Background and aimFew studies have evaluated the impact of biologic therapy on endoscopic findings and stenoses of small intestinal lesions in Crohn’s disease (CD). This study aimed to compare the endoscopic effectiveness and stenotic changes induced by anti-tumor necrosis factor inhibitors (anti-TNF) and ustekinumab (UST) in patients with CD, along with histological and molecular comparisons of stenosis between the groups.MethodsWe retrospectively enrolled patients with CD who underwent balloon-assisted enteroscopy before and after initiating anti-TNF therapy or UST. For pathological and molecular evaluation of stenosis, we analyzed resected ileal specimens from patients with CD treated with anti-TNF, UST, or those who were biologic-naïve (bio-naïve).ResultsThe anti-TNF group (n = 18) showed a higher improvement rate in endoscopic activity scores compared to the UST group (n = 19). However, 27.8% of patients in the anti-TNF group experienced worsened stenosis, significantly higher than that in the UST group (0%). Histologically, the UST group showed a lower fibrosis score and reduced collagen III protein expression in the inactive ileum compared to both the anti-TNF and bio-naïve groups. Additionally, the UST group exhibited lower mRNA levels of IL22, TGFB1, and TNF in both active and inactive ilea. Immunostaining revealed fewer α-smooth muscle actin-positive cells in the UST group compared to the anti-TNF and bio-naïve groups in both active and inactive ileum.ConclusionThis study suggests that inhibition of the IL-22/TGF-β pathway by anti-IL-23 treatment with UST may reduce myofibroblasts and improve small intestinal fibrous stenosis in patients with CD.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12876-025-04386-w.

Background:Unlike infliximab, ustekinumab (UST) has shown inconsistent associations between drug concentration and clinical efficacy across studies, with varying cutoff therapeutic trough levels (TLs) proposed.Objectives:Given that patients have different histories of biologic use, we aimed to evaluate whether therapeutic TLs of ustekinumab require optimization in patients with Crohn’s disease.Design:Cohort study.Methods:To assess whether ustekinumab has a potential therapeutic cutoff value, we evaluated and compared its 1-year TLs in 14 biologic-naïve patients and in 26 patients who were prescribed the drug after experiencing a loss of response to previous biologic therapies.Results:The mean TL in the biologic-naïve patients was 3.41 µg/mL, which was significantly higher than that in the biologic-experienced patients (1.46 µg/mL; p = 0.007). The duration of prior biologic therapy and disease activity correlated with the ustekinumab TLs. With regard to the optimal cutoff value for predicting deep remission at 1 year, the threshold was 2.34 µg/mL for the biologic-naïve patients (area under the receiver operating characteristic curve (AUC) = 0.909, p < 0.001) and 1.18 µg/mL for the biologic-experienced patients (AUC = 0.892, p < 0.001).Conclusion:Ustekinumab TLs in patients may differ according to their prior exposure to biologic agents and disease activity. Accordingly, rather than applying a uniform threshold, ustekinumab levels should be interpreted using individualized, patient-specific strategies in clinical practice.

Background/Objectives: Crohn’s disease (CD) is a chronic immune-mediated disorder with heterogeneous response to biologic therapies. Ustekinumab (UST), an anti-IL-12/23 monoclonal antibody, is effective in CD, but predictive biomarkers of treatment response remain lacking. This study aimed to investigate cytokine dynamics during UST induction and to evaluate their association with clinical and biochemical outcomes in an observational cohort of CD patients. Methods: We prospectively recruited 31 adult patients with moderate-to-severe active CD initiating UST therapy at a tertiary referral center. Peripheral blood and stool samples were collected at baseline and weeks 4, 8, and 16. UST trough concentrations, C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin, albumin, and 13 serum cytokines (including IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17, IL-23, TNF-α, and OSM) were analyzed. Response was defined as a ≥70% reduction in FC at week 16, or, alternatively, CRP < 5 mg/L or a Harvey–Bradshaw Index < 3. Results: Eighteen patients (58%) achieved response at week 16. Responders showed significant reductions in FC, CRP, and disease activity, while non-responders exhibited limited biochemical improvement. Overall, UST induction was associated with a global decrease in proinflammatory cytokines, particularly TNF-α and IL-1β. Responders displayed distinct cytokine patterns, with higher IL-13 levels at week 8 and lower IL-8 concentrations at week 16 compared with non-responders. UST trough levels tended to be higher in responders, and inverse correlations were observed between drug concentrations and several cytokines, including IL-6, IL-8, IL-13, and IL-23. Conclusions: UST induction leads to measurable immunological changes in CD, with differential cytokine dynamics distinguishing responders from non-responders. These findings support the potential of cytokine signatures, in combination with therapeutic drug monitoring, as pharmacodynamic biomarkers to optimize personalized treatment strategies in CD.

ABSTRACTThe gut microbiota composition in Crohn's disease (CD) patients may influence their response to ustekinumab (UST) therapy. A total of 51 patients with active CD undergoing UST therapy were prospectively enrolled. Clinical activity was evaluated using the Crohn's Disease Activity Index (CDAI), and faecal microbiota were characterised by 16S rRNA sequencing at baseline and week 24. Microbial compositional and functional alterations were assessed, and their correlations with clinical outcomes were examined. At week 24, 46.7% of patients achieved clinical remission and 82.2% achieved clinical response. At baseline, Megamonas (p = 0.009) and Erysipelatoclostridium (p = 0.030) were enriched in the remission group, whereas Fusobacterium (p = 0.016) was more abundant in the non‐remission group and correlated positively with C‐reactive protein (CRP) but negatively with body mass index (BMI) and serum albumin (ALB). Longitudinal analysis showed that CR patients exhibited increased Clostridium sensu stricto 1 (p = 0.028) and decreased Granulicatella (p = 0.043) after 24 weeks. This study provides real‐world evidence supporting the clinical efficacy of UST in Asian patients with active CD. The observed association between elevated baseline Fusobacterium abundance and poorer treatment response suggests a potential microbial influence on therapeutic outcomes. These findings highlight the potential of Fusobacterium as a predictive biomarker for UST response and could provide a rationale for integrating microbiota‐modulating strategies to enhance the efficacy of biologics in the future.

BackgroundLimited evidence exists on the long-term efficacy of ustekinumab (UST) in perianal fistulizing Crohn’s disease (PFCD), and the optimal UST trough level for predicting fistula remission remains uncertain. This study aimed to assess both short- and long-term effectiveness of UST in PFCD and to identify thresholds predicting fistula clinical remission.MethodsThis retrospective cohort included 89 PFCD patients treated with UST. Evaluations utilized the Harvey-Bradshaw Index (HBI), Perianal Crohn’s Disease Activity Index (PDAI), and Fistula Drainage Assessment (FDA). Magnetic resonance imaging (MRI) with the Van Assche Index (VAI) was performed at 52 weeks. Receiver operating characteristic (ROC) curves identified UST trough levels predictive of clinical remission.ResultsThe fistula clinical remission rates were 66.3% (59/89) at 16/20 weeks and 74.2% (66/89) at 52 weeks. Biochemical markers, including CRP, ESR, and PLT, significantly decreased, while RBC and HB levels increased after treatment (p < 0.05). MRI showed fistula improvement in 54.7% (35/64) of patients and complete healing in 21.8% (14/64). Comparative analysis revealed that anti-TNF-naïve patients had significantly higher rates of fistula remission, whereas seton insertion did not affect long-term fistula healing. ROC analysis identified UST trough concentrations ≥3.95 µg/mL at 16/20 weeks as predictive of clinical fistula remission (AUC: 0.791; sensitivity: 73.8%; specificity: 78.6%).ConclusionUST achieves 74.2% fistula clinical remission at 52 weeks in PFCD, with trough concentrations at 16/20 weeks predictive of clinical remission. These findings support the use of therapeutic drug monitoring(TDM) to optimize clinical outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12876-025-04323-x.

Background/Objectives: Ustekinumab (UST) and upadacitinib (UPA) are molecules that have been used in patients with ulcerative colitis (UC) since 2019 and 2022, respectively. Both agents are generally preferred for biologically experienced UC patients. However, the number of head-to-head studies comparing the efficacy and adverse events of UST and UPA in this patient group is limited. Methods: This was a retrospective cohort study evaluating the efficacy and safety of UST (n = 57) and UPA (n = 32) in biologically experienced UC patients during the induction and 24-week maintenance treatment periods. Most patients in both groups had received prior anti-TNF treatment (98.2% and 96.9%, respectively). Clinical response and remission rates were determined based on the partial Mayo score (PMS). Additionally, patients’ pre-treatment laboratory parameters were compared with their results at week 24. Results: During the induction phase, clinical response and remission were achieved in 84.2% and 43.9% of the UST group and 93.8% and 50% of the UPA group, respectively (OR [95% CI] = 2.81 [0.57–6.87] and 1.28 [0.54–3.05]). At week 24, the clinical response and remission rates in the UST and UPA groups were similar (77.1% vs. 80% and 58.3% vs. 63.3%, respectively). No statistically significant difference was found between the groups (p > 0.05). Both UST and UPA provided a marked reduction in fecal calprotectin and CRP levels. Regarding safety, UPA treatment led to increased total, LDL, and HDL cholesterol levels, whereas UST did not. In both groups, glucose; HbA1c; and thyroid, renal, and liver functions remained stable. No serious adverse events were observed in either group. At week 24, treatment continuation rates were 68.4% (n = 39) for UST and 78.2% (n = 25) for UPA (OR = 0.61 [0.22–1.66]). Conclusions: In biologically experienced ulcerative colitis, both UST and UPA are effective and safe treatment options. This study did not statistically demonstrate the superiority of UPA over UST. Given the preliminary nature and limited patient numbers of this investigation, our findings require confirmation through future multicenter, large-scale, and long-term prospective studies.

ObjectivesWe investigated whether body composition parameters assessed on baseline computed tomography enterography (CTE) could predict transmural healing (TH) in patients with Crohn’s disease (CD) receiving Ustekinumab (UST).Materials and methodsAdult patients with active CD treated with standard UST from August 2020 to August 2022 were enrolled. Body composition, including creeping fat (CF, mesenteric creeping fat index (MCFI) and fibrofatty proliferation score), skeletal muscle, visceral adipose, and subcutaneous adipose-related parameters were assessed on baseline CTE. Cox regression analysis was performed to identify independent predictors of TH.ResultsThis study included 113 patients, and TH occurred in 26 (23. 0%) patients. The results of the univariable analysis indicated a statistically significant association of the presence of sarcopenia, higher MCFI score, and higher fibrofatty proliferation score with an increased failure rate of TH. We found no evidence that skeletal muscle index, subcutaneous adipose index, visceral adipose index, and visceral adipose/subcutaneous adipose area ratio were associated with TH. Multivariable analysis revealed that sarcopenia (Hazard ratio (HR): 0.35, 95% CI: 0.14–0.87, p = 0.023), MCFI score (HR: 0.67, 95% CI: 0.49–0.91, p = 0.010) and fibrofatty proliferation score (HR: 0.50, 95% CI: 0.29–0.85, p = 0.011) remained significant. MCFI score (χ2-df = 5.58) was the most critical factor for TH prediction, followed by fibrofatty proliferation score (χ2-df = 5.43) and sarcopenia (χ2-df = 4.12).ConclusionsAmong all the body composition parameters, MCFI and fibrofatty proliferation score assessed on baseline CTE were independently associated with TH, and they demonstrated greater predictive efficacy compared to sarcopenia.Critical relevance statementCreeping fat on baseline CTE was an important predictive factor for transmural healing in patients with Crohn’s disease receiving Ustekinumab, which enables early risk stratification of patients and has potential implications for decision-making.Key PointsIdentifying predictors of transmural healing may provide insight into earlier dose optimization to improve the rate of transmural healing.Higher creeping fat scores (mesenteric creeping fat index and fibrofatty proliferation) were independently associated with a lower rate of transmural healing.Mesenteric creeping fat index and fibrofatty proliferation score demonstrated greater predictive efficacy compared to sarcopenia.Graphical

BackgroundFor patients with Crohn’s disease (CD) who develop secondary loss of response (SLR) to infliximab (IFX), it remains unclear whether IFX optimization or direct conversion to ustekinumab (UST) offers better outcomes. This study aimed to identify risk factors for IFX optimization failure and to compare the clinical efficacy of IFX optimization versus UST conversion.MethodsWe retrospectively analyzed clinical data from patients with CD admitted to the First Affiliated Hospital of Wannan Medical College and the First Affiliated Hospital of the University of Science and Technology of China between January 2017 and January 2025. Rates of clinical, steroid-free, and endoscopic remission were assessed. Univariate and multivariate analyses were performed to identify independent risk factors for IFX optimization failure.ResultsIn total, 65 patients with CD who developed SLR to IFX were included. The patients were divided into three groups: IFX optimization success (Group 1), IFX optimization failure followed by UST (Group 2), and direct UST conversion (Group 3). Of the 28 patients who received IFX optimization, only 6 achieved success, yielding a failure rate of 78.6%. Multivariate logistic regression showed that a baseline albumin concentration of < 40 g/L was an independent predictor of IFX optimization failure (p = 0.047, odds ratio: 15.00, 95% confidence interval: 1.031–218.300). When comparing UST-treated groups, the rate of clinical response at week 6 was significantly higher in Group 3 than in Group 2 (35.1% vs. 9.1%, p = 0.039). By week 52, clinical remission rates were similar (86.4% vs. 89.2%, p > 0.05).ConclusionsGiven the high failure rate of IFX optimization, direct conversion to UST may provide greater benefit and reduce treatment costs in patients with CD who develop SLR to IFX.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12876-025-04319-7.

Background/Objectives: Ustekinumab (UST) has shown to be effective and safe in patients with moderate-to-severe UC in the UNIFI trials. However, real-life data on its effectiveness, particularly for histological remission, are still limited. To assess the real-world effectiveness and safety of UST in refractory UC patients. Methodology: This multicentric, retrospective cohort study included UC patients treated with UST from September 2020 to June 2023. The primary endpoint was steroid-free clinical remission (partial Mayo score of ≤2 with no subscore > 1) at week 16. Secondary endpoints included clinical, endoscopic, histological response and remission. Results: 120 patients with moderate–severe UC were included across 16 centers. Median disease duration was 11 years (1–74 y), and 81 (68%) patients had previously failed ≥2 biological therapies. At week 16, steroid-free clinical remission was achieved in 34% (41/120) of patients, with endoscopic and histological remission in, respectively, 19% (23/120) and 8% (3/37). By week 52, 44% (38/85) of patients were in steroid-free clinical remission, with endoscopic and histological remission, respectively, in 25% (13/52) and 11% (5/45). Active smoking was a negative predictor for steroid-free remission (OR 0.412, p = 0.011). UST drug persistence by week 52 was 70.8%. Active smoking (aOR 3.058, p = 0.02), prior vedolizumab non-response (OR 2.592, p = 0.03) and a high Nancy baseline score (OR 2.46, p = 0.04) were associated with early UST failure. No new safety signals were observed. Conclusions: In this real-life cohort, UST shows acceptable remission rates and high treatment persistence in refractory UC patients, with a favorable safety profile.

There is a lack of safety and efficacy data for newer biologic agents among adults ≥ 60years old with inflammatory bowel disease (IBD) given their limited inclusion in clinical trials. We conducted a retrospective cohort study comparing the safety and efficacy of ustekinumab (UST) or vedolizumab (VDZ) use in older adults as compared to younger adults with IBD. This single-center retrospective study compared individuals 18 to 59years old to individuals ≥ 60years old with a confirmed diagnosis of IBD who began VDZ or UST treatment between 2014 and 2022. The primary efficacy and safety outcomes were endoscopic remission and serious infection, respectively. Secondary outcomes included endoscopic response, clinical remission, and non-severe adverse events. Multivariable regression was used to identify factors independently associated with safety and efficacy. Overall, 948 individuals were included, with 779 (82.2%) < 60years-old. In total, 548 (57.8%) had Crohn's disease, 367 (38.7%) had ulcerative colitis, 33 (3.5%) had indeterminate colitis, and a total of 403 individuals (42.5%) initiated VDZ whereas 545 (57.5%) initiated UST. When assessing efficacy, younger and older individuals had comparable rates of endoscopic remission (< 60years-old 27.5% vs 29.0% ≥ 60years-old, p = 0.69) as well as clinical remission (< 60years-old 26.4% vs 26.6% ≥ 60years-old, p = 0.96). When assessing safety, serious infection rates (< 60years-old 8.9% vs 8.9% ≥ 60years-old, p = 0.99) and non-severe adverse event rates (< 60years-old 12.3% vs 8.9% ≥ 60years-old, p = 0.21) were not significantly different. On multivariable analysis, measures of disease severity (prior advanced therapy use, prior corticosteroid use, severe disease) significantly decreased the odds of endoscopic and clinical remission. Additionally, prior advanced therapy use and the presence of comorbidities increased the odds of serious infections. The use of UST and VDZ had similar efficacy and safety outcomes in older adults as compared to younger individuals with IBD. Decisions to utilize these biologics should be driven by overall disease burden and comorbidities, and not be deferred due to advanced chronological age alone.

Crohn disease (CD) treatment incurs high costs due to biologics and frequent hospitalizations. Insurance policies favoring hospitalization may increase costs by discouraging outpatient care. We conducted a mediation analysis to examine whether balanced inpatient and outpatient reimbursement reduces CD treatment costs and improves biologic persistence, mediated by outpatient treatment. In this retrospective cohort study, we analyzed 133 CD patients initiating ustekinumab (UST) in 2022 at a tertiary hospital. The exposure was balanced insurance coverage (Hangzhou Medical Insurance) versus hospitalization-favored coverage (Zhejiang Province Card Insurance). The mediator was outpatient UST treatment. Primary outcome was total CD-related treatment costs; secondary outcomes included CD-related inpatient stays, outpatient visits, and UST persistence. Causal mediation analysis, adjusted for age, gender, and disease severity, estimated natural direct effects, natural indirect effects (NIE), and proportion mediated. Patients with balanced coverage had lower total CD-related costs (adjusted mean difference: −CNY 6362; 95% CI: −11,658 to − 1067), fully mediated by increased outpatient treatment (NIE: −CNY 10,125; 95% CI: −15,920 to − 4330; proportion mediated: 100%). They had fewer inpatient stays (−1.64; 95% CI: −2.10 to − 1.18; NIE: −0.84; 95% CI: −1.33 to − 0.37; proportion mediated: 50%) and more outpatient visits (6.53; 95% CI: 5.48 to 7.57). Balanced coverage reduced UST discontinuation risk by 73% (adjusted HR: 0.27; 95% CI: 0.10–0.74), not mediated by outpatient treatment. Balanced insurance coverage reduces CD treatment costs and inpatient stays via increased outpatient treatment and improves UST persistence independently. Policymakers should equalize coverage to optimize CD care efficiency.

A comparative analysis of persistence of advanced therapies among patients with inflammatory bowel disease in Taiwan.

ABSTRACT Background Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn’s disease (CD). Although UST has demonstrated good efficacy and safety in CD, long-term real-world data in Chinese patients are relatively scarce. Methods A single-center, observational retrospective study was conducted in the First Affiliated Hospital of Anhui Medical University. Comprehensive baseline demographic characteristics, clinical parameters, potential predictors of clinical remission of CD patients treated with UST from January 2020 to January 2024 were collected and analyzed. Results A total of 348 CD patients were included. At week 52, the clinical remission rate was 70.95%, endoscopic remission 24.68%, C-Reactive Protein (CRP) normalization 54.11%, and fecal calprotectin (FCP) normalization 48.57%. Prior biologic exposure, CRP reduction at week 8, and baseline hemoglobin level were independent predictors of clinical remission. The mean survival duration with UST was 172 weeks (SE = 6, 95% CI: 160–185). Conclusions This study demonstrated favorable effectiveness, persistence, and safety of UST in CD patients. Prior biologic exposure, early CRP reduction and hemoglobin level were associated with clinical remission at 52 weeks.

Physiologically based pharmacokinetic model of IgG to predict mother-to-fetus transfer of ustekinumab in pregnant patients with inflammatory bowel disease.

Background:Evidence suggests a relationship between ustekinumab (UST) concentrations and therapeutic outcomes in inflammatory bowel disease.Objectives:This study aimed to evaluate the association between UST concentrations during the induction phase and treatment outcomes at week 24 in patients with Crohn’s disease (CD) and ulcerative colitis (UC). The primary outcome was endoscopic remission at week 24, defined as a simple endoscopic score (SES-CD) ⩽2 for CD and a Mayo endoscopic score = 0 for UC. Secondary outcomes included endoscopic response, clinical remission, and treatment persistence.Design:This was a prospective observational study assessing clinical and endoscopic outcomes in CD and UC patients starting UST therapy.Methods:Consecutive patients with CD and UC were included at the initiation of UST treatment. Trough UST concentrations were measured at weeks 8, 16, and 24 after the first intravenous dose, and the main outcomes were assessed at week 24. Endoscopic and clinical parameters were used to evaluate treatment efficacy and persistence.Results:Seventy patients (45 with CD) were enrolled. Those achieving endoscopic remission and response at week 24 had higher UST levels at week 8 (4.5 vs 2.6 μg/mL, p = 0.0028; 4.1 vs 2.4 μg/mL, p = 0.0024, respectively). Patients with UST concentrations in the fourth quartile (Q4) at week 8 (>4.5 μg/mL) had higher rates of endoscopic remission (66.7% (Q4) vs 20% (Q1); 33.3% (Q2); 28.6% (Q3); p = 0.012). A UST concentration threshold of 4.5 μg/mL at week 8 was the best predictor of endoscopic remission (AUC = 0.7, sensitivity 54.5%, specificity 83.8%), while 3.5 μg/mL predicted endoscopic response (AUC = 0.732, sensitivity 53.8%, specificity 87%). Longer disease duration correlated with a higher risk of UST discontinuation (odds ratio, 1.034, 95% confidence interval, 1.002–1.068, p = 0.035). Higher UST concentrations in Q4 did not result in greater drug persistence (p = 0.319).Conclusion:UST concentrations at week 8 were positively associated with endoscopic outcomes at week 24, with a threshold of 4.5 μg/mL reliably predicting endoscopic remission. Further randomized clinical trials are warranted to explore whether optimizing UST treatment based on post-induction concentrations can enhance therapeutic outcomes.

Background:A reliable approach to predict the response to Ustekinumab (UST) in patients with Crohn’s disease (CD) is lacking.Objectives:This study aims to develop and validate machine learning (ML) models to predict the response to UST and further achieve personalized therapy.Design:Retrospective multi-center study.Methods:This study included 162 CD patients treated with UST between May 2022 and May 2024. Four ML algorithms (extreme gradient boosting, random forest, logistic regression, and support vector machine) were integrated to identify the optimal model, and Shapley Additive exPlanations (SHAP) interpretation was used for visual explainability. Two models were established to forecast the response to UST, with the outcomes of the response situation at week 26 and secondary loss of response (sLOR) status at week 52, respectively. Eighty-two CD patients from the other five centers were applied for the week-26 model’s external validation.Results:XGBoost performed excellently among the four ML algorithms. The week-26 model exhibited good performances of 0.88 area under the receiver operating characteristic curve (AUC), 0.92 area under the precision-recall curve, and 0.86 F1 score. The sLOR model demonstrated acceptable predictive performance with 0.74 AUC.Conclusion:We developed and validated models to predict UST response for CD patients and interpreted related factors by the SHAP method. We hope that the models can assist physicians in identifying patients who are suitable for UST at baseline and further explore who are at high risk for sLOR.

Background:Despite the established efficacy of ustekinumab (UST) in Crohn’s disease (CD), real-world studies reveal suboptimal treatment persistence and limited endoscopic healing. Current optimization paradigms remain constrained by suboptimal durability and escalating therapeutic demands.Objectives:To evaluate the clinical utility and safety of intravenous (IV) ustekinumab maintenance therapy in CD.Design:This was a single-center retrospective cohort study.Methods:This study included CD patients receiving ⩾2 IV-UST maintenance infusions between June 2020 and October 2023 (N = 234). The protocol featured weight-based induction-equivalent dosing (260–520 mg) at response-guided intervals. The primary endpoint was the corticosteroid-free clinical remission rate at Week 24.Results:At 24 weeks, 88.1% (185/210) achieved steroid-free remission with C-reactive protein (CRP) normalization in 90.0% (44/88). Median Harvey-Bradshaw Index decreased from 4 (interquartile range (IQR) 2–5) to 2 (IQR 1–3; p < 0.001). 52-week endoscopic remission (simplified endoscopic score for Crohn’s disease ⩽3) reached 48.7% (56/115), with fecal calprotectin normalization in 33.6% (35/104). Multivariate analysis identified baseline CRP >5 mg/L (adjusted odds ratio (aOR) 3.62, 1.16–11.25), intensive dosing (⩾6 cycles/year; aOR 12.06, 1.99–73.05), and disease duration ⩾1 year (aOR 3.53, 1.08–11.54) as predictors of endoscopic non-remission. Safety analysis demonstrated 44.4% adverse event incidence (104/234) and 3.0% serious adverse events (7/234).Conclusion:IV-UST maintenance demonstrates high rates of corticosteroid-free clinical remission and endoscopic healing with manageable safety in CD.

Background: Ustekinumab (UST) is a monoclonal antibody (mAb) used in the treatment of inflammatory bowel disease (IBD). Elevated serum concentrations are typically associated with improved therapeutic outcomes, and therapeutic drug monitoring (TDM) is a useful tool for guiding mAbs treatment. This study aimed to develop a dried blood spot (DBS) method for TDM of UST in patients with IBD. Methods: The commercial enzyme-linked immunosorbent assay for plasma samples was optimized for DBS samples and subsequently validated according to international guidelines for classical and DBS-specific validation parameters. It was then applied to analyze serum and DBS samples obtained from venous and capillary blood of IBD patients undergoing UST therapy. Results: The method was linear (3–12 mg/L) with acceptable inter-day accuracy (90.1–106%) and precision (<12%). We confirmed that there was no hematocrit effect and that DBS samples were stable for one month under room conditions. A linear model was developed between venous DBS and serum UST concentrations, which showed no systemic bias, and 71% of the samples were within ±20% of the mean. In addition, a linear correlation between venous DBS and capillary DBS samples was established, showing no significant bias, with 84% of samples within ±20% of the mean. Finally, a novel strategy was developed to overcome the limitations of poor-quality samples (irregular shapes) based on area image analysis. Conclusions: The newly developed DBS method is the first to enable reliable measurement of UST in capillary blood, appropriate clinical interpretation of the measured concentrations, and remote monitoring of patients in the early phase of therapy.

The systematic review and meta-analysis (SRMA) evaluates the safety and effectiveness of combining biologics and/or small molecules in treating refractory inflammatory bowel diseases (IBD). Our 2022 SRMA identified 13 studies published until November 3, 2020. An updated systematic search was completed from May 2020 through January 31, 2024. Random-effects inverse variance model was used to calculate pooled estimates for adverse events (AEs) and clinical and endoscopic-radiologic response/remission rates in IBD patients. Twenty-seven eligible studies had 619 patients and 631 therapeutic trials (TTs). Upadacitinib (UPA) + vedolizumab (VDZ) and tofacitinib (Tofa) + anti-TNF (aTNF) had the lowest AEs rate (0%, 2 TTs) and (9.2%, 33 TTs), respectively. Higher AE rates were seen in natalizumab (NAT) + aTNF (92.3%, 52 TTs) and aTNF + guselkumab (63.4%, 71 TTs). No serious AEs (SAEs) were observed in NAT + aTNF (52 TTs), Tofa + ustekinumab (UST) (23 TTs), and UPA + VDZ (2 TTs). The highest rate of SAEs was observed in UPA + UST (23%, 17 TTs). UPA + UST and UPA + VDZ had 100% clinical response rates and the highest clinical remission rates (83.3%, 12 TTs) and (100%, 2 TTs), respectively. High clinical response rates were also seen in Tofa + aTNF (82.7%, 34 TTs), UST + aTNF (82.1%, 63 TTs), and VDZ + UST (82.0%, 71 TTs). Combining biologics and/or small molecules may be effective for IBD patients who fail to achieve remission with monotherapy; however, safety profiles need to be carefully considered prior to implementing these strategies in clinical practice.

A phase 3, randomized, double-blind, active-controlled clinical study to compare BAT2206, a ustekinumab biosimilar, with ustekinumab reference product in patients with moderate-to-severe psoriasis: Treatment period 2 results (post Week 28 to Week 52).