Early Initiation of Antitumor Necrosis Factor Therapy Reduces Postoperative Recurrence of Crohn's Disease Following Ileocecal Resection
Axelrad, Jordan E; Li, Terry; Bachour, Salam P; Nakamura, Takahiro I; Shah, Ravi; Sachs, Michael C; Chang, Shannon; Hudesman, David P; Holubar, Stefan D; Lightner, Amy L; Barnes, Edward L; Cohen, Benjamin L; Rieder, Florian; Esen, Eren; Remzi, Feza; Regueiro, Miguel; Click, Benjamin
BACKGROUND:Postoperative recurrence (POR) of Crohn's disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR). METHODS:We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (â‰¥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab). RESULTS:We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis. CONCLUSION/CONCLUSIONS:Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited.
Tofacitinib Response in Ulcerative Colitis (TOUR): Early Response After Initiation of Tofacitinib Therapy in a Real-world Setting
Long, Millie D; Afzali, Anita; Fischer, Monika; Hudesman, David; Abdalla, Maisa; McCabe, Robert; Cohen, Benjamin L; Ungaro, Ryan C; Harlan, Will; Hanson, John; Konijeti, Gauree; Polyak, Steven; Ritter, Timothy; Salzberg, Bruce; Seminerio, Jennifer; English, Emily; Zhang, Xian; Sharma, Puza P; Herfarth, Hans H
BACKGROUND:Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study. METHODS:Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI <5) and remission (SCCAI â‰¤2) by clinical factors. RESULTS:Of all included patients (n = 96), 67% had failed â‰¥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (-1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (-0.3; P < .003), bleeding (-0.3; P < .0002) and urgency (-0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low. CONCLUSIONS:In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.
Long-Term Improvement in the Patient-Reported Outcomes of Rectal Bleeding, Stool Frequency, and Health-Related Quality of Life with Tofacitinib in the Ulcerative Colitis OCTAVE Clinical Program
Hudesman, David P; Torres, Joana; Salese, Leonardo; Woolcott, John C; Mundayat, Rajiv; Su, Chinyu; Mosli, Mahmoud H; Allegretti, Jessica R
BACKGROUND:Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The tofacitinib OCTAVE clinical program included phase III induction (OCTAVE Induction 1 and 2) and maintenance (OCTAVE Sustain) studies, and an open-label, long-term extension study (OCTAVE Open). OBJECTIVE:This post hoc analysis assessed selected long-term, disease-specific patient-reported outcome (PRO) and health-related quality-of-life (HRQoL) measurements in patients with UC receiving tofacitinib in the OCTAVE clinical program. METHODS:Analyses included patients from OCTAVE Open assigned to tofacitinib 5Â mg twice daily (subpopulation in remission at Week 52 of OCTAVE Sustain). OCTAVE Open data from the final analyses are shown to Month 48. Endpoints included rectal bleeding subscore (RBS)Â =Â 0, stool frequency subscore (SFS) â‰¤Â 1, and HRQoL measure, Inflammatory Bowel Disease Questionnaire (IBDQ) remission (IBDQ total score â‰¥ 170); with non-responder imputation for missing data at all visits, and last observation carried forward for visits after a patient advanced to the next study (NRI-LOCF). Observed cases were also assessed. RESULTS:At Month 48, of 175 patients, 95 (54.3%) and 96 (54.9%) achieved/maintained RBSÂ =Â 0 and SFSÂ â‰¤Â 1, respectively (NRI-LOCF). Additionally, 93 (53.1%) patients achieved/maintained IBDQ remission at Month 48 (NRI-LOCF). CONCLUSIONS:Among patients who entered OCTAVE Open in remission, most maintained normalization of rectal bleeding and improvement in stool frequency for â‰¤ 4Â years of follow-up in OCTAVE Open. IBDQ remission was also generally maintained in OCTAVE Open. These data show robust maintenance of key UC PROs and durability of response with tofacitinib 5 mg twice daily. TRIAL REGISTRATION/BACKGROUND:http://www. CLINICALTRIALS/RESULTS:gov (NCT01465763 [21/10/2011]; NCT01458951 [21/10/2011]; NCT01458574 [21/10/2011]; NCT01470612 [21/10/2011]).
A Joint Effort: Improving the Identification of Spondyloarthritis in Patients With Inflammatory Bowel Disease [Editorial]
Hong, Simon J; Hudesman, David P; Scher, Jose U
In individuals with inflammatory bowel disease (IBD), extraintestinal manifestations (EIMs) represent a significant burden of illness, with reported prevalence rates of up to 50%.1 Of the various types of EIMs, the most commonly involved organ system is the musculoskeletal system.
The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results from the SUCCESS Consortium
Johnson, Amanda M; Barsky, Maria; Ahmed, Waseem; Zullow, Samantha; Galati, Jonathan; Jairath, Vipul; Narula, Neeraj; Peerani, Farhad; Click, Benjamin H; Coburn, Elliot S; Dang, ThucNhi Tran; Gold, Stephanie; Agrawal, Manasi; Garg, Rajat; Aggarwal, Manik; Mohammad, Danah; Halloran, Brendan; Kochhar, Gursimran S; Todorowski, Hannah; Ud Din, Nabeeha Mohy; Izanec, James; Teeple, Amanda; Gasink, Chris; Muser, Erik; Ding, Zhijie; Swaminath, Arun; Lakhani, Komal; Hogan, Dan; Datta, Samit; Ungaro, Ryan C; Boland, Brigid S; Bohm, Matthew; Fischer, Monika; Sagi, Sashidhar; Afzali, Anita; Ullman, Thomas; Lawlor, Garrett; Baumgart, Daniel C; Chang, Shannon; Hudesman, David; Lukin, Dana; Scherl, Ellen J; Colombel, Jean-Frederic; Sands, Bruce E; Siegel, Corey A; Regueiro, Miguel; Sandborn, William J; Bruining, David; Kane, Sunanda; Loftus, Edward V; Dulai, Parambir S
OBJECTIVE:We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS:This study utilized a retrospective, multicenter, multinational, consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remission were assessed using time-to-event and clinical predictors were assessed by multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS:A total of 1113 patients (51.8% female, 90% prior anti-TNF exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remission at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naÃ¯ve patients achieved significantly higher rates of clinical and endoscopic remission at 63% and 55%, respectively. On multivariable analyses, prior anti-TNF (HR, 0.72; 95% CI, 0.49-0.99) and vedolizumab exposure (HR, 0.65; 95% CI, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77/102 (75%) underwent dose optimization, and 44/77 (57%) achieved clinical response. An additional 152/681 (22.3%) patients were dose optimized as a result of primary non- or incomplete response to UST, of whom 40.1% (61/152) responded. Serious infections occurred in 3.4% of patients, while other non-infectious adverse events [lymphoma (n=1), arthralgia (n=6), rash (n=6), headache (n=3), hepatitis (n=3), hair loss (n=3), neuropathy (n=1), and vasculitis (n=1)] occurred in 2.4% of patients. CONCLUSIONS:UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in bio-naive patients, and dose escalation may recapture clinical response.
Histologic Predictors of Clinical Outcomes and Healthcare Utilization in Patients With Ileal Pouch-Anal Anastomosis
Chang, Shannon; Hong, Simon; Hudesman, David; Remzi, Feza; Sun, Katherine; Cao, Wenqing; Tarik Kani, H; Axelrad, Jordan; Sarkar, Suparna A
BACKGROUND:The prognostic significance of histology in ileal pouch-anal anastomosis (IPAA) remains unclear. The aim of this study was to evaluate if histologic variables are predictive of IPAA clinical outcomes and healthcare utilization. METHODS:This was a retrospective cohort study of patients with IPAA undergoing surveillance pouchoscopy at a tertiary care institution. Pouch body biopsies were reviewed by gastrointestinal pathologists, who were blinded to clinical outcomes, for histologic features of acute or chronic inflammation. Charts were reviewed for clinical outcomes including development of acute pouchitis, chronic pouchitis, biologic or small molecule initiation, hospitalizations, and surgery. Predictors of outcomes were analyzed using univariable and multivariable logistic and Cox regression. RESULTS:A total of 167 patients undergoing surveillance pouchoscopy were included. Polymorphonuclear leukocytes (odds ratio [OR], 1.67), ulceration and erosion (OR, 2.44), chronic inflammation (OR, 1.97), and crypt distortion (OR, 1.89) were associated with future biologic or small molecule initiation for chronic pouchitis. Loss of goblet cells was associated with development of chronic pouchitis (OR, 4.65). Pyloric gland metaplasia was associated with hospitalizations (OR, 5.24). No histologic variables were predictive of development of acute pouchitis or surgery. In an exploratory subgroup analysis of new IPAA (<1 year), loss of goblet cells was associated with acute pouchitis (OR, 14.86) and chronic pouchitis (OR, 12.56). Pyloric gland metaplasia was again associated with hospitalizations (OR, 13.99). CONCLUSIONS:Histologic findings may be predictive of IPAA outcomes. Pathologists should incorporate key histologic variables into pouchoscopy pathology reports. Clinicians may need to more closely monitor IPAA patients with significant histologic findings.
Ustekinumab and Vedolizumab Are Not Associated With Subsequent Cancer in IBD Patients with Prior Malignancy
Hong, Simon J; Zenger, Cameron; Pecoriello, Jillian; Pang, Alice; Vallely, Margaret; Hudesman, David P; Chang, Shannon; Axelrad, Jordan E
BACKGROUND:There is little data regarding the risk of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a prior history of cancer who are exposed to ustekinumab or vedolizumab. We assessed the risk of subsequent cancer in patients exposed to these agents. METHODS:We performed a retrospective cohort study of patients with IBD and a history of cancer at an academic medical center between January 2013 and December 2020. We collected data on demographics, IBD and cancer disease characteristics, and drug exposures. The primary exposure was immunosuppressive therapy after diagnosis of cancer. The primary outcome was interval development of new or recurrent cancer. RESULTS:Of 390 patients with IBD and a previous history of cancer, 37 were exposed to vedolizumab, 14 ustekinumab, 41 antitumor necrosis factor (anti-TNF), and 31 immunomodulator; and 267 were not exposed to immunosuppression following cancer diagnosis. During a total median follow-up time of 52 months, 81 (20%) patients developed subsequent cancer: 6 (16%) were exposed to vedolizumab, 2 (14%) to ustekinumab, 3 (10%) to immunomodulators, 12 (29%) to anti-TNF, and 56 (21%) with no immunosuppression (P = .41). In a multivariable Cox model adjusting for age, IBD subtype, smoking, cancer recurrence risk, and cancer stage, there was no increase in subsequent cancer with vedolizumab (adjusted hazard ratio, 1.36; 95% CI, 0.27-7.01) or ustekinumab (adjusted hazard ratio, 0.96; 95% CI, 0.17-5.41). Patients with more than 1 biologic exposure also did not have an increased risk of subsequent cancer. CONCLUSIONS:Exposure to ustekinumab or vedolizumab in patients with IBD and a prior history of cancer does not appear to be associated with an increased risk of subsequent new or recurrent cancer.
Increasing rates of venous thromboembolism among hospitalised patients with inflammatory bowel disease: a nationwide analysis
Faye, Adam S; Lee, Kate E; Dodson, John; Chodosh, Joshua; Hudesman, David; Remzi, Feza; Wright, Jason D; Friedman, Alexander M; Shaukat, Aasma; Wen, Timothy
BACKGROUND:Venous thromboembolism (VTE) is a significant cause of morbidity and mortality among patients with inflammatory bowel disease (IBD). However, data on national trends remain limited. AIMS/OBJECTIVE:To assess national trends in VTE-associated hospitalisations among patients with IBD as well as risk factors for, and mortality associated with, these events METHODS: Using the U.S. Nationwide Inpatient Sample from 2000-2018, temporal trends in VTE were assessed using the National Cancer Institute's Joinpoint Regression Program with estimates presented as the average annual percent change (AAPC) with 95% confidence intervals (CIs). RESULTS:Between 2000 and 2018, there were 4,859,728 hospitalisations among patients with IBD, with 128,236 (2.6%) having a VTE, and 6352 associated deaths. The rate of VTE among hospitalised patients with IBD increased from 192 to 295 cases per 10,000 hospitalisations (AAPC 2.4%, 95%CI 1.4%, 3.4%, pâ€‰<â€‰0.001), and remained significant when stratified by ulcerative colitis (UC) and Crohn's disease as well as by deep vein thrombosis and pulmonary embolism. On multivariable analysis, increasing age, male sex, UC (aOR: 1.30, 95%CI 1.26, 1.33), identifying as non-Hispanic Black, and chronic corticosteroid use (aOR: 1.22, 95%CI 1.16, 1.29) were associated with an increased risk of a VTE-associated hospitalisation. CONCLUSION/CONCLUSIONS:Rates of VTE-associated hospitalisations are increasing among patients with IBD. Continued efforts need to be placed on education and risk reduction.
EXTENDED THERAPY WITH OZANIMOD FOR DELAYED RESPONDERS TO OZANIMOD IN MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: DATA FROM THE TRUE NORTH OPEN-LABEL EXTENSION STUDY [Meeting Abstract]
Panaccione, R; Afzali, A; Hudesman, D; Lawlor, G; Osterman, M T; Memaj, A; Regueiro, M; Ghosh, S
Introduction: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, is approved in the US and Europe for the treatment of moderately to severely active ulcerative colitis (UC) in adults. In the phase 3, randomized, double-blind, placebocontrolled True North study (NCT02435992), ozanimod led to statistically significant improvements in clinical, endoscopic, and histologic outcomes at Weeks 10 and 52 compared to placebo in patients with moderately to severely active UC. Aims & Methods: The aims of this analysis were to describe the characteristics of patients who did not achieve clinical response at Week 10 of ozanimod induction in True North, and to determine the proportion of patients who benefited from additional ozanimod treatment. In True North, patients were randomized 2:1 to receive double-blind ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or placebo (Cohort 1) or open-label ozanimod 0.92 mg (Cohort 2). Those who did not have clinical response at Week 10 were eligible to receive ozanimod in an open-label extension (OLE). This analysis examined patients in Cohort 1 who were treated with double-blind ozanimod but did not achieve clinical response at Week 10 and subsequently continued ozanimod in the OLE (n=150). Demographics and disease characteristics were assessed at induction baseline, and disease activity was assessed at induction baseline and Week 10 (baseline for OLE entry). Symptomatic clinical response, defined as a reduction from induction baseline in the partial Mayo score of >=1 point and >=30% with at least 1 point decrease in rectal bleeding subscore (RBS) or absolute RBS <=1, during the OLE was determined using nonresponder imputation.
Result(s): A total of 150 patients who received ozanimod in Cohort 1 did not achieve clinical response at Week 10 of the induction period and entered the OLE. These patients had a mean age of 38.6 years, 66.0% were men, 44.0% had extensive disease, and the mean total Mayo score at baseline was 9.2 points. Despite not achieving clinical response at Week 10, these patients had a mean total Mayo score that improved from 9.2 at baseline to 8.5 at Week 10, with a larger percentage of patients having an RBS of 0 at Week 10 (23.3%; 35/150) than at baseline (0.7%; 1/150). Almost half of the patients who did not achieve clinical response at Week 10 had symptomatic clinical response at OLE Week 10 (48.7%; 73/150), with 44% (66/150) achieving symptomatic clinical response at OLE Week 5.
Conclusion(s): This analysis of the True North OLE found that approximately half of the patients who failed to achieve a clinical response after 10 weeks of ozanimod treatment benefited from an additional 5 to 10 weeks of ozanimod therapy
Methotrexate and TNF inhibitors affect long-term immunogenicity to COVID-19 vaccination in patients with immune-mediated inflammatory disease
Haberman, Rebecca H; Um, Seungha; Axelrad, Jordan E; Blank, Rebecca B; Uddin, Zakwan; Catron, Sydney; Neimann, Andrea L; Mulligan, Mark J; Herat, Ramin Sedaghat; Hong, Simon J; Chang, Shannon; Myrtaj, Arnold; Ghiasian, Ghoncheh; Izmirly, Peter M; Saxena, Amit; Solomon, Gary; Azar, Natalie; Samuels, Jonathan; Golden, Brian D; Rackoff, Paula; Adhikari, Samrachana; Hudesman, David P; Scher, Jose U