Ustekinumab in Ulcerative Colitis: A Real-Life Effectiveness Study Across Multiple Belgian Centers (SULTAN)

Background Histological remission is an aspirational therapeutic target in Ulcerative Colitis (UC) associated with lower relapse rates.1Ustekinumab (UST), a monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 has shown in the UNIFI trials to be effective and safe in patients with moderate-to-severe UC. However, real-life data on histological remission rates are sparse. The aim of the study was to assess the real-life histological response and remission rates of UST in patients with UC across Belgian hospitals. Methods In this multicentric, retrospective observational study, patients with UC who initialised UST treatment between September 2020 and July 2023 were included. Histological remission was defined as Nancy score = 0, response as Nancy ≤ 1 and assessed at week 16 and 52 by the local pathologist. Other endpoints included steroid-free clinical remission (partial Mayo ≤ 2 with no subscore >1), endoscopic remission (endoscopic Mayo = 0), endoscopic response (Mayo score ≤ 1) and clinical response (decrease in partial Mayo score ≥ 3 points and ≥ 30% plus a decrease in rectal bleeding score ≥ 1 or an absolute rectal bleeding score ≤ 1). UST drug persistence was analyzed by Cox regression analysis, predictors of other endpoints by logistic regression. Results 120 patients with moderate to severe UC (86% patients with ≥S2 severity) were included across 16 participating centers. Median disease duration was 11 years (IQR 9) and 81 (68%) of patients had previously failed 2 or more biologicals. Histological remission was achieved in 3/37 (8%) and 5/45 (11%) at W16 and W52, while histological response was seen in 10.8% (4/37) and 26.7% (12/45) respectively. Steroid-free clinical remission rates were 41/120 (34%) and 38/85 (44%) while endoscopic remission was seen in 23/120 (19%) and 13/52 (25%) at W16 and 52 respectively. Two patients (40%) in histological remission at W52 had an endoscopic Mayo 0 score, while 3 had a Mayo 1 (60%) at the time of evaluation. Active smoking was a negative predictor for achieving steroid-free remission (OR 0.412, p=0.011). No significant predictors for histological remission or response could be identified. UST drug persistence by week 52 was 70.8%. Active smoking (OR 3.058, p=0.02), vedolizumab non-response (OR 2.592, p=0.03) and a high Nancy baseline score (OR 2.46, p=0.04)) were associated with UST failure Conclusion In this multi-centric, real-life cohort with highly refractory UC patients, UST shows acceptable clinical and endoscopic remission rates, but histological remission rates remain low after one year of treatment.

Background Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon.1 Ustekinumab (UST), a monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 has shown in the UNIFI trials to be effective and safe in patients with moderate-to-severe UC.2 Real-life data are still limited.3 The aim of this study was to assess the real-world effectiveness and safety of UST in patients with UC across Belgian hospitals. Methods In this multicentric, retrospective observational study, patients with UC who received UST from September 2020 onwards were included. Clinical and biochemical response was assessed at baseline, week 8, 16 and 52. The primary endpoint was steroid-free remission defined as partial Mayo score of ≤ 2 with no subscore > 1 at week 16. Secondary endpoints included clinical and biochemical response (defined respectively as a decrease in partial Mayo score ≥ 3 points and ≥ 3 plus a decrease in rectal bleeding score ≥ 1 or an absolute rectal bleeding score ≤ 1 and a decline of 50% or more in CRP and/or fecal calprotectin). Results 107 patients with moderate-severe UC (86% patients with ≥ S2 severity) were included across 16 participating centers. Median disease duration was 10 years (1-73y) and 69 (64%) of patients had previously failed 2 or more biologicals. At week 16, 35 patients reached the primary endpoint of steroid-free clinical remission (33%), while 67 had a clinical response (62.6%) (Fig 1). There was a statistically significant decline in partial mayo score (median at baseline 6.0 range (1-9); W16 2.0 (0-9, p<.001), CRP (3.85 mg/L (0.4-181) vs 3.15 (0.88-10.3); p<.001) and calprotectin (1040 (13-6000) vs 300 (3.8-2980); p<.001) (Fig 2 and 3). Biochemical response was seen in 41 patients (38%). No predictors for steroid-free remission could be identified. At the end of follow-up at week 52, 75 patients were still treated with UST (70%). Reasons for discontinuation were primary non-response (N=18 (17%), loss of response (N=8 (7.5%) and adverse events (N=2 (1.9%)). No predictor for UST failure could be identified. Eight patients needed to be referred for colectomy (7.5%). In 7 patients dose optimization via IV reinduction occurred. No difference in occurrence of extra-intestinal manifestations was noted during treatment, severe infections occurred in 1 patient (0.9%). No other new safety signals were observed. Conclusion In this multi-centric, real-life cohort with highly refractory UC patients, UST was associated with a clinical response rate of 63% at 16 weeks while steroid-free remission was achieved in 33% of patients. No important new safety signals were observed.

BackgroundFaecal microbiota transplantation (FMT) administered via the lower GI tract effectively induces remission in ulcerative colitis (UC). Orally administered FMT capsules may improve patient tolerability and facilitate maintenance therapy while it is unclear if pre-FMT antibiotics enhance therapeutic efficacy.MethodsWe performed a dual-centre randomised, double blind, placebo-controlled trial of oral lyophilised FMT in adults with mild-moderately active UC (total Mayo 4–10). All subjects received 2-weeks of pre-FMT antibiotics (amoxycillin, metronidazole and doxycycline) before 1:1 randomisation to either oral FMT (0.35g stool content per capsule from 1 of 2 healthy donors) or identical placebo for 8 weeks. Enforced tapering and cessation of corticosteroids was mandated. The primary endpoint was week 8 steroid-free clinical remission with endoscopic remission or response (total Mayo score ≤2 with subscores ≤ 1 for rectal bleeding, stool frequency and endoscopic appearance, and ≥1-point reduction from baseline in endoscopy subscore). Responders to FMT induction were re-randomised to either continue maintenance FMT or withdrawal of FMT with final outcomes assessed at week 56.ResultsRecruitment was paused due to the COVID-19 pandemic. 37 patients were randomised. Baseline patient and disease characteristics were balanced between the randomised groups. The primary outcome was achieved in 8/16 (50%) receiving FMT versus 3/19 (16%) receiving placebo (OR: 4.63; 95%CI: 1.74–12.30; P=0.002). Steroid-free clinical remission rates and endoscopic remission rates were 69% vs 26% (P=0.012) and 44% vs 16% (P=0.074) in the FMT and placebo arms, respectively. Reported SAE were worsening colitis (2 FMT, 1 placebo) and PR bleeding relating to previous anal surgery (placebo). Ten patients entered the maintenance withdrawal study. Steroid-free clinical, endoscopic and histologic remission was achieved in 4/4 patients who continued daily oral FMT, with all 6 patients randomised to FMT withdrawal having a flare of disease with a median time to relapse of 6 months.ConclusionOral lyophilised FMT following antibiotic pre-treatment for mild-moderately active ulcerative colitis was associated with a significant increased rate of clinical remission with endoscopic remission or response versus antibiotic treatment alone at week 8. Pre-treatment antibiotics had an additive impact upon treatment efficacy compared with previous studies utilising FMT. Maintenance FMT therapy was associated with sustained clinical, endoscopic and histologic remission at week 56. Treatment was well tolerated and there were no new safety signals related to FMT therapy.

Background Long-term real-life data on the efficacy of the Janus kinase inhibitor tofacitinib in moderate-to-severe ulcerative colitis (UC) are limited. We here report efficacy of tofacitinib in refractory UC patients with an emphasis on endoscopic and histologic outcome. Methods Fifty-four consecutive UC patients (Mayo endoscopic sub-score ≥2) initiating tofacitinib in 2 tertiary IBD referral centres were prospectively included (Table 1). Almost all were refractory to both anti-TNF (96.4%) and vedolizumab (92.7%) and received tofacitinib in standard dosage. Steroid-free clinical remission was defined as partial Mayo score of ≤2 with no single sub-score >1 and without any steroid exposure at assessment. Biological remission was defined as faecal calprotectin <250mcg/g, endoscopic remission as Mayo endoscopic sub-score of 0, endoscopic improvement as Mayo endoscopic sub-score of ≤1, and histologic remission as Nancy histology index of 0. A combination of endoscopic and histologic remission was referred as mucosal healing. All outcomes were assessed at year 1. Non-responder imputation and last observation carried forward analysis were applied. Results Patients were followed for a median [IQR] of 91.7 [67.2–102.4] weeks, with an exposure to tofacitinib of 23.9 [14.6–51.6] weeks. By year one, 31.5% of patients were in steroid-free clinical remission (Figure 1). Biological remission was observed in 26.9% of patients. Endoscopic improvement, endoscopic remission, histologic remission and mucosal healing, were observed in 31.5%, 24.1%, 22.0% and 18.0% of patients, respectively. Multivariate analysis identified baseline Mayo endoscopic sub score (OR 0.03, p=0.03); endoscopic improvement by week 16 (OR 36.5, p=0.008) and disease extent (OR 0.11, p=0.05) as independent predictors for endoscopic remission at year 1. Patients with left-sided colitis or proctitis experienced higher endoscopic remission rates (33.3% and 25.0%) then patients with extensive colitis (10.5%, p=0.09; p=0.6). Ultimately, 61.1% of all patients discontinued tofacitinib therapy after a median of 15.9 [9.2–24.5] weeks, due to primary non-response (n=25), loss-of-response (n=6) or (serious) adverse events (n=2). Thirteen patients (24.1%) required colectomy. During follow-up, no venous thrombo-embolisms or cancers were observed. One patient had to be admitted at ICU due to several life-threatening opportunistic infections. Conclusion In this highly refractory cohort of UC patients, tofacitinib induced and maintained endoscopic and histologic remission in up to one quarter of patients. UC patients with moderate left-sided colitis and proctitis had a numeric higher likelihood for a sustained effect than patients with extensive colitis.

Background Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC. Methods We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs. Conclusion This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

Background Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicenter cohort of Brazilian patients with UC. Methods We conducted a multicenter retrospective observational cohort study, including patients with moderate-to-severe UC (total Mayo score 6–12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of 0) within 1 year from baseline. Secondary endpoints included clinical response between weeks 12 and 16, endoscopic response within 1 year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results A total of 50 patients were included (female, n = 36, 72.0%), with a median disease duration of 9.2 years (1–27). Most patients had extensive colitis (n = 38, 76.0%), and 43 (86.0%) were steroid dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n = 31; vedolizumab [VDZ], n = 27). The co-primary endpoints of clinical remission at 1 year and endoscopic remission within 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12–16 was 56.0%, and endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 46.5%, and 50.0%, respectively. The UST treatment persistence rate at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and 3 patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-seven adverse events (AEs) were reported, 16 of which were considered as serious AEs. Conclusions In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

Background The therapeutic options for Inflammatory Bowel Disease (IBD) have expanded with the introduction of JAK inhibitors. However, real-world data on upadacitinib (UPA) in patients with moderate to severe Crohn’s disease (CD) are scarce. Our aim was to assess the long-term effectiveness and safety of UPA in multi-refractory Belgian patients. Methods Data from all patients with active CD initiating UPA between September 2022 and January 2024 were retrospectively collected from 17 Belgian centres. Effectiveness endpoints were evaluated at week 24 and 52. Steroid-free clinical response and remission were defined using the two-component patient-reported outcome. Endoscopic response was defined as a decrease in baseline Simple Endoscopic Score (SES-CD) with ≥50%, and endoscopic remission as SES- CD ≤ 4 or absence of ulcers. Adverse events (AE), treatment discontinuation, CD-related hospitalization and surgery were assessed throughout follow-up. Non-response imputation was applied for clinical evaluation. Results A total of 140 patients were included (Table 1) with a median follow-up of 33 weeks (IQR: 3-97). The majority of patients (89%) were exposed to at least 3 biologics. At week 24, 53% and 40% of patients achieved steroid-free clinical response and remission, respectively (Figure 1). At week 52, these numbers were 37% and 29%. Endoscopic data were available in 48/140 patients at week 24, of whom 52% and 27% reached endoscopic response and remission. At week 52, these numbers were 63% and 37%. Of patients with active articular extra-intestinal manifestations at baseline 37% and 34% had a quiescent articular disease by week 24 and 52, respectively. 5 out of 9 patients with active perianal disease at baseline and on UPA by week 52, had persistent perianal active disease. Overall, 66 patients (47%) discontinued UPA during follow-up: 23 due to primary non response, 13 due to secondary loss of response, 16 due to AE, 3 due to patient’s choice and 11 due to CD-related surgery. 16 patients required CD-related hospitalization within 52 weeks. AE occurred in 60% of patients (84/140). Of these patients, 11% experienced serious AE of which 2 cardiovascular events: 1 transit ischemic attack and 1 deep venous thrombosis. The most common reported AE were herpes simplex reactivation (5/140), respiratory tract infection (7/140), cutaneous reactions (7/140) and acne (17/140). Only 3 patients had reactivation of herpes zoster infection. Conclusion In this real-world cohort of highly refractory CD patients, UPA effectively induced both steroid-free clinical remission and endoscopic remission by week 52. UPA was relatively well tolerated with respect to adverse events.

Background Ustekinumab has proved its efficacy and safety in moderate-to-severe Crohn′s disease (CD). However, the real practice setting differs from clinical trials. Our aim was to evaluate the effectiveness and safety of ustekinumab in a cohort of real-life practice patients with CD mostly refractory to anti-TNF α agents. Methods Observational retrospective single-center study. All patients undergoing treatment with ustekinumab at the Digestive Diseases Department of the Regional University Hospital of Málaga and at least 16 weeks of follow-up after induction were included. The primary outcome was steroid-free clinical remission (Harvey-Bradshaw Index ≤4) at 24 and 52 weeks. Secondary objectives were combined biological remission (fecal calprotectin levels <250 mcg/g and C-reactive protein <10 mg/dl), safety and persistence of ustekinumab during the follow-up period. Results A total of 89 patients with CD treated with ustekinumab (59,6% women; median disease duration 10 years) were included. The median follow-up was 60 weeks and 55 patients reached one year of follow-up. A 39,3% of the patients had history of previous abdominal surgery and 27% had been treated with 2 or more biologics. A 25,8% and 12,4% of the patients were on steroids and immunosupresants at the induction. The percentages of steroid-free clinical remission at 24 and 52 weeks were 42% and 54% respectively (Figure 1). Combined biological remission at 24 and 52 weeks was achieved in 33% and 45% of the patients respectively. Ustekinumab persistence was 88% at 12 months of follow-up (Figure 2). There were 14 suspensions mainly due to lack of response. Only 13 adverse events were documented in 9 patients (11.5%), none of them serious. Figure 1. Steroid-free clinical and biological remission percentages of ustekinumab at 16,24,52,76 and 104 weeks. Figure 2. Kaplan-Meier curve showing the durability of ustekinumab throughout the follow-up period. Conclusion Ustekinumab was effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs in this real-life practice cohort.

Background Ustekinumab (UST), an antibody targeting the p40 subunit of interleukin-12/23, has demonstrated efficacy in patients with Crohn’s disease (CD). However, comparative real-world data regarding the positioning of biologic therapies, particularly UST versus anti-tumour necrosis factor (TNF) agents, remain limited. This study aimed to compare the effectiveness and safety of UST and anti-TNF agents in biologic-naïve and biologic-failure CD patients. Methods A multicentre retrospective cohort study was conducted, including patients with moderate to severe CD initiating first- or second-line biologic treatment with UST or anti-TNF agents [infliximab (IFX) or adalimumab (ADA)]. Propensity score adjustment (1/PS) was applied to address confounders. Primary endpoints were clinical remission (Harvey-Bradshaw Index ≤3), endoscopic remission (SES-CD ≤3 or Rutgeerts score I0), and steroid-free clinical remission at week 52. Secondary outcomes included clinical response, primary/secondary loss of response, treatment persistence, biochemical remission, adverse events (AEs), hospitalisation, and surgeries. Results A total of 536 CD patients (172 IFX, 132 ADA, 236 UST) were analysed. Clinical remission at week 52 was achieved by 78.1% of UST and 75.7% of anti-TNF patients in the biologic-naïve group (p=0.25), and 52.2% of UST and 50.5% of anti-TNF in biologic-failure patients (p=0.31). Steroid-free clinical remission rates were similar between UST and anti-TNF groups: 80.5% vs 80.1% (p=0.99) in biologic-naïve and 81.2% vs 77.3% (p=0.46) in biologic-failure patients. Endoscopic remission was observed in 74.8% of UST vs 68.8% of anti-TNF patients (p=0.81) in biologic-naïve, and 50.6% vs 46.8% (p=0.72) in biologic-failure. Serious AEs were more frequent with anti-TNF agents in biologic-failure patients (28.3% vs 12.5%; p<0.01). UST demonstrated higher treatment persistence in biologic-naïve patients (96.9% vs 80.8%; p=0.029) and lower CD relapse rates (3.08% vs 11.11%; p=0.01). Conclusion UST and anti-TNF agents exhibit comparable effectiveness for CD treatment regardless of prior biologic exposure. UST showed superior treatment persistence and a better safety profile, particularly in biologic-naïve patients.

Background Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved in Australia for the treatment of adults with moderate to severe Crohn’s disease (CD) in 2017. The aim of this retrospective single centre study was to study the efficacy and safety of UST in CD in a real world cohort. Methods Patients with CD who began UST therapy between June 2017 and July 2019 were included. UST induction was given as an infusion (6 mg/kg) at week 0 followed by 90 mg subcutaneous injection (SC) at week 8 and 90 mg SC every 8 weeks as maintenance. Primary endpoint (PE) was steroid free clinical remission or steroid free clinical response at week 24. Secondary endpoints (SE) were: endoscopic response or remission, radiological response or remission, biochemical response (CRP < 5 mg/L or Calprotectin <150 μg/g), clinical response or remission at week 52. Results Seventy-six patients with CD were included in the study. 64.5% failed ≥1 anti-TNF and 13.1% failed anti-TNF and vedolizumab; 26(34.2%) patients were biologic-naïve. Median follow-up was 61 weeks. Ten patients (13.1%) discontinued UST, and the median time to discontinuation was 48 weeks; eight patients due to loss of response, one patient due to paradoxical worsening of arthralgia, one patient chose to stop treatment. Six patients underwent surgery whilst on UST. At week 12, 48 (63.1%) of patients achieved steroid free clinical remission or response [19/26 (73%) Anti-TNF naive and 29/49 (59%) anti-TNF exposed]; of these patients, 16/19 (84%) in the anti-TNF naive group and 19/29(65.5%) in the anti-TNF exposed group achieved PE. Forty-seven (61.8%) patients achieved PE. At 52 weeks, 68.2% (30/44), 67.5% (27/40), 56.1% (23/41), 69% (29/42) achieved endoscopic, radiological, biochemical and clinical endpoints respectively. Achieving steroid free clinical response or remission at week 12 was associated with achieving PE (79% vs. 42.8%, OR 3.6, p 0.01) and clinical SE (83.3 vs. 58.3%, p 0.001). Patients with B2/3 vs. B1(54% vs. 82%, p 0.09), ≥2 biological failure (72% vs. 33%, p 0.09), CRP < 6 baseline (55 % vs. 67.5%, p 0.3) were less likely to attain PE. Conclusion In a real-world cohort, UST appears efficacious and safe in medium and long term, with modest clinical, biochemical, radiological and endoscopic outcomes. Patients who achieve steroid-free clinical remission or response at 12 weeks are more likely to be in clinical remission or response at 24 and 52 weeks.

Background: This study aimed to explore whether differences exist between males and females in a cohort of bio-experienced UC patients treated with vedolizumab (VDZ), ustekinumab (UST), or tofacitinib (TOFA) in a 48-week retrospective study. Methods: We evaluated intra- and inter-treatment sex-specific differences regarding clinical response, remission, steroid-free remission, sustained clinical response, late remission, and changes in faecal calprotectin and inflammatory markers at 8, 24, and 48 weeks, as well as endoscopic response and remission at 48 weeks. Results: Among 602 patients (50.2% female), males treated with UST had higher rates of clinical (p = 0.029) and steroid-free clinical remission (p = 0.013) at 24 weeks. Conversely, females on TOFA showed higher clinical remission at 8 weeks (p = 0.043). In males, VDZ demonstrated a superior clinical response over time (p < 0.05), while TOFA showed the highest remission rate at 48 weeks. In females, TOFA was superior for clinical remission at 8 and 24 weeks (p < 0.05). Males had a higher late remission rate (p = 0.04) with an increased likelihood (aOR 1.958, 95%CI 1.088–3.524, p = 0.025). Endoscopic outcomes and faecal calprotectin levels showed no significant sex-specific differences. Conclusions: Sex-based profiling may guide individualised therapeutic strategies in UC patients in this setting.

Background Although adalimumab (ADM), golimumab (GOL), infliximab (IFX), tofacitinib (TFC), ustekinumab (UST) and vedolizumab (VDZ) have been shown efficacious for the treatment of moderate-to-severe ulcerative colitis (UC), data on treatment of patients with ulcerative proctitis (UP, inflammation up to 15cm from the anal verge) are scarce. We therefore aimed to evaluate the effect of these advanced therapies on UP. Methods We conducted a retrospective study in which we included 74 patients (median age at induction 41 (IQR 32–52) years) with active UP (Mayo endoscopy sub-score of ≥2) initiating a biological therapy (ADM, GOL, IFX, UST, and VDZ) or small molecule (TFC) in our tertiary referral centre between 02-2005 and 02-2021. The primary endpoint was steroid-free clinical remission at week 20 without prior need for dose optimization. Clinical remission was defined as a total Mayo score ≤2 with no individual sub-score &amp;gt;1. We also evaluated clinical response at short-term follow up (FU), as well as outcomes at long-term FU. The adapted Mayo score (sum of stool frequency subscore and rectal bleeding subscore) was used to rate the long-term treatment outcome, since colonoscopy was not routinely performed. We collected demographic, clinical, biochemical, endoscopic and treatment-related data. Results In total 74 patients (57% male) undergoing 93 courses of therapy for UP (16 ADM, 5 GOL, 19 IFX, 4 UST, 44 VDZ, 5 TFC) were included. In Table 1 the baseline characteristics are displayed. At week 20, 31/93 (33.3%) patients achieved steroid-free clinical remission, and 48/93 (51.6%) patients achieved steroid-free clinical response, both without prior need for dose optimization (Table 2). No predictors of steroid-free clinical remission could be identified. Of the 93 patients 91 had a FU under the index-therapy beyond week 20. The median duration of FU was 15.5 (IQR 3–31) months. Of the 31 patients with initial steroid-free clinical remission, 26 patients (83.8%) had sustained steroid-free clinical remission. The treatment-discontinuation-free survival of the entire study population is shown in Figure 1. Only one patient developed a serious adverse event, namely a tuberculosis infection. Conclusion Biological therapies and small molecules are a safe treatment for patients with UP, with an overall steroid-free clinical remission rate of 34.4% (32/93) at short-term FU. Our results are lower than in previous studies, probably because of the more stringent definitions of clinical remission and response.

Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis [UC], but head-to-head trials are lacking. We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-tumour necrosis factor [anti-TNF] failure in UC patients. In this multicentre study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses [inverse probability of treatment weighting]. Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity score analysis, steroid-free clinical remission [SFCR] [partial Mayo score ≤2] was achieved at week 16 in 38.0% and 40.3% of patients treated with vedolizumab and ustekinumab, respectively (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [0.39-3.13], p = 0.85). Rates of SFCR in patients exposed to one, two, and three lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% [p = 0.52], 44.4% vs 33.8% [p = 0.52], and 2.6% vs 19.1% [p = 0.027]. Endoscopic remission [SFCR and endoscopic Mayo score ≤1] and histological remission [SFCR, endoscopic remission, and Nancy histological index ≤1] at week 16 were achieved in respectively 5.3% vs 17.5% (aOR = 3.77 [1.25-11.36], p = 0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47-23.30], p = 0.012) in the vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51-2.08], p = 0.92) was observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR = 0.31 [0.11-0.82], p = 0.018) was significantly associated with a decreased rate of SFCR among patients treated with ustekinumab. While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC.

Positioning Infliximab and Vedolizumab in the Treatment of Moderate-to-Severe Ulcerative Colitis

Real-world data on ustekinumab for the treatment of pediatric Crohn's disease (CD) are limited. This study sought to evaluate the effectiveness, long-term durability, and safety of ustekinumab in the treatment of children with CD. A retrospective longitudinal cohort study of children with CD treated with ustekinumab from two large centers between 2015 and 2020 was performed. The primary outcome was frequency of steroid-free clinical remission at 1 year. Secondary outcomes included time to steroid-free clinical remission, frequency of clinical and biochemical remission, drug escalation and discontinuation, serum level data, and adverse events. Standard descriptive and comparative statistics were performed. Logistic regression was used to identify factors associated with steroid-free remission at 1 year. Kaplan-Meier curves were used to visualize time-to-event relationships for outcomes. A total of 101 patients were included. Median follow-up time on ustekinumab was 16.6 months (interquartile range [IQR]: 8.71-31.2) with drug failure in 28% at 1 year. Fifty-nine patients were in steroid-free clinical remission at 1 year. Higher baseline disease activity (odds ratio [OR]: 0.91 (95% confidence interval [CI]: 0.84-0.97), p = 0.01) and stricturing/penetrating disease phenotype (OR: 0.14 (95% CI: 0.03-0.65), p = 0.02) were associated with decreased likelihood of steroid-free clinical remission at 1-year. Ustekinumab drug escalation occurred in 70% of patients, and after escalation, 50 (70%) achieved clinical remission, and 49 (69%) achieved steroid-free remission at the last follow-up. Adverse events were rare and did not require therapy discontinuation. Ustekinumab is effective and safe in the treatment of children with CD. Escalation of therapy occurs frequently but results in sustained durability.