NICE guidance states (1):
Ustekinumab is recommended, within its marketing authorisation, as an option for treating moderately to severely active Crohn's disease, that is, for adults who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNF-alpha inhibitor or have medical contraindications to such therapies.
- choice of treatment between ustekinumab or another biological therapy should be made on an individual basis after discussion between the patient and their clinician about the advantages and disadvantages of the treatments available. If more than 1 treatment is suitable, the least expensive should be chosen (taking into account administration costs, dosage and price per dose)
- Ustekinumab should be given until treatment failure (including the need for surgery) or until 12 months after the start of treatment, whichever is shorter. People should then have their disease reassessed:
- should only be continued if there is clear evidence of ongoing active disease as determined by clinical symptoms, biological markers and investigation, including endoscopy if necessary
- specialists should discuss the risks and benefits of continued treatment with patients and consider a trial withdrawal from treatment for all patients who are in stable clinical remission
- people who continue treatment with infliximab or adalimumab should have their disease reassessed at least every 12 months to determine whether ongoing treatment is still clinically appropriate
- people whose disease relapses after treatment is stopped should have the option to start treatment again.
Ustekinumab (2,3,4):
- studies have linked IL-12 and IL-23 to the pathogenesis of Crohn's disease with interleukin (IL)-12 found to be overexpressed and actively released by intestinal lamina propria mononuclear cells
- is a fully human IgG1 kappa monoclonal antibody that inhibits the p40 subunit shared by the proinflammatory cytokines, the interleukin (IL)-12 and -23
- blockade leads to dampening of the inflammatory cascade and differentiation of inflammatory T cells
- most widely accepted hypothesis for IBD (inflammatory bowel disease) pathogenesis is that environmental triggers in genetically predisposed individuals induce abnormalities in the innate and adaptive immune response, modulated by the presence of gut microbiota
- IL-12 and IL-23 are major players in activating adaptive immunity
- Ustekinumab prevents IL-12/23 cytokine binding with IL-12 receptor (IL-12R) beta1 subunit; thereby reducing immune cell activation
Reference:
- NICE (12 July 2017). Ustekinumab for moderately to severely active Crohn’s disease after previous treatment
- Wils P, Bouhnik Y, Michetti P, et al. Long-term efficacy and safety of ustekinumab in 122 refractory Crohn's disease patients: a multicentre experience. Alimentary Pharmacology & Therapeutics. 2018 Mar;47(5):588-595. DOI: 10.1111/apt.14487. PMID: 29315694.
- Simon EG, Ghosh S, Iacucci M, Moran GW. Ustekinumab for the treatment of Crohn's disease: can it find its niche?. Therap Adv Gastroenterol. 2016;9(1):26-36. doi:10.1177/1756283X15618130
- Kotze PG, Ma C, Almutairdi A, Panaccione R. Clinical utility of ustekinumab in Crohn's disease. J Inflamm Res. 2018;11:35-47. Published 2018 Feb 8. doi:10.2147/JIR.S157358