Background
Small bowel stricture is one of the most common complications in patients with Crohn’s disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid ...surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD.
Methods
Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available.
Results
A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation.
Conclusions
In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD.
Abstract
Background
Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present the final analysis of a 60-week post-marketing surveillance (PMS) study of ...tofacitinib in patients (pts) with UC in Japan.
Methods
A final analysis of safety and effectiveness data from a PMS study was conducted (final data as of 30 September 2022). All pts with UC in Japan receiving tofacitinib were registered. All adverse drug reactions (ADRs) during tofacitinib treatment were recorded. Data were excluded for 13 pts from 2 hospitals that did not obtain pt consent and were therefore not permitted for publication. In the risk-management plan, several ADRs were identified as clinically important events or as potential risks, for which all treatment-period data were used to calculate cumulative incidence rates (IRs; unique pts with events per 100 pt-years PY of exposure). Effectiveness was assessed by partial Mayo score as observed.
Results
In total, 2043 pts receiving tofacitinib were enrolled in the PMS study, of whom 1982 and 1969 were included in the final safety and effectiveness analyses, respectively. In total (safety analysis set), 60.5% of pts were male and mean age was 42.5 years, with 2706.4 PY of exposure. ADRs and serious ADRs were observed in 462 (23.3%) and 46 (2.3%) pts, respectively; one death occurred due to an intestinal abscess (not related to study drug per investigator’s assessment). Herpes zoster (HZ; non-serious/serious) was the most commonly reported infection (89 pts 4.5%). The IRs of malignancy, cardiovascular events and venous thromboembolic events were all <0.5 per 100 PY of exposure (Table). At Week 60, 735 of 870 ongoing pts (84.5%) were in remission (Figure). Overall, 1038/1982 pts (52.4%) discontinued treatment, most commonly due to inadequate clinical response (508/1038 pts 48.9%).
Conclusion
In this final analysis, the overall safety profile during the treatment period from PMS reports of tofacitinib in pts with UC in Japan was generally comparable with tofacitinib safety data previously reported in PMS reports from Japan and worldwide,1 and in the tofacitinib UC clinical programme.2 However, rates of HZ were higher in this final analysis than in the tofacitinib UC clinical programme.2 Tofacitinib was effective in Japanese pts with UC in a clinical practice setting. The majority of pts with evaluable partial Mayo scores achieved remission during the 60-week observation period, consistent with previously reported data from the tofacitinib UC clinical programme.2
References:
1. Rubin et al. Aliment Pharmacol Ther 2022;55:302–10
2. Sandborn et al. Aliment Pharmacol Ther 2022;55:464–78
Study sponsored by Pfizer. Medical writing support provided by C Duncan, CMC Connect; funded by Pfizer
Abstract
Background
Several Janus kinase inhibitors have recently been launched for the treatment of ulcerative colitis (UC). However, there are few reports comparing the efficacy and safety of each ...drug in patients with refractory UC, especially with filgotinib (FIL), which was recently launched and can be concomitantly used with thiopurines. We herein aimed to compare the real-world efficacy and safety of tofacitinib (TOF) and FIL in induction therapy for patients with refractory UC.
Methods
Patients with refractory UC, who received either TOF 20mg/day or FIL 200mg/day from May 2018 to October 2023 in Hyogo Medical University Hospital were included in this study. Primary outcomes were clinical response rates at 2, 4, and 8 weeks after administration of TOF or FIL. Clinical response was defined as a decrease of partial Mayo Score (pMS) of ≥2 from baseline and rectal bleeding subscore is ≤1 or a decrease of ≥1 from baseline. Secondary outcomes were cumulative incidences of adverse events during the observation period.
Results
Of the 230 refractory patients with UC, 197 received TOF and 33 received FIL treatment. The median age was 37 IQR 27–49 and 49 33–54 years, and the median disease duration was 3 1–10 and 5 2–10 years, respectively. Median durations of observation were 118 52–188 weeks in the TOF group and 41 29–60 weeks in the FIL group, median baseline pMS were 6 5–7 and 5 5–6, and serum CRP levels were 3.8 1.3–12.3 and 1.8 0.3–3.3 mg/L, respectively. Thirty-eight (19.3%) patients in the TOF group and 3 (9.0%) patients in the FIL group received systemic steroids, and 8 (24.2%) in the FIL group received thiopurine at baseline. The clinical response rates at 2, 4 and 8 weeks were 58.4%, 59.4% and 62.9% in the TOF group, and 42.4%, 57.6% and 48.9% in the FIL group, respectively, and the rate tended to be higher in the TOF group than in the FIL group at 2 weeks (p = 0.092). Of the patients who did not respond at 4 weeks, the TOF group had a significantly higher clinical response rate (31.3%) than the FIL group (0%) at 8 weeks (p = 0.032). Among 124 patients with prior anti-TNF-α antibody failure, 59.6% (65/109) of patients in the TOF group and 46.7% (7/15) in the FIL group achieved comparable clinical responses at 8 weeks (p = 0.407). Fifteen of 197 (7.6%) patients in the TOF group and 2 of 33 (6.1%) in the FIL group did not continue treatment until 8 weeks due to adverse events, but there were no significant differences between the groups.
Conclusion
Even in patients without a response for up to 4 weeks, TOF treatment may provide a higher clinical response than FIL treatment at 8 weeks.
Abstract
Background
Serum leucine-rich alpha-2 glycoprotein (LRG) is a biomarker reflecting endoscopic activity in patients with inflammatory bowel disease (IBD). However, it remains unclear whether ...serum LRG can predict the effectiveness of anti-cytokine biologics (biologics) in patients with IBD. This study aimed to evaluate whether serum LRG could predict the effectiveness and serum trough concentrations of biologics in patients with IBD.
Methods
This was a multicentre prospective cohort study including patients with IBD (including ulcerative colitis UC or Crohn’s disease CD) who received the biologics ustekinumab (UST), anti-tumor necrosis factor (anti-TNF) from January 2019 to March 2023 at 15 hospitals participating in the Osaka Gut Forum. The effectiveness of biologics was evaluated by clinical remission (CR) at week 8. We defined CR as a partial Mayo score of 2 or lower, with each subscore of 0 or 1 for UC and a CD activity index of < 150 for CD. Factors associated with CR at week 8 such as backgrounds, disease activities and concomitant medications at week 0 were analyzed by Cox proportional hazards model. For each biologic, we compared the effectiveness of biologics in the high LRG group with that in the low LRG group divided by the median serum LRG levels at week 0 (cut-off = 18.2 μg/mL).
Results
A total of 184 patients with IBD (UC, 80; CD, 104) were enrolled (UST/ anti-TNF, 119/ 65; biologic exposure, 31.5%; median disease duration, 6 years Interquartile range (IQR) 1-14). Median serum LRG levels at week 0 and serum C-reactive protein levels at week 0 were 18.2 μg/mL IQR 12.5-28.1 and 0.19 mg/dL IQR 0.03-0.77, respectively. At week 0, 63 (34.2%) and 64 (34.8%) patients concomitantly received corticosteroids and immunomodulators, respectively. In 184 patients with IBD, multivariate analysis revealed that serum LRG level at week 0 < 18.2 μg/mL was extracted as a significant factor for CR at week 8 (Odds ratio: OR 2.70, 95% confidence interval: CI 1.22-5.96). In patients who received UST, the proportion of CR at week 8 in the low-LRG group (76.9%) was significantly higher than that in the high-LRG group (59.3%, P = 0.038). In patients who received anti-TNF, however, the proportion of CR in the low-LRG group (84.6%) was not differ from that in the high-LRG group (82.1%, P = 0.781). Median serum trough concentrations of UST at week 8 in the low-LRG group (10.9 μg/mL, IQR 6.7-13.4) was significantly higher than that in the high-LRG group (5.3 μg/mL, IQR 2.4-8.3, P < 0.001).
Conclusion
Serum LRG could predict the effectiveness and serum trough concentrations of UST and be a biomarker for selecting biologics in patients with IBD.
Abstract
Background
The number of elderly patients with inflammatory bowel disease (IBD) is increasing, but the outcomes of patients with elderly onset (EO) IBD treated with anti-tumor necrosis ...factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD.
Methods
This was a multicenter retrospective observational study including bio-naïve patients with IBD who started anti-TNF treatment from, 2010 to, 2019 at, 18 hospitals of the Osaka Gut Forum. Elderly patients were defined as those, 60 years and older, and elderly patients with IBD were further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). The clinical symptoms were evaluated by partial Mayo score (pMayo) for UC and Harvey-Bradshaw index (HBI) for CD, and the clinical remission rate at, 52 weeks after the start of treatment was analyzed retrospectively. Clinical remission was defined as pMayo ≤, 2 and each subscore ≤, 1 for UC and HBI ≤, 4 for CD.
Results
A total of, 432 patients were enrolled, comprising, 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and, 352 under age, 60 (Non-elderly, 81.5%). After, 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and, 60.8%; P = 0.001, and, 35.9% and, 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission Odds ratio (OR), 0.49, 95% confidence interval (CI), 0.25–0.96 and steroid-free remission OR, 0.51, 95%CI, 0.26–0.99 after, 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly lower in Elderly-EO than in Non-elderly (P = 0.007), but comparable between Elderly-NEO and Non-elderly.
Conclusion
Anti-TNF treatment is less effective for bio-naïve EO-IBD than for elderly patients with younger onset and non-elderly, and may raise safety concerns in this group of patients.
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