This article reviews the available data regarding the efficacy of ustekinumab across published randomized clinical trials and open-label experience from tertiary medical centers, safety data, including in pregnancy, and its use in patients who have failed tumor necrosis factor (TNF) antagonists as well as patients who have not failed TNF antagonists. We have proposed an algorithm for positioning the use of ustekinumab among other agents (TNF antagonists, vedolizumab) in moderate-severe Crohn’s disease. The article also enumerates drugs that are specific interleukin-23 blockers, including brazikumab (MEDI2070), risankizumab, LY3074828, tildrakizumab, and guselkumab, and the current status of their clinical trials.
Key points
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Ustekinumab binds to the p40 subunit of interleukin (IL)-12 and IL-23 and prevents their interaction with the cell surface IL-12/23 receptors and downstream signaling and cytokine production.
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Approved dosing for induction regimen is weight based: 260 mg intravenous (IV) for less than 55 kg body weight, 390 mg IV for 55 to 85 kg, and 520 mg IV for greater than 85 kg followed by maintenance regimen, which is fixed dose: 90 mg subcutaneous every 8 weeks.
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Clinical response at week 6 was observed at 6 mg/kg induction dose in 33.7% of UNITI-I (prior exposure to TNF antagonists) and 55.5% in UNITI-II (naive to TNF antagonists) subjects.
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Ustekinumab is a Food and Drug Administration pregnancy category-B medication, with no signal for any infectious, cardiac, or malignancy-related adverse events seen in UNITI-I, II, or IM-UNITI trials.
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Specific IL-23 blockers are currently either in phase 2 trials (brazikumab [MEDI2070], risankizumab, and LY3074828) or are awaiting testing (tildrakizumab and guselkumab) in Crohn’s disease.
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