997 results on '"Edward V Loftus"'
Search Results
2. Obesity in inflammatory bowel disease: A review of its role in the pathogenesis, natural history, and treatment of IBD
- Author
-
Amanda M Johnson and Edward V Loftus
- Subjects
crohn's disease ,inflammatory bowel disease ,obesity ,ulcerative colitis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
In contrast to previous perceptions that inflammatory bowel disease (IBD) patients are generally malnourished and underweight, there is mounting evidence to suggest that rates of obesity in IBD now mirror that of the general population. IBD is an immune-mediated condition that appears to develop in individuals who have not only a genetic predisposition to immune dysregulation but also likely exposure to various environmental factors which further potentiate this risk. With the surge in obesity alongside the rising incidence of IBD, particularly in developing nations, the role that obesity may play, not only in the pathogenesis but also in the natural history of disease has become a topic of growing interest. Currently available data exploring obesity's impact on the natural history of IBD are largely conflicting, potentially limited by the use of body mass index as a surrogate measure of obesity at varying time points throughout the disease course. While there are pharmacokinetic data to suggest possible detrimental effects that obesity may have on the response to medical therapy, results in this realm are also inconsistent. Moreover, not only is it unclear whether weight loss improves IBD outcomes, little is known about the safety and efficacy of available weight-loss strategies in this population. For these reasons, it becomes increasingly important to further understand the nature of any interaction between obesity and IBD.
- Published
- 2021
- Full Text
- View/download PDF
3. Efficacy and Safety of Adalimumab in Canadian Patients with Moderate to Severe Crohn’s Disease: Results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn’s DiseaSe (ACCESS) Trial
- Author
-
Remo Panaccione, Edward V Loftus, David Binion, Kevin McHugh, Shamsul Alam, Naijun Chen, Benoît Guérette, Parvez Mulani, and Jingdong Chao
- Subjects
Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
OBJECTIVE: To evaluate open-label adalimumab therapy for clinical effectiveness, fistula healing, patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn’s disease (CD) who were either naive to or previously exposed to antitumour necrosis factor (anti-TNF) therapy.
- Published
- 2011
- Full Text
- View/download PDF
4. Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology
- Author
-
Mark S Silverberg, Jack Satsangi, Tariq Ahmad, Ian DR Arnott, Charles N Bernstein, Steven R Brant, Renzo Caprilli, Jean-Frédéric Colombel, Christoph Gasche, Karel Geboes, Derek P Jewell, Amir Karban, Edward V Loftus, A Salvador Peña, Robert H Riddell, David B Sachar, Stefan Schreiber, A Hillary Steinhart, Stephan R Targan, Severine Vermeire, and Bryan F Warren
- Subjects
Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn’s disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.
- Published
- 2005
- Full Text
- View/download PDF
5. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease
- Author
-
Edward V. Loftus, Julian Panés, Ana P. Lacerda, Laurent Peyrin-Biroulet, Geert D’Haens, Remo Panaccione, Walter Reinisch, Edouard Louis, Minhu Chen, Hiroshi Nakase, Jakob Begun, Brigid S. Boland, Charles Phillips, Mohamed-Eslam F. Mohamed, Jianzhong Liu, Ziqian Geng, Tian Feng, Elena Dubcenco, and Jean-Frederic Colombel
- Subjects
General Medicine - Published
- 2023
6. The cost of inflammatory bowel disease in high-income settings: a Lancet Gastroenterology & Hepatology Commission
- Author
-
Johan Burisch, Mirabella Zhao, Selwyn Odes, Peter De Cruz, Severine Vermeire, Charles N Bernstein, Gilaad G Kaplan, Dana Duricova, Dan Greenberg, Hans O Melberg, Mamoru Watanabe, Hyeong Sik Ahn, Laura Targownik, Valérie E H Pittet, Vito Annese, KT Park, Konstantinos H Katsanos, Marte L Høivik, Zeljko Krznaric, María Chaparro, Edward V Loftus, Peter L Lakatos, Javier P Gisbert, Willem Bemelman, Bjorn Moum, Richard B Gearry, Michael D Kappelman, Ailsa Hart, Marieke J Pierik, Jane M Andrews, Siew C Ng, Renata D'Inca, and Pia Munkholm
- Subjects
Hepatology ,Gastroenterology - Abstract
The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers.
- Published
- 2023
7. Efficacy, Safety, Patient Experience, and Tolerability of Risankizumab Administered by On-Body Injector for Moderate to Severe Crohn’s Disease
- Author
-
Edward V. Loftus, Jenny Griffith, Ezequiel Neimark, Alexandra Song, Kori Wallace, Sujani Nannapaneni, Ji Zhou, Rachel Byrne, Kristina Kligys, Yinuo Pang, Xiaomei Liao, Jasmina Kalabic, and Marla Dubinsky
- Subjects
Pharmacology (medical) ,General Medicine - Published
- 2023
8. Endoscopic Bariatric Therapies for the Management of Obesity in Patients with Inflammatory Bowel Disease
- Author
-
Amanda M. Johnson, Andrew C. Storm, Tala Mahmoud, Rabih Ghazi, Babusai Rapaka, Donna M. Abboud, Edward V. Loftus, and Barham K. Abu Dayyeh
- Subjects
Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Surgery - Published
- 2022
9. The epidemiology of inflammatory bowel disease in Asia and Asian immigrants to Western countries
- Author
-
Satimai Aniwan, Priscila Santiago, Edward V. Loftus, and Sang Hyoung Park
- Subjects
Oncology ,Gastroenterology - Abstract
Inflammatory bowel disease (IBD), which comprises Crohn's disease and ulcerative colitis, is an idiopathic inflammatory condition of the gastrointestinal tract. The incidence and prevalence of IBD are rapidly increasing worldwide, particularly in newly industrialized regions such as Asia. Although a large medical armamentarium is available for treating this chronic disease, IBD imposes a marked global disease burden. To understand the complex etiopathogenesis of this condition, it is important to consider the rapidly changing trends in its epidemiology in Asia. During the past few decades, the incidence and prevalence of IBD have significantly increased in both Asian countries and Asian immigrants in Western countries. In this review, we aimed to study and update the epidemiology of IBD in diverse Asian regions and among Asian immigrants in North America and Europe. Moreover, we highlighted that this population exhibits a unique disease phenotype, such as male predominance and high frequency of perianal fistula in Crohn's disease. Also, a different disease phenotype including more complicated disease such as perianal complications was noted in Asian Americans and Asian Europeans.
- Published
- 2022
10. Multicentre Real-world Experience of Upadacitinib in the Treatment of Crohn’s Disease
- Author
-
Rishika Chugh, Manuel B Braga-Neto, Thomas W Fredrick, Guilherme P Ramos, Jonathan Terdiman, Najwa El-Nachef, Edward V Loftus, Uma Mahadevan, and Sunanda V Kane
- Subjects
Gastroenterology ,General Medicine - Abstract
Background Upadacitinib is a selective Janus kinase inhibitor approved for the management of ulcerative colitis and is under evaluation for the management of Crohn’s disease [CD] in Phase 3 clinical trials. Aims Our goal was to describe our real-world experience with upadacitinib in CD. Methods This is a two-centre retrospective cohort study of adult patients with moderate to severe CD on upadacitinib. The primary outcome was clinical response and remission as determined by stool frequency and abdominal pain scores. Secondary endpoints included endoscopic response and remission as determined by change in Simple Endoscopic Score for CD. Outcomes were assessed at 3 months after starting upadacitinib and at the patient’s most recent follow-up. We further evaluated adverse events and dose-related response. Results A total of 45 CD patients received upadacitinib and were included in the safety analysis. Thirty-six patients received upadacitinib for CD, whereas nine received it for inflammatory arthritis [n = 8] or pyoderma [n = 1]. Thirty-three patients received upadacitinib for 3 months or longer and were included in the efficacy analysis. At the 3-month follow-up, 21 patients achieved clinical response [63.6%] and nine achieved clinical remission [27.2%]. At time of last follow-up, 23 patients had clinical response [69.7%], ten achieved clinical remission [30.3%] and four [28.6%] achieved endoscopic remission. Adverse events occurred in 12 patients [26.7%]. Two patients had a serious adverse event [4.5%] without associated mortality. Conclusion In this real-world cohort of highly refractory CD patients, upadacitinib was effective in inducing remission and had an acceptable safety profile.
- Published
- 2022
11. Effect of risankizumab on health‐related quality of life in patients with Crohn's disease: results from phase 3 <scp>MOTIVATE</scp> , <scp>ADVANCE</scp> and <scp>FORTIFY</scp> clinical trials
- Author
-
Laurent Peyrin‐Biroulet, Subrata Ghosh, Scott D. Lee, Wan‐Ju Lee, Jenny Griffith, Kori Wallace, Sofie Berg, Xiaomei Liao, Julian Panes, Edward V. Loftus, and Edouard Louis
- Subjects
Hepatology ,Gastroenterology ,Pharmacology (medical) - Abstract
Crohn's disease has a substantial negative impact on health-related quality of life (HRQoL).To examine the effects of risankizumab on HRQoL in Crohn's disease METHODS: We analysed data from patients with Crohn's disease from 12-week induction trials ADVANCE (N = 850) and MOTIVATE (N = 569) with risankizumab 600 mg or 1200 mg intravenous (IV) versus placebo IV and a 52-week maintenance trial FORTIFY (N = 462) with risankizumab 180 or 360 mg subcutaneous (SC) versus placebo SC. Outcomes included Inflammatory Bowel Disease Questionnaire (IBDQ), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), 36-item Short Form Health Survey (SF-36), EuroQol 5-Dimension-5-Level (EQ-5D-5L) and work productivity. The mean change and percentages of patients achieving clinically meaningful improvement in all outcomes were determined at weeks 12 and 52.At week 12, more patients in the risankizumab 600 or 1200 mg groups achieved IBDQ response than with placebo (ADVANCE: 70.2%, 75.5% vs. 47.8%, p ≤ 0.001; MOTIVATE: 61.7%, 68.5% vs. 48.2%, p ≤ 0.01) and FACIT-F response (ADVANCE: 51.3%, 48.0% vs. 35.7%, p ≤ 0.01; MOTIVATE: 44.2%, 49.1% vs. 33.7%, p 0.05). These improvements persisted at week 52 with risankizumab maintenance treatment. Similar trends were observed for SF-36 physical and mental component summary scores, EQ-5D-5L and activity impairment within work productivity measures.Risankizumab induction therapy (600 or 1200 mg IV) led to clinically meaningful improvements in disease-specific and general patient-reported outcomes, including fatigue, in patients with moderate to severe Crohn's disease. These improvements were sustained after 52 weeks of risankizumab (180 or 360 mg SC) maintenance therapy.
- Published
- 2022
12. Clostridium difficile Infection in Patients with Ulcerative Colitis Treated with Tofacitinib in the Ulcerative Colitis Program
- Author
-
Edward V Loftus, Daniel C Baumgart, Krisztina Gecse, Jami A Kinnucan, Susan B Connelly, Leonardo Salese, Chinyu Su, Kenneth K Kwok, John C Woolcott, and Alessandro Armuzzi
- Subjects
Gastroenterology ,Immunology and Allergy - Abstract
Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Patients with inflammatory bowel disease are susceptible to Clostridium difficile infection (CDI). Here, we evaluate CDI in the tofacitinib UC clinical program. Methods Events from 4 randomized, placebo-controlled studies (phase [P] 2 or P3 induction [NCT00787202; NCT01465763; NCT01458951], P3 maintenance [NCT01458574]) and an open-label, long-term extension (OLE) study (NCT01470612), were analyzed as 3 cohorts: Induction (P2/P3 induction), Maintenance (P3 maintenance), and Overall (patients receiving tofacitinib 5 or 10 mg twice daily [BID] in P2, P3, and OLE studies; including final data from the OLE study, as of August 24, 2020). Proportions and incidence rates (unique patients with events per 100 patient-years of exposure) of CDI were evaluated. Results The overall cohort comprised 1157 patients who received ≥1 dose of tofacitinib 5 or 10 mg BID, with a total of 2814.4 patient-years of tofacitinib exposure and up to 7.8 years of treatment. A total of 82.6% of patients received predominantly tofacitinib 10 mg BID. In the induction, maintenance, and overall cohorts, 3 (2 tofacitinib treated, 1 placebo treated), 3 (all placebo treated), and 9 patients had CDI, respectively; the overall cohort incidence rate was 0.31 (95% confidence interval, 0.14-0.59). CDI were all mild–moderate in severity and resolved with treatment in 8 patients. Six of 9 patients continued tofacitinib treatment without interruption. Two patients had events reported as serious due to hospitalization. Two patients were receiving corticosteroids when the CDI occurred. Conclusion CDIs among patients with UC receiving tofacitinib were infrequent, cases were mild–moderate in severity, and most resolved with treatment.
- Published
- 2022
13. Adalimumab Therapeutic Drug Monitoring Improves Treatment Outcome in Patients with Psoriasis
- Author
-
Afsaneh Alavi and Edward V. Loftus
- Subjects
Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2023
14. Economic Burden Of Fatigue In Inflammatory Bowel Disease
- Author
-
Ashwin N Ananthakrishnan, Raj Desai, Wan-Ju Lee, Jenny Griffith, Naijun Chen, and Edward V Loftus
- Subjects
Gastroenterology - Abstract
Background This retrospective study gathered medical/pharmacy claims data on patients with IBD between 01/01/2000 and 03/31/2019 from the IBM® MarketScan® commercial claims database to assess the real-world impact of fatigue on healthcare costs in patients newly diagnosed with inflammatory bowel disease (IBD). Methods Eligible participants were ≥18 years, newly diagnosed with IBD (≥2 separate claims) and had ≥12 months of continuous database enrollment before and after fatigue diagnosis. The date of fatigue diagnosis was the index date; participants were followed for 12 months post-index. Patients with (cases) or without (controls) fatigue were matched 1:1 by propensity score matching. Patients with evidence of prior IBD diagnosis/treatment, or those with a chronic disease other than IBD wherein fatigue is the primary symptom, were excluded. Healthcare resource utilization (HCRU), including hospitalizations, inpatient and outpatient visits, and associated costs was compared between cases and controls. Results Matched IBD cohorts (21,321 cases/21,321 controls) were identified (42% CD and 58% UC) with similar baseline characteristics (average age: 46 years; 60% female). Cases versus controls had significantly more all-cause outpatient visits (incidence rate ratio [IRR], 95% confidence intervals [95% CI]: 1.64 [1.61, 1.67], P Conclusions Presence of fatigue is associated with an increase in HCRU and total medical costs among patients newly diagnosed with IBD.
- Published
- 2023
15. Systematic Review and Meta-analysis: The Association Between Serum Ustekinumab Trough Concentrations and Treatment Response in Inflammatory Bowel Disease
- Author
-
Abhinav Vasudevan, Vivek Tharayil, Laura H Raffals, David H Bruining, Michelle Becker, Mohammad Hassan Murad, and Edward V Loftus
- Subjects
Gastroenterology ,Immunology and Allergy - Abstract
Background Optimizing therapy and monitoring response are integral aspects of inflammatory bowel disease treatment. We conducted a systematic review and meta-analysis to determine whether serum ustekinumab trough concentrations during maintenance therapy were associated with ustekinumab treatment response in patients with inflammatory bowel disease. Methods A systematic review was performed to March 21, 2022, to identify studies using MEDLINE, EMBASE, and the Cochrane library. We included studies that reported the association between serum ustekinumab trough concentrations with clinical or endoscopic remission. Outcome measures were combined across studies using the random-effects model with an odds ratio (OR) for binary outcomes of endoscopic and clinical remission. Results We identified 14 observational studies that were included in the analysis for clinical remission (919 patients, 63% with Crohn’s disease) or endoscopic remission (290 patients, all with Crohn’s disease). Median ustekinumab trough concentrations were higher amongst individuals achieving clinical remission compared with those not achieving remission (mean difference, 1.6 ug/mL; 95% confidence interval [CI], 0.21-3.01 ug/mL). Furthermore, individuals with median serum trough concentration in the fourth quartile were significantly more likely to achieve clinical (OR, 3.61; 95% CI, 2.11-6.20) but not endoscopic remission (OR, 4.67; 95% CI, 0.86-25.19) compared with those with first quartile median trough concentrations. Conclusion Based on the results of this meta-analysis primarily relating to patients with Crohn’s disease on maintenance ustekinumab treatment, it appears that there is an association between higher ustekinumab trough concentration and clinical outcomes. Prospective studies are required to determine whether proactive dose adjustments of ustekinumab therapy provides additional clinical benefit.
- Published
- 2023
16. The Global Incidence of Peptic Ulcer Disease Is Decreasing Since the Turn of the 21st Century: A Study of the Organisation for Economic Co-Operation and Development (OECD)
- Author
-
Hassan Azhari, James A. King, Stephanie Coward, Joseph W. Windsor, Christopher Ma, Shailja C. Shah, Siew C. Ng, Joyce W.Y. Mak, Paulo G. Kotze, Shomron Ben-Horin, Edward V. Loftus, Charlie W. Lees, Richard Gearry, Johan Burisch, Peter L. Lakatos, Xavier Calvet, Francisco Javier Bosques Padilla, Fox E. Underwood, and Gilaad G. Kaplan
- Subjects
Hospitalization ,Peptic Ulcer ,Hepatology ,Incidence ,Gastroenterology ,Humans ,Organisation for Economic Co-Operation and Development ,Patient Discharge - Abstract
Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century.The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models.The overall median hospitalization rate was 42.4 with an interquartile range of 29.7-60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = -3.9%; 95% CI: -4.4, -3.3) and morality rates (AAPC = -4.7%; 95% CI: -5.6, -3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021.PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum.
- Published
- 2022
17. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials
- Author
-
Silvio Danese, Séverine Vermeire, Wen Zhou, Aileen L Pangan, Jesse Siffledeen, Susan Greenbloom, Xavier Hébuterne, Geert D'Haens, Hiroshi Nakase, Julian Panés, Peter D R Higgins, Pascal Juillerat, James O Lindsay, Edward V Loftus, William J Sandborn, Walter Reinisch, Min-Hu Chen, Yuri Sanchez Gonzalez, Bidan Huang, Wangang Xie, John Liu, Michael A Weinreich, Remo Panaccione, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
Treatment Outcome ,Double-Blind Method ,Nasopharyngitis ,Acne Vulgaris ,Humans ,Colitis, Ulcerative ,General Medicine ,Creatine Kinase ,Heterocyclic Compounds, 3-Ring ,Severity of Illness Index - Abstract
BACKGROUND There is a great unmet need for advanced therapies that provide rapid, robust, and sustained disease control for patients with ulcerative colitis. We assessed the efficacy and safety of upadacitinib, an oral selective Janus kinase 1 inhibitor, as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. METHODS This phase 3, multicentre, randomised, double-blind, placebo-controlled clinical programme consisted of two replicate induction studies (U-ACHIEVE induction [UC1] and U-ACCOMPLISH [UC2]) and a single maintenance study (U-ACHIEVE maintenance [UC3]). The studies were conducted across Europe, North and South America, Australasia, Africa, and the Asia-Pacific region at 199 clinical centres in 39 countries (UC1), 204 clinical centres in 40 countries (UC2), and 195 clinical centres in 35 countries (UC3). Patients aged 16-75 years with moderately to severely active ulcerative colitis (Adapted Mayo score 5-9; endoscopic subscore 2 or 3) for at least 90 days were randomly assigned (2:1) to oral upadacitinib 45 mg once daily or placebo for 8 weeks (induction studies). Patients who achieved clinical response following 8-week upadacitinib induction were re-randomly assigned (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks (maintenance study). All patients were randomly assigned using web-based interactive response technology. The primary endpoints were clinical remission per Adapted Mayo score at week 8 (induction) and week 52 (maintenance). The efficacy analyses in the two induction studies were based on the intent-to-treat population, which included all randomised patients who received at least one dose of treatment. In the maintenance study, the primary efficacy analyses reported in this manuscript were based on the first 450 (planned) clinical responders to 8-week induction therapy with upadacitinib 45 mg once daily. The safety analysis population in the induction studies consisted of all randomised patients who received at least one dose of treatment; in the maintenance study, this population included all patients who received at least one dose of treatment as part of the primary analysis population. These studies are registered at ClinicalTrials.gov, NCT02819635 (U-ACHIEVE) and NCT03653026 (U-ACCOMPLISH). FINDINGS Between Oct 23, 2018, and Sept 7, 2020, 474 patients were randomly assigned to upadacitinib 45 mg once daily (n=319) or placebo (n=155) in UC1. Between Dec 6, 2018, and Jan 14, 2021, 522 patients were randomly assigned to upadacitinib 45 mg once daily (n=345) or placebo (n=177) in UC2. In UC3, a total of 451 patients (21 from the phase 2b study, 278 from UC1, and 152 from UC2) who achieved a clinical response after 8 weeks of upadacitinib induction treatment were randomly assigned again to upadacitinib 15 mg (n=148), upadacitinib 30 mg (n=154), and placebo (n=149) in the primary analysis population. Statistically significantly more patients achieved clinical remission with upadacitinib 45 mg (83 [26%] of 319 patients in UC1 and 114 [34%] of 341 patients in UC2) than in the placebo group (seven [5%] of 154 patients in UC1 and seven [4%] of 174 patients; p
- Published
- 2022
18. Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results
- Author
-
Julián Panés, Jean-Frederic Colombel, Geert R. D’Haens, Stefan Schreiber, Remo Panaccione, Laurent Peyrin-Biroulet, Edward V. Loftus, Silvio Danese, Satoshi Tanida, Yusuke Okuyama, Edouard Louis, Alessandro Armuzzi, Marc Ferrante, Harald Vogelsang, Toshifumi Hibi, Mamoru Watanabe, Jessica Lefebvre, Tricia Finney-Hayward, Yuri Sanchez Gonzalez, Thao T. Doan, Nael M. Mostafa, Kimitoshi Ikeda, Wangang Xie, Bidan Huang, Joel Petersson, Jasmina Kalabic, Anne M. Robinson, William J. Sandborn, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
Hepatology ,Monoclonal Antibody ,moderately to severely active ulcerative colitis ,Remission Induction ,Inflammatory Bowel Disease ,Adalimumab ,Gastroenterology ,clinical trial result ,Treatment Outcome ,Clinical Protocols ,Double-Blind Method ,Clinical Trial Result ,inflammatory bowel disease ,monoclonal antibody ,Humans ,Colitis, Ulcerative ,Moderately to Severely Active Ulcerative Colitis - Abstract
BACKGROUND & AIMS: SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis. METHODS: This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens. RESULTS: In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069). In the integrated (main + Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (nominal P = .045). Safety profiles were comparable between dosing regimens. CONCLUSION: Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis. CLINICALTRIALS: gov, Number: NCT002209456. ispartof: GASTROENTEROLOGY vol:162 issue:7 pages:1891-1910 ispartof: location:United States status: published
- Published
- 2022
19. Observational data from the adalimumab post‐marketing PYRAMID registry of patients with Crohn's disease who became pregnant: A post hoc analysis
- Author
-
Ailsa Hart, Geert D’Haens, Mareike Bereswill, Tricia Finney‐Hayward, Jasmina Kalabic, Gweneth Levy, Huifang Liang, Cynthia H. Seow, Edward V. Loftus, Remo Panaccione, Walter Reinisch, Jack Satsangi, Gastroenterology and Hepatology, and Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
PYRAMID registry ,anti-tumour necrosis factor ,Infant, Newborn ,Gastroenterology ,Crohn's disease ,Crohn Disease ,Oncology ,Prenatal Exposure Delayed Effects ,adalimumab ,Product Surveillance, Postmarketing ,Humans ,Female ,Registries ,pregnancy ,Retrospective Studies - Abstract
Background: PYRAMID was an international post-marketing registry that aimed to collect data on the long-term safety and effectiveness of adalimumab treatment per local standard of care in patients with moderately to severely active Crohn's disease (CD). Here, we present post hoc analyses of observational data from patients who became pregnant while participating in this registry and receiving adalimumab. Methods: From the subpopulation of patients receiving adalimumab who became pregnant while taking part in PYRAMID, data on patient characteristics, pregnancy outcomes, and complications of pregnancy were analysed retrospectively. Results: Across the PYRAMID registry, 293 pregnancies occurred in patients who had gestational adalimumab exposure (average disease duration at last menstrual period: 8.6 years), resulting in 300 pregnancy outcomes. A total of 197 pregnancies (67.2%) were exposed to adalimumab in all trimesters per physician's decision. Of the known reported outcomes (96.3%), 81.7% (236/289) were live births, 10.4% (30/289) were spontaneous abortions, 4.8% (14/289) elective terminations, 2.8% (8/289) ectopic pregnancies, and 0.3% (1/289) was a stillbirth. Congenital malformations (pulmonary valve stenosis and tricuspid valve incompetence) were reported in one infant. In addition to the pregnancy outcomes described above, 23 complications of pregnancy were reported in 20 patients. Conclusions: This analysis showed that adalimumab treatment in patients with CD, who became pregnant whilst participating in the PYRAMID registry, contributed no additional adverse effects during the pregnancy course or on pregnancy outcomes.
- Published
- 2022
20. The Epidemiology of Microscopic Colitis in Olmsted County, Minnesota: Population-Based Study From 2011 to 2019
- Author
-
Darrell S. Pardi, William S. Harmsen, Kanika Sehgal, Amrit K. Kamboj, Patricia P. Kammer, Sahil Khanna, June Tome, Edward V. Loftus, and William J. Tremaine
- Subjects
Colitis, Lymphocytic ,Male ,Lymphocytic colitis ,medicine.medical_specialty ,Minnesota ,Colitis, Collagenous ,Population ,Article ,Microscopic colitis ,Rochester Epidemiology Project ,Epidemiology ,medicine ,Humans ,education ,education.field_of_study ,Hepatology ,Collagenous colitis ,business.industry ,Incidence ,Incidence (epidemiology) ,Gastroenterology ,Odds ratio ,medicine.disease ,Colitis, Microscopic ,Female ,business ,Demography - Abstract
BACKGROUND: Epidemiological studies from Europe and North America report an increasing incidence of microscopic colitis (MC) in the late twentieth century followed by a plateau. This population-based study assessed recent incidence trends and the overall prevalence of MC over the past decade. METHODS: Residents of Olmsted County, Minnesota diagnosed with collagenous colitis (CC) or lymphocytic colitis (LC) between January 1, 2011 and December 31, 2019 were identified using the Rochester Epidemiology Project. Clinical variables were abstracted by chart review. Incidence rates were age- and sex-adjusted to the 2010 US population. Associations between incidence and age, sex, and calendar periods were evaluated using Poisson regression analyses. RESULTS: A total of 268 incident cases of MC were identified with a median age at diagnosis of 64 years (range, 19–90); 207 (77%) were women. The age- and sex-adjusted incidence of MC was 25.8 (95% confidence interval [CI] 22.7–28.9) cases per 100,000 person-years. The incidence of LC was 15.8 (95% CI, 13.4–18.2) and CC 9.9 (95% CI, 8.1–11.9) per 100,000 person-years. A higher MC incidence was associated with increasing age and female sex (p
- Published
- 2022
21. Trial of Mesalamine for the Treatment of Active Microscopic Colitis
- Author
-
Paul E. Evans MD, William J. Sandborn MD, Edward V. Loftus MD, Thomas C. Smryk MD, Willaim Tremaine MD, and Darrell S. Pardi MD
- Published
- 2011
22. Corticosteroid-Sparing Effects of Filgotinib in Moderately to Severely Active Ulcerative Colitis: Data from the Phase 2b/3 SELECTION Study
- Author
-
Edward V Loftus, Séverine Vermeire, Brian G Feagan, Franck-Olivier Le Brun, Alessandra Oortwijn, Ulrik Moerch, William J Sandborn, and Toshifumi Hibi
- Subjects
Gastroenterology ,General Medicine ,Filgotinib ,corticosteroids ,ulcerative colitis - Abstract
Background and Aims Corticosteroid-free remission is an important treatment goal for patients with ulcerative colitis [UC]. The corticosteroid-sparing effects of filgotinib, an oral, Janus kinase 1 preferential inhibitor, were assessed in SELECTION, a placebo-controlled, phase 2b/3 trial in moderately to severely active UC. Methods These post hoc analyses assessed 1-, 3-, 6-, and 8-month rates of corticosteroid-free clinical remission at Week 58 and change in median daily prednisone-equivalent dose over time. A matching-adjusted indirect comparison [MAIC] of maintenance studies assessed corticosteroid-free remission with filgotinib 200 mg, intravenous vedolizumab, subcutaneous vedolizumab, and oral tofacitinib. Results The Maintenance Study full analysis set included 199 patients receiving filgotinib 200 mg and 98 receiving placebo. Among patients receiving corticosteroids at Maintenance Study baseline, at Week 58, 30.4%, 29.3%, 27.2%, and 21.7% receiving filgotinib had been in corticosteroid-free remission for ≥1, ≥3, ≥6, or ≥8 months, respectively, versus 6.4% receiving placebo across thresholds [p Conclusions Filgotinib 200 mg demonstrated corticosteroid-sparing effects and maintained corticosteroid-free clinical remission in patients with UC. MAIC results should be interpreted cautiously given the large CIs and differences in study design and patient populations. [ClinicalTrials.gov: NCT02914522].
- Published
- 2023
23. Effectiveness of Hepatitis B Vaccination for Patients With Inflammatory Bowel and Celiac Disease
- Author
-
Jessica A. Ulrich, Nawras W. Habash, Yasmine A. Ismail, William J. Tremaine, Amy L. Weaver, Joseph A. Murray, Edward V. Loftus, and Imad Absah
- Subjects
Hepatology ,Gastroenterology - Published
- 2023
24. The Incidence of Pouch Neoplasia Following Ileal Pouch–Anal Anastomosis in Patients With Inflammatory Bowel Disease
- Author
-
Siri A Urquhart, Bryce P Comstock, Mauricio F Jin, Courtney N Day, John E Eaton, William S Harmsen, Laura E Raffals, Edward V Loftus, and Nayantara Coelho-Prabhu
- Subjects
Gastroenterology ,Immunology and Allergy - Abstract
BackgroundIleal pouch–anal anastomosis (IPAA) is the standard restorative procedure following proctocolectomy in patients with inflammatory bowel disease (IBD) who require colectomy. However, removal of the diseased colon does not eliminate the risk of pouch neoplasia. We aimed to assess the incidence of pouch neoplasia in IBD patients following IPAA.MethodsAll patients at a large tertiary center with International Classification of Diseases–Ninth Revision/International Classification of Diseases–Tenth Revision codes for IBD who underwent IPAA and had subsequent pouchoscopy were identified using a clinical notes search from January 1981 to February 2020. Relevant demographic, clinical, endoscopic, and histologic data were abstracted.ResultsIn total, 1319 patients were included (43.9% women). Most had ulcerative colitis (95.2%). Out of 1319 patients, 10 (0.8%) developed neoplasia following IPAA. Neoplasia of the pouch was seen in 4 cases with neoplasia of the cuff or rectum seen in 5 cases. One patient had neoplasia of the prepouch, pouch, and cuff. Types of neoplasia included low-grade dysplasia (n = 7), high-grade dysplasia (n = 1), colorectal cancer (n = 1), and mucosa-associated lymphoid tissue lymphoma (n = 1). Presence of extensive colitis, primary sclerosing cholangitis, backwash ileitis, and rectal dysplasia at the time of IPAA were significantly associated with increased risk of pouch neoplasia.ConclusionsThe incidence of pouch neoplasia in IBD patients who have undergone IPAA is relatively low. Extensive colitis, primary sclerosing cholangitis, and backwash ileitis prior to IPAA and rectal dysplasia at the time of IPAA raise the risk of pouch neoplasia significantly. A limited surveillance program might be appropriate for patients with IPAA even with a history of colorectal neoplasia.
- Published
- 2023
25. Induction and Maintenance Treatment With Upadacitinib Improves Health-Related Quality of Life in Patients With Moderately to Severely Active Ulcerative Colitis: Phase 3 Study Results
- Author
-
Julian Panés, Edward V Loftus, Peter D R Higgins, James O Lindsay, Wen Zhou, Xuan Yao, Dapo Ilo, Charles Phillips, Jacinda Tran, Yuri Sanchez Gonzalez, and Séverine Vermeire
- Subjects
clinical trials ,quality of life ,Gastroenterology ,Immunology and Allergy ,socioeconomical and psychological endpoints - Abstract
Background We evaluated the health-related quality of life (HRQoL) benefits of upadacitinib (UPA) induction and maintenance treatment in a phase 3 study of patients with ulcerative colitis (UC) across a broad range of patient-centered outcomes. Methods Patients received UPA 45 mg once daily or placebo as induction treatment for 8 weeks. Patients who achieved clinical response were rerandomized to receive once daily UPA 15 mg, 30 mg, or placebo as maintenance treatment for 52 weeks. The percentages of patients reporting a clinically meaningful within-person change from baseline in the Ulcerative Colitis Symptoms Questionnaire, Inflammatory Bowel Disease Questionnaire, Work Productivity and Impairment Questionnaire, 36-Item Short Form Survey, and European Quality of Life-5 Dimension 5 Levels were evaluated at weeks 2 and 8 of induction and at weeks 0 and 52 of maintenance. Results Significant improvements from baseline in all HRQoL measures except the Work Productivity and Impairment Questionnaire–absenteeism were achieved with UPA (P Conclusions Induction treatment with UPA 45 mg significantly improved HRQoL measures. A significantly higher percentage of patients who responded to induction treatment with UPA maintained clinically meaningful improvements consistently across a wide range of HRQoL outcomes after 52 weeks of maintenance therapy with UPA (15 mg and 30 mg) compared with placebo. (ClinicalTrials.gov, Numbers: NCT02819635, NCT03653026).
- Published
- 2023
26. Therapeutic Drug Monitoring for Subcutaneous Infliximab? Too Early to Conclude
- Author
-
Edward V, Loftus, S, Paul, and X, Roblin
- Subjects
Hepatology ,Gastroenterology - Published
- 2023
27. Assessment of Safety and Efficacy of Tofacitinib, Stratified by Age, in Patients from the Ulcerative Colitis Clinical Program
- Author
-
Gary R Lichtenstein, Brian Bressler, Carlos Francisconi, Severine Vermeire, Nervin Lawendy, Leonardo Salese, Gosford Sawyerr, Hongjiong Shi, Chinyu Su, Donna T Judd, Thomas Jones, and Edward V Loftus
- Subjects
safety ,Science & Technology ,tofacitinib ,Gastroenterology & Hepatology ,OPPORTUNISTIC INFECTIONS ,JANUS KINASE INHIBITOR ,Gastroenterology ,clinical response ,THERAPY ,CANCER ,age ,RISK-FACTORS ,Immunology and Allergy ,Life Sciences & Biomedicine ,ulcerative colitis ,INFLAMMATORY-BOWEL-DISEASE - Abstract
Background In patients with ulcerative colitis (UC), risks of infection and malignancies increase with age. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. This analysis assessed age as a risk factor for adverse events of special interest (AESI) in the tofacitinib UC clinical program. Methods Data were from phase 2 and 3 induction studies, a phase 3 maintenance study, and an open-label, long-term extension study. Efficacy and/or safety outcomes were analyzed in the Induction, Maintenance, and Overall Cohorts (patients who received ≥ 1 dose of tofacitinib), stratified by age. The effects of baseline demographic and disease-related factors on AESI incidence were assessed by Cox proportional-hazards regression analysis. Results In the Overall Cohort (1157 patients with ≤ 6.8 years’ tofacitinib treatment), age was a statistically significant predictor of herpes zoster (HZ), malignancies excluding nonmelanoma skin cancer (NMSC), and NMSC. Other statistically significant predictors included prior tumor necrosis factor inhibitor failure for HZ, NMSC, and opportunistic infection events, and prior duration of UC for malignancies excluding NMSC. In the Induction and Maintenance Cohorts, a higher proportion of tofacitinib-treated than placebo-treated patients (numerical difference) achieved the efficacy endpoints (endoscopic improvement, clinical remission, clinical response) across all age groups. Conclusions Older individuals receiving tofacitinib as induction and maintenance therapy to treat UC may have an increased risk of HZ, malignancies (excluding NMSC), and NMSC versus similarly treated younger patients, consistent with findings from the general population. Across all age groups, tofacitinib demonstrated greater efficacy than placebo as an induction and maintenance therapy. ClinicalTrials.gov Registration Numbers NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612.
- Published
- 2023
28. Microscopic colitis, checkpoint inhibitor colitis, and other miscellaneous inflammatory and structural disorders of the colon
- Author
-
Amanda M. Johnson, Eugene F. Yen, Edward V. Loftus, and Darrell S. Pardi
- Published
- 2022
29. Prevalence of Pulmonary Diseases in Association with Inflammatory Bowel Disease
- Author
-
Gayatri Pemmasani, Edward V. Loftus, and William J. Tremaine
- Subjects
Physiology ,Gastroenterology - Published
- 2022
30. Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis
- Author
-
Yiran Zhang, Satimai Aniwan, A Weiss, Gursimran Kochhar, Sunanda V. Kane, Bo Shen, Matthew Bohm, Siddharth Singh, Eugenia Shmidt, Jean-Frederic Colombel, Corey A. Siegel, David Faleck, Edward V. Loftus, James P. Campbell, Mahmoud A. Rahal, Siri Kadire, Ronghui Xu, William J. Sandborn, David Hudesman, Arun Swaminath, Joseph Meserve, Robert Hirten, Vipul Jairath, Ryan C. Ungaro, Bruce E. Sands, Karen Lasch, Jenna L. Koliani-Pace, Brigid S. Boland, Parambir S. Dulai, Dana J. Lukin, Shreya Chablaney, Monika Fischer, Adam Winters, Gloria Tran, Shannon Chang, and Sashidhar Varma
- Subjects
Ulcerative ,Gastroenterology ,0302 clinical medicine ,Monoclonal ,Humanized ,Cancer ,Hazard ratio ,Colitis ,Ulcerative colitis ,Treatment Outcome ,6.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Patient Safety ,medicine.drug ,Cohort study ,medicine.medical_specialty ,Clinical Sciences ,Biologics ,Antibodies, Monoclonal, Humanized ,Autoimmune Disease ,Antibodies ,Article ,Vedolizumab ,03 medical and health sciences ,Gastrointestinal Agents ,Clinical Research ,Internal medicine ,medicine ,Humans ,Adverse effect ,Retrospective Studies ,Gastroenterology & Hepatology ,Hepatology ,Tumor Necrosis Factor-alpha ,business.industry ,Inflammatory Bowel Disease ,Evaluation of treatments and therapeutic interventions ,medicine.disease ,Health Outcomes ,Confidence interval ,Infliximab ,Propensity score matching ,Comparative Research ,Colitis, Ulcerative ,Tumor Necrosis Factor Inhibitors ,Digestive Diseases ,business - Abstract
Background & Aims We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. Methods A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist–naive and –exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. Results A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist–naive and −exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist−treated patients. However, in TNF-antagonist−naive patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). Conclusions Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist−naive patients.
- Published
- 2022
31. Safety and efficacy of tofacitinib for treatment of ulcerative colitis: final analysis of OCTAVE Open, an open‐label, long‐term extension study with up to 7.0 years of treatment
- Author
-
Chinyu Su, William J. Sandborn, Julián Panés, Ailsa Hart, Edward V. Loftus, Xiang Guo, Donna T. Judd, Aderson Omar Mourão Cintra Damião, Irene Modesto, Nervin Lawendy, Wenjin Wang, Silvio Danese, and Iris Dotan
- Subjects
medicine.medical_specialty ,Tofacitinib ,Hepatology ,business.industry ,Deep vein ,Gastroenterology ,medicine.disease ,Ulcerative colitis ,Confidence interval ,Pyrimidines ,Treatment Outcome ,medicine.anatomical_structure ,Piperidines ,Tolerability ,Internal medicine ,medicine ,Humans ,Colitis, Ulcerative ,Pyrroles ,Pharmacology (medical) ,Skin cancer ,Adverse effect ,business ,Janus kinase inhibitor - Abstract
BACKGROUND Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open-label, long-term extension study. AIMS The primary objective of OCTAVE Open was to assess the safety and tolerability of long-term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective. METHODS Eligible patients included OCTAVE Induction 1&2 non-responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient-years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit). RESULTS In OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient-years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09-0.54); serious infections, 1.61 (1.14-2.20); herpes zoster (non-serious and serious), 3.16 (2.47-3.97); opportunistic infections, 0.87 (0.54-1.33); major adverse cardiovascular events, 0.16 (0.04-0.42); malignancies (excluding non-melanoma skin cancer), 1.03 (0.67-1.52); non-melanoma skin cancer, 0.75 (0.45-1.19); deep vein thrombosis, 0.04 (0.00-0.23); pulmonary embolism, 0.21 (0.07-0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively. CONCLUSION Tofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long-term efficacy beyond the 52-week maintenance study.
- Published
- 2021
32. The Natural History of Inflammatory Bowel Disease
- Author
-
Edward V. Loftus and Satimai Aniwan
- Subjects
medicine.medical_specialty ,Colorectal cancer ,business.industry ,Gastroenterology ,medicine.disease ,digestive system ,Inflammatory bowel disease ,digestive system diseases ,Review article ,Primary sclerosing cholangitis ,Therapeutic goal ,Natural history ,Young age ,Internal medicine ,Risk of mortality ,medicine ,business - Abstract
The evolution of our management armamentarium for inflammatory bowel disease (IBD) has changed the therapeutic goal beyond symptom control and towards altering the disease course. This review article aims to update the natural history of IBD. In the biologic era, the disease phenotype at the time of IBD diagnosis is generally similar to that of historical reports. More than half of patients with IBD achieved disease remission within 5 years after diagnosis. The rates of hospitalization and surgery and the risk of colorectal cancer have been decreasing over time. IBD did not increase the risk of mortality. Factors associated with disease-related complications include young age at diagnosis, extensive anatomical involvement, intestinal complicating behavior, and concurrent primary sclerosing cholangitis, while the introduction of immunomodulators and biologics was associated with better disease outcomes. New evidence supports the favorable impact of modern-day IBD care on the natural history of IBD.
- Published
- 2021
33. Prevalence and Impact of Obesity in a Population-Based Cohort of Patients With Crohn’s Disease
- Author
-
Amanda M. Johnson, William Scott Harmsen, Satimai Aniwan, William J. Tremaine, Laura E. Raffals, Barham K. Abu Dayyeh, and Edward V. Loftus
- Published
- 2022
34. Evaluating cost per remission and cost of serious adverse events of advanced therapies for ulcerative colitis
- Author
-
Vipul Jairath, Russell D. Cohen, Edward V. Loftus, Ninfa Candela, Karen Lasch, and Bob G. Schultz
- Subjects
Gastroenterology ,General Medicine - Abstract
Background Determining the relative cost-effectiveness between advanced therapeutic options for ulcerative colitis (UC) may optimize resource utilization. We evaluated total cost per response, cost per remission, and cost of safety events for patients with moderately-to-severely active UC after 52 weeks of treatment with advanced therapies at standard dosing. Methods An analytic model was developed to estimate costs from the US healthcare system perspective associated with achieving efficacy outcomes and managing safety outcomes for advanced therapies approved for the treatment of UC. Numbers needed to treat (NNT) for response and remission, and numbers needed to harm (NNH) for serious adverse events (SAEs) and serious infections (SIs) were derived from a network meta-analysis of pivotal trials. NNT for induction and maintenance were combined with drug regimen costs to calculate cost per clinical remission. Cost of managing AEs was calculated using NNH for safety outcomes and published costs of treating respective AEs. Results Costs per remission were $205,240, $249,417, $267,463, $365,050, $579,622, $750,200, and $787,998 for tofacitinib 10 mg, tofacitinib 5 mg, infliximab, vedolizumab, golimumab, adalimumab, and ustekinumab, respectively. Incremental costs of SAEs and SIs collectively were $136,390, $90,333, $31,888, $31,061, $20,049, $12,059, and $0 for tofacitinib 5 mg, golimumab, adalimumab, tofacitinib 10 mg, infliximab, ustekinumab, and vedolizumab (reference), respectively. Conclusions Tofacitinib was associated with the lowest cost per response and cost per remission, while vedolizumab had the lowest costs related to SAEs and SIs. Balancing efficacy versus safety is important when evaluating the costs associated with treatment of moderate-to-severe UC.
- Published
- 2022
35. Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment
- Author
-
Edward V. Loftus, Jean-Frederic Colombel, Ken Takeuchi, Xiang Gao, Remo Panaccione, Silvio Danese, Marla Dubinsky, Stefan Schreiber, Dapo Ilo, Tricia Finney-Hayward, Wen Zhou, Charles Phillips, Yuri Sanchez Gonzalez, Lei Shu, Xuan Yao, Qing Zhou, and Séverine Vermeire
- Subjects
Hepatology ,Upadacitinib ,Gastroenterology ,Ulcerative Colitis ,Rapid Symptom Relief - Abstract
BACKGROUND & AIMS: We evaluated the efficacy of once-daily (QD) upadacitinib 45 mg, an oral, reversible Janus kinase inhibitor, on early symptomatic improvement for ulcerative colitis (UC). Post hoc analyses were performed on pooled data from 2 replicate, phase 3, multicenter induction trials, U-ACHIEVE Induction and U-ACCOMPLISH, to determine the earliest time point of efficacy onset. METHODS: Diary entry data through 14 days from the first dose of placebo or upadacitinib 45 mg QD were analyzed for daily improvement in UC symptoms (stool frequency, rectal bleeding, abdominal pain, and bowel urgency). Changes in inflammatory markers, high-sensitivity C-reactive protein (hs-CRP), and fecal calprotectin (FCP) were assessed at week 2 and quality of life (QoL) at weeks 2 and 8. Regression analysis determined the association between changes in UC symptoms and the likelihood of achieving clinical remission/response per Adapted Mayo score at week 8. RESULTS: Overall, 988 patients (n = 328 placebo, n = 660 upadacitinib) were analyzed. Patients treated with upadacitinib demonstrated significant improvements vs placebo in all UC symptoms between days 1 and 3 and maintained through day 14. A >50% reduction from baseline in hs-CRP and FCP levels was achieved by 75.7% and 48.2% of patients, respectively (P < .001 vs placebo). Increased rates of clinical remission/response per Partial Mayo score from week 2 (26.9%/59.4% upadacitinib 45 mg QD vs 4.3%/22.3% placebo, P < .001) and significant improvements in QoL at weeks 2 and 8 were observed. Early improvement in stool frequency and bowel urgency by day 3 and reductions in hs-CRP and FCP by week 2 were significantly associated with clinical remission/response at week 8. CONCLUSIONS: Upadacitinib 45 mg QD provided rapid relief of UC symptoms from day 1. CLINICALTRIALS: gov: U-ACHIEVE Induction (NCT02819635) and U-ACCOMPLISH (NCT03653026). ispartof: Clin Gastroenterol Hepatol pages:S1542-3565(22)01109-0- ispartof: location:United States status: Published online
- Published
- 2022
36. Novel Therapies for Patients With Inflammatory Bowel Disease
- Author
-
Priscila, Santiago, Manuel B, Braga-Neto, and Edward V, Loftus
- Subjects
Column - Abstract
The implementation of biologic therapy has improved the treatment and clinical course of patients with inflammatory bowel disease since the initial approval of infliximab for Crohn’s disease in 1998. However, the efficacy and safety profiles of currently available therapies are still less than optimal in several ways, highlighting the need for novel therapeutic targets. Several new drug classes (Janus kinase inhibitors, anti-integrins, sphingosine-1-phosphate receptor modulators, anti–interleukin-23 antibodies, and stem cell therapies) are currently being studied in Crohn’s disease and ulcerative colitis with promising results. This article reviews the current literature and provides an updated overview of the emerging therapies.
- Published
- 2022
37. Upadacitinib Was Efficacious and Well-tolerated Over 30 Months in Patients With Crohn's Disease in the CELEST Extension Study
- Author
-
Geert D’Haens, Julian Panés, Edouard Louis, Ana Lacerda, Qian Zhou, John Liu, Edward V. Loftus, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
Treatment Outcome ,Crohn Disease ,Double-Blind Method ,Hepatology ,CDAI ,JAK inhibitor ,IBD ,Gastroenterology ,ABT-494 ,Humans ,Creatine Kinase ,Heterocyclic Compounds, 3-Ring - Abstract
Background & Aims: The long-term efficacy and safety of upadacitinib was evaluated in an open-label extension (OLE) of a phase II, double-blind, randomized trial of patients with Crohn's disease. Methods: Patients who completed the 52-week study (CELEST) received upadacitinib in the CELEST OLE as follows: those who had received immediate-release upadacitinib 3, 6, or 12 mg twice daily or 24 mg once daily (QD) received extended-release upadacitinib 15 mg QD and those who had received immediate-release upadacitinib 12 or 24 mg twice daily as rescue therapy received extended-release upadacitinib 30 mg QD. If any patient initiating upadacitinib 15 mg QD in CELEST OLE lost response at or after week 4, the dose was escalated to upadacitinib 30 mg QD (dose-escalated group). Clinical, endoscopic, inflammatory and quality-of-life measures were assessed. Results: A total of 107 CELEST study completers entered CELEST OLE. The proportion of patients with clinical remission 2.8/1.0 was maintained between week 0 and month 30 in all groups (month 30: 15 mg, 61%; 30 mg, 54%; dose-escalation, 55%). Endoscopic response was maintained in all groups (month 24: 68%, 67%, and 40%, respectively). The rates of adverse events (AEs), serious AEs, AEs leading to discontinuation, infections, serious infections, herpes zoster, and creatine phosphokinase elevation were higher with upadacitinib 30 mg vs 15 mg. Conclusion: Sustained long-term benefit at 30 months and further endoscopic improvements to month 24 were observed in patients with Crohn's disease receiving upadacitinib. Safety over 30 months was consistent with the known safety profile of upadacitinib. Clinicaltrials.gov ID no: NCT02782663.
- Published
- 2022
38. Approach to medical therapy in perianal Crohn’s disease
- Author
-
Laura E. Raffals, Abhinav Vasudevan, William A. Faubion, Edward V. Loftus, David H. Bruining, and Eric C. Ehman
- Subjects
Opinion Review ,medicine.medical_specialty ,Fistula ,Stem cells ,Disease ,Biologics ,Inflammatory bowel disease ,Vedolizumab ,law.invention ,Crohn Disease ,Quality of life ,Randomized controlled trial ,law ,Ustekinumab ,Adalimumab ,Humans ,Rectal Fistula ,Medicine ,Intensive care medicine ,Tumor Necrosis Factor-alpha ,business.industry ,Gastroenterology ,General Medicine ,medicine.disease ,Infliximab ,Treatment Outcome ,Quality of Life ,Tumor Necrosis Factor Inhibitors ,Surgery ,business ,medicine.drug - Abstract
Perianal Crohn’s disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn’s disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn’s disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn’s disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn’s disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed.
- Published
- 2021
39. Osteonecrosis in Inflammatory Bowel Disease: Clinical Features, Risk Factor Analysis, and Outcomes
- Author
-
Zeinab Bakhshi, Siddhant Yadav, W Scott Harmsen, Jithinraj Edakkanambeth Varayil, Kevin A Karls, William J Tremaine, and Edward V Loftus
- Subjects
Gastroenterology ,Immunology and Allergy - Abstract
Background Avascular necrosis (AVN) is a known adverse event associated with corticosteroid (CS) usage. Inflammatory bowel disease (IBD) is often treated with a CS for induction of remission. We sought to describe clinical features and outcomes of IBD patients with AVN. Methods In this retrospective, single-center, case-control study, patients with IBD who had a diagnosis of osteonecrosis, aseptic necrosis, or AVN from 1976 to 2009 were included, and each was matched with up to 2 controls (IBD but no AVN) on age, sex, IBD subtype, geographic area of residence, and date of IBD diagnosis. We abstracted risk factor data from the medical records. Conditional logistic regression was performed accounting for minor differences in age and date of first IBD visit to assess the relationship between putative risk factors and AVN, expressed as odds ratio and 95% confidence interval. Results Eighty-five patients were diagnosed with IBD-AVN and were matched with 163 controls. The mean age at AVN diagnosis was 47.5 years. AVN was diagnosed a median of 12.2 years after IBD diagnosis, and the control group was followed for a median of 15 years after IBD diagnosis to ensure that they did not have AVN. Ten percent of patients with AVN did not have any CS exposure. History of arthropathy or estrogen use in Crohn’s disease and use of CS, osteoporosis, and history of arthropathy in ulcerative colitis were significantly associated with AVN. Conclusions Most patients with IBD-AVN had multifocal involvement. Most had received CS, but many patients had other risk factors including arthropathy.
- Published
- 2022
40. Prevalence and Impact of Obesity on Disease-specific Outcomes in a Population-based Cohort of Patients with Ulcerative Colitis
- Author
-
Edward V. Loftus, W. Scott Harmsen, William J. Tremaine, Amanda M. Johnson, Barham K. Abu Dayyeh, and Satimai Aniwan
- Subjects
Adult ,Male ,medicine.medical_specialty ,Population ,Overweight ,Inflammatory bowel disease ,Body Mass Index ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Outcome Assessment, Health Care ,Prevalence ,Humans ,Medicine ,Obesity ,Prospective Studies ,Correlation of Data ,Prospective cohort study ,education ,Analysis of Variance ,education.field_of_study ,business.industry ,Hazard ratio ,Gastroenterology ,Original Articles ,General Medicine ,Middle Aged ,medicine.disease ,030220 oncology & carcinogenesis ,Cohort ,Colitis, Ulcerative ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,Underweight ,business ,Body mass index - Abstract
Background and Aims There remains a historical misconception that inflammatory bowel disease [IBD] patients are underweight. However, recent data suggest rates of obesity in IBD parallel to those of the general population. The impact obesity has on the natural history of IBD is unclear. We aimed to determine obesity rates at the time of IBD diagnosis in a population-based cohort of ulcerative colitis [UC] patients. Methods Chart review was performed on patients diagnosed with UC over 1970–2010. Data were collected on demographics, body mass index [BMI], disease characteristics, IBD-specific hospitalisations, intestinal resection, and corticosteroid use. The proportion of patients who were obese at the time of their diagnosis was evaluated over time, and survival free of IBD-related complications was assessed using Kaplan-Meier survival analysis. Results A total of 417 adults were diagnosed with UC over 1970–2010, 55.4% of whom were classified as either overweight [34.8%] or obese [20.6%]. The prevalence of obesity increased 2–3-fold over the 40-year study period. Obese patients had a 72% increased risk of hospitalisation (hazard ratio [HR],1.72; 95% confidence interval [CI], 1.10–2.71; p = 0.018) when compared with normal weight patients. Additionally, with each incremental increase in BMI by 1 kg/m2, the risk of hospitalisation increased by 5% [HR,1.05; 95% CI, 1.01–1.08; p = 0.008] and risk of corticosteroid use increased by 2.6% [HR,1.026; 95% CI, 1.00–1.05; p = 0.05]. Conclusions The prevalence of obesity in the UC population is increasing and may have negative prognostic implications, specifically regarding risk of future hospitalisation and corticosteroid use. Additional prospective studies are necessary to more clearly define these associations.
- Published
- 2021
41. S770 Health-Related Quality of Life With Ustekinumab vs Adalimumab for Induction and Maintenance Therapy in Biologic-Naïve Patients With Moderate-To-Severe Crohn’s Disease: IBDQ in the SEAVUE Study
- Author
-
Matthieu Allez, Christopher Gasink, Silvio Danese, Bruce E. Sands, Peter M. Irving, Zhijie Ding, Erik Muser, Remo Panaccione, Tony Ma, Edward V. Loftus, James L. Izanec, Timothy Hoops, and James D. Lewis
- Subjects
Moderate to severe ,Health related quality of life ,medicine.medical_specialty ,Crohn's disease ,Hepatology ,business.industry ,Gastroenterology ,medicine.disease ,Therapy naive ,Maintenance therapy ,Internal medicine ,Ustekinumab ,Adalimumab ,medicine ,business ,medicine.drug - Published
- 2021
42. S722 Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Active Ulcerative Colitis Receiving 16 Weeks Extended Induction Treatment Followed by 52 Weeks Maintenance Treatment in U-ACHIEVE/U-ACCOMPLISH Trials
- Author
-
Remo Panaccione, Silvio Danese, Wen Zhou, Justin Klaff, Dapo Ilo, Xuan Yao, Gweneth Levy, Peter D. Higgins, Edward V. Loftus, and Séverine Vermeire
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
43. S983 Baseline Demographics and Disease Characteristics of Patients With Ulcerative Colitis Who Responded to Vedolizumab at Week 6
- Author
-
Andres Yarur, Vipul Jairath, Edward V. Loftus, Bruce E. Sands, Sharif Uddin, and Qasim Rana Khan
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
44. S753 Mirikizumab Significantly Improves Abdominal Pain in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies
- Author
-
Edward V. Loftus, Theresa Hunter Gibble, Alison Potts Bleakman, Xingyuan Li, Nathan Morris, Emily Hon, and Vipul Jairath
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
45. S822 Fatigue Improvement Correlates With Reductions in Work Productivity Impairment and Related Indirect Cost in Patients With Crohn’s Disease: Post Hoc Analysis of Phase 3 Rizankizumab Induction Trials
- Author
-
Edouard Louis, Julian Panés, Subrata Ghosh, Britta Siegmund, Wan-Ju Lee, Huiwen Deng, Kristina Kligys, Jasmina Kalabic, and Edward V. Loftus
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
46. S955 Effectiveness of Vedolizumab in Patients With Inflammatory Bowel Disease and Concomitant Primary Sclerosing Cholangitis
- Author
-
Priscila Santiago, Anthony Robateau, Rachel G. Lopdrup, Manuel B. Braga Neto, Laura Raffals, John Eaton, Guilherme Ramos, and Edward V. Loftus
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
47. Higher vs Standard Adalimumab Induction Dosing Regimens and Two Maintenance Strategies: Randomized SERENE CD Trial Results
- Author
-
Geert R. D’Haens, William J. Sandborn, Edward V. Loftus, Stephen B. Hanauer, Stefan Schreiber, Laurent Peyrin-Biroulet, Remo Panaccione, Julián Panés, Filip Baert, Jean-Frederic Colombel, Marc Ferrante, Edouard Louis, Alessandro Armuzzi, Qian Zhou, Venkata S. Goteti, Nael M. Mostafa, Thao T. Doan, Joel Petersson, Tricia Finney-Hayward, Alexandra P. Song, Anne M. Robinson, Silvio Danese, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
Adult ,Biologic Agent ,Dose-Response Relationship, Drug ,Hepatology ,Biologic agent ,Monoclonal Antibody ,Remission Induction ,Inflammatory Bowel Disease ,Adalimumab ,Gastroenterology ,TNF Inhibitor ,C-Reactive Protein ,Treatment Outcome ,Crohn Disease ,Double-Blind Method ,inflammatory bowel disease ,monoclonal antibody ,Humans ,TNF inhibitor - Abstract
BACKGROUND & AIMS: Dose-optimization strategies for biologic therapies in Crohn's disease (CD) are not well established. The SERENE CD (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Crohn's Disease) trial evaluated higher vs standard adalimumab induction dosing and clinically adjusted (CA) vs therapeutic drug monitoring (TDM) maintenance strategies in patients with moderately to severely active CD. METHODS: In this phase 3, randomized, double-blind, multicenter trial, eligible adults (Crohn's Disease Activity Index score of 220-450, endoscopic evidence of mucosal inflammation, and previous failure of standard therapies) were randomized to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3; n = 308) or standard induction regimen (adalimumab 160 mg at week 0 and 80 mg at week 2; n = 206) followed by 40 mg every other week from week 4 onward. Co-primary end points included clinical remission at week 4 and endoscopic response at week 12. At week 12, patients were re-randomized to maintenance therapy optimized by Crohn's Disease Activity Index and C-reactive protein (CA; n = 92) or serum adalimumab concentrations and/or clinical criteria (TDM; n = 92); exploratory end points were evaluated at week 56. RESULTS: Similar proportions of patients receiving higher induction regimen and standard induction regimen achieved clinical remission at week 4 (44% in both; P = .939) and endoscopic response at week 12 (43% vs 39%, respectively, P = .462). Week 56 efficacy was similar between CA and TDM. Safety profiles were comparable between dosing regimens. CONCLUSIONS: Higher induction regimen was not superior to standard induction regimen, and CA and TDM maintenance strategies were similarly efficacious. Adalimumab therapy was well tolerated, and no new safety concerns were identified. (ClinicalTrials.gov, Number: NCT02065570). ispartof: GASTROENTEROLOGY vol:162 issue:7 pages:1876-1890 ispartof: location:United States status: published
- Published
- 2022
48. Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial
- Author
-
Marc Ferrante, Remo Panaccione, Filip Baert, Peter Bossuyt, Jean-Frederic Colombel, Silvio Danese, Marla Dubinsky, Brian G Feagan, Tadakazu Hisamatsu, Allen Lim, James O Lindsay, Edward V Loftus, Julián Panés, Laurent Peyrin-Biroulet, Zhihua Ran, David T Rubin, William J Sandborn, Stefan Schreiber, Ezequiel Neimark, Alexandra Song, Kristina Kligys, Yinuo Pang, Valerie Pivorunas, Sofie Berg, W Rachel Duan, Bidan Huang, Jasmina Kalabic, Xiaomei Liao, Anne Robinson, Kori Wallace, Geert D'Haens, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
Crohn Disease ,Double-Blind Method ,Antibodies, Monoclonal ,Humans ,General Medicine ,Abdominal Pain - Abstract
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.
- Published
- 2022
49. Quality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn’s Disease
- Author
-
Yuri Sanchez Gonzalez, Qian Zhou, Edouard Louis, Laurent Peyrin-Biroulet, Subrata Ghosh, Edward V. Loftus, and Ana P. Lacerda
- Subjects
Adult ,Quality of life ,Moderate to severe ,medicine.medical_specialty ,Dose ,Visual analogue scale ,Efficiency ,Placebo ,Inflammatory bowel disease ,European Quality of Life-5 Dimensions Visual Analog Scale ,Crohn Disease ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Work Productivity and Activity Impairment Questionnaire ,CELEST ,Original Research ,Janus kinase 1 ,Crohn's disease ,business.industry ,General Medicine ,medicine.disease ,Rheumatology ,Treatment Outcome ,Upadacitinib ,Inflammatory Bowel Disease Questionnaire ,business ,Heterocyclic Compounds, 3-Ring - Abstract
Introduction In the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn’s disease. We present the health-related quality of life and work productivity improvement results with upadacitinib from CELEST. Methods CELEST (NCT02365649) was a double-blind study where patients were randomized 1:1:1:1:1:1 in the 16-week induction period to placebo or upadacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg BID, 24 mg BID, or 24 mg once daily (QD). Patients completing the induction period were re-randomized 1:1:1 to receive upadacitinib 3 mg BID, 12 mg BID, or 24 mg QD for 36 weeks or 3 mg BID, 6 mg BID, or 12 mg BID (after amendment). Inflammatory Bowel Disease Questionnaire (IBDQ), European Quality of Life-5 Dimensions visual analog scale (EQ-5D VAS), and Work Productivity and Activity Impairment (WPAI) questionnaire outcomes were assessed at baseline and Weeks 8, 16, and 52. Results At Week 16, a significant percentage (P ≤ 0.05) of patients receiving upadacitinib 6-mg BID dose or higher achieved IBDQ response (IBDQ score change ≥ 16 points; 49%–57% for upadacitinib vs. 24% for placebo) and IBDQ remission, except 24 mg QD (IBDQ score ≥ 170; 26%–39% for upadacitinib vs. 11% for placebo). Greater improvements in IBDQ total score, EQ-5D VAS, and activity impairment from baseline (P ≤ 0.1) versus placebo were also observed. Larger improvements (P ≤ 0.1) in IBDQ response and total score and EQ-5D VAS were observed at Week 8 with 6 and 24 mg BID versus placebo, with improvements for all dosages maintained or greater at Week 52 for IBDQ, EQ-5D VAS, and WPAI endpoints, in particular for the 12-mg BID group. Conclusion Improvements in health-related quality of life and work productivity were achieved and sustained with upadacitinib in patients with moderate to severe Crohn’s disease. Trial Registration ClinicalTrials.gov identifier, NCT02365649. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01660-7.
- Published
- 2021
50. Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Nonmelanoma Skin Cancer Rates From the Ulcerative Colitis Clinical Program
- Author
-
Arif Soonasra, Julián Panés, Millie D. Long, Rajiv Mundayat, Chinyu Su, Walter Reinisch, Bruce E. Sands, Chudy I. Nduaka, Gary Chan, Gary S. Friedman, Nervin Lawendy, and Edward V. Loftus
- Subjects
Oncology ,medicine.medical_specialty ,Skin Neoplasms ,Ibdjnl/9 ,Piperidines ,Clinical Research ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Risk factor ,Janus kinase inhibitor ,AcademicSubjects/MED00260 ,ulcerative colitis ,Tofacitinib ,tofacitinib ,Proportional hazards model ,business.industry ,Hazard ratio ,Gastroenterology ,medicine.disease ,Ulcerative colitis ,Pyrimidines ,Cohort ,nonmelanoma skin cancer ,Colitis, Ulcerative ,Skin cancer ,business - Abstract
Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present integrated analyses of nonmelanoma skin cancer (NMSC) incidence in the tofacitinib UC clinical program. Methods Nonmelanoma skin cancer events were evaluated from 3 randomized, placebo-controlled studies: 2 identical, 8-week induction studies (NCT01465763, NCT01458951), a 52-week maintenance study (NCT01458574), and an open-label, long-term extension study (NCT01470612). Cohorts analyzed were: Induction, Maintenance, and Overall (patients receiving ≥1 dose of tofacitinib 5 mg or 10 mg twice daily [BID]). An independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique patients with events per 100 patient-years of exposure) for NMSC were evaluated. A Cox proportional hazards model was used for risk factor analysis. Results Nonmelanoma skin cancer was evaluated for 1124 patients (2576.4 patient-years of tofacitinib exposure; ≤6.8 years’ treatment). In the Induction Cohort, NMSC IR was 0.00 for placebo and 1.26 for 10 mg BID. Nonmelanoma skin cancer IR was 0.97 for placebo, 0.00 for 5 mg BID and 1.91 for 10 mg BID in the Maintenance Cohort, and 0.73 (n = 19) in the Overall Cohort. No NMSC was metastatic or led to discontinuation. In the Overall Cohort, Cox regression identified prior NMSC (hazard ratio [HR], 9.09; P = 0.0001), tumor necrosis factor inhibitor (TNFi) failure (3.32; P = 0.0363), and age (HR per 10-year increase, 2.03; P = 0.0004) as significant independent NMSC risk factors. Conclusions For patients receiving tofacitinib, NMSC occurred infrequently. Older age, prior NMSC, and TNFi failure, which are previously reported NMSC risk factors in patients with UC, were associated with increased NMSC risk.
- Published
- 2021
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.