Intravenous Ustekinumab Reinduction Is Effective in Prior Biologic Failure Crohn’s Disease Patients Already on Every-4-Week Dosing (original) (raw)
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Inflammatory Bowel Diseases
Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required...
Ustekinumab dose escalation improves clinical responses in refractory Crohn’s disease
Therapeutic Advances in Gastroenterology, 2020
Background: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn’s disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. Methods: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as “failing” standard dosing at 42 weeks who were not dose escalated. Results: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 ( p
Ustekinumab for the Treatment of Refractory Crohnʼs Disease
Inflammatory Bowel Diseases, 2016
on behalf of the USTEK Study Group Background: Ustekinumab is a fully human monoclonal antibody against IL-12/23. Ustekinumab induced clinical response and maintained higher rate of response than placebo in patients with Crohn's disease (CD). This study aims to assess the effectiveness and safety of ustekinumab in refractory patients with CD in real-life practice. Methods: Consecutive patients with CD who were treated with subcutaneous ustekinumab between March 2010 and December 2014 were retrospectively included in a multicenter open-label study. Clinical response was defined by Harvey-Bradshaw index score and assessed after the loading doses, 6, 12 months, and last follow-up. Results: One hundred sixteen patients were included, with a median follow-up of 10 months (interquartile range: 5-21). Clinical response after loading ustekinumab was achieved in 97/116 (84%) patients. The clinical benefit at 6, 12 months, and at the end of the follow-up was 76%, 64%, and 58%, respectively. Dose escalation was effective in 8 of 11 (73%) patients. Perianal disease also improved in 11 of 18 (61%) patients with active perianal fistulae. The initial response to ustekinumab and previous use of more than 2 immunosuppressant drugs were associated with a clinical response to ustekinumab maintenance therapy. In contrast, previous bowel resection predicted a long-term failure with ustekinumab. Adverse events were reported in 11 (9.5%) patients, but none required ustekinumab withdrawal. Conclusions: Subcutaneous ustekinumab is effective and safe in a high proportion of patients with CD that were resistant to conventional immunosuppressant and antitumor necrosis factor drugs.
Alimentary pharmacology & therapeutics, 2018
Long-term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. To evaluate the long-term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure-free persistence in a cohort of anti-TNF refractory CD patients. We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD-related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. Eighty-eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4-34.4) months. Forty-seven patients (54%) continu...
United European Gastroenterology Journal, 2020
Introduction Ustekinumab is an effective treatment of Crohn’s disease (CD). Real-world data addressing the efficacy and safety of ustekinumab are scarce. Aim Our aim was to assess the safety and efficacy of ustekinumab in a large national patient cohort. Methods A prospective multicenter study, in which we followed patients with active CD treated with ustekinumab for 24 weeks. Induction dose was intravenous ranging from 260 to 520 mg, according to body weight, followed by 90 mg doses given subcutaneously every 8 weeks. Clinical response was defined as a reduction of at least 1 severity category, as defined by Harvey–Bradshaw index (HBI). Patients with HBI
Journal of Crohn's and Colitis, 2020
Background Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice. Methods Retrospective, multicentre study (>60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) >4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery ...
Predictors of Ustekinumab Failure in Crohn’s Disease After Dose Intensification
Inflammatory Bowel Diseases, 2020
Background Many patients with Crohn’s disease (CD) who lose response to the standard ustekinumab dose interval of every 8 weeks (q8w) undergo dose intensification to q4w or q6w. However, baseline factors that predict success or failure after dose intensification are unknown. We sought to identify predictors of failure of ustekinumab after dose intensification for patients with CD. Methods This was a retrospective cohort study of adult CD patients undergoing ustekinumab dose intensification at a tertiary referral center between January 1, 2016, and January 31, 2019. Electronic health records were reviewed to obtain patient demographics, CD history, and laboratory data. The primary outcome was failure to achieve corticosteroid-free remission (Harvey-Bradshaw Index <5) within 12 months after intensification. The secondary outcome assessed was time to new biologic therapy after dose intensification. We used multivariable logistic regression and Cox regression to identify predictors o...
Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease
The New England journal of medicine, 2016
Background Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. Methods We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ...
Effectiveness of Ustekinumab Dose Escalation in Patients With Crohn’s Disease
Clinical Gastroenterology and Hepatology, 2020
BACKGROUND & AIMS: A subset of patients with Crohn's disease (CD) do not respond to ustekinumab at the standard dose of 90 mg every 8 weeks. Little is known about the efficacy of shortening the interval between doses. METHODS: We performed a retrospective study to determine the effectiveness of ustekinumab dose interval shortening, collecting data from 506 patients with CD who received subcutaneous ustekinumab 90 mg every 8 weeks at a single center. We obtained data from 110 patients who initially received subcutaneous ustekinumab 90 mg every 8 weeks and then had their interval shortened to every 4 weeks. Harvey Bradshaw Index (HBI) scores before and after the dose interval shortening was available for 78 patients in the cohort (71%), levels of C-reactive protein (CRP) for 60 patients (55%), and levels of fecal calprotectin for 8 patients (7%). RESULTS: Following dose interval shortening, the patients' median HBI decreased from 4.5 to 3 (P = .002), the median level of CRP decreased from 8 mg/L to 3 mg/L (P = .031), and median level of fecal calprotectin decreased from 378 μg/g to 157 μg/g (P = .57). Among patients who had an HBI >4, a level of CRP ≥5mg/dL, a level of fecal calprotectin >250ug/g, or endoscopic evidence for disease activity before dose interval shortening, after the dose interval was shortened, 28% achieved clinical remission (an HBI score ≤4), 22% had a normal level of CRP (<5 mg/dL), 50% had reduced levels of fecal calprotectin, and 36% achieved endoscopic remission. CONCLUSIONS: Shortening the ustekinumab 90 mg dose interval to 4 weeks for patients with CD who did not respond to doses every 8 weeks improved clinical and biological indices of disease activity. Patients who lose response to the standard dose of ustekinumab might benefit from dose interval shortening, which was effective and safe.