Ustekinumab in New Zealand

Kaitlyn Doak Specialty clinical nurse, Waitaha, Canterbury Kaitlyn.doak@cdhb.health.nz

Inflammatory bowel disease (IBD) is a lifelong, incurable disease that causes chronic inflammation of your Gastro Intestinal tract. Crohns disease and ulcerative colitis sit under the IBD Umbrella along with IBD unclassified.

New Zealand has one of the highest rates of IBD in the world with well over 20,000 people affected (BPACNZ, 2021). The exact cause of IBD remains unknown but is believed to be prompted by environmental factors in genetically suspected individuals. A change in diet, changes to the gut microbiota, antibiotic use, pollution and allergen exposure are possible environmental factors contributing to the development of Inflammatory Bowel Disease.

Management of IBD includes both pharmacological and surgical interventions, there are four groups of medicines that are used to treat symptoms: amino salicylates, corticosteroids, immunomodulatory medicines and biologics (BPACNZ, 2021). Biologics are used to treat patients with moderate to severe IBD and up until recently the only biologic medications available in NZ were Infliximab and Adalimumab.

Initially up to 30% of patients do not respond to treatment and about 23-46% of patients lose response overtime leaving them with limited medical options (Roda et al., 2016). Ongoing symptoms often leads to reduced quality of life, limited ability to attend work and education and an increase in hospital admissions. Many patients, who are commonly of a young age will require bowel resections with some resulting in a permanent stoma (McCombie et al., 2020).

A burden-of-disease report published in 2017 reported that IBD costs New Zealand an estimated $245,000,000 in healthcare costs and lost productivity (Kahui et al., 2017).

Pharmac announced last year that as of February 2023 two new biologic medications will be made available for the treatment of IBD. One of these, Ustekinumab is funded for treatment of people with IBD disease that has not responded to prior biologic therapies.

Ustekinumab is a human monoclonal antibody first approved for the treatment of psoriasis but is now an effective therapy for IBD patients. It has a different mechanism of action to Infliximab and Adalimumab as it specifically binds to the p40 protein of human cytokines interleukin 12 (IL-12) and interleukin 23 (IL-23) (Medsafe, 2023). It blocks the binding of p40 to the IL12Rbeta1 receptor protein made on the surface of immune cells, consequently inhibiting the bioactivity of human IL-12 and IL-23 which have been associated as important contributors of chronic inflammation in Crohns disease and Ulcerative Colitis (Sandborn et al., 2022).

As these biologics work on the immune system differently to anti-TNF drugs, patients are more likely to respond to Ustekinumab if they have failed Infliximab or Adalimumab.

Ustekinumab is available to patients with moderate to severe Crohns disease or ulcerative colitis who have either lost response, had inadequate response or had a reaction to a TNFa antagonist (Sandborn et al., 2022). It is administered as a one off single initial dosing up to 6 mg/kg IV infusion for the first dose followed by eight weekly sub cutaneous injections of 90mg that people can self-administer at home (Medsafe, 2023).

The IV infusion dose is calculated on the patient’s weight, prepared and administered by a healthcare professional and administered over an hour. The following subcutaneous injections are all 90mg and the patient will come in to see the IBD nurse for training and education on technique, signs of adverse reactions, travel and storage of the drug before continuing to self-administer the injections at home. Ustekinumab therapy is well tolerated with under 4% of patients having an infusion related reaction (Sandborn et al., 2022). The common adverse events from Ustekinumab include vomiting, injection site reactions, bronchitis, pruritis, sinusitis and nasopharyngitis.

Randomised controlled clinical trials were conducted to evaluate the efficacy of Ustekinumab. A double blind, randomised, placebo controlled 8-week induction phase, then followed by a 44-week maintenance study. They found a favourable clinical response after only a single IV induction dose at 6mg/kg. Half of patients demonstrating response 3 weeks post induction and 65% 6 weeks post infusion (Sandborn et al., 2022). Clinical response was a reduction in the CDAI score of more than 100 points however, Inflammatory markers including C-reactive protein (CRP) a faecal calprotectin significantly decreased during these trials.

In Canterbury alone as of March 2023 we have commenced 21 patients on Ustekinumab who have previously failed adalimumab or Infliximab. One patient with a complex history of Crohns disease and multiple surgeries had this to say “I was first diagnosed with Crohn’s disease at 20 years old and have been managing it for 34 years now.

I’ve had several surgeries in that time, and used treatments such as prednisone, azathioprine, Humira etc. I’ve been using Ustekinumab for several months now, having started with an infusion, and since had four 8-weekly injections. Ustekinumab has been very beneficial, and since starting I have had a less pain and discomfort, more formed bowel motions, and put on several kilograms in weight.

Having been at quite a low ebb and run down with weight heading down towards my all-time low when I started on Ustekinumab, it has certainly proven to be the best and most effective treatment I have used.”

With two new options available and funded in New Zealand we hope to see an increase of patients in remission, less hospital admissions and less surgical treatment for our IBD patients.

Thank you to the NZgNC for their financial support.

References

• Inflammatory bowel disease - a focus on Crohn’s disease and ulcerative colitis | bpacnz. (2021, February 1). Best Practice Advocacy Centre New Zealand. https://bpac.org.nz/2021/ibd.aspx

• Kahui S, Snively S, Ternent M, Crohn’s, Staff CNZ. Reducing the Growing Burden of Inflammatory Bowel Disease in New Zealand: Crohn’s & Colitis New Zealand; 2017.

• McCombie, A., Arnold, M., O’Connor, M., Stein, R., Fulforth, J., Brown, B., & Gearry, R. (2020). Why does Pharmac neglect Inflammatory bowel disease? New Zealand Medical Journal, 133(1527), 111-115. https:// journal.nzma.org.nz/journal-articles/why-doespharmac-neglect-inflammatory-bowel-disease

• Medsafe. Stelara. https://www.medsafe.govt.nz/ profs/datasheet/s/stelarainj.pdf (accessed on March 7th, 2023).

• Roda, G., Jharap, B., Neeraj, N., & Colombel, J. F. (2016). Loss of Response to Anti-TNFs: Definition, Epidemiology, and Management. Clinical and translational gastroenterology, 7(1), e135. https://doi. org/10.1038/ctg.2015.63

• Sandborn, W. J., Rebuck, R., Wang, Y., Zou, B., Adedokun, O. J., Gasink, C., Sands, B. E., Hanauer, S. B., Targan, S., Ghosh, S., De Villiers, W. J., Colombel, J., Feagan, B. G., & Lynch, J. P. (2022). Five-year efficacy and safety of Ustekinumab treatment in Crohn’s disease: The IM-UNITI trial. Clinical Gastroenterology and Hepatology, 20(3), 578-590.e4. https://doi. org/10.1016/j.cgh.2021.02.025