Introduction

Tofacitinib is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC). The recommended induction scheme is 10 mg twice daily (BID) for at least 8 weeks followed by a maintenance dose of 5 mg BID. However, some patients require 10mg bid, for 16 weeks at the induction phase. Our study aimed to assess the demographics and disease characteristics of such patients and their outcome at 24 weeks.

Aims & Methods

This was a multicenter, retrospective, observational study which included patients with moderate to severe UC, who received induction therapy with Tofacitinib 10mg bid for a 16-week period. Data were collected between July 2018 and November 2022. The primary objective was disease outcome, defined as clinical remission and/or the need of steroids. Secondary outcomes were treatment withdrawal, treatment de-escalation and adverse events.

Results

In total 31 patients, are currently enrolled in our study, from 10 IBD centres [males: 51.6%, mean age at study entry: 40.0 years, median disease duration: 7 years]. Patient demographic and clinical characteristics at baseline are shown in table 1. Four patients (12.9%) discontinued treatment before week 24, due to inadequate response. De-escalation of dosing to 5mg bid tofacitinib was attempted in 13 of 27 patients (48.1%) and was successful in 7 patients (53.8%) who maintained clinical response until week 24 of the study. Of the other 6 out of 13 patients, 6 patients received again the higher dose (10 mg bid) and regained response and only one patient discontinued treatment. Overall, 85.7% (6/7) of the patients who received tofacitinib 5mg bid and 66.7% (14/21) who received 10mg bid at 24 weeks, had received more than one biologic prior to tofacitinib (P=0.34). At week 24, the partial Mayo score was available in 26 patients; 13 patients were in steroid-free clinical remission (pMayo <2). Twelve patients had mild active disease (pMayo 2-4) and 9 of them had stopped steroids. No major adverse events were observed during the entire observation period.

Conclusion

In a real-world setting, a 24-week treatment with tofacitinib 10mg BID is safe and the majority of patients achieve clinical remission and manage to stop steroids. De-escalation at 5mg bid is successful in more than half of them. We prospectively follow up our cohort to investigate whether these preliminary results will be confirmed for a longer period.

Introduction

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical response at Week(W) 12 and maintaining clinical remission through W52 in patients with moderately-to-severely active Crohn’s disease (CD) as shown in the phase 3 treat-through trial VIVID-1 (NCT03926130).¹ Here, we present analysis of maintenance outcomes through W52 for Patient-Reported Outcome (PRO) clinical responders and nonresponders at W12.

Aims & Methods

The analysis set includes patients randomized to mirikizumab at baseline, who did or did not achieve PRO clinical response at W12 after intravenous (IV) induction treatment (900 mg mirikizumab IV every 4 weeks [Q4W]) before entering subcutaneous (SC) maintenance treatment (300 mg mirikizumab SC Q4W). Descriptive statistics are used to summarize the data, applying nonresponder imputation for missing binary endpoints. As a treat-through study, no rerandomization was applied.

Results

From a total of 551 patients who entered SC maintenance treatment, baseline characteristics of age, duration of CD, and baseline Crohn’s Disease Activity Index (CDAI) were similar between W12 PRO responders (n=402, 73.0%) and W12 PRO nonresponders (n=149, 27.0%). PRO responders at W12 had a higher objective inflammatory burden at baseline (faecal calprotectin, c-reactive protein, and Simple Endoscopic Score-CD), whereas concomitant or prior medication usage was similar between the groups. For W12 PRO responders, SC mirikizumab treatment from W12 to W52 resulted in an increase in CDAI clinical remission from 52.2% to 65.4%, PRO clinical remission from 53.2% to 65.4%, and endoscopic response from 35.1% to 54.7%, respectively (Table 1). Among W12 PRO nonresponders, PRO response was achieved by 39.6% at W16, 45.6% at W20, 44.3% at W24, and 56.4% at W52 with continued mirikizumab SC treatment, while CDAI clinical remission and PRO clinical remission were achieved by 33.6% and 31.5% at W52, respectively. Endoscopic response increased from 30.2% at W12 to 40.3% at W52 among W12 PRO nonresponders (Table 1).

Conclusion

Subcutaneous mirikizumab maintenance treatment over 40 weeks leads to incremental and sustained improvements in rates of clinical and endoscopic response regardless of PRO clinical response status after induction. A substantial proportion of clinical nonresponders at W12 improved early during maintenance treatment suggesting continued treatment with mirikizumab can be beneficial and lead to long-term response.

References

1. Ferrante, Marc et al. Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study. Lancet. 2024;404(10470):2423-2436. doi:10.1016/S0140-6736(24)01762-8

Introduction

Upper gastrointestinal bleeding (UGIB) poses a significant threat in patients presenting to the emergency department, particularly in those with associated hemodynamic instability. Despite major advancements in medical and endoscopic therapeutic options, mortality rates have not shown a substantial decline over the years. This study aimed to assess clinical practice patterns in order to gain a clearer understanding of the pre-endoscopic assessment for patients with acute UGIB.

Aims & Methods

This study was an international online survey based on a prospective two-phase data collection approach, conducted between April 2023 and November 2023. The survey targeted practicing physicians actively involved in managing patients with UGIB. Data collection and management were performed through Research Electronic Data Capture (REDCap), an electronic data collection tool. The survey comprised four key domains: demographics and clinical practice, definitions of hemodynamic instability, pre-endoscopic assessment, and optimal timing of endoscopy, encompassing a total of 33 questions. The primary analysis provided a descriptive assessment of responses reported as proportions. Secondary analyses explored differences in responses based on years of clinical experience, practice setting, and the estimated annual number of UGIB cases encountered

Results

A total of 533 clinicians from 50 countries completed our survey. Among respondents, 54.6% work in university-based hospitals, and 67.7% reported managing over 100 UGIB patients annually. Regarding clinical experience, 55.7% have less than 10 years, with 44.3% with over 10 years of experience. Only 47.1% of respondents reported that their hospitals implement a triage system for UGIB patients. Additionally, 39.6% indicated that they do not use any risk stratification scores at the time of patient presentation. For initial fluid resuscitation, 0.9% saline (40.9%) and balanced crystalloid fluids (39.5%) were almost equally preferred. The rate of fluid resuscitation was reported to depend on the patient’s hemodynamic status by 40.2% of respondents. Most respondents indicated that hemodynamically unstable patients are primarily managed in the emergency department or intensive care unit. A total of 34.3% of respondents indicated that they do not routinely use prokinetics prior to endoscopy in UGIB patients, while 27.6% reported not commonly using them even in cases involving severe bleeding or known gastric emptying disorders. Proton pump inhibitors are administered prior to upper GI endoscopy in all cases by 70.4% of respondents, while vasoconstricting agents are used by 61% in cases of suspected variceal bleeding.

Conclusion

Our survey found considerable variability among respondents regarding the pre-endoscopic management of patients presenting with upper gastrointestinal hemorrhage. The overall adherence to international guidelines was low, which can potentially result in a significant negative impact on patient outcomes.