Introduction

Irritable bowel syndrome is one of the most common Disorders of gut-brain interaction, with diarrhea being the predominant subtype. At present, there are limited drugs for effective management of irritable bowel syndrome.
Compound glutamine entersoluble capsules are composed of traditional chinese medicine formulas Sijunzi Tang and L-glutamine. The Sijunzi Tang, which has been used in traditional complementary and alternative integrated medicine, has been used for the treatment of irritable bowel syndrome for many years. However, there is a lack of evidence from modern evidence-based medicine, its clinical efficacy and safety need to be confirmed. L-glutamine has the function of repairing damaged intestinal mucosa.

Aims & Methods

This study performed a multicenter randomized double-blind placebo-controlled withdrawal trial to explore the effectiveness and safety of compound glutamine entersoluble capsules in the treatment of diarrhea predominant irritable bowel syndrome.
The selected participants received the investigational drug for four weeks during the first single arm stage. The responding participants were randomly assigned to the compound glutamine entersoluble capsules and placebo groups in a 1:1 ratio for another 4 weeks.
The primary efficacy endpoint of the study was the response rate of both the improvement in abdominal pain and bowel movements after treatment in randomized controlled trial subjects (50% of the treatment course met the requirement of at least 30% improvement in abdominal pain severity (NRS pain score) and a reduction of at least 50% in bowel movement days for Bristol 6 or 7 types).

Results

A total of 558 subjects in 22 centers, of which 493 subjects were successfully screened and entered the placebo introduction period. During the placebo introduction period, there were a total of 493 subjects, of which 481 subjects were successfully rescreened and entered the single arm period. 437 subjects entered the randomized controlled trial period and were randomly divided into a treatment group of 217 subjects and a placebo group of 220 subjects.
For the primary efficacy endpoint, the number of response cases in the experimental group and placebo group were 114 (54.55%) and 89 (41.20%), respectively (P=0.0059). For secondary efficacy endpoints: (1) The number of improvements in NRS pain scores in the experimental group and placebo group were 138 (66.03%) and 107 (49.54%), respectively (P=0.0006); (2) The number of improved bowel movements in the experimental group and placebo group were 157 (75.12%) and 118 (54.63%), respectively (P<0.0001); (3) The median (quartile) relative baseline change of IBS-SSS scale in the experimental group was -47.00 (-97.00, -14.00) points; The median (quartile) relative baseline change in the placebo group was -17.00 (-63.00, 16.00) points, and there was a statistically significant difference between the two groups (P<0.0001); (4) The median (quartile) relative baseline change of IBS-QOL in the experimental group was -11.46 (-43.01, 0.00) points; The median (quartile) relative baseline change in the placebo group was -3.57 (-39.43,0.00) points (P=0.0007).
During the randomized controlled trial period, the incidence of all adverse events in the 217 subjects in the trial group was 18.89%, the placebo group was 22.27%, the incidence of TEAEs related to the drug in the trial group was 2.30%, and the placebo group was 3.18%.

Conclusion

Compound glutamine entersoluble capsule can effectively improve the clinical symptoms of diarrhea predominant irritable bowel syndrome with a satisfactory safety.

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).

		PRO Nonresponders at W12 (N=149)	PRO Responders at W12 (N=402)
CDAI clinical remission, n (%)a	W12	8 (5.4%)	210 (52.2%)
	W16	16 (10.7%)	208 (51.7%)
	W20	28 (18.8%)	243 (60.4%)
	W24	35 (23.5%)	242 (60.2%)
	W52	50 (33.6%)	263 (65.4%)
Endoscopic response, n (%)a	W12	45 (30.2%)	141 (35.1%)
	W52	60 (40.3%)	220 (54.7%)
aPercentage of response is calculated by n/Nx*100%. CDAI, Clinical Disease Activity Index; PRO, patient-reported outcome

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

To examine the evolution of the ulcerative colitis (UC) treatment pathway in advanced therapy (AT) naïve and later line EU4+UK patients over time, as well as identifying how treatment goals may have changed.

Aims & Methods

A multi-centre online medical chart review study of patients with UC was conducted between Jan – Mar 2018, Jul – Sep 2020 and Jan – Mar 2023, among EU4+UK (UK, FR, DE, IT & ES) gastroenterologists practicing across hospital and private practices. Recruited physicians were screened for duration of practice in their specialty and caseload. Respondents completed patient record forms of their next 4 UC patients seen following receipt of the survey.

Results

The total number of sampled gastroenterologists recruited in this survey and reported UC patients are in Table 1.

Table 1: Sampled physician and reported patient sample size

Timepoint	Q1 2018	Q3 2020	Q1 2023
Surveyed gastroenterologists	207	211	220
Reported UC patients	816	844	880

Between Q1’18 – Q3’20 - Q1’23 the percentage usage of total adalimumab volume in reported UC patients dropped (30% vs 15% vs 13%, respectively), as well as the proportion of these patients reported as first line adalimumab patients (90% vs 88% vs 87%, respectively). In addition, the proportion of reported patients who experienced a switch from one TNF to another also drops between Q1’18 – Q3’20 (14% vs 10%, respectively). Conversely, the proportion of reported UC patients receiving a non-TNF therapy increases over time (12% vs 29% vs 43%, respectively); specifically, the proportion of reported non-TNF first line patients increased (5% vs 12% vs 25%, respectively). Switches from non-TNFs to TNFs increased between Q1’18 – Q3’20 (8% vs 11%, respectively). The proportion of the overall sample occupied by first line patients decreased between Q1’18 – Q3’20 (84% vs 77%, respectively).

Conclusion

In this study cohort, use of adalimumab molecule decreases over time, seemingly in favour of non-TNF therapies, as more products become available in the gastroenterology landscape. This trend is seen across both the overall market and at first line of therapy, suggesting a move away from use of the more ‘traditional’ therapies in general, as well as more frequently choosing a non-TNF as a first line option. The increasing proportion of non-TNF 1st line patients, as well as the increasing proportion of those switching from non-TNFs to TNFs, suggests an increasing proclivity to use non-TNF products earlier in the treatment algorithm. TNF cycling also decreases, suggesting an increased tendency to use non-TNF products. This, along with the decreasing proportion of the sample occupied by first line patients, could indicate an increased propensity by gastroenterologists to switch patients between therapies sooner. Further investigation using comparator cohort is warranted to further investigate impact of increasing numbers of approved UC treatment options.