Abstract
Background and Aims
Ustekinumab is approved for the treatment of Crohn’s disease CD. Systematically registered prospective real-world data are scarce. We therefore aimed to study the ...effectiveness, safety and usage of ustekinumab for CD in everyday practice.
Methods
We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index HBI), biochemical (C-reactive protein CRP and faecal calprotectin FCP), extra-intestinal manifestations and, peri-anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at weeks 0, 12, 24, and 52. The primary outcome was corticosteroid-free clinical remission.
Results
In total, 221 CD patients were included (98.6% anti-tumour necrosis factor TNF and 46.6% vedolizumab exposed) with a median follow-up of 52.0 weeks interquartile range 49.3–58.4. Corticosteroid-free clinical remission rates at weeks 24 and 52 were 38.2% and 37.1%, respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate 20.0% vs 42.6%, p = 0.01, but comparable corticosteroid-free clinical remission at week 52 (46.3% q8w vs 34.6% q12w, p = 0.20). There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy combi 40.6% vs mono 36.0%, p = 0.64. At baseline, 28 patients had active peri-anal fistula, of whom 35.7% showed complete clinical resolution after 24 weeks. During follow-up we encountered six severe infections 3.5 per 100 patient-years, with all patients being on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 33.9% patients mainly due to lack of response.
Conclusion
Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti-TNF and anti-integrin therapies.
Summary
Background
Both vedolizumab and ustekinumab can be considered for the treatment of Crohn’s disease (CD) when anti‐TNF treatment fails. However, head‐to‐head trials are currently not available ...or planned.
Aim
To compare vedolizumab and ustekinumab in Crohn´s disease patients in a prospective registry specifically developed for comparative studies with correction for confounders.
Methods
Crohn´s disease patients, who failed anti‐TNF treatment and started vedolizumab or ustekinumab in standard care as second‐line biological, were identified in the observational prospective Dutch Initiative on Crohn and Colitis Registry. Corticosteroid‐free clinical remission (Harvey Bradshaw Index ≤4), biochemical remission (C‐reactive protein ≤5 mg/L and fecal calprotectin ≤250 µg/g), combined corticosteroid‐free clinical and biochemical remission, and safety outcomes were compared after 52 weeks of treatment. To adjust for confounding and selection bias, we used multiple logistic regression and propensity score matching.
Results
In total, 128 vedolizumab‐ and 85 ustekinumab‐treated patients fulfilled the inclusion criteria. After adjusting for confounders, ustekinumab‐treated patients were more likely to achieve corticosteroid‐free clinical remission (odds ratio OR: 2.58, 95% CI: 1.36‐4.90, P = 0.004), biochemical remission (OR: 2.34, 95% CI: 1.10‐4.96, P = 0.027), and combined corticosteroid‐free clinical and biochemical remission (OR: 2.74, 95% CI: 1.23‐6.09, P = 0.014), while safety outcomes (infections: OR: 1.26, 95% CI: 0.63‐2.54, P = 0.517; adverse events: OR: 1.33, 95% CI: 0.62‐2.81, P = 0.464; hospitalisations: OR: 0.67, 95% CI: 0.32‐1.39, P = 0.282) were comparable between the two groups. The propensity score matched cohort with sensitivity analyses showed comparable results.
Conclusions
Ustekinumab was associated with superior effectiveness outcomes when compared to vedolizumab, while safety outcomes were comparable after 52 weeks of treatment in CD patients who have failed anti‐TNF treatment.
Objective
It is unknown whether ustekinumab (UST) levels can predict clinical outcomes in Crohn’s disease (CD) patients. We assessed the exposure–response relationship of UST trough concentrations ...with biochemical outcomes at week 24 in a prospective, real-world setting.
Methods
We performed a prospective study in patients with CD starting UST in four academic centres in the Netherlands. All patients received a weight-adjusted intravenous (IV) UST induction dose, followed by one subcutaneous (SC) dose of 90 mg UST at 8 weeks. Maintenance therapy consisted of 90 mg subcutaneous UST every 8 or 12 weeks. Individual UST concentration time course during treatment were estimated using a population pharmacokinetic (PK) model. Quartile analysis and logistic regression were performed to analyse if UST concentrations at week 8 were associated with biochemical remission rates at week 24 (C-reactive protein (CRP) ≤ 5 mg/L and / or faecal calprotectin (FC) ≤ 250 mg/kg).
Results
In total, 124 patients with CD were included. Patients achieving biochemical remission at week 12 and 24 had significantly higher UST levels at week 8 compared to patients without biochemical remission (6.6 µg/mL versus 3.9 µg/mL, P < 0.01 and 6.3 µg/mL versus 3.9 µg/mL, P < 0.01, respectively). In quartile analysis, patients with UST levels in the highest quartile (≥ 6.3 µg/mL at week 8) had higher biochemical remission rates at week 12 and week 24. There was no association between UST levels at and corticosteroid-free clinical remission rates.
Conclusion
In this real-world cohort of patients with CD, UST levels in the highest quartile (≥ 6.3 µg/mL) at week 8 were associated with higher biochemical remission rates at week 24.
LINKED CONTENT
This article is linked to Biemans et al and Liu et al papers. To view these articles, visit https://doi.org/10.1111/apt.15745 and https://doi.org/10.1111/apt.16009
LINKED CONTENT
This article is linked to Biemans et al and Bertani et al papers. To view these articles, visit https://doi.org/10.1111/apt.15745 and https://doi.org/10.1111/apt.15920
LINKED CONTENT
This article is linked to Biemans et al and Lo et al papers. To view these articles, visit https://doi.org/10.1111/apt.15689 and https://doi.org/10.1111/apt.16468
Prospective data of vedolizumab treatment for patients with inflammatory bowel disease (IBD) beyond 1 year of treatment is scarce but needed for clinical decision making. We prospectively enrolled ...310 patients with IBD (191 with Crohn's disease (CD) and 119 patients with ulcerative colitis (UC)) with a follow-up period of 104 weeks (interquartile range: 103-104) in a nationwide registry. The corticosteroid-free clinical remission rate (Harvey Bradshaw Index ≤ 4, Short Clinical Colitis Activity index ≤ 2) at weeks 52 and 104 were 28% and 19% for CD and 27% and 28% for UC, respectively. Fifty-nine percent maintained corticosteroid-free clinical remission between weeks 52 and 104. Vedolizumab with concomitant immunosuppression showed comparable effectiveness outcomes compared with vedolizumab monotherapy (week 104: 21% vs. 23%; P = 0.77), whereas 8 of 13 severe infections occurred in patients treated with concomitant immunosuppression. To conclude, the clinical effect was 19% for CD and 28% for UC after 2 years of follow-up regardless of concomitant immunosuppression.
Summary
Background
Both tioguanine and low‐dose thiopurines combined with allopurinol (LDTA) can be considered for the treatment of inflammatory bowel disease (IBD) when conventional thiopurines fail ...due to adverse events.
Aim
To compare the safety of tioguanine and LDTA in IBD patients.
Methods
Inflammatory bowel disease patients who failed conventional thiopurines due to adverse events and initiated LDTA in standard care were identified in the prospective ICC Registry. IBD patients who failed conventional thiopurines due to adverse events and initiated tioguanine were enrolled in three university hospitals. Patients on concomitant biologicals were excluded. The primary outcome was discontinuation of therapy due to adverse events. Secondary outcomes included: safety outcomes and surgery‐, biological‐ and corticosteroid‐free clinical remission (physician global assessment = 0) after 104 weeks. Both multiple logistic regression and propensity score matching were used to correct for confounders.
Results
In total, 182 IBD patients treated with tioguanine (n = 94) or LDTA (n = 88) were included with a median follow‐up of 104 weeks (IQR 91‐104). Of these, 19% (tioguanine: 20%, LDTA: 18%) of patients discontinued therapy due to adverse events. After adjusting for confounders, there were no differences in terms of discontinuation rate due to adverse events (OR 0.50, 95% CI 0.15‐1.68, P = 0.26), adverse events (OR 0.89, 95% CI 0.44‐1.81, P = 0.75), infections (OR 1.05, 95% CI 0.40‐2.73, P = 0.93), hospitalisations (OR 2.00, 95% CI 0.64‐6.23, P = 0.23) or clinical remission (OR 0.74, 95%CI 0.33‐1.68, P = 0.48). All results are comparable with the propensity score matched cohort.
Conclusion
Nineteen percent of IBD patients with prior failure to conventional thiopurines due to adverse events discontinued therapy with tioguanine or LDTA due to adverse events. Either therapy may be considered before escalating to biological therapy.
Summary
Background
Few data are available on the effects of age and comorbidity on treatment outcomes of vedolizumab and ustekinumab in inflammatory bowel disease (IBD).
Aims
To evaluate the ...association between age and comorbidity with safety and effectiveness outcomes of vedolizumab and ustekinumab in IBD.
Methods
IBD patients initiating vedolizumab or ustekinumab in regular care were enrolled prospectively. Comorbidity prevalence was assessed using the Charlson Comorbidity Index (CCI). Association between age and CCI, both continuously assessed, with safety outcomes (any infection, hospitalisation, adverse events) during treatment, and effectiveness outcomes (clinical response and remission, corticosteroid‐free remission, clinical remission combined with biochemical remission) after 52 weeks of treatment were evaluated. Multivariable logistic regression was used to adjust for confounders.
Results
We included 203 vedolizumab‐ and 207 ustekinumab‐treated IBD patients, mean age 42.2 (SD 16.0) and 41.6 (SD 14.4). Median treatment duration 54.0 (IQR 19.9‐104.0) and 48.4 (IQR 24.4‐55.1) weeks, median follow‐up time 104.0 (IQR 103.1‐104.0) and 52.0 weeks (IQR 49.3‐100.4). On vedolizumab, CCI associated independently with any infection (OR 1.387, 95% CI 1.022‐1.883, P = 0.036) and hospitalisation (OR 1.586, 95% CI 1.127‐2.231, P = 0.008). On ustekinumab, CCI associated independently with hospitalisation (OR 1.621, 95% CI 1.034‐2.541, P = 0.035). CCI was not associated with effectiveness, and age was not associated with any outcomes.
Conclusions
Comorbidity ‐ but not age ‐ is associated with an increased risk of hospitalisations on either treatment, and with any infection on vedolizumab. This underlines the importance of comorbidity assessment and safety monitoring of IBD patients.
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