULTS: 134 patients were included in the effectiveness analysis. 70 (52%) were ustekinumab-experienced. Clinical remission rates were 69%, 64%, and 54% at weeks 12, 26, and 52, respectively. Steroid-free clinical remission rates at 12, 26, and 52 weeks were 58%, 58%, and 50% respectively. Remission rates in ustekinumab-experienced patients were not statistically lower compared to naïve patients, and in a multivariate analysis, prior ustekinumab treatment was not associated with lower odds of achieving steroid-free clinical remission at one year. Adverse effects were assessed in 243 patients and were consistent with previous literature. CONCLUSIONS: This large real-world experience with risankizumab with long-term follow-up demonstrates effectiveness and safety in patients with CD; there was comparable effectiveness in ustekinumab-naïve and ustekinumab-experienced patients.

3.
Clin Gastroenterol Hepatol ; 22(3): 611-620.e12, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37734581

RESUMEN

BACKGROUND AND AIMS: Prospective long-term real-world safety data after fecal microbiota transplantation (FMT) remain limited. We reported long-term outcomes of FMT from a population-based FMT registry in Hong Kong. METHODS: We recruited patients undergoing FMT for recurrent Clostridioides difficile infection (CDI) and non-CDI indications from clinical trials, from June 2013 to April 2022 in Hong Kong. We captured data on demographics, FMT indications and procedures, clinical outcomes and short- to long-term safety. New medical diagnoses were obtained from electronic medical records and independently adjudicated by clinicians. Long-term safety in patients with recurrent CDI was compared with a control group treated with antibiotics. RESULTS: Overall, 123 subjects (median age 53 years, range 13-90 years; 52.0% male) underwent 510 FMTs and were prospectively followed up for a median of 30.3 (range, 1-57.9) months. The most common indication for FMT was type 2 diabetes mellitus. The most common short-term adverse events within 1 month of FMT included diarrhea and abdominal pain. At long-term follow-up beyond 12 months, 16 patients reported 21 new-onset medical conditions confirmed by electronic medical records. All were adjudicated to be unlikely to be related to FMT. There was no new case of inflammatory bowel disease, irritable bowel syndrome, allergy, diabetes mellitus, or psychiatric disorder. In a subgroup of patients with recurrent CDI, FMT was associated with a significantly higher cumulative survival probability compared with matched control subjects. CONCLUSIONS: This prospective real-world data from Asia's first FMT registry demonstrated that FMT has an excellent long-term safety profile. The risk of developing new medical conditions beyond 12 months after FMT is low.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Trasplante de Microbiota Fecal/efectos adversos , Trasplante de Microbiota Fecal/métodos , Heces , Hong Kong , Estudios Prospectivos , Resultado del Tratamiento , Recurrencia , Infecciones por Clostridium/terapia
4.
Gastroenterology ; 165(6): 1443-1457, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37659673

RESUMEN

BACKGROUND & AIMS: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy. METHODS: In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical nonresponders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period). RESULTS: The primary analysis population included patients with baseline modified Mayo scores ≥5 and ≤9 (intravenous guselkumab 200 mg, n = 101; 400 mg, n = 107; placebo, n = 105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P < .001). Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24. Safety was similar among guselkumab and placebo groups. CONCLUSIONS: Guselkumab intravenous induction was effective vs placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups. CLINICALTRIALS: gov number: NCT04033445.


Asunto(s)
Colitis Ulcerosa , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/complicaciones , Método Doble Ciego , Inmunosupresores/uso terapéutico , Inducción de Remisión , Resultado del Tratamiento
5.
Clin Gastroenterol Hepatol ; 22(10): 2096-2106, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38492904

RESUMEN

BACKGROUND & AIMS: Upadacitinib, an oral Janus kinase inhibitor, achieved significantly higher rates of clinical remission and endoscopic response vs placebo during induction (U-EXCEL [NCT03345849], U-EXCEED [NCT03345836]) and maintenance (U-ENDURE [NCT03345823]) treatment in patients with moderate-to-severe Crohn's disease. Prior biologic failure is often associated with reduced responses to subsequent therapies. This post hoc analysis assessed upadacitinib efficacy by prior biologic failure status. METHODS: Patients were randomized to placebo or upadacitinib 45 mg (UPA45) for 12 weeks (induction). UPA45 clinical responders were enrolled in U-ENDURE and rerandomized to placebo, upadacitinib 15 mg, or upadacitinib 30 mg (UPA30) for 52 weeks. Assessments were by prior biologic failure. RESULTS: Of 1021 patients, 733 (71.8%) had prior biologic failure. Across outcomes and subgroups, upadacitinib-treated patients achieved higher rates vs placebo. During induction, upadacitinib had higher rates vs placebo for clinical remission based on stool frequency/abdominal pain score (without failure: 54.0% vs 28.3%; with failure: 42.2% vs 14.1%) and endoscopic response (without failure: 52.0% vs 16.2%; with failure: 35.7% vs 5.3%). In maintenance, the greatest treatment effect (upadacitinib vs placebo) was among patients with prior biologic failure treated with UPA30 (clinical remission without failure: 58.5% vs 32.7%; with failure: 42.5% vs 8.7%; endoscopic response without failure: 43.9% vs 17.9%; with failure: 38.9% vs 4.0%). Patients without vs with prior biologic failure had fewer adverse events. CONCLUSIONS: Upadacitinib led to higher absolutes rates of clinical and endoscopic outcomes in patients without vs with prior biologic failure. Patients treated with upadacitinib achieved greater rates of clinical and endoscopic improvements vs placebo, regardless of prior biologic exposure. CLINICALTRIALS: gov: NCT03345849, NCT03345836, NCT03345823.


Asunto(s)
Enfermedad de Crohn , Compuestos Heterocíclicos con 3 Anillos , Humanos , Masculino , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/complicaciones , Femenino , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Placebos/administración & dosificación , Método Doble Ciego , Inhibidores de las Cinasas Janus/uso terapéutico , Adulto Joven
6.
Artículo en Inglés | MEDLINE | ID: mdl-38871152

RESUMEN

BACKGROUND & AIMS: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium. METHODS: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach. RESULTS: Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on 6 structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with long-standing (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus and anorectal carcinoma. Risk factors for squamous cell carcinoma of the anus, notably human papilloma virus, should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an examination under anesthesia with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers. CONCLUSIONS: Inflammatory bowel disease clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.

7.
BMC Gastroenterol ; 24(1): 314, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289603

RESUMEN

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at risk of developing dysplasia and, subsequently, colorectal cancer (CRC) owing to chronic inflammation. Patients may also experience other severe disease complications, such as hospitalization and surgery. Several biologics are available for the treatment of patients with IBD and some patients require multiple lines of treatment owing to loss of response or tolerability to their prescribed biologic. Previous studies suggest that the choice of initial biologic treatment may impact the outcomes of later treatment lines. In this study, we assessed adverse clinical outcomes in patients with Crohn's disease (CD) or ulcerative colitis (UC) who received different biologic treatment sequences. METHODS: ROTARY part B was a retrospective cohort study using the Optum® Clinical Database that evaluated the incidences of IBD-related hospitalization, IBD-related surgery, dysplasia, CRC, and infections in patients with CD or UC who received two biologics successively. First-line biologics included adalimumab, infliximab, ustekinumab (CD only), and vedolizumab; second-line biologics included infliximab and adalimumab. RESULTS: In patients with CD, the treatment sequence of ustekinumab to infliximab was associated with the highest overall incidences of hospitalization (51.9%), surgery (40.7%), CRC (3.7%), and infection (37.0%). Vedolizumab followed by an anti-tumor necrosis factor alpha (anti-TNFα) treatment was associated with a significantly lower risk of experiencing an adverse medical event (hospitalization, surgery, or infection) than two successive anti-TNFα treatments (odds ratio, 1.526; 95% confidence interval, 1.004-2.320; P < 0.05). In patients with UC, the treatment sequence of vedolizumab to adalimumab resulted in the lowest overall incidence of adverse outcomes (20.3%, 6.3%, 0.0%, 6.3%, and 4.7% for hospitalization, surgery, CRC, dysplasia, and infection, respectively). CONCLUSIONS: We describe differences in adverse clinical outcomes associated with sequencing of biologics in patients with CD or UC and demonstrate favorable results in patients who received vedolizumab as a first-line biologic. These results provide potential guidance to clinicians choosing sequences of biologic treatments in patients with IBD.


Asunto(s)
Adalimumab , Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa , Enfermedad de Crohn , Hospitalización , Infliximab , Ustekinumab , Humanos , Estudios Retrospectivos , Masculino , Femenino , Adalimumab/uso terapéutico , Adalimumab/efectos adversos , Infliximab/uso terapéutico , Infliximab/efectos adversos , Adulto , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/cirugía , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/cirugía , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Hospitalización/estadística & datos numéricos , Ustekinumab/uso terapéutico , Ustekinumab/efectos adversos , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico
8.
Curr Gastroenterol Rep ; 26(2): 31-40, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38243153

RESUMEN

PURPOSE OF REVIEW: Intestinal ultrasound (IUS) is a non-invasive, accurate, and well-tolerated tool that provides real-time assessment of inflammatory bowel disease (IBD) activity and is therefore an ideal monitoring tool. This review describes the evolving role of IUS in each phase of clinical management of IBD. RECENT FINDINGS: Accumulating evidence has demonstrated that IUS is an excellent tool for the assessment of suspected IBD, with a very high negative predictive value. It accurately assesses disease activity, disease complications, and in the pre-treatment phase, provides a benchmark for subsequent follow-up. IUS can detect early therapeutic response and correlates well with other established monitoring modalities with arguably superior predictive capabilities and ability to assess a deeper degree of remission, transmural healing (TH). IUS has a crucial role in the management of IBD and has ushered in a new era of monitoring with more rapid evaluation and the opportunity for early optimization, deeper therapeutic targets, and improved outcomes.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico por imagen , Enfermedades Inflamatorias del Intestino/terapia , Enfermedades Inflamatorias del Intestino/complicaciones , Intestinos/diagnóstico por imagen , Ultrasonografía
9.
Dig Dis Sci ; 69(2): 355-359, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38112840

RESUMEN

BACKGROUND AND AIMS: Ongoing efforts to break the therapeutic ceiling in inflammatory bowel disease include combination therapy approaches. Dual-targeted therapy (DTT) has been reported in case reports and small case series. This report describes our experience with ustekinumab (UST) and upadacitinib (UPA) as DTT in patients with Crohn's disease (CD). METHODS: In this retrospective, observational study, we reviewed medical records of patients with CD treated with combined UST and UPA between April 2021 and July 2022. Clinical remission was defined as Harvey-Bradshaw Index (HBI) ≤ 4, and clinical response was defined as decrease in HBI ≥ 3 or physician's assessment of clinical response. RESULTS: We identified 10 CD patients treated with UST/UPA, with median follow-up period of 10 months (interquartile range (IQR) 7.3-12). Median age was 35.5 years (IQR 28.3-43.8) and median number of prior biologic treatment exposures was 4 (IQR 4-5). Indications for UST/UPA were active CD (n = 6), extraintestinal manifestations (EIM) (n = 2), and both active CD and EIM (n = 2). Five of six patients with active CD achieved clinical remission with UST/UPA. Two patients with active EIM (joint pain) achieved resolution of their symptoms. One patient exhibited improvement in both conditions. Three patients developed mild respiratory symptoms and one experienced bowel obstruction. Two patients developed nausea resulting in de-escalation of treatment interval or discontinuation altogether. CONCLUSION: Based on our case series, combination therapy with UST and UPA may be effective and appears safe in refractory Crohn's disease and for patients with co-existing extraintestinal manifestations.


Asunto(s)
Enfermedad de Crohn , Ustekinumab , Humanos , Adulto , Ustekinumab/efectos adversos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/inducido químicamente , Estudios Retrospectivos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Inducción de Remisión , Resultado del Tratamiento , Estudios Observacionales como Asunto
10.
Dig Dis Sci ; 69(8): 2955-2960, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38811503

RESUMEN

BACKGROUND: The Endoscopic Healing Index (EHI) analyzes biomarkers in a patient's peripheral blood to assess mucosal healing. We aimed to characterize the effectiveness of the EHI as a predictor of disease activity in a real world clinical setting. METHODS: This retrospective study looked at patients treated and followed up at the University of Chicago Medicine IBD center who had EHI tests done as part of routine clinical care. The results of the EHI were compared with radiological imaging or endoscopy performed within 3 months of the EHI in order to determine accuracy at diagnosing active inflammation. RESULTS: Fifty-five patients with CD and with an available EHI were included in this study. Four (50%) patients with an EHI of < 20 (n = 8) had evidence of objective inflammation. A cutoff of ≤ 20 had a sensitivity of 89% and specificity of 23.5% for predicting no evidence of any objective inflammation with an AUROC of 0.69. This score had a negative predictive value (NPV) of 50% and positive predictive value (PPV) of 72.3%. A cutoff EHI of 30 tended to classify patients as either having objective evidence of inflammation or not more often than FCAL (Correctly classifying inflammation: 89% vs 64%, respectively; p = 0.32). CONCLUSION: In this real world analysis, the EHI showed poor predictive value for the absence of active inflammation as assessed by imaging or endoscopy, has limited utility in confirming deep remission and should be used with another objective modality.


Asunto(s)
Enfermedad de Crohn , Humanos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/sangre , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Centros de Atención Terciaria , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Biomarcadores/sangre , Adulto Joven , Endoscopía Gastrointestinal , Cicatrización de Heridas , Mucosa Intestinal/patología , Mucosa Intestinal/diagnóstico por imagen
11.
Dig Dis Sci ; 69(2): 579-587, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38087126

RESUMEN

BACKGROUND: Ozanimod is a first-in-class Sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC). Real world data describing use of ozanimod are limited. AIM: To provide 1-year follow-up results of our UC patient cohort treated with ozanimod. METHODS: This prospective, observational cohort study includes consecutive patients who initiated ozanimod at the University of Chicago IBD Center between 5/2021 and 12/2022. We collected demographic, clinical, and laboratory data. Clinical disease activity was prospectively assessed using the Simple Clinical Colitis Activity Index. RESULTS: Forty-five patients with UC initiated ozanimod therapy and were included in the effectiveness analysis. The median age was 35 years (interquartile range (IQR) 28-52), median disease duration of 6 years (IQR 3-13), 26 (58%) were male, 23 (51%) had extensive colitis, 34 (76%) had previous advanced therapy exposure. Thirty-four patients had clinically active UC at the time of ozanimod initiation; week 10 clinical response and remission rates were 58% and 53%, respectively. By week 52, the rates were 25% for both clinical response and remission. In the 12 (39%) patients with a > 75% reduction in absolute lymphocyte count, numerically greater induction clinical response and remission rates were observed (80% vs 54%, p = 0.4 and 75% vs 53%, p = 0.4, respectively). There were no episodes of symptomatic bradycardia and no other new safety signals. CONCLUSION: Ozanimod effectively induced clinical response and remission patients with largely treatment refractory UC, however, had modest long-term effectiveness. The safety profile was favorable with no new signals.


Asunto(s)
Colitis Ulcerosa , Indanos , Oxadiazoles , Humanos , Masculino , Adulto , Femenino , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Estudios de Seguimiento , Estudios Prospectivos , Resultado del Tratamiento , Factores Inmunológicos/uso terapéutico , Inducción de Remisión
12.
Dig Dis Sci ; 69(7): 2333-2344, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38700629

RESUMEN

BACKGROUND: Crohn's disease (CD) significantly affects patients' health-related quality of life and well-being. AIMS: Communicating Needs and Features of IBD Experiences (CONFIDE) survey explores the experience and impact of moderate-to-severe CD symptoms on patients' lives and identifies communication gaps between patients and health care professionals (HCPs). METHODS: Online, quantitative, cross-sectional surveys of patients, and HCPs were conducted in the United States (US), Europe (France, Germany, Italy, Spain, United Kingdom), and Japan. Criteria based on previous treatment, steroid use, and/or hospitalization defined moderate-to-severe CD. US and Europe data are presented as descriptive statistics. RESULTS: Surveys were completed by 215 US and 547 European patients and 200 US and 503 European HCPs. In both patient groups, top three symptoms currently (past month) experienced were diarrhea, bowel urgency, and increased stool frequency, with more than one-third patients wearing diaper/pad/protection at least once a week in past 3 months due to fear of bowel urgency-related accidents. HCPs ranked diarrhea, blood in stool, and increased stool frequency as the most common symptoms. Although 34.0% US and 27.2% European HCPs ranked bowel urgency among the top five symptoms affecting patient lives, only 12.0% US and 10.9% European HCPs ranked it among top three most impactful symptoms on treatment decisions. CONCLUSION: Bowel urgency is common and impactful among patients with CD in the US and Europe. Differences in patient and HCP perceptions of experiences and impacts of bowel urgency exist, with HCPs underestimating its burden. Proactive communication between HCPs and patients in clinical settings is crucial for improving health outcomes in patients with CD.


Asunto(s)
Enfermedad de Crohn , Humanos , Enfermedad de Crohn/psicología , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/terapia , Estudios Transversales , Femenino , Masculino , Estados Unidos/epidemiología , Europa (Continente)/epidemiología , Adulto , Persona de Mediana Edad , Calidad de Vida , Índice de Severidad de la Enfermedad , Personal de Salud/psicología , Adulto Joven , Actitud del Personal de Salud , Encuestas y Cuestionarios , Percepción
13.
Lancet ; 399(10340): 2031-2046, 2022 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-35644155

RESUMEN

BACKGROUND: There is a great unmet need for new therapeutics with novel mechanisms of action for patients with Crohn's disease. The ADVANCE and MOTIVATE studies showed that intravenous risankizumab, a selective p19 anti-interleukin (IL)-23 antibody, was efficacious and well tolerated as induction therapy. Here, we report the efficacy and safety of subcutaneous risankizumab as maintenance therapy. METHODS: FORTIFY is a phase 3, multicentre, randomised, double-blind, placebo-controlled, maintenance withdrawal study across 273 clinical centres in 44 countries across North and South America, Europe, Oceania, Africa, and the Asia-Pacific region that enrolled participants with clinical response to risankizumab in the ADVANCE or MOTIVATE induction studies. Patients in ADVANCE or MOTIVATE were aged 16-80 years with moderately to severely active Crohn's disease. Patients in the FORTIFY substudy 1 were randomly assigned again (1:1:1) to receive either subcutaneous risankizumab 180 mg, subcutaneous risankizumab 360 mg, or withdrawal from risankizumab to receive subcutaneous placebo (herein referred to as withdrawal [subcutaneous placebo]). Treatment was given every 8 weeks. Patients were stratified by induction dose, post-induction endoscopic response, and clinical remission status. Patients, investigators, and study personnel were masked to treatment assignments. Week 52 co-primary endpoints were clinical remission (Crohn's disease activity index [CDAI] in the US protocol, or stool frequency and abdominal pain score in the non-US protocol) and endoscopic response in patients who received at least one dose of study drug during the 52-week maintenance period. Safety was assessed in patients receiving at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03105102. FINDINGS: 712 patients were initially assessed and, between April 9, 2018, and April 24, 2020, 542 patients were randomly assigned to either the risankizumab 180 mg group (n=179), the risankizumab 360 mg group (n=179), or the placebo group (n=184). Greater clinical remission and endoscopic response rates were reached with 360 mg risankizumab versus placebo (CDAI clinical remission was reached in 74 (52%) of 141 patients vs 67 (41%) of 164 patients, adjusted difference 15% [95% CI 5-24]; stool frequency and abdominal pain score clinical remission was reached in 73 (52%) of 141 vs 65 (40%) of 164, adjusted difference 15% [5-25]; endoscopic response 66 (47%) of 141 patients vs 36 (22%) of 164 patients, adjusted difference 28% [19-37]). Higher rates of CDAI clinical remission and endoscopic response (but not stool frequency and abdominal pain score clinical remission [p=0·124]) were also reached with risankizumab 180 mg versus withdrawal (subcutaneous placebo; CDAI clinical remission reached in 87 [55%] of 157 patients, adjusted difference 15% [95% CI 5-24]; endoscopic response 74 [47%] of 157, adjusted difference 26% [17-35]). Results for more stringent endoscopic and composite endpoints and inflammatory biomarkers were consistent with a dose-response relationship. Maintenance treatment was well tolerated. Adverse event rates were similar among groups, and the most frequently reported adverse events in all treatment groups were worsening Crohn's disease, arthralgia, and headache. INTERPRETATION: Subcutaneous risankizumab is a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active Crohn's disease and offers a new therapeutic option for a broad range of patients by meeting endpoints that might change the future course of disease. FUNDING: AbbVie.


Asunto(s)
Enfermedad de Crohn , Dolor Abdominal , Anticuerpos Monoclonales/efectos adversos , Enfermedad de Crohn/tratamiento farmacológico , Método Doble Ciego , Humanos
14.
Lancet ; 399(10340): 2015-2030, 2022 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-35644154

RESUMEN

BACKGROUND: Risankizumab, an interleukin (IL)-23 p19 inhibitor, was evaluated for safety and efficacy as induction therapy in patients with moderately to severely active Crohn's disease. METHODS: ADVANCE and MOTIVATE were randomised, double-masked, placebo-controlled, phase 3 induction studies. Eligible patients aged 16-80 years with moderately to severely active Crohn's disease, previously showing intolerance or inadequate response to one or more approved biologics or conventional therapy (ADVANCE) or to biologics (MOTIVATE), were randomly assigned to receive a single dose of intravenous risankizumab (600 mg or 1200 mg) or placebo (2:2:1 in ADVANCE, 1:1:1 in MOTIVATE) at weeks 0, 4, and 8. We used interactive response technology for random assignment, with stratification by number of previous failed biologics, corticosteroid use at baseline, and Simple Endoscopic Score for Crohn's disease (SES-CD). All patients and study personnel (excluding pharmacists who prepared intravenous solutions) were masked to treatment allocation throughout the study. Coprimary endpoints were clinical remission (defined by Crohn's disease activity index [CDAI] or patient-reported outcome criteria [average daily stool frequency and abdominal pain score]) and endoscopic response at week 12. The intention-to-treat population (all eligible patients who received at least one dose of study drug in the 12-week induction period) was analysed for efficacy outcomes. Safety was assessed in all patients who received at least one dose of study drug. Both trials were registered on ClinicalTrials.gov, NCT03105128 (ADVANCE) and NCT03104413 (MOTIVATE), and are now complete. FINDINGS: Participants were enrolled between May 10, 2017, and Aug 24, 2020 (ADVANCE trial), and Dec 18, 2017 and Sept 9, 2020 (MOTIVATE trial). In ADVANCE, 931 patients were assigned to either risankizumab 600 mg (n=373), risankizumab 1200 mg (n=372), or placebo (n=186). In MOTIVATE, 618 patients were assigned to risankizumab 600 mg (n=206), risankizumab 1200 mg (n=205), or placebo (n=207). The primary analysis population comprised 850 participants in ADVANCE and 569 participants in MOTIVATE. All coprimary endpoints at week 12 were met in both trials with both doses of risankizumab (p values ≤0·0001). In ADVANCE, CDAI clinical remission rate was 45% (adjusted difference 21%, 95% CI 12-29; 152/336) with risankizumab 600 mg and 42% (17%, 8-25; 141/339) with risankizumab 1200 mg versus 25% (43/175) with placebo; stool frequency and abdominal pain score clinical remission rate was 43% (22%, 14-30; 146/336) with risankizumab 600 mg and 41% (19%, 11-27; 139/339) with risankizumab 1200 mg versus 22% (38/175) with placebo; and endoscopic response rate was 40% (28%, 21-35; 135/336) with risankizumab 600 mg and 32% (20%, 14-27; 109/339) with risankizumab 1200 mg versus 12% (21/175) with placebo. In MOTIVATE, CDAI clinical remission rate was 42% (22%, 13-31; 80/191) with risankizumab 600 mg and 40% (21%, 12-29; 77/191) with risankizumab 1200 mg versus 20% (37/187) with placebo; stool frequency and abdominal pain score clinical remission rate was 35% (15%, 6-24; 66/191) with risankizumab 600 mg and 40% (20%, 12-29; 76/191) with risankizumab 1200 mg versus 19% (36/187) with placebo; and endoscopic response rate was 29% (18%, 10-25; 55/191) with risankizumab 600 mg and 34% (23%, 15-31; 65/191) with risankizumab 1200 mg versus 11% (21/187) with placebo. The overall incidence of treatment-emergent adverse events was similar among the treatment groups in both trials. Three deaths occurred during induction (two in the placebo group [ADVANCE] and one in the risankizumab 1200 mg group [MOTIVATE]). The death in the risankizumab-treated patient was deemed unrelated to the study drug. INTERPRETATION: Risankizumab was effective and well tolerated as induction therapy in patients with moderately to severely active Crohn's disease. FUNDING: AbbVie.


Asunto(s)
Productos Biológicos , Enfermedad de Crohn , Dolor Abdominal , Anticuerpos Monoclonales , Productos Biológicos/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Quimioterapia de Inducción
15.
Gastroenterology ; 162(5): 1396-1408, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35101421

RESUMEN

Ulcerative colitis (UC) has been characterized by inflammation limited to the mucosa. Although sustained and durable remission has been associated with mucosal healing, the recurrent phenomenon of persistent clinical disease activity despite mucosal healing has been observed in clinical practice and across pivotal trials. Over time, UC appears to confer an increased risk of progression, defined as changes of disease phenotype; adverse transmural effects on the bowel wall; increased risk of neoplasia development; worsening colorectal function; and increased risk of colectomy, hospitalizations, and other extraintestinal comorbidities. Although the treatment paradigm for Crohn's disease has shifted toward early aggressive intervention to prevent disease progression and irreversible bowel damage, such urgency in efforts to halt disease progression in UC have been largely overlooked. This review summarizes the multiple facets of UC contributing to a modified perception of the disease as a progressive one. We propose further study of the natural history and priorities for further treatment goals that include these considerations.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Colectomía , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/terapia , Progresión de la Enfermedad , Humanos , Inflamación
16.
Artículo en Inglés | MEDLINE | ID: mdl-37879517

RESUMEN

Value-based care focuses on improving the quality, effectiveness, and efficiency of health care while controlling costs. Low-value care implies services or interventions that provide little or no benefit to patients, have the potential to cause harm, incur unnecessary cost to patients, or waste limited health care resources. In this review, we discuss common instances of low-value care along the spectrum of management in inflammatory bowel diseases (IBD). These include low value care in: (1) diagnosis and monitoring of IBD: utilization of serological markers to screen and diagnose IBD, over-reliance on symptoms for monitoring disease, failure to employ treat-to-target strategies in symptomatic patients with IBD, and annual surveillance colonoscopies in patients at low risk of developing dysplasia; (2) treatment of IBD: use of 5-aminosalicylates in Crohn's disease, continuation of 5-aminosalicylates after escalation to immunosuppressive therapy, chronic corticosteroid use without steroid-sparing strategies, step therapy for Crohn's disease, failure to optimize tumor necrosis factor antagonists in patients with active disease and subsequently de-intensification of therapies in those who have achieved stable remission; and (3) management of hospitalized patients with IBD: routine cross-sectional imaging for patients with IBD presenting to the emergency department, withholding pharmacological prophylaxis for venous thromboembolism in patients hospitalized with IBD flare, and prolonged use of high-dose intravenous corticosteroids in patients with acute severe ulcerative colitis. This review is meant to bring attention to value-based care in IBD and provide guidance to treating practitioners. Future studies on systematic evaluation of high- and low-value care in patients with IBD are warranted.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38065372

RESUMEN

L23 is a recognized cytokine involved in the pathogenesis of inflammatory bowel diseases (IBDs).1 The first IL23-targeting agent that became available for clinical use in IBD was Ustekinumab, a monoclonal antibody that targets p40, a shared subunit of both IL23 and IL12.2,3 Risankizumab (Skyrizi; Abbvie) is a humanized IgG1 monoclonal antibody which binds to the p19 subunit and therefore selectively inhibits IL23.4 In June 2022, it was approved by the United States Food and Drug Administration for the treatment of moderately to severely active Crohn's disease (CD). Here, we describe the effectiveness and safety of risankizumab throughout the induction period in a real-world setting of a large tertiary center.

18.
Clin Gastroenterol Hepatol ; 21(9): 2407-2409.e2, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-35381385

RESUMEN

Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon and rectum. Long-term therapy is generally required to achieve and maintain disease control.1 In May 2021 the US Food and Drug Administration approved the use of ozanimod in patients with moderate to severe UC. We describe the first report of the use of ozanimod in real-world clinical practice.


Asunto(s)
Colitis Ulcerosa , Estados Unidos , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Indanos/uso terapéutico , Oxadiazoles/uso terapéutico
19.
Clin Gastroenterol Hepatol ; 21(7): 1913-1923.e2, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36898598

RESUMEN

BACKGROUND & AIMS: Upadacitinib is a novel selective Janus kinase 1 inhibitor that has shown efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), and has received Food and Drug Administration approval for UC. We report a large real-world experience with upadacitinib in UC and CD. METHODS: We performed a prospective analysis of clinical outcomes on upadacitinib in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and fecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events. RESULTS: A total of 105 patients were followed up for 8 weeks on upadacitinib, 84 of whom (44 UC patients, 40 CD patients) were initiated because of active luminal or perianal disease and included in the analysis. One hundred percent previously received anti-tumor necrosis factor therapy, and 89.3% had received 2 or more advanced therapies. At 4 and 8 weeks of treatment for UC, 19 of 25 (76.0%) and 23 of 27 (85.2%) achieved clinical response and 18 of 26 (69.2%) and 22 of 27 (81.5%) achieved clinical remission, respectively. Of those who previously were tofacitinib-exposed, 7 of 9 (77.8%) achieved clinical remission by 8 weeks. In CD, 13 of 17 (76.5.%) achieved clinical response and 12 of 17 (70.6%) achieved clinical remission by 8 weeks. Of those with increased fecal calprotectin and C-reactive protein levels, 62% and 64% normalized by week 8, respectively. Results were seen as early as week 2 in both UC and CD, with clinical remission rates of 36% and 56.3.%, respectively. Acne was the most commonly reported adverse event, occurring in 24 of 105 patients (22.9%). CONCLUSIONS: In this large real-world experience in medically resistant patients with UC or CD, we report that upadacitinib is rapidly effective and safe, including in those who had prior tofacitinib exposure. This study was approved by the Institutional Review Board at the University of Chicago (IRB20-1979).


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Proteína C-Reactiva/metabolismo , Inducción de Remisión , Complejo de Antígeno L1 de Leucocito , Resultado del Tratamiento
20.
Gastroenterology ; 163(6): 1555-1568, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35963369

RESUMEN

BACKGROUND & AIMS: Current therapies for ulcerative colitis (UC) fail to achieve satisfactory disease control. Selective inhibition of Janus kinase (JAK) type 1 may improve clinical outcomes in patients with UC while avoiding the side effects associated with pan-JAK inhibition. The safety and efficacy of the selective JAK1 inhibitor ivarmacitinib (formerly SHR0302) were evaluated in patients with moderate-to-severe, active UC. METHODS: AMBER2 was a double-blind, placebo-controlled, phase II trial conducted at 63 clinical centers in China, the United States, and Europe. Patients (N = 164) were randomized 1:1:1:1 to receive oral ivarmacitinib 8 mg once daily (QD), 4 mg twice daily (BID), or 4 mg QD, or placebo for 8 weeks, followed by an 8-week extension period. The primary endpoint was clinical response rate at week 8. Hochberg's procedure was used to control the study-wise type 1 error at alpha=0.1. RESULTS: A total of 146 (89.0%) patients completed 8 weeks of treatment. Week 8 clinical response rates were significantly higher in the 8 mg QD (46.3%; P = .066), 4 mg BID (46.3%; P = .059), and 4 mg QD (43.9%; P = .095) groups vs placebo (26.8%). Week 8 rates of clinical remission were 22.0% (P = .020), 24.4% (P = .013), and 24.4% (P = .011) in the 3 ivarmacitinib treatment groups, respectively, vs 4.9% for placebo. During the initial 8-week period, treatment-emergent adverse events occurred in 43.9% to 48.8% of ivarmacitinib-treated patients and in 39.0% of the placebo group, and were predominantly mild. There were no deaths, or major adverse cardiovascular or thromboembolic events. CONCLUSION: Ivarmacitinib demonstrated clinical efficacy and was well tolerated in patients with moderate-to-severe, active, UC. Ivarmacitinib represents a promising new treatment for moderate-to-severe UC. CLINICALTRIALS: gov number, NCT03675477.


Asunto(s)
Colitis Ulcerosa , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Inhibidores de las Cinasas Janus , Humanos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Inhibidores de las Cinasas Janus/efectos adversos , China
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