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Effectiveness of Ustekinumab Dose Escalation in Patients With Crohn’s Disease

Published:February 25, 2020DOI:https://doi.org/10.1016/j.cgh.2020.02.035

      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.

      Keywords

      Abbreviations used in this paper:

      CD (Crohn’s disease), CRP (C-reactive protein), FCP (fecal calprotectin), HBI (Harvey-Bradshaw Index), IQR (interquartile range), SC (subcutaneous), SES-CD (Simple Endoscopic Score for Crohn’s Disease), TNF (tumor necrosis factor)
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      References

        • Ben-Horin S.
        • Chowers Y.
        Review article: loss of response to anti-TNF treatments in Crohn's disease.
        Aliment Pharmacol Ther. 2011; 33: 987-995
        • Colombel J.F.
        • Feagan B.G.
        • Sandborn W.J.
        • et al.
        Therapeutic drug monitoring of biologics for inflammatory bowel disease.
        Inflamm Bowel Dis. 2012; 18: 349-358
        • Dulai P.S.
        • Siegel C.A.
        • Colombel J.F.
        • et al.
        Systematic review: monotherapy with antitumour necrosis factor alpha agents versus combination therapy with an immunosuppressive for IBD.
        Gut. 2014; 63: 1843-1853
        • Qiu Y.
        • Chen B.L.
        • Mao R.
        • et al.
        Systematic review with meta-analysis: loss of response and requirement of anti-TNFalpha dose intensification in Crohn's disease.
        J Gastroenterol. 2017; 52: 535-554
        • Ungar B.
        • Levy I.
        • Yavne Y.
        • et al.
        Optimizing anti-TNF-alpha therapy: serum levels of infliximab and adalimumab are associated with mucosal healing in patients with inflammatory bowel diseases.
        Clin Gastroenterol Hepatol. 2016; 14: 550-557.e2
        • Lichtenstein G.R.
        • Loftus E.V.
        • Isaacs K.L.
        • et al.
        ACG clinical guideline: management of Crohn's disease in adults.
        Am J Gastroenterol. 2018; 113: 481-517
        • Rubin D.T.
        • Ananthakrishnan A.N.
        • Siegel C.A.
        • et al.
        ACG Clinical Guideline: ulcerative colitis in adults.
        Am J Gastroenterol. 2019; 114: 384-413
        • Rosario M.
        • Wyant T.
        • Leach T.
        • et al.
        Vedolizumab pharmacokinetics, pharmacodynamics, safety, and tolerability following administration of a single, ascending, intravenous dose to healthy volunteers.
        Clin Drug Investig. 2016; 36: 913-923
        • Shmidt E.
        • Kochhar G.
        • Hartke J.
        • et al.
        Predictors and management of loss of response to vedolizumab in inflammatory bowel disease.
        Inflamm Bowel Dis. 2018; 24: 2461-2467
        • Feagan B.G.
        • Sandborn W.J.
        • Gasink C.
        • et al.
        Ustekinumab as induction and maintenance therapy for Crohn's disease.
        N Engl J Med. 2016; 375: 1946-1960
        • Harvey R.F.
        • Bradshaw J.M.
        A simple index of Crohn's-disease activity.
        Lancet. 1980; 1: 514
        • Afif W.
        • Loftus Jr., E.V.
        • Faubion W.A.
        • et al.
        Clinical utility of measuring infliximab and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease.
        Am J Gastroenterol. 2010; 105: 1133-1139
        • Yarur A.J.
        • Rubin D.T.
        Therapeutic drug monitoring of anti-tumor necrosis factor agents in patients with inflammatory bowel diseases.
        Inflamm Bowel Dis. 2015; 21: 1709-1718
        • Brandse J.F.
        • Mathot R.A.
        • van der Kleij D.
        • et al.
        Pharmacokinetic features and presence of antidrug antibodies associate with response to infliximab induction therapy in patients with moderate to severe ulcerative colitis.
        Clin Gastroenterol Hepatol. 2016; 14 (e1–2): 251-258
        • Ordas I.
        • Mould D.R.
        • Feagan B.G.
        • et al.
        Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms.
        Clin Pharmacol Ther. 2012; 91: 635-646
        • Billioud V.
        • Sandborn W.J.
        • Peyrin-Biroulet L.
        Loss of response and need for adalimumab dose intensification in Crohn's disease: a systematic review.
        Am J Gastroenterol. 2011; 106: 674-684
        • Gisbert J.P.
        • Panes J.
        Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review.
        Am J Gastroenterol. 2009; 104: 760-767
        • Khorrami S.
        • Ginard D.
        • Marin-Jimenez I.
        • et al.
        Ustekinumab for the treatment of refractory Crohn's disease: the Spanish experience in a large multicentre open-label cohort.
        Inflamm Bowel Dis. 2016; 22: 1662-1669
        • Ma C.
        • Fedorak R.N.
        • Kaplan G.G.
        • et al.
        Long-term maintenance of clinical, endoscopic, and radiographic response to ustekinumab in moderate-to-severe crohn's disease: real-world experience from a multicenter cohort study.
        Inflamm Bowel Dis. 2017; 23: 833-839

      Linked Article

      • Ustekinumab 90 mg Every 2 Weeks for the Treatment of Inflammatory Bowel Disease
        Clinical Gastroenterology and HepatologyVol. 19Issue 7
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          We read with interest the article “Effectiveness of Ustekinumab Dose Escalation in Patients With Crohn's Disease” by Ollech et al.1 They describe ustekinumab (UST) dose interval shortening from 90 mg every 8 weeks to every 4 weeks in 110 patients with Crohn’s disease. Clinical remission Harvey Bradshaw Index ([HBI], ≤4) was achieved in 50.9% at the last follow-up evaluation, with no serious adverse events reported. This is an important study that adds to the limited data to date supporting dose optimization at greater than 90 mg every 8 weeks.
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