Effectiveness and safety of Ustekinumab for Crohn's disease; systematic review and pooled analysis of real-world evidence

Engel, Tal; Yung, Diana E; Ma, Christopher; Pariente, Benjamin; Wils, Pauline; Eliakim, Rami; Ungar, Bella; Ben‐Horin, Shomron; Kopylov, Uri

doi:10.1016/j.dld.2019.05.002

Cited by 66 publications

(81 citation statements)

References 41 publications

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“…The safety of ustekinumab in patients with chronic immune-mediated inflammatory diseases (IMIDs) has been extensively evaluated in numerous clinical trials and in post-marketing observational studies included in controlled trials. [19][20][21] In the UNITI trial, the incidence of serious adverse event with ustekinumab was similar to that with placebo.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of ustekinumab induction therapy for 103 patients with ulcerative colitis: a GETAID multicentre real‐world cohort study

Amiot¹,

Filippi²,

Abitbol³

et al. 2020

Aliment Pharmacol Ther

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Background: Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis (UC), but few real-world data are currently available.Aim: To assess short-term effectiveness and safety of ustekinumab in patients with UC.Methods: From January to September 2019, all patients with UC treated with ustekinumab in 20 French GETAID centres were retrospectively included. The primary outcome was steroid-free clinical remission (partial Mayo Clinic score ≤2) at weeks 12-16 without a rectal bleeding subscore >1.Results: Among the 103 patients included, 70% had been previously exposed to ≥2 anti-TNF agents and 85% to vedolizumab. At weeks 12-16, steroid-free clinical remission and clinical remission rates were 35.0% and 39.8% respectively; the absence of rectal bleeding with normal stool frequency was noted in 19.4% of patients. Two patients discontinued ustekinumab before the week 12-16 visit and underwent surgery. In multivariable analysis, a partial Mayo Clinic score >6 at inclusion (18.6% vs 46.7%, P = 0.003) and a history of both exposure to anti-TNF and vedolizumab therapies (27.3% vs 80.0%, P = 0.001) were negatively associated with steroid-free clinical remission at weeks 12-16. Adverse events occurred in 7.8% of patients and serious adverse events in 3.9% of patients. Conclusion:In a cohort of highly refractory patients with UC with multiple prior drug failures, ustekinumab provided steroid-free clinical remission in one-third of cases at weeks 12-16. Clinical severity and previous use of anti-TNF and vedolizumab therapies were associated with ustekinumab failure at weeks 12-16.

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Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of ustekinumab induction therapy for 103 patients with ulcerative colitis: a GETAID multicentre real‐world cohort study

Amiot¹,

Filippi²,

Abitbol³

et al. 2020

Aliment Pharmacol Ther

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“…Primary and secondary nonresponse and treatment discontinuation are frequent for all treatments in IBD, including ustekinumab, with rates of treatment discontinuation approaching 40% 7,13 . These high rates of nonresponse are not surprising considering the refractoriness of the patients included in the real‐life cohorts published so far 9 …”

Section: Discussionmentioning

confidence: 99%

“…UST is effective for treatment of Crohn's disease (CD) and ulcerative colitis 1‐4 . In addition to randomised controlled trials, multiple real‐world studies corroborated the effectiveness of UST in the treatment of CD 5‐19 . However, the risk of primary and secondary loss of response to UST has not been extensively reported.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard‐dose subcutaneous maintenance therapy

Kopylov¹,

Hanžel²,

Liefferinckx³

et al. 2020

Aliment Pharmacol Ther

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Summary Background Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose‐optimisation for ustekinumab nonresponse is limited. Aim To assess the effectiveness of dose escalation of ustekinumab. Methods This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation. Results A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission. Conclusions Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.

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“…Ustekinumab is a fully human monoclonal antibody, which has low immunogenicity, and reportedly shows effectiveness for Crohn's disease comparable to that of anti-TNF-alpha therapy [5]. Engel et al analyzed real-world ustekinumab usage in 578 patients and demonstrated clinical response rates of 60%, 62%, and 49% at 12, 24, and 52 weeks, respectively, a 1-year endoscopic response rate of 63%, serious AEs in 19 patients (3.2%), and infections in 38 patients (6%); none of their patients had tuberculosis [10]. Furthermore, a 5-year, long-term analysis of patients with psoriasis showed that serious drugrelated and other possible treatment-related AEs occurred in 9/774, 3/253, and 0/391 patients who received adalimumab, infliximab, and ustekinumab, respectively, indicating the latter to be safe [6].…”

Section: Discussionmentioning

confidence: 99%

“…Serious adverse effects (AEs), including elevated risks of infectious diseases and malignant tumors, for example, lymphomas, have been reported in patients treated with TNF-alpha inhibitors; hence, these drugs must be administered with care to elderly patients [2][3][4]. Although ustekinumab is considered to be a relatively safe drug, neither its effectiveness nor its safety has been determined in elderly patients with Crohn's disease [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Elderly-onset Crohn’s disease remarkably responsive to ustekinumab: a case report

Iwamoto

Kato

Moriyama

2019

Int J Colorectal Dis

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Background Crohn's disease is intractable and is frequently diagnosed in younger people. No clear policies exist regarding medical treatment for seniors with this disease, and its diagnosis and treatment are often hindered by difficulties attributable to comorbidities, complex differential diagnoses, and polypharmacy. We describe an elderly-onset Crohn's disease patient showing a marked remission-maintaining effect with no adverse events after administration of ustekinumab. Methods and results A 75-year-old patient with Crohn's disease and a history of pulmonary tuberculosis had first presented to our hospital at age 64 years and was hospitalized. Based on physical examinations, colonoscopy, and blood test results, Crohn's disease was diagnosed. The patient experienced secondary losses of responsiveness to two tumor necrosis factor (TNF)-alpha inhibitors, and after repeated hospital admissions, she was administered ustekinumab. The patient's symptoms, endoscopic findings, Crohn's Disease Activity Index, serum albumin, and physical activity levels improved markedly, and disease remission has been maintained for 2 years to date. Conclusion Ustekinumab is an effective treatment option for elderly patients with intractable Crohn's disease when TNF-alpha inhibitors are ineffective.

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Effectiveness and safety of Ustekinumab for Crohn's disease; systematic review and pooled analysis of real-world evidence

Cited by 66 publications

References 41 publications

Effectiveness and safety of ustekinumab induction therapy for 103 patients with ulcerative colitis: a GETAID multicentre real‐world cohort study

Effectiveness and safety of ustekinumab induction therapy for 103 patients with ulcerative colitis: a GETAID multicentre real‐world cohort study

Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard‐dose subcutaneous maintenance therapy

Elderly-onset Crohn’s disease remarkably responsive to ustekinumab: a case report

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