Introduction

​Biologic therapies play a pivotal role in the management of ulcerative colitis (UC). Anti-TNFα agents are recommended as first-line biologics according to ECCO guidelines; however, JAK inhibitors have recently emerged as a viable alternative (1). Vedolizumab has also demonstrated effectiveness when introduced early in the disease course with a greater 52-week treatment persistence and reduced hospitalisation rates compared to anti-TNFα agents as second-line therapy (2). The AGA guidelines (3) now favour biologics such as anti-IL-23 and JAK inhibitors over Vedolizumab or S1P receptor modulators in patients previously exposed to anti-TNFα agents. Notably, Guselkumab is not yet approved for UC treatment in the UK. The latest ECCO guidelines (1) do not address the role of biologics in third-line or subsequent treatment settings, and there remains a lack of clear clinical guidance.

Aims & Methods

This study aimed to retrospectively evaluate the effectiveness of third-line biologic therapies in adult patients with UC over a 12-month period. Clinical response was assessed using the Simple Clinical Colitis Activity Index (SCCAI), Partial Mayo Score, and Physician Global Assessment, while biochemical and endoscopic responses were measured at 3, 6, and 12 months post-induction. Biochemical markers included faecal calprotectin and CRP levels. Endoscopic response was assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Colectomy rates were also recorded. Patients treated at a UK tertiary care centre were included up to March 2025. Statistical analyses were conducted using SPSS.

Results

A total of 24 patients were included in the analysis, with 13 receiving anti-IL-23 therapy and 11 treated with JAK inhibitors. Within the anti-IL-23 group, 5 patients received Mirikizumab and 8 Ustekinumab; Risankizumab was not used in this cohort. In the JAK group, 3 patients were treated with Upadacitinib, 4 with Filgotinib, and 4 with Tofacitinib. A statistically significant reduction in SCCAI scores at 6 months was observed in the JAK groups compared to anti-IL-23 (7.64 ± 3.61 vs 4.90 ± 1.97, p = 0.047). However, biochemical response, assessed by faecal calprotectin reduction, did not reach statistical significance at either 3 or 6 months (p = 1.000 and p = 0.314, respectively). Endoscopic response, measured by changes in UCEIS at 12 months, also showed no significant difference between groups (p = 0.668). Subgroup analysis within the anti-IL-23 cohort revealed no significant difference in SCCAI reduction between Ustekinumab and Mirikizumab at 3 months. Similarly, while Upadacitinib was associated with the greatest SCCAI reduction among the JAK inhibitors at 3 months, the difference among the three agents was not statistically significant (p = 0.106). Subtotal colectomy was performed in one patient in the Mirikizumab group following completion of induction therapy, and in two additional patients within three months of initiating the same agent (Table 1).

Conclusion

JAK inhibitors showed an improvement in SCCAI at 6 months compared to anti-IL-23 agents. No significant differences were found in biochemical or endoscopic response.

References

1. Raine T, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. Journal of Crohn’s and Colitis. 2022 Jan 28;16(1):2–17.
2. Miller C, Kwok H, Harrow P, Vega R, Seward E, Mehta S, et al. Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab. Frontline Gastroenterol. 2022 Sep;13(5):392–401.
3. Singh S, Loftus EV, Limketkai BN, Haydek JP, Agrawal M, Scott FI, et al. AGA Living Clinical Practice Guideline on Pharmacological Management of Moderate-to-Severe Ulcerative Colitis. Gastroenterology. 2024 Dec;167(7):1307–43.

Introduction

There has been a rise in the uptake of endoscopic submucosal dissection (ESD) for superficial pharyngeal cancers, including in patients with previous history of radiotherapy, whether as salvage treatment of residual lesions or for metachronous lesions inside the irradiated field. Previous studies have demonstrated the safety and effectiveness of ESD for pharyngeal cancers¹. However, the safety and the effectiveness of pharyngeal ESD in cases with previous history of radiotherapy is not clear^2,3.

Aims & Methods

Our aim was to investigate whether radiotherapy affects outcomes after pharyngeal ESD. We conducted a retrospective cohort study of consecutive patients who underwent pharyngeal ESD between December 2016 and February 2025 at our institution. All the cases were managed together with otolaryngologists, including the daily assessment of the wound and swallowing function with the transnasal flexible laryngoscope in order to decide the timing of the re-initiation of food after ESD. The ESD itself, as well as the short and long-term outcomes were compared between the patients with or without history of radiotherapy.

Results

There were 22 cases (25 lesions) of ESD performed with previous history of radiotherapy and 32 cases (33 lesions) without prior radiotherapy. The median age was 71 (range 55-85) and 98.3% were men. Radiotherapy dose ranged from 54 to 70 Gy. There were no significant differences in the baseline characteristics between the groups of patients with or without prior radiotherapy including the age, sex, or the proportion of patients with previous history of pharyngeal ESD. En-bloc resection was achieved in all cases. ESD in the pharynx post-radiotherapy was associated with an increased percentage of cases with severe fibrosis (41% vs. 14% p<0.05), and the speed of dissection was slower (33.4mm²/min vs. 45.8mm²/min p=0.03), but there were no significant differences in the short-term outcomes between the groups of patients with or without prior radiotherapy in terms of of bleeding (0% vs. 3%), aspiration pneumonia (8% vs. 9%), the duration to the resumption of food (median 4 vs. 5 days) or hospital stay (median 9 vs. 9 days). During a median follow-up period of 906.5 days (range 22-3021 days), the 3-year overall survival rate was lower in patients with previous history of radiotherapy compared to patients without prior radiotherapy (55.1% vs. 100%, p=0.000177). Of the patients with previous history of radiotherapy, one patient died from metastatic recurrence of pharyngeal cancer, but the other five deaths were not directly associated with pharyngeal cancer (1=acute cardiac death, 1=unknown cause but unrelated to pharyngeal cancer, 1=lung cancer, 1=mantle cell lymphoma, 1=sinonasal neuroendocrine cancer) . There were no significant differences in the 3-year recurrence-free survival and the 3-year disease-related survival rates between the patients with and without prior history of radiotherapy (92.9% vs. 91.7% and 92.3% vs. 100%, respectively).

Conclusion

Previous history of radiotherapy increases the risk of severe fibrosis during ESD and is associated with slower speed of dissection, but does not compromise the safety or the swallowing function. In the long-term, ESD is an effective method for the treatment of superficial pharyngeal cancers, including in patients with previous history of radiotherapy. Furthermore, ESD is a minimally-invasive and surgery-sparing treatment option, which may be all the more important in patients with prior history of radiotherapy, given the worse prognosis from illnesses other than pharyngeal cancers in this group of patients.

References

1. Watanabe A, Taniguchi M, Kimura Y, Hosokawa M, Ito S, Tsukamoto S, Sasaki S. Synopsis of transoral endoscopic laryngopharyngeal surgery for superficial pharyngeal cancers. Head Neck. 2017 Sep;39(9):1779-1787.
2. Yoshida T, Shimizu Y, Ono S, Oridate N, Kato M, Asaka M. Successful salvage endoscopic mucosal resection for residual superficial hypopharyngeal carcinoma after chemoradiotherapy, with long-term survival. Endoscopy. 2009 Jun;41(6):568-9.
3. Satake H, Yano T, Yoda Y, Fujii S, Zenda S, Tomioka T, Shinozaki T, Miyazaki M, Kaneko K, Hayashi R. Feasibility of salvage endoscopic resection for patients with locoregional failure after definitive radiotherapy for pharyngeal cancer. Endosc Int Open. 2015 Aug;3(4):E274-80.

Introduction

STRIDE-II has underscored the importance of achieving timely, pre-defined therapeutic targets predictive of favorable long-term outcomes in patients with Inflammatory Bowel Disease. Early targets include post-induction clinical response (Clin-Resp), and clinical remission (Clin-Rem), whereas endoscopic healing is, currently proposed as the optimal long-term endpoint.

Aims & Methods

This study aims to record rates of Clin-Resp, Clin-Rem and endoscopical healing and evaluate their predictive value for long-term outcomes in patients with Ulcerative Colitis (UC), in a real-world setting. It is a retrospective cohort study of patients who have been followed up in the GI unit of “Sotiria” hospital, and commenced treatment with either infliximab, vedolizumab, or ustekinumab. We compared patients who achieved Clin-Resp (drop of UC-PRO2≥50%) without Clin-Rem at the end of induction to those with Clin-Rem (UC-PRO2=0) regarding rates of drug continuation, clinical remission, steroid-free clinical remission, and mucosal healing at one year on treatment. Additionally, we compared patients with endoscopic MAYO score (endo-MAYO) of 0 or 1 on treatment, regarding drug continuation rates 1, 2, 3 and 4 years post-endoscopy. SPSS 23 (IBM, Armonk, NY, USA) was used for the statistical analysis.

Results

In total, 145 patients were included [mean age=41.6 years (SD=16.6), men: 50.3% (n=73)]. Sixty-eight (46.9%) received infliximab, 41 (28.3%) vedolizumab and 36 (24.8%) ustekinumab. At the end of induction, 90 patients (62.1%) had Clin-Resp and 72 (49.7%) Clin-Rem. After one year of treatment, higher rates of drug continuation (94.4% vs 55.6%, P<0.001), clinical remission (87.5% vs 44.4%, P<0.001), steroid-free clinical remission (85.9% vs 33.3%, P<0.001) and mucosal healing (57.6% vs 23.5%, P=0.001) were reported for patients in Clin-Rem at the end of induction compared to those with sole Clin-Resp. Patients with endo-MAYO=0, at their first endoscopic evaluation after drug commencement, demonstrated higher rates of 1- (100% vs 70.6%, log-rank P=0.007) and 2-year (81.6% vs 41.7%, log-rank P=0.033) drug continuation, compared to those with endo-MAYO=1. No statistically significant difference was recorded regarding their 3- (61.5% vs 22.2%, log-rank P=0.088) and 4-year (33.3% vs 22.2%, log-rank P=0.254) drug continuation rates.

Conclusion

In ulcerative colitis, the achievement of clinical remission at the end of induction is a major predictive factor of long-term effectiveness of treatment. Simultaneously, our analysis shows the importance of optimal control of inflammation as a therapeutic target, since patients with complete endoscopic healing have a higher probability of prolonged drug continuation.

Disclosure

GB: Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma, Adacyte Therapeutics, Amgen, Ferring, Cooper; Funding (Grants/Honoraria): Pfizer, Takeda, Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda.

Introduction

The STRIDE-2 consensus emphasizes achieving specific endoscopic targets in ulcerative colitis (UC), but robust evidence on the effectiveness of the Treat-to-Target (T2T) approach in UC is limited in the real-world setting.

Aims & Methods

TACTIC-UC is a monocentric, retrospective, observational study evaluating UC patients managed according to a T2T algorithm. Eligible patients: 1) were receiving anti-TNF (aTNF), vedolizumab (VDZ) or ustekinumab (UST) at standard doses, 2) had quiescent/mild clinical activity (stool frequency and rectal bleeding <1), 3) had moderate/severe endoscopic activity (endoscopic Mayo score, eMS≥2). All patients received dose optimization and had at least 1 follow-up endoscopy. Observation period lasted from optimization until 1 year /drug discontinuation/last available follow-up. The primary outcome was the probability of mucosal healing (MH, eMS≤1) within 1 year. Secondary outcomes included: 1) probability of endoscopic remission (ER, eMS=0) within 1 year, 2) adverse events (AEs) incidence. Inverse probability of treatment weighting was used to adjust cohorts’ imbalances. False discovery rate correction was applied for multiple comparisons.

Results

The cohort included 178 patients (main characteristics in Table 1); after IPTW, no significant differences were observed. The cumulative probabilities of achieving MH within the first year were 41%, 11% and 23% for aTNF, VDZ and UST, respectively. At pair-wise comparison, aTNF was superior to both VDZ and UST(p<.05), with UST trending towards superiority (p=.05) over VDZ. Cox-regression (bootstrapping, 1000 iterations) identified factors associated with a significantly reduced (p<.05) probability of achieving MH: difficult-to-treat UC (aHR 0.6, 95%CI 0.5-0.7), E3 (aHR 0.7, 95%CI 0.5-0.9), elevated CRP (aHR0.96, 95%CI 0.94-0.9), and elevated FCP (aHR 0.98, 95%CI 0.97-0.99); aTNF was associated with increased probability of MH compared to VDZ (aHR 1.4, 95%CI 1.1-1.7, p<.05) and UST (aHR 1.4, 95%CI 1.2-2.0, p<.05). For ER, the cumulative probabilities at 1 year were 13%, 3% and 9% for aTNF, VDZ and UST, respectively. Pairwise comparisons showed that aTNF was superior to VDZ (p<.05), and UST trended towards superiority over VDZ (p=.05). Cox regression (bootstrapping, 1000 iterations) found that difficult-to-treat UC (aHR 0.6, 95%CI 0.5-0-8), E3 (aHR 0.7, 95%CI 0.6-0.), higher CRP (aHR 0.97, 95% CI 0.95-0.99), higher FCP (aHR 0.99, 95%CI 0.98-1.0) were significantly (p<.05) associated with reduced probability of achieving ER; aTNF was associated with increased probability of achieving ER compared to VDZ (aHR 1.3, 95%CI 1.1-1.7, p<.05) and UST (aHR 1.4, 95%CI 1.1-2.0, p<.05), with no significant difference for VDZ vs UST. AEs were infrequent and mild across all groups (mostly infections and infusion reactions), with no significant differences in safety profiles. No serious AE was reported.
Table 1.

Conclusion

In this cohort of UC patients treated according to an endoscopy-driven T2T approach, aTNF outperformed VDZ and UST in inducing MH and ER. Disease severity markers were associated with reduced probabilities of achieving endoscopic targets. Safety profiles were comparable across therapies.