Ustekinumab In Crohn Research Articles

S1164 Head-to-Head Comparison of Biologics vs Ustekinumab for Crohn’s Disease: A Systematic Review of Efficacy

S1164 Head-to-Head Comparison of Biologics vs Ustekinumab for Crohn’s Disease: A Systematic Review of Efficacy

Vedolizumab versus ustekinumab in Crohn's disease with prior anti-tumor necrosis factor failure: an updated meta-analysis.

Ustekinumab and vedolizumab are key treatment options for Crohn's disease patients who fail anti-tumor necrosis factor (TNF) therapy. This updated meta-analysis aims to compare the efficacy and safety of these two drugs. We performed a systematic review in PubMed, Embase , and Cochrane databases searching for randomized and nonrandomized studies comparing vedolizumab versus ustekinumab in patients with Crohn's disease with previous anti-TNF failure or intolerance. The primary outcome was steroid-free clinical remission (SFR) at the pos-induction (12-16 weeks) and maintenance period (48-52 weeks). The odds ratio (OR) was used for binary outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I2 statistics. This meta-analysis included 11 studies and 2724 patients. There was a significant difference favoring ustekinumab in SFR at pos-induction (OR, 1.44; 95% CI, 1.11-1.88; P = 0.006; I2 = 27%) and maintenance periods (OR, 1.86; 95% CI, 1.23-2.82; P = 0.003; I2 = 80%), in clinical remission at pos-induction period (OR, 2.04; 95% CI, 1.58-2.63; P < 0.001; I2 = 3%), and in treatment discontinuation due to adverse events (OR, 0.31; 95% CI, 0.16-0.60; P < 0.001; I2 = 0%). In patients with Crohn's disease with prior anti-TNF failure, ustekinumab showed higher SFR during both the pos-induction and maintenance period and a lower rate of treatment discontinuation due to adverse events.

P1084 Persistence and efficacy of Ustekinumab in Crohn's disease after antiTNF failure. May the response of the second biologic therapy be better than the first one?

Abstract Background After antiTNF failure, a second antiTNF in Crohn's disease (CD) is effective to achieve and maintain remission, but only50% remain with the drug after 12 months of treatment. Ustekinumab (UST) has a better persistence as second-line treatment and is effective to induce and maintain long-term remission. Methods Retrospective and observational study retrieved from a prospective database of Crohn's disease patients treated with UST, after approval of Research Ethics Committee. Data were collected at the beginning of treatment and after 4, 8, 16, 24 weeks, 12, 24, 36, 48, 60 months and at the end of follow-up (UST discontinuation or March 2023 if treatment continues). Primary Objective evaluate the persistence with UST and clinical (Harvey-Bradshaw index (HBI)&amp;lt;4) and biological remission (C-reactive protein (CRP)&amp;lt;5 mg/dl and/or fecal calprotectin (FC)&amp;lt;250 mg/kg) in each period of follow up. Clinical remission in perianal disease was defined as absence of drainage both spontaneous and after soft pressure. Persistence of the first biologic therapy, reasons of treatment change, dose optimization, surgery, hospitalizations and adverse events were also evaluated. Results 68 patients were included (Table 1). Median survival of antiTNF is 1.65 years (IC95% 1.18-2.56). 72.06% patients receive antiTNF 1 year, 45.59% 2 years, 30.88% 3 years and only 8.82% are treated during 10 years. Persistence with UST was longer than with antiTNF. 93.2% of patients receive UST 1 year, 89.4% 2 years and 86.1% 3 years. There was a significant reduction of fecal calprotectin values during follow-up (p=0.0002). 7 patients with perianal disease achieved clinical remission (70.00%) and 4 complete fistula healing in magnetic resonance enterography (40.00%) at the end of follow-up. 60.29% patients received 90 mg every 8 weeks, but 36.76% required dose optimization (23.50% 90mg sq/4 weeks and 13.24%130mg/4 weeks ev). 86.76% continue UST at the end of follow-up, with a mean duration of treatment of 27.65 months (SD 18.27). 9 patients (13.24%) stopped treatment (1 primary non response, 5 loss of response, 3 adverse events). 11 patients (16.18%) needed surgery and hospitalization during follow up; 63.60% of them had stricturing disease. Conclusion Persistence with UST as a second line therapy was superior to antiTNF in first-line. 86.76% continued treatment with UST after 2 years. UST achieved early and long-term clinical remission in approximately two thirds of patients. 36.76% of patients required dose optimization. UST was effective in perianal disease after antiTNF failure. Figure 1 shows clinical remission in patients with basal HBI&amp;gt;4.

Long-term real-world data of ustekinumab in Crohn's disease: the Stockholm ustekinumab study.

Ustekinumab is used to treat inflammatory bowel disease mainly in patients failing anti-tumour necrosis factor (TNF)-agents. To provide real-world data in unselected patients with Crohn's disease (CD), treated with ustekinumab. Longitudinal retrospective study at four hospitals in Stockholm, Sweden. Disease activity (Harvey-Bradshaw index and physician global assessment), laboratory parameters, endoscopic findings and drug persistence were assessed. Follow-up data were obtained in patients that stopped ustekinumab. In total, 322 patients (median age 38 years, 48% women) were included. All had luminal disease and 22% also fistulizing disease. A total of 271 (84%) had failed ⩾1 and 148 (46%) ⩾2 anti-TNF drugs; 34% failed vedolizumab. At inclusion, 93% had active disease; 28% were on oral corticosteroids and 18% on thiopurines. The median follow-up on treatment was 13.5 months; overall 67% were followed at least 24 months. By intention to treat analysis, response rate at 3 and 12 months was 43% and 42%, respectively. Among patients with ongoing ustekinumab, 19% were in steroid-free remission at 3 months and 64% at 12 months. The median faecal calprotectin level decreased from 460 µg/g at baseline to 156 µg/g at 3 months and was 182 µg/g at 12 months. C-reactive protein remained stable at 4 mg/L whereas serum albumin increased slightly. About 31% of patients were withdrawn during the first 12 months, mainly due to persisting disease activity 21%, adverse events 5%, bowel surgery 0.6% or malignancy 0.3%. The overall persistence on ustekinumab was 88%, 51%, 34% and 20% at 3, 12, 24 and 36 months, respectively. Within 12 months following withdrawal of ustekinumab in 121 patients, 64% had active disease most of the time, 68% needed another biologic and 24% underwent surgery. Among difficult-to-treat patients with CD, ustekinumab was effective in the majority, with high drug persistence at 12 and 24 months in combination with a favourable safety profile.

Comments to “Cost per responder for vedolizumab and ustekinumab in Crohn’s disease patients after failure of TNF-α inhibitors in Italy”

Comments to “Cost per responder for vedolizumab and ustekinumab in Crohn’s disease patients after failure of TNF-α inhibitors in Italy”

P481 Visceral fat to skeletal muscle area ratio predicts for Ustekinumab loss of response.

Abstract Background Loss of response (LOR) to anti-TNFα therapy in inflammatory bowel disease (IBD) is common and biologic therapies such as anti-IL12/23 agents have shown greater durability in efficacy. Anti-TNFα LOR is increased in higher body mass index (BMI) patients however the evidence for the association between body composition or BMI and Ustekinumab’s (Ust) therapeutic response is limited, with the latter not impacting clinical efficacy in the ‘IM-MUNITI’ post-hoc analyses. This study’s primary aim was to evaluate the impact of body composition on time to LOR to Ustekinumab in Crohn’s disease (CD) patients. Methods 99 adult CD patients aged ≥16 yrs. from two tertiary IBD centres were studied retrospectively. Included patients had received Ust ≥12 weeks, abdominal imaging (CT or MRI) within 6 months of Ust induction, and documented follow up until 30th April 2022. A single experienced abdominal radiologist blinded to the clinical information measured the area of visceral fat (VFA), skeletal muscle (SMA), and subcutaneous fat at the mid L3 vertebral level. Each compartment was corrected for height2 to derive visceral fat (VFI), skeletal muscle (SMI) and subcutaneous fat (SFI) indices. VFA:SMA ratio was also calculated. Clinico-demographic details including therapeutic and surgical history were recorded. Kaplan Meir survival analyses, univariate and multivariate cox regression analyses were performed to evaluate factors predictive of Ust LOR. Results 99 patients met the inclusion criteria with mean age (±SE) 46.6yrs (±1.6) and 49 (49.5%) male. 63 (63.6%) patients were bio-experienced. Univariate Cox regression analyses of age, sex, BMI, peak C-reactive protein (CRP) and nadir Albumin level within 3 months of the CT/MRI scan, disease duration, prior biologic failure and concurrent immunomodulator used within 6 months of Ust induction showed that none of these were predictive of Ust LOR (P&amp;gt;0.05). There was a numerical trend for the middle VFI tertile (40.01-79.99cm2/m2) to having a lower risk for LOR compared to the lowest and highest VFI tertile (Fig. 1a), (HR=0.37, 95%CI= 0.13, 1.11, P=0.08), as well as a higher SMI for having a lower risk of LOR (Fig. 1b), (HR= 0.6, 95%CI= 0.24,1.31, P= 0.18), but these were not statistically significant. A higher VFA: SMA ratio however, was a significant predictor of LOR (HR=2.98, 95%CI 1.2,7.3, P= 0.02) (Fig. 1c), which persisted when it was adjusted on multivariate analysis for age, sex, albumin, CRP, BMI, disease duration, prior biologic failure and concurrent immunomodulator use (HR= 10.6, 95%CI 2.8-39.8, P=&amp;lt;0.0001). Conclusion The ratio of VFA:SMA, but not BMI, is a superior predictor of losing response to Ustekinumab.

OP03 Highly stable epigenome-wide peripheral blood DNA methylation signatures accurately predict endoscopic response to adalimumab, vedolizumab and ustekinumab in Crohn’s disease patients: The EPIC-CD study

Abstract Background Despite the proven efficacy of biological treatments in Crohn’s disease (CD), many patients fail to respond or lose response over time. Therefore, predictive biomarkers for treatment efficacy would be of extreme value. Previous epigenome-wide association studies associated differential DNA methylation with CD-specific phenotypes, suggesting a potential use in classification and prediction of response to treatment. Methods We prospectively collected and measured longitudinal peripheral blood DNA methylation profiles of 184 adult CD patients prior to (T1) and after a median of 28 weeks (T2) following biological treatment with Adalimumab (ADA), Vedolizumab (VEDO) or Ustekinumab (USTE) in a discovery (n=88) and independently collected internal validation cohort (n=96) using the Illumina EPIC BeadChip array. Response (R) was defined as the combination of endoscopic response (≥50% reduction in SES-CD score) and steroid-free clinical response (≥3 point drop in HBI or HBI ≤4 AND no systemic steroids) and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Biomarker identification and classification analyses were performed using stability selection gradient boosting on samples taken at T1 whereas samples taken at T2 and intraclass correlation (ICC) data were used to assess long-term stability of our identified CpG loci1. Results A total of 58 ADA-patients (NR=29, NNR=29), 64 VEDO-patients (NR=36, NNR=28) and 62 USTE-patients (NR=30, NNR=32) were included. Prior to treatment, at T1, we identified distinct panels of 100 ADA-, 22 VEDO- and 68 USTE-associated CpG loci that, in combination, predict clinical- and endoscopic response with high accuracy (AUC ADA=0.73, VEDO=0.89 and USTE=0.94) upon validation. Notably, for these CpG loci, methylation levels did not significantly differ between T1 and T2, implicating stability during both induction and maintenance treatment, irrespective of inflammatory status and therapeutic intervention. In addition, the majority of these CpG loci (&amp;gt;60%) demonstrated long-term hyper stability (ICC-values ≥0.90). Furthermore, genes annotated to the CpGs of interest suggest drug specific involvement in TNF-signaling, endothelial cell-cell adhesion, integrin dependent T-cell homing, the innate immune system and Th17/Treg differentiation, corroborating to the mode of action of each drug. Conclusion Here, we report on 3 validated panels of highly stable, epigenetic biomarkers that predict clinical and endoscopic response in CD patients treated with ADA, VEDO or USTE. Additional external- and clinical validation as part of EPIC-CD and the OMICROHN clinical trial are currently ongoing.

DOP51 Mucosa-associated microbial signatures associate with objective response prior to the start of anti-TNFα but not vedolizumab or ustekinumab in Crohn’s disease patients

Abstract Background Crohn’s disease (CD) is a complex immune-mediated disease of the gastrointestinal tract where the gut microbiome plays an important role. Current biological treatment options in CD include the anti-TNFα agents adalimumab (ADA) and infliximab (IFX), vedolizumab (VDZ), and ustekinumab (USTE). Finding biomarkers to predict therapy response is still a clinical unmet need, as the majority of CD patients fail to reach endoscopic remission within 1 year of treatment. While the majority of studies focus on fecal samples, mucosa-adherent bacterial signature could bring forth stable biomarkers. In this study, we sought to identify signatures of the adherent microbiome in intestinal biopsies aimed at differentiating responders (R) from non-responders (NR), prior to the start of biological treatment. Methods We prospectively collected paired ileal and colonic biopsies (stored snapfrozen in -80 ºC) from adult CD patients scheduled to start anti-TNFα (IFX and ADA), VDZ and USTE treatment during baseline endoscopies. After 6-12 months of follow-up, patients were classified as either R or NR based on endoscopic response (≥50% reduction in SES-CD score) in combination with steroid-free clinical response (≥3 point drop in HBI or HBI ≤4) and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a basal CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Microbiome composition of the biopsies was determined using 16S RNA gene V3V4 amplicon sequencing. Results For the anti-TNFα cohort, we included in total 36 CD patients (21R and 18 NR), for VDZ cohort a total of 44 patients (28 R and 16 NR) and for USTE cohort a total of 40 patients (20R and 20 NR).When comparing α-diversity and β-diversity between R and NR, we did not find significant differences in ileal and colonic samples at baseline for the VDZ and USTE cohorts. Notable, for the anti-TNFα cohort (table 1), we obtained significant differences when comparing α-diversity (p=0.028) and β-diversity between R and NR. We demonstrated differences between colonic R and NR in taxa abundance for ASVs associated with the phyla Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria (figure 1). Furthermore, ASVs associated with Firmicutes, Bacteroidetes, Actinobacteria are different in abundance between ileal R and NR (figure 2). Figure 1: Differential taxa abundance colonic R vs NR anti-TNFα Figure 2: Differential taxa abundance ileal R vs NR anti-TNFα Figure 3: graphical summary Conclusion Here, we investigated the microbial signature of R and NR before the start of treatment of three separate cohorts and we demonstrated that the mucosa-associated microbiome differentiates R and NR to anti-TNFα therapy. Further analyses as part of the EPIC Pioneer study, are ongoing.

Cost per responder for vedolizumab and ustekinumab in Crohn’s disease patients after failure of TNF-α inhibitors in Italy

Background: The aim of this economic evaluation was to compare the cost per responder between vedolizumab and ustekinumab in patients with Crohn’s disease (CD) after failure of tumor necrosis factor-α inhibitors in Italy. Methods: Clinical efficacy was assessed using the results of an Italian large multicentre observational retrospective cohort study. The aim of the study was to compare the effectiveness of ustekinumab and vedolizumab as second line therapy in Crohn’s disease patients in which tumour necrosis factor-α inhibitors failed. Clinical efficacy of vedolizumab and ustekinumab was measured by clinical response and clinical remission. Treatment costs were based on the number of administrations at 26 or 52 weeks. Cost per responder, based on clinical efficacy and clinical response, was used as a cost-effectiveness indicator. Results: Regardless of the clinical efficacy measure used and the treatment duration considered, the cost per responder was consistently lower for vedolizumab compared with ustekinumab on all clinical measures. Considering the clinical response, the cost per responder at 26 weeks was € 15,640 for vedolizumab and € 23,667 for ustekinumab and at 52 weeks was € 23,927 for vedolizumab and € 30,820 for ustekinumab. Considering the clinical remission, the cost per responder at 26 weeks was € 22,832 for vedolizumab and € 33,786 for ustekinumab and at 52 weeks was € 29,488 for vedolizumab and € 46,847 for ustekinumab. Sensitivity analysis confirmed the validity of results. Conclusion: These results suggest that vedolizumab is a cost-effective option compared with ustekinumab from the perspective of the Italian health service in patients with CD after failure of TNF-α inhibitors.

Effectiveness and safety of ustekinumab in bio-naïve Crohn's disease patients: a multicentre observational retrospective study.

Clinical trials have demonstrated the efficacy and safety of ustekinumab in Crohn's disease (CD). However, more data are necessary on the effectiveness of ustekinumab in bio-naïve patients in real-life studies. The aim of our study was to evaluate the effectiveness and safety of ustekinumab in patients with CD refractory or intolerant to conventional therapy and without previous exposure to biological drugs. We performed a nationwide, observational, retrospective, multicentre study including patients with CD, in which ustekinumab was used as the first biological drug. The corticosteroid-free clinical and biological response and remission were analysed at weeks 16, 24, 52 and 72. Clinical remission was defined as Harvey-Bradshaw index ⩽ 4 and biological remission as a faecal calprotectin (FC) <250 mg/g and C-reactive protein (CRP) <5 mg/L. Moreover, the persistence of the treatment and any adverse events were assessed. In all, 84 patients were included in the study, males and females were equally distributed, with a median age of 63 years [interquartile range (IQR): 51-75] and a median disease duration of 6.8 years [IQR: 3.6-17.0]. The majority (86.9%) of patients were treated with ustekinumab as monotherapy, without concomitant immunosuppressive medication. The proportion of patients in corticosteroid-free clinical remission or response at weeks 16, 24, 52 and 72 was 93.3% (56/60), 86.8% (46/53), 82.2% (37/45) and 71.4% (30/42), respectively. CRP returned to normal values in 47.6%, 43.2%, 50% and 52.4% of patients at weeks 16, 24, 52 and 72, respectively. Similarly, FC was normalized in 45.5%, 45.5%, 48.6% and 50% of patients at weeks 16, 24, 52 and 72, respectively. The cumulative probability of remaining on ustekinumab treatment was 84.8% (95% confidence interval: 73.3-91.6) after 72 weeks. Ustekinumab was discontinued in 10 patients (11.9%) within 72 weeks of follow-up. Reasons for discontinuing treatment were lack of response (n = 4), adverse events (n = 4) and death (n = 2). There were no discontinuations because of stable remission. Ustekinumab was effective and safe in Spanish bio-naïve CD patients, showing a quicker and more durable response than obtained in patients with previous biological treatment. In this cohort of bio-naïve patients starting on ustekinumab, the average age was high. Effectiveness and safety of ustekinumab in Crohn's disease patients not previously exposed to other biological therapies Evidence on the use of ustekinumab in biological naïve real-world patients is scarce. Here, we present real-world data evaluating the effectiveness and safety of ustekinumab in 84 bio-naïve patients from 17 Spanish hospitals. We report high rates of both clinical and biological remission. Moreover, after 1 year, 90.4% of patients remained being treated with ustekinumab. The safety profile of ustekinumab in these patient population was favourable. In conclusion, our results show that in patients with CD, ustekinumab could be considered as first-line therapy.

Successful treatment of ileocolonic anastomotic stricture with ustekinumab in Crohn’s disease: a case report

Successful treatment of ileocolonic anastomotic stricture with ustekinumab in Crohn’s disease: a case report

S2752 New Onset Inflammatory Bowel Disease Due to Anti-IL-17 Therapy With a Unique Twist

Introduction: Both psoriasis and inflammatory bowel disease (IBD) are driven by inappropriate immune responses. Antibody therapy to the pro-inflammatory cytokine interlukin-17 (IL-17) has been associated with de-novo IBD. We describe two cases of new onset IBD in patients started on anti-IL-17 antibodies ixekizumab and secukinumab, both with unique clinical courses. Case Description/Methods: Patient 1: A 47-year-old woman with hypertension, type 2 diabetes mellitus, and psoriasis presented with 2 weeks of abdominal cramping and rectal bleeding. She had been stable on brodalumab but switched to ixekizumab two months prior to presentation. She denied a family history of IBD. Her labs were notable for mild leukocytosis, thrombocytosis, and elevated CRP. CT showed evidence of descending colitis. Colonoscopy revealed multifocal colitis, with biopsies suggesting IBD or drug-induced colitis. She was started on ustekinumab for Crohn's disease which resolved her GI symptoms. Repeat colonoscopy one year later confirmed endoscopic and histologic remission. Patient 2: A 36-year-old woman with pre-diabetes and psoriasis presented with watery diarrhea, abdominal cramping and stool discharge per vagina one week after switching from adalimumab to secukinumab. She reported a family history of Crohn’s disease in her mother. Her labs were notable for leukocytosis, thrombocytosis, and elevated CRP. CT revealed left sided colitis and MR showed a rectovaginal fistula. Colonoscopy revealed ileo-pancolitis and biopsies were consistent with IBD or drug-induced colitis. Secukinumab was discontinued. One week after discharge, the patient reported cessation of stool discharge per vagina and improvement in diarrhea and abdominal pain. Discussion: These case reports add to the literature that describes a relationship between IL-17 antagonism and IBD. Patient 1 is unique in that she was exposed to two different IL-17 antibodies prior to her diagnosis of IBD and she represents the first reported case of ustekinumab rescue of ixekizumab-induced IBD. Patient 2 is the only case of IL-17-induced IBD with a rectovaginal fistula described in the literature. Although recent meta-analyses do not show a statistically significant relationship between anti-IL-17 therapy and de-novo IBD, further study is warranted. Providers should avoid anti-IL-17 therapies for patients with a personal history of IBD and should monitor patients on these therapies closely for the development of IBD.

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn’s Disease

In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure. STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat. Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ= 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value= 73%). In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients. gov number: NCT03107793.

Ustekinumab in Crohn’s Disease: New Data for Positioning in Treatment Algorithm

The treatment of patients with moderate to severe Crohn’s disease [CD] is still challenging. Therapeutic options include steroids, immunosuppressants, anti-TNFα agents, vedolizumab, and ustekinumab. Ustekinumab is a monoclonal antibody blocking the p40 subunit of IL-12 and IL-23. It showed to be effective and safe in randomised clinical trials and real-life studies and is currently approved for the management of CD patients who are naive to biologics and those who have already been treated with such medications. However, to date, a detailed and approved therapeutic algorithm is not available. The aim of this review is to report the most recent and updated data on the efficacy and safety of ustekinumab for the treatment of patients with moderate to severe CD and to define the optimal management of these patients.

Real-world Short-term Effectiveness of Ustekinumab in Crohn's Disease: Results from a Multicenter, Prospective Study in China.

Lay Summary Ustekinumab effectively induced a clinical response and clinical remission, with remission rates superior to those in the UNITI-1 study. Ustekinumab is more effective in biologic-naive patients with Crohn’s disease than those who were not responsive to anti–tumor necrosis factor treatment.

Treat to target with ustekinumab for Crohn's disease

The clinical care strategy in Crohn's disease has evolved over time to emphasise a treat-to-target approach in which treatment effectiveness is determined using specific objective treatment goals, in particular healing of the intestinal mucosa on endoscopy.1 The STRIDE-II initiative of the International Organisation∼ for the Study of Inflammatory Bowel Disease defined clinical and endoscopic remission as ultimate targets for Crohn's disease and recommended regular assessment of short-term and intermediate-term targets to adjust therapy for tight control of inflammation.

Treatment patterns, persistence with therapy, and outcomes of ustekinumab in Crohn's disease: Real-world data analysis.

Background and AimIn 2017, ustekinumab (UST) was included in Israel's National Basket of Health Services for treatment of biologic‐experienced Crohn's disease (CD) patients with moderately to severely active disease. This study aims to provide real‐world evidence on persistence and clinical outcomes among early users of UST.MethodsThis retrospective cohort study was conducted using data from Maccabi Healthcare Services (MHS; 2.5‐million‐member state‐mandated health provider, Israel). Adult patients with a CD diagnosis code who had ≥1 dispensed UST prescription in 2017–2018 and at least 12 months of prior continuous health plan enrollment were included. Outcomes, including treatment discontinuation, dose‐escalation (based on shortened intervals between purchases), CD‐related surgery, CD‐related hospitalization, corticosteroid (CS) discontinuation, and use of opioids were evaluated from the date of first dispensed UST through the end of 2019 using Kaplan–Meier analysis.ResultsA total of 162 eligible patients (81 [49.4%] female; median age 34.4 years [IQR 23.2–46.3]; median years since CD diagnosis 8.6 [IQR 4·8–16.0]) were enrolled in the study. Discontinuation rate after 365 and 540 days of follow‐up was 27.8% and 35.6%. Dose escalation was estimated at 15.4% and 28.6%, respectively. The first‐year cumulative rate of CD‐related surgery and CD‐related hospitalization were estimated at 4.7% and 9.8%, respectively.ConclusionIn this real‐world CD cohort of UST users, results suggest persistence is relatively high as compared to other biologics for CD. Comparative effectiveness of different biologic treatments for CD in this population should be further explored.

P334 Effectiveness and safety of ustekinumab in Crohn’s disease: short and long-term results of a multi-refractory cohort

Abstract Background To evaluate the short and long-term effectiveness and safety of ustekinumab (UST) in a real-world multirefractory Crohn’s disease (CD) cohort. Methods An observational, retrospective and single-center study of CD patients treated with UST since June, 2017, with at least, 16 weeks of treatment. All patients were identified in the ENEIDA Registry. Demographic, disease, and outcome variables were collected. Clinical remission and response (measured by the physician global assessment and Harvey Bradshaw Index (HBI) score) as well as biological response (measured by C-reactive protein (CRP) and fecal calprotectin) were evaluated at weeks, 16, 26, 52 and at the end of the follow-up. Kaplan-Meier survival curves were performed to analyze drug persistence and multivariate analysis to identify predictors of response. Treatment-related adverse events were assessed. Results 64 patients included, mean age of, 49 years (35–60), 56.2% men and CD duration of, 15.5 years (8–22)., 53% had ileocolic involvement and, 59% stricturing and/or penetrating disease., 40% presented perianal disease, 35% active smoking and, 33% patients had extraintestinal manifestations., 92.2% had prior failure to biologics (44% failed at, 1 and, 48.5% failed ³2) and, 9.4% had failed to vedolizumab., 57.8% required prior surgery for IBD., 40.6% initiated UST for treatment of postoperative recurrence. Baseline clinical activity was present in, 87.5% patients (60% moderate-severe activity). Rates of clinical remission, response and no response were, respectively, 40.7%, 47.5% and, 12% at week, 16;, 56.8%, 32.8% and, 10.3% at week, 26;, 60%, 30% y, 10% at week, 52. At the end of the follow-up, more than, 2/3 of patients (76.3%) had clinical response or remission (figure 1). Overall, a significant reduction of HBI score was observed from baseline to week, 16 and maintained at W26 and W52 (figure 2). Likewise, a biological response was observed with a significant reduction of CRP (baseline of, 26.7 mg/dL) at different times of evaluation (figure 3)., 74.9% continued with UST for up to three years (figure 4). In the multivariate analysis, the only independent factor associated with non-response was previous therapy with vedolizumab (OR:, 0.055 [IC95%:, 0.005–0.551], p=0.001). The safety profile was favorable; only, 2 patients (3.1%) stopped the drug due to side effects (arthralgias and bladder neoplasia). Fig, 1. Remission, response, and no response rates. Fig, 2. Evolution of HBI score from baseline to W52. Fig, 3. Evolution of CRP from baseline to W52. Fig, 4. Persistence of ustekinumab during the follow-up period. Conclusion UST is effective and safe in a real-life refractory CD cohort, with a persistence of the drug of, 75% at, 3 years. Previous vedolizumab therapy is associated with UST treatment failure.

DOP88 Long-term real-world data of ustekinumab in Crohn’s Disease – the Stockholm ustekinumab study – STOCUSTE

Abstract Background Ustekinumab (UST), an anti-interleukin-12/23 antibody, has successfully been introduced in the treatment of IBD, mainly in patients failing anti-TNF-agents. The STOCUSTE study includes IBD patients treated with UST at four teaching hospitals in Stockholm to provide long-term follow-up data. Here, we report the outcome in Crohn’s disease over the first 12 months. Methods This retrospective study includes patients diagnosed with Crohn’s disease and treated with UST who were followed until withdrawal of treatment for any reason, or until end of study, July 31, 2021. Disease activity (Harvey-Bradshaw Index (HBI); Physician Global Assessment (PGA), laboratory parameters and drug persistence were assessed. The primary outcome was remission (HBI ≤4; PGA = 0) and response (decrease HBI ≥3; PGA ≥1 from baseline) at 3 and 12 months, respectively. Results 120 patients, 61 women (51%), with a median age of 27 (IQR 27) at start of UST were included. All patients had luminal disease and 19 (16%) also fistulizing disease. 109 (91%) had failed ≥1 and 59 (49%) ≥2 anti-TNF drugs. In addition, 50 patients (42%) failed vedolizumab. At inclusion, 106 (88%) had active disease; 40 (33%) were on corticosteroid treatment and 22 (18%) on thiopurines. The persistence on UST was high, 93% at 3 months and 56% at 12 months. Of patients on UST at 3 months, 38% were in remission, and, at 12 months, 53%. An additional 26% were in response at 12 months. Of the 40 patients initially on corticosteroids, 17 (43%) and 28 (70%) had stopped steroids at 3 and 12 months, respectively. The median faecal calprotectin level declined from 272 (90–1763) at baseline to 75 (49–99) µg/g at 3 months (p&amp;lt;0.01). There was a slight decrease in CRP over 12 months, from 3 (2–12) to 1 (1–2) mg/l, together with increases in haemoglobin and serum albumin (n.s). Withdrawal from treatment during the first 12 months was 44% (53/120), mainly due to persisting disease activity. Four patients were withdrawn due to adverse events, three needed bowel surgery, two had malignancy and one patient suffered from systemic infection. Conclusion In this group of difficult-to-treat patients with Crohn’s disease, UST was shown to be effective in the majority, with high drug persistence at 12 months in combination with a favorable safety profile.