NICE guidance - Ustekinumab for treating moderately to severely active ulcerative colitis

NICE guidance states (1):

• Ustekinumab is recommended as an option for treating moderately to severely active ulcerative colitis in adults when conventional therapy or a biological agent cannot be tolerated, or the disease has responded inadequately or lost response to treatment, only if:
  • a tumour necrosis factor-alpha inhibitor has failed (that is the disease has responded inadequately or has lost response to treatment) or
  • a tumour necrosis factor-alpha inhibitor cannot be tolerated or is not suitable, and
  • a the company provides ustekinumab at the same price or lower than that agreed with the Commercials Medicines Unit

Ustekinumab (1,2,3,4)

• a non-selective anti-interleukin (IL)12/23 p40 monoclonal antibody
• appears to have a swift and lasting effect with potential for mucosal healing and systemic anti-inflammatory response with no known immunogenicity
• may be preferred over anti-TNF therapy in older patients with increased risk for infections and malignancy, as concurrent immunosuppression may not be required due to its low immunogenicity
• is used in combination with methotrexate, 6-mercaptopurine, azathioprine, or steroids, which may not affect the safety or efficacy of ustekinumab
• is not approved for use in pregnancy or breastfeeding; it may pass through the placenta or milk
• possible side effects include:
  • an increased risk of infections from a reduced ability to mount an immune response
  • reactivation of latent infections which involves an increased risk of infections
  • serious microbial infections include TB, viral, and fungal diseases
  • patients who are predisposed to genetic variation in the proteins IL12 and IL-23 are at a higher risk for disseminated (systemic) infectious diseases such as Salmonella, Mycobacteria, and Bacillus Calmette-Guerin (BCG)
• may provide clinical benefit in a range of settings in patients with ulcerative colitis, even for those with multiple treatment failures, which are relatively common in daily clinical practice (4)

Reference:

• NICE (17 June 2020). Ustekinumab for treating moderately to severely active ulcerative colitis
• Chen AY, Oz HS. Rapid Induction and Maintenance of Remission in Refractory Ulcerative Colitis with Ustekinumab. Diseases. 2019;7(4):55.
• Ochsenkuhn T, Tillack C, Szokodi D, Janelidze S, Schnitzler F. Clinical outcomes with ustekinumab as rescue treatment in therap-refractory or therapy-intolerant ulcerative colitis. United European Gastroenterol J. 2020;8(1):91-98.
• Biancone L, Ardizzone S, Armuzzi A, Castiglione F, D'Inca R, Danese S, Daperno M, Gionchetti P, Rizzello F, Scribano ML, Vecchi M, Orlando A. Ustekinumab for treating ulcerative colitis: an expert opinion. Expert Opin Biol Ther. 2020 Nov;20(11):1321-1329.