Response to Upadacitinib in Patients with Inflammatory Bowel Disease Previously Treated with Tofacitinib.

BACKGROUND AND AIMS: Upadacitinib is an oral selective Janus kinase (JAK) inhibitor approved in the United States for ulcerative colitis (UC) and Crohn's disease (CD). However, data regarding its use following prior treatment with the JAK inhibitor tofacitinib is sparse. As such, we aimed to evaluate the effectiveness of upadacitinib therapy following tofacitinib exposure. METHODS: This is a multicenter retrospective study of patients with confirmed diagnosis of UC or CD who received upadacitinib after prior treatment with tofacitinib. The primary outcome of interest was patient-reported clinical improvement at first follow-up. Secondary outcome included discontinuation of corticosteroids, change in Mayo Endoscopic Score (MES) and change in inflammatory marker levels. RESULTS: A total of 31 patients met the inclusion criteria. Following upadacitinib initiation, 80.6% (25/31) of patients had clinical improvement, including 92.3% (24/26) of those with UC and 20% (1/5) of those with CD. Of the patients initially requiring systemic corticosteroid therapy, 80% (12/15) were able to discontinue corticosteroids. Individual mean change of fecal calprotectin was a decrease of 501.5 mcg/g ± 608.6 (P value = 0.01) while C-reactive protein decreased on average by 14.8 mg/L ± 25.3 (P value = 0.02) compared to when patients were on tofacitinib, with significant changes observed in the UC cohort. In patients with UC, individual MES after initiating upadacitinib decreased compared to prior to tofacitinib discontinuation (P value = 0.04). CONCLUSION: Our study demonstrates that upadacitinib therapy in patients with prior tofacitinib exposure is associated with clinical improvement and a decrease in objective markers of inflammation in patients with UC.

The Effect of the Coronavirus (COVID-19) Pandemic on Gender and Medical School Diversity in Gastroenterology Fellowship Matching.

Background and Aims: The COVID-19 pandemic brought unprecedented changes to the medical field, including the gastroenterology (GI) fellowship application process. This study aimed to assess the impact of the pandemic on GI fellowship applications, with a focus on applicants' gender and medical school training type. Methods: Data from the GI match results for 2018-2022 were collected, including the number and percentage of matched applicants per year, categorized by gender, US medical graduates, international medical graduates (IMGs), and Doctors of Osteopathic Medicine (DOs). Statistical analyses were performed to evaluate trends and changes in matching rates, both before and during the pandemic. Results: There was a significant increase in the number of females matching into GI fellowships over the 5-year period. DOs also witnessed a significant increase in matching rates during the COVID-19-impacted years (2021-2022). However, no significant changes were observed for US medical graduates and IMGs. Conclusion: The study highlights positive trends in gender and DO representation in GI fellowships. Despite these improvements, gender disparities persist, necessitating continued efforts to promote diversity and equity in the field. Additionally, challenges for IMGs remain, requiring attention to structural barriers. The long-term effects of the pandemic on fellowship matching and diversity warrant further investigation to inform future policies and practices in GI training programs.

Metformin Is Associated With Improved Inflammatory Bowel Disease Outcomes in Patients With Type 2 Diabetes Mellitus: A Propensity-Matched Cohort Study.

BACKGROUND: Metformin exerts anti-inflammatory properties through a positive effect on oxidative stress, gut barrier integrity, and the gut microbiota. Our aim was to evaluate the influence of metformin on inflammatory bowel disease (IBD) outcomes in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a retrospective cohort study using the TriNetX database in patients with IBD and T2DM who initiated metformin vs oral hypoglycemics or insulin (control cohort) between August 31, 2002, and August 31, 2022. One-to-one propensity score matching was performed. Primary outcomes were need for intravenous (IV) steroid use or IBD-related surgery within 1, 2, and 3 years after metformin initiation. RESULTS: Our cohorts included 1323 patients with ulcerative colitis (UC) (mean age 58.7 ±â€…12.2 years, 50.1% female, 77.3% White) and 1278 patients with Crohn's disease (CD) (mean age 56.3 ±â€…12.6 years, 58.2% female, 76.5% White). At 1 year, patients with UC and CD were less likely to require IV steroids (UC: adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.34-0.59; P < .01; CD: aOR, 0.67; 95% CI, 0.53-0.85; P < .01). The decreased need for IV steroids persisted in all metformin groups at 2 and 3 years. Patients with CD were at a lower risk for IBD-related surgery at year 1 (aOR, 0.5; 95% CI, 0.31-0.81; P < .01), and this finding persisted at 3 years (aOR, 0.62; 95% CI, 0.43-0.89; P < .01). Metformin did not affect risk for surgery in patients with UC. CONCLUSIONS: Patients with IBD and T2DM on metformin had a decreased likelihood of worse IBD outcomes.

Our study shows that metformin is associated with decreased risk of corticosteroids in patients with ulcerative colitis and Crohn's disease and decreased risk of surgery in patients with Crohn's disease.

Single center assessment of the role of Oakland score among patients admitted for acute lower gastrointestinal bleeding.

BACKGROUND/OBJECTIVES: The Oakland score was developed to predict safe discharge in patients who present to the emergency department with lower gastrointestinal bleeding (LGIB). In this study, we retrospectively evaluated if this score can be implemented to assess safe discharge (score ≤ 10) at WellStar Atlanta Medical Center (WAMC). METHODS: A retrospective cohort study of 108 patients admitted at WAMC from January 1, 2020 to December 30, 2021 was performed. Patients with LGIB based on the ICD-10 codes were included. Oakland score was calculated using 7 variables (age, sex, previous LGIB, digital rectal exam, pulse, systolic blood pressure (SBP) and hemoglobin (Hgb)) for all patients at admission and discharge from the hospital. The total score ranges from 0 to 35 and a score of ≤ 10 is a cut-off that has been shown to predict safe discharge. Hgb and SBP are the main contributors to the score, where lower values correspond to a higher Oakland score. Descriptive and multivariate analysis was performed using SPSS 23 software. RESULTS: A total of 108 patients met the inclusion criteria, 53 (49.1%) were female with racial distribution was as follows: 89 (82.4%) African Americans, 17 (15.7%) Caucasian, and 2 (1.9%) others. Colonoscopy was performed in 69.4% patients; and 61.1% patients required blood transfusion during hospitalization. Mean SBP records at admission and discharge were 129.0 (95% CI, 124.0-134.1) and 130.7 (95% CI,125.7-135.8), respectively. The majority (59.2%) of patients had baseline anemia and the mean Hgb values were 11.0 (95% CI, 10.5-11.5) g/dL at baseline prior to hospitalization, 8.8 (95% CI, 8.2-9.5) g/dL on arrival and 9.4 (95% CI, 9.0-9.7) g/dL at discharge from hospital. On admission, 100/108 (92.6%) of patients had an Oakland score of > 10 of which almost all patients (104/108 (96.2%)) continued to have persistent elevation of Oakland Score greater than 10 at discharge. Even though, the mean Oakland score improved from 21.7 (95% CI, 20.4-23.1) of the day of arrival to 20.3 (95% CI, 19.4-21.2) at discharge, only 4/108 (3.7%) of patients had an Oakland score of ≤ 10 at discharge. Despite this, only 9/108 (8.33%) required readmission for LGIB during a 1-year follow-up. We found that history of admission for previous LGIB was associated with readmission with adjusted odds ratio 4.42 (95% CI, 1.010-19.348, p = 0.048). CONCLUSIONS: In this study, nearly all patients who had Oakland score of > 10 at admission continued to have a score above 10 at discharge. If the Oakland Score was used as the sole criteria for discharge most patients would not have met discharge criteria. Interestingly, most of these patients did not require readmission despite an elevated Oakland score at time of discharge, indicating the Oakland score did not really predict safe discharge. A potential confounder was the Oakland score did not consider baseline anemia during calculation. A prospective study to evaluate a modified Oakland score that considers baseline anemia could add value in this patient population.

Sirolimus Use in Refractory Crohn's Disease.

Treatment options for patients with inflammatory bowel disease are constantly evolving; however, medication-refractory disease remains an issue. Pediatric case series show the potential benefit of sirolimus therapy in refractory Crohn's disease (CD); however, limited data exist in adult patients. As such, we retrospectively identified and report clinical outcomes for 4 patients prescribed sirolimus for treatment of refractory CD. Despite a median sirolimus therapy duration of 524 days and some therapeutic benefits, all patients discontinued therapy due to adverse effects. Our findings suggest that while sirolimus may have clinical utility, its role may be limited by treatment-derived adverse effects.

Utility of a Third Heplisav-B Dose in Patients With Inflammatory Bowel Disease Without Immunity After 2-Dose Heplisav-B Vaccination.

INTRODUCTION: Hepatitis B virus (HBV) vaccination is recommended in patients with inflammatory bowel disease (IBD). Although the 2-dose Heplisav-B vaccine has proven effective, more than 20% of patients with IBD do not seroconvert. We prospectively evaluated the effectiveness of a third Heplisav-B dose in patients with IBD lacking HBV immunity despite 2-dose vaccination. METHODS: Adults with IBD who had received 2-dose Heplisav-B vaccination between 2018 and 2023 were identified. Seroconversion was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L measured at ≥4 weeks after vaccination. Patients who did not seroconvert were prospectively offered a third Heplisav-B dose, followed by repeat HBsAb measurement. Demographic, clinical, medication, and vaccination data were compared between those who did and did not seroconvert. RESULTS: Of 192 patients identified, 71.9% (138/192) seroconverted after 2-dose Heplisav-B vaccination. The 54 patients (28.1%) who did not seroconvert were more likely to be male, have diabetes, chronic kidney disease, or elevated Charlson Comorbidity Index. Of the 54 patients, 30 (55.6%) elected to receive a third Heplisav-B dose, with 56.7% (17/30) achieving seroconversion (median HBsAb titer 376 IU/L, IQR 47-1,000 IU/L) despite a median intervaccination time of 416 days (IQR 90.8-667.8). No differences were noted between patients who did vs did not seroconvert after third-dose vaccination. DISCUSSION: In patients with IBD lacking HBV immunity despite 2-dose Heplisav-B vaccination, administration of a third dose resulted in a 56.7% seroconversion rate. Our results suggest that administration of an additional Heplisav-B dose may be an effective strategy in patients lacking immunity despite primary 2-dose vaccination.

Improved Outcomes Associated With Teduglutide Use in Patients With Both Short Bowel Syndrome and Crohn's Disease.

Introduction: Crohn's disease (CD) with short bowel syndrome (SBS) can present as chronic intestinal failure (CIF) often requiring nutritional support. Teduglutide is a treatment option for these patients. We investigated clinical outcomes of CD-CIF patients with SBS treated with teduglutide. Methods: Adults with CD-CIF and SBS who received teduglutide were identified at a tertiary care academic center between 2012 and 2023. Data was collected retrospectively. Primary outcome measured was reduction in parenteral support (PS) by ≥20% volume, with PS defined as utilization of parenteral nutrition (PN) or intravenous fluids (IVF). Several secondary outcomes included immunosuppressive medication changes, subjective symptom improvement, and stool output. Results: We identified 32 patients with CD-CIF and SBS receiving teduglutide. Comparing clinical outcomes before and after teduglutide, 26 of 32 patients achieved the primary outcome of ≥20% PS reduction. A decrease was seen in patients requiring PN + IVF, with corresponding increases in patients requiring PN only and IVF only. Among all 3 groups, a total of 23 patients received PN prior to teduglutide, which decreased to 14 following teduglutide. Weekly PN volume reduced from 7.00 to 3.55 L and weekly frequency decreased from 7.00 to 3.00 instances (P < .01). Reductions in weekly volume and frequency were observed among all patients receiving IVF support (25 vs 15). Secondary outcomes showed improvement in patient reported subjective symptoms (84.4%), stool output (90.6%), patients meeting criteria for diarrhea/high ostomy output (27 vs 14), and use of unique antidiarrheal medications (3.0 vs 2.0). Conclusions: This retrospective case series demonstrated improved clinical outcomes in patients with CD-CIF and SBS treated with teduglutide resulting in decreased PS requirements, antidiarrheal medications requirement, and stool output without significant effects on immunosuppressive therapy.

Electronic Health Record Burden Among Gastroenterology Providers Associated With Subspecialty and Training.

INTRODUCTION: Use of the electronic health record (EHR) has become increasingly widespread. Higher EHR burden is associated with burnout, but this has not been specifically investigated among gastroenterology (GI) providers. METHODS: We retrospectively collected measures of EHR use for outpatient GI providers during a 6-month period. We compared metrics across provider sex, subspecialty, and training (physicians vs nonphysician providers [NPPs]). RESULTS: Data collected represented more than 16,000 appointments from 41 providers across the Division of Gastroenterology and Hepatology. Inflammatory bowel disease (IBD) and hepatology specialists spent more time per appointment in the EHR, clinical review, and outside regular hours compared with other subspecialists. NPPs spent more EHR time than physicians. DISCUSSION: IBD and hepatology specialists and NPPs may have disproportionally high EHR burden. More work is needed to understand differences in provider workload to combat burnout.

Clostridium difficile Infection in Patients with Ulcerative Colitis Treated with Tofacitinib in the Ulcerative Colitis Program.

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.

The incidence of Clostridium difficile infection in the tofacitinib ulcerative colitis clinical program was evaluated. C. difficile infection among patients with ulcerative colitis receiving tofacitinib were infrequent; cases were mild­moderate in severity, and most resolved with treatment.

Association of C-reactive Protein and Partial Mayo Score With Response to Tofacitinib Induction Therapy: Results From the Ulcerative Colitis Clinical Program.

BACKGROUND: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). These post hoc analyses assessed associations between C-reactive protein (CRP), partial Mayo score (PMS), and efficacy outcomes during tofacitinib induction in UC. METHODS: Patients received tofacitinib 10 mg twice daily (BID) in an 8-week, phase 2 induction study and 2 identical, 8-week, phase 3 induction studies (OCTAVE Induction 1&2); induction nonresponders (IndNR) received an additional 8 weeks of tofacitinib 10 mg BID in an open-label, long-term extension study. Associations between CRP and PMS, and efficacy outcomes (clinical response, clinical remission, endoscopic improvement, and endoscopic remission) were analyzed using univariate and multivariable logistic regression and receiver operating characteristic curves. RESULTS: Changes from baseline in the logarithm of CRP ([log]CRP) and PMS at week 4 were associated with clinical response at week 8 (univariate: per unit, odds ratio [OR], 0.55 [95% confidence interval (CI), 0.48-0.62]; and 0.42 [0.37-0.47], respectively). Among IndNR, change from baseline in PMS at week 8 was associated with clinical response at week 16 (univariate: per unit, OR, 0.59; 95% CI, 0.46-0.75). C-reactive protein at week 4 (area under the curve [AUC] > 0.6) and PMS at weeks 2 and 4 (AUC, > 0.7) generally exhibited predictive value for week 8 efficacy outcomes. CONCLUSIONS: Patients who achieved clinical response at week 8 had larger decreases in CRP and PMS at week 4 than patients who did not. IndNR who achieved clinical response at week 16 with extended tofacitinib induction had a larger decrease in PMS at week 8 vs those who did not. ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01470612.

Early decreases in partial Mayo score and C-reactive protein were found to be associated with achieving efficacy outcomes following tofacitinib 10 mg twice daily induction therapy in the ulcerative colitis clinical program.

Creation of an Inflammatory Bowel Disease Referral Pathway for Identifying Patients Who Would Benefit From Inflammatory Bowel Disease Specialist Consultation.

BACKGROUND: Recommendations regarding signs and symptoms that should prompt referral of patients with inflammatory bowel disease (IBD) to an IBD specialist for a consultation could serve to improve the quality of care for these patients. Our aim was to develop a consult care pathway consisting of clinical features related to IBD that should prompt appropriate consultation. METHODS: A scoping literature review was performed to identify clinical features that should prompt consultation with an IBD specialist. A panel of 11 experts was convened over 4 meetings to develop a consult care pathway using the RAND/UCLA Appropriateness Method. Items identified via scoping review were ranked and were divided into major and minor criteria. Additionally, a literature and panel review was conducted assessing potential barriers and facilitators to implementing the consult care pathway. RESULTS: Of 43 features assessed, 13 were included in the care pathway as major criteria and 15 were included as minor criteria. Experts agreed that stratification into major criteria and minor criteria was appropriate and that 1 major or 2 or more minor criteria should be required to consider consultation. The greatest barrier to implementation was considered to be organizational resource allocation, while endorsements by national gastroenterology and general medicine societies were considered to be the strongest facilitator. CONCLUSIONS: This novel referral care pathway identifies key criteria that could be used to triage patients with IBD who would benefit from IBD specialist consultation. Future research will be required to validate these findings and assess the impact of implementing this pathway in routine IBD-related care.

This study aimed to develop a care pathway consisting of clinical features that should prompt inflammatory bowel disease expert consultation. A scoping literature review was performed to identify attributes, and an expert panel finalized the structure and components of the pathway.

Incidence, Burden, and Predictors of Readmission for Acute Alcoholic Pancreatitis: A National Analysis over 11 Months.

BACKGROUND/OBJECTIVES: Data regarding incidence, health-care burden, and predictors for readmission in patients with acute alcoholic pancreatitis (AAP) is scarce. We aim to identify incidence, health-care burden, and predictors of readmission over an 11-month period. METHODS: Retrospective cohort study using the 2016 National Readmission Database of adult patients admitted with a principal diagnosis of AAP in January and 11-month readmission follow up for all-cause readmission. Incidence of all-cause readmission, mortality rate, morbidity, length of stay (LOS), total hospitalization charges and costs were evaluated. Independent risk factors for all-cause readmission were identified using a Cox multivariate logistic regression analysis. RESULTS: A total of 6633 patients were included in the study. The mean age was 45.7 years and 28.9% of patients were female. 73.1% of patients had a modified BISAP score of 0. The 11-month readmission rate was 43.1%. The main cause of readmission was another episode of AAP. The mortality rate of readmission was 0.5% and the mortality rate during the index admission (IA) was 1.1% (P = 0.03). The mean LOS, total hospitalization charges and costs for readmission were 4.5 days, $34,307 and $8958, respectively. Independent predictors of readmission were Charlson Comorbidity Index score of ≥ 3, associated chronic alcoholic pancreatitis, and chronic pancreatitis (CP) from other causes. CONCLUSION: Among patients admitted with AAP, the 11-month readmission rate was 43.1%. Over one-third of readmissions were due to another episode of AAP. Readmission associated with significant resource utilization. Special attention should be placed in patients with underlying CP due to the increased risk of readmission.

Cronkhite-Canada Syndrome: A Rare Case of Chronic Diarrhea With Ectodermal Changes.

Cronkhite-Canada syndrome (CCS) is a rare cause of chronic diarrhea and malabsorption where patients develop multiple polyps throughout the gastrointestinal (GI) tract, accompanied by ectodermal changes. Due to its rarity, early detection and diagnosis are challenging for physicians, inevitably leading to high mortality. CCS patients have a higher prevalence of GI cancer compared to the general population. Therefore, a follow-up endoscopy is necessary. We report a new case of CCS in an 85-year-old male who presented with chronic watery diarrhea, weight loss, and skin changes including alopecia, nail dystrophy, and hyperpigmentation. Laboratory results showed anemia and hypoalbuminemia. He underwent an endoscopy that found diffuse edematous polyposis in the stomach, duodenum, terminal ileum, and large intestine. The biopsy result confirmed the diagnosis of CCS. The patient received supportive treatment with total parenteral nutrition with improvement in his symptoms. He was placed on corticosteroid taper and azathioprine upon discharge. At the one-year follow-up, he was found in endoscopic remission.

Ustekinumab-Associated Posterior Reversible Encephalopathy Syndrome in a Patient With Crohn's Disease.

Ustekinumab is a common biologic therapy for the treatment of inflammatory bowel disease. Posterior reversible encephalopathy syndrome (PRES) is an uncommon condition consisting of a constellation of neurologic findings and characteristic findings on imaging. The association between ustekinumab and PRES is not well defined. We present a case of PRES in a patient with Crohn's disease on ustekinumab and a brief review of the literature. Clinicians should be aware of this rare complication with high morbidity in patients with inflammatory bowel disease on ustekinumab and be able to recognize clinical symptoms.

Transient Neurogenic Bowel Dysfunction in a Case of Cocaine-Induced Spinal Cord Infarction.

A 23-year-old male presented to the hospital with altered mental status (AMS) and hypoglycemia requiring admission to the ICU. He had improvement in AMS after administration of dextrose 50% and naloxone and endorsed the use of alcohol, cocaine, and marijuana that morning. It was confirmed with a positive urine toxicology screen for cocaine and tetrahydrocannabinol (THC). During this hospital admission, his physical examination was notable for paraplegia with no motor abilities from the T6 dermatome and below. Sensation was intact throughout all dermatomes but he was found to have urinary retention. Workup included an abnormal MRI showing T2 signal spanning from T2-T8, raising a high suspicion of a probable acute ischemic spinal cord infarction. Several hours after admission, the patient began to exhibit the first signs of abnormal bowel function and experienced one episode of hematemesis, prolonging his ICU stay.

Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study.

BACKGROUND & AIMS: Despite rescue therapy, more than 30% of patients with acute severe ulcerative colitis (ASUC) require colectomy. Tofacitinib is a rapidly acting Janus kinase inhibitor with proven efficacy in ulcerative colitis. Tofacitinib may provide additional means for preventing colectomy in patients with ASUC. METHODS: A retrospective case-control study was performed evaluating the efficacy of tofacitinib induction in biologic-experienced patients admitted with ASUC requiring intravenous corticosteroids. Tofacitinib patients were matched 1:3 to controls according to gender and date of admission. Using Cox regression adjusted for disease severity, we estimated the 90-day risk of colectomy. Rates of complications and steroid dependence were examined as secondary outcomes. RESULTS: Forty patients who received tofacitinib were matched 1:3 to controls (n = 113). Tofacitinib was protective against colectomy at 90 days compared with matched controls (hazard ratio [HR], 0.28, 95% confidence interval [CI], 0.10-0.81; P = .018). When stratifying according to treatment dose, 10 mg three times daily (HR, 0.11; 95% CI, 0.02-0.56; P = .008) was protective, whereas 10 mg twice daily was not significantly protective (HR, 0.66; 95% CI, 0.21-2.09; P = .5). Rate of complications and steroid dependence were similar between tofacitinib and controls. CONCLUSIONS: Tofacitinib with concomitant intravenous corticosteroids may be an effective induction strategy in biologic-experienced patients hospitalized with ASUC. Prospective trials are needed to identify the safety, optimal dose, frequency, and duration of tofacitinib for ASUC.