Dataset Information

Effectiveness of ustekinumab in patients with refractory Crohn's disease: a multicentre real-life study in Italy.

ABSTRACT:

Background

The effectiveness of ustekinumab in patients with refractory Crohn's disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD.

Methods

All patients who had started on ustekinumab after failure of or intolerance to antitumour necrosis factor-α (TNF-α) treatment at five tertiary centres between November 2018 and February 2020 were retrospectively enrolled. The coprimary outcome was corticosteroid-free clinical remission, defined as a Harvey-Bradshaw Index (HBI) score of ⩽4, at weeks 26 and 52. The secondary outcomes were changes in the HBI and C-reactive protein (CRP) values at weeks 8, 26, and 52 from baseline and the normalization of CRP in patients with initially abnormal values.

Results

Totally, 140 patients who had previously received at least one anti-TNF-α agent were enrolled; 40.0% received two anti-TNF-α agents and 20.0% received vedolizumab. At baseline, 108 patients (77.1%) had HBI scores of >4; of these, 56.5% and 58.3% achieved corticosteroid-free clinical remission at weeks 26 and 52, respectively. Significant decreases in HBI and CRP values were observed at weeks 8, 26, and 52 in the entire study cohort (all p < 0.0001). The CRP values were normalized in 34.9%, 37.8%, and 49.3% of the patients by weeks 8, 26, and 52, respectively. The baseline HBI score of ⩾8 was a negative predictor of corticosteroid-free clinical remission at week 52 (odds ratio: 0.21, 95% confidence interval: 0.08-0.56, p = 0.002). The probability of remaining on ustekinumab after 52 weeks was 92.1%. Eleven (7.9%) patients discontinued ustekinumab (three for adverse events).

Conclusion

Our study findings confirm the effectiveness and safety of ustekinumab in patients with CD after failure of or intolerance to anti-TNF-α therapy.

SUBMITTER: Scribano ML

PROVIDER: S-EPMC8848093 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Effectiveness of ustekinumab in patients with refractory Crohn's disease: a multicentre real-life study in Italy.

Scribano Maria Lia ML Aratari Annalisa A Neri Benedetto B Bezzio Cristina C Balestrieri Paola P Baccolini Valentina V Falasco Giuliano G Camastra Caterina C Pantanella Paolo P Monterubbianesi Rita R Tullio Alessandro A Saibeni Simone S Papi Claudio C Biancone Livia L Cosintino Rocco R Faggiani Roberto R

Therapeutic advances in gastroenterology 20220214

<h4>Background</h4>The effectiveness of ustekinumab in patients with refractory Crohn's disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD.<h4>Methods</h4>All patients who had started on ustekinumab after failure of or intolerance to antitumour necrosis factor-α (TNF-α) treat ...[more]

PMID: 35186121

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Project description:BackgroundClinical 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.ObjectivesThe 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.DesignWe performed a nationwide, observational, retrospective, multicentre study including patients with CD, in which ustekinumab was used as the first biological drug.MethodsThe 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.ResultsIn 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.ConclusionsUstekinumab 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.Plain language summaryEffectiveness 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.

Project description:BackgroundUstekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn's disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure-response relationship in CD treatment in the real-world setting.MethodsWe retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn's disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn's disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis.ResultsNineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 μg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 μg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02).ConclusionsUST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 μg/mL was associated with endoscopic remission at week 16/20 after UST initiation. Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021).

Project description:BackgroundTreatment with antitumor necrosis factor alpha (anti-TNF-α) is safe and effective as first-line therapy; however, its efficacy is limited due to primary nonresponse (PNR) and secondary loss of response (LOR), resulting in treatment discontinuation in approximately 40%-50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapies could be good alternatives in patient with anti-TNF failure; however, no head-to-head randomized comparison of these drugs as second- or third-line treatments has been made.ObjectivesThis study aimed to assess the treatment persistence and comparative effectiveness of UST and VDZ in patients with refractory Crohn's disease (CD).DesignIn this nationwide retrospective study, patients with CD on UST or VDZ maintenance therapy were enrolled. Clinical data at baseline, after induction, and at week 52 were obtained.MethodsClinical and biochemical activities as well as corticosteroid-free remission (SFR) rates were assessed, while concomitant medications, comorbidities, hospitalizations, and surgeries were recorded during the follow-up to detect any predictors.ResultsA total of 161 UST- and 65 VDZ-treated patients completed the follow-up. No significant difference in clinical or biochemical remission rates was observed after induction between the two treatment groups; however, clinical remission rate at week 52 was higher in UST group. UST showed superior drug persistence than VDZ (86.5%, 57.9%, p < 0.0001). The drug type was predictive of clinical SFR at week 52 [p = 0.011, odds ratio (OR) = 2.39 with UST]. Drug failure rates were higher for VDZ than those for UST (PNR rates: 21.54% and 4.97%, respectively, p < 0.001, OR = 8.267, p = 0.001). LOR and escalations were more common during UST treatment (61.5% versus 36.9%, p < 0.001; 64.2% versus 23.1%, p < 0.001). Hospital and surgical admission rates did not differ significantly. Only one adverse event occurred with VDZ at week 20, which led to drug cessation.ConclusionsVDZ and UST were safe and effective for treating patients with CD in whom anti-TNF therapy failed. UST showed superior drug persistence than VDZ, but dose escalation was more frequent. Biologicals used in lower treatment lines resulted in better drug persistence.

Dataset Information

Effectiveness of ustekinumab in patients with refractory Crohn's disease: a multicentre real-life study in Italy.

Background

Methods

Results

Conclusion

Publications

Effectiveness of ustekinumab in patients with refractory Crohn's disease: a multicentre real-life study in Italy.

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