Proposal to fund ustekinumab for inflammatory bowel disease, and infliximab for inflammatory bowel disease-associated arthritis

Medicines Consultation Closed

What we’re proposing

We are seeking feedback on a proposal to: 

  • fund ustekinumab (brand name Stelara), a new treatment for the treatment of people with inflammatory bowel disease (Crohn’s disease or ulcerative colitis) that has not responded to prior biologic treatments, or where the treatment was not tolerated, or is contraindicated, from 1 February 2023 
  • fund infliximab (brand name Remicade) for patients with inflammatory bowel disease-associated arthritis from 1 February 2023. 

The provisional agreement with the supplier of ustekinumab and infliximab, Janssen-Cilag Pty Ltd (Janssen), also includes a price reduction and other amendments to the existing contractual terms for Remicade. 

Further details on this proposal, including how to provide feedback, can be found below. 

We welcome your feedback on this proposal. Consultation closes at 4 pm on Wednesday 26 October 2022 and feedback can be emailed to consult@pharmac.govt.nz. 

Ustekinumab for inflammatory bowel disease

What would the effect be?

From 1 February 2023 ustekinumab (Stelara) would be funded for people with Crohn’s disease or ulcerative colitis for whom prior biologic therapy has not provided sufficient clinical benefit, was not tolerated, or is contraindicated, subject to eligibility criteria. 

Our clinical advisors have told us that evidence suggests that ustekinumab offers clinically significant health benefit in terms of response and remission in people with Crohn’s disease or ulcerative colitis, which are forms of inflammatory bowel disease (IBD). This proposal to fund ustekinumab is in addition to another proposal we recently consulted on to fund vedolizumab for people with IBD. The clinical advice we have received is that funding both of these agents would make a significant contribution to addressing the unmet health need for patients with IBD in Aotearoa New Zealand. 

We estimate that approximately 500 people with IBD would benefit in the first year increasing up to a total of 1500 people after a few years. 

We are unsure of the relative proportion of Māori or Pacific people that would benefit from treatment, as there is an absence of data on the prevalence of moderate-to-severe IBD in these populations. The advice we have received suggests that Māori and Pacific people make up a small but increasing proportion of all IBD cases. 

Who we think will be interested

  • People with IBD and their whānau, and caregivers
  • Gastroenterologists, general surgeons, specialist nurses, and other health professionals involved in the care of people with IBD.
  • Hospital and community pharmacists, Te Whatu Ora and wholesalers
  • Pharmaceutical suppliers
  • Other organisations with an interest in IBD and its treatment 

About inflammatory bowel disease

IBD is a chronic inflammatory condition of the gastrointestinal tract. Crohn’s disease and ulcerative colitis are the most common forms of IBD. These two conditions are differentiated by the location of intestinal inflammation, as well as the depth of involvement of the bowel wall. 

In Crohn’s disease, inflammation can occur in any part of the gastrointestinal tract, tends to have a patchier distribution, and can penetrate deep into the bowel wall, causing abscesses and fistulae. In contrast, inflammation in ulcerative colitis is typically confined to the large colon, is more continuous in its presentation, and affects the top layers of the bowel wall. 

Both conditions are characterised by a relapsing and remitting pattern of symptoms which commonly include diarrhoea, abdominal pain and cramping, blood in the stool, reduced appetite, weight loss and fatigue. In some patients with IBD, inflammation can also extend beyond the bowel and include skin, eye, musculoskeletal, and kidney involvement. 

While the management of IBD is individualised to the specific patient, periods of relapse are typically treated with conventional therapies such as immunosuppressants and corticosteroids, followed by anti-TNF biologic agents. In some patients, IBD requires surgical management. 

About ustekinumab

Ustekinumab is a targeted biologic therapy that selectively blocks cytokines involved in immune and inflammatory responses, thus selectively interrupting the inflammatory processes that cause IBD. 

Ustekinumab would offer an alternative method of action to control periods of intestinal inflammation for patients whose disease has not responded to treatment with funded biologic treatments, or in whom those treatments are not tolerated or are contraindicated. 

Ustekinumab is Medsafe approved for: 

  • the treatment of adult patients with moderate to severe Crohn's disease who have had an inadequate response with, or lost response to, either conventional therapy or anti-TNF therapy or for whom this treatment is not tolerated
  • the treatment of adult patients with moderate to severely active ulcerative colitis. 

Ustekinumab is not Medsafe approved for treatment of adolescents and children below the age of 18. The paediatric criteria for Crohn’s disease in this proposal reflect the advice that we have received from our advisors that separate criteria would be preferable for those aged 18 and below, given the differences in the disease activity scoring indices between the age groups. 

Ustekinumab is administered initially as an intravenous infusion with a tiered weight-based dosing regimen, and then as a prefilled syringe every 8 weeks thereafter at a dose of 90mg.

This means that patients can be trained to self-administer the medication under the care of a healthcare professional. Our advisors have told us that funding ustekinumab would lead to a significant reduction in overall hospital infusion hours. 

Why we’re proposing this

A funding application(external link) for ustekinumab for the treatment of severe Crohn’s disease in people for whom conventional therapies have been ineffective or not tolerated, was reviewed by Pharmac’s Pharmacology and Therapeutics Advisory Committee (PTAC) in May 2018 [PDF, 267 KB]. PTAC recommended that ustekinumab be funded with a medium priority for the treatment of patients who have either had failure of, become refractory to, or experienced severe and intractable side effects from anti-TNF agents. 

The application(external link) for Crohn’s disease was also reviewed by Pharmac’s Gastrointestinal Subcommittee (now the Gastrointestinal Advisory Committee) in October 2018 [PDF, 113 KB] and it recommended that ustekinumab be funded with a high priority for patients that have not experienced response to infliximab or adalimumab. 

In addition, PTAC reviewed a funding application for ustekinumab for the treatment of moderately to severely active ulcerative colitis in May 2020(external link) and recommended that ustekinumab be funded for patients who have experienced either: inadequate response to, intolerable side effects from, contraindications to, or loss of response from, infliximab with a medium priority. 

Our advisors have told us that there is a need for additional treatment options for patients with IBD for whom previous biologic therapies have been ineffective, and that ustekinumab offers a significant clinical benefit for these patients in terms of disease response and remission. 

We are proposing to fund ustekinumab for patients whose disease has not responded to previous biologic therapies, or where previous biologic therapies have caused intolerable side effects. This is in addition to a separate proposal to fund vedolizumab. These proposals would enable greater clinician and patient choice for the treatment of IBD. 

We are proposing to fund ustekinumab now as we have reached a provisional agreement with the supplier, Janssen, that includes a price reduction on another funded medicine. This, in combination with our recent budget uplift, has enabled us to progress this proposal. 

Details about our proposal

The following presentations of ustekinumab (Stelara) would be listed in Part II of Section H of the Pharmaceutical Schedule from 1 February 2023 at the following prices and subsidies (ex-manufacturer, excluding GST): 

Chemical Formulation Brand Pack size Price and subsidy
Ustekinumab Inj 130 mg vial Stelara 1 $4,162.00
Ustekinumab Inj 90 mg per ml, 1 ml prefilled syringe Stelara 1 $4,162.00

The following presentation of ustekinumab (Stelara) would be listed in Section B of the Pharmaceutical Schedule from 1 February 2023 at the following prices and subsidies (ex-manufacturer, excluding GST): 

Chemical Formulation Brand Pack size Price and subsidy
Ustekinumab Inj 90 mg per ml, 1 ml prefilled syringe Stelara 1 $4,162.00

A confidential rebate would apply to all presentations of ustekinumab (Stelara) that would reduce the net price to the Funder. Stelara would have protection from delisting and subsidy reduction until 31 January 2027. 

Crohn’s disease

Ustekinumab would be listed in Section B and Part II of Section H subject to the following eligibility criteria:

Special Authority for Subsidy/Hospital Indication Restrictions

Initial application – (Crohn’s disease – Adult) from any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria:
All of the following:

  1. Patient has severe active Crohn’s disease; and
  2. Any of the following:
    1. Patient has a CDAI score of greater than or equal to 300, or HBI score of greater than or equal to 10; or
    2. Patient has extensive small intestine disease affecting more than 50 cm of the small intestine; or
    3. Patient has evidence of short gut syndrome or would be at risk of short gut syndrome with further bowel resection; or
    4. Patient has an ileostomy or colostomy, and has intestinal inflammation; and
  3. Any of the following:
    1. Patient has tried but had experienced an inadequate response to (including lack of initial response and/or loss of initial response) from any biologic therapy; or
    2. Patient has experienced intolerable side effects from any biologic therapy; or
    3. Other biologic therapies are contraindicated; and
  4. Surgery (or further surgery) is considered clinically inappropriate.

Renewal – (Crohn’s disease – Adult) any relevant practitioner. Approvals valid for 12 months for application meeting the following criteria:

Both:

  1. Any of the following:
    1. CDAI score has reduced by 100 points, or HBI score has reduced by 3 points, from when the patient was initiated on ustekinumab; or
    2. CDAI score is 150 or less, or HBI is 4 or less; or
    3. The patient has experienced an adequate response to treatment, but CDAI score and/or HBI score cannot be assessed; and
  2. Ustekinumab to administered at a dose no greater than 90 mg every 8 weeks. 

Initial application – (Crohn’s disease – children*) any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria: 

All of the following:

  1. Paediatric patient has severe active Crohn’s disease; and
  2. Any of the following:
    1. Patient has a Paediatric Crohn’s Disease Activity Index (PCDAI) score of greater than or equal to 30; or
    2. Patient has extensive small intestine disease; or
    3. Patient has an ileostomy of colostomy, and has intestinal inflammation; and
  3. Any of the following:
    1. Patient has experienced an inadequate response to (including lack of initial response and/or loss of initial response) from any biologic therapy; or
    2. Patient has experienced intolerable side effects from any biologic therapy; or
    3. Other biologic therapies are contraindicated; and
  4. Surgery (or further surgery) is considered clinically inappropriate. 

Renewal – (Crohn’s disease – children*) any relevant practitioner. Approvals valid for 12 months for application meeting the following criteria: 

Both:

  1. Any of the following:
    1. PCDAI score has reduced by 10 points from the PCDAI score when the patient was initiated on ustekinumab; or
    2. PCDAI score is 15 or less; or
    3. The patient has experienced an adequate response to treatment, but PCDAI score cannot be assessed; and
  2. Ustekinumab to administered at a dose no greater than 90mg every 8 weeks. 

Note: Indication marked with * is an unapproved indication

Ulcerative colitis

Ustekinumab criteria: 

Initial application – (ulcerative colitis) from any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria:

All of the following:

  1. Patient has histologically confirmed ulcerative colitis; and
  2. Either
    1. Patient’s SCCAI score greater than or equal to 4; or
    2. Patient’s PUCAI score is greater than or equal to 65*; and
  3. Any of the following:
    1. Patient has tried but had experienced an inadequate response to (including lack of initial response and/or loss of initial response) from any biologic therapy; or
    2. Patient has experienced intolerable side effects from any biologic therapy; or
    3. Other biologic therapies are contraindicated; and
  4. Surgery (or further surgery) is considered clinically inappropriate

Renewal – (ulcerative colitis) from any relevant practitioner. Approvals valid for 12 months for application meeting the following criteria:

Both:

  1. Either
    1. The SCCAI score has reduced by 2 points or more from the SCCAI score since initiation on ustekinumab; or
    2. The PUCAI score has reduced by 30 points or more from the PUCAI score since initiation on ustekinumab*; and
  2. Ustekinumab to be administered at a dose no greater than 90 mg every 8 weeks. 

Note: Indication marked with * is an unapproved indication

Infliximab

About inflammatory bowel disease associated arthritis and infliximab

A proportion of patients with IBD systemic inflammation can lead to extraintestinal symptoms such as arthritis. 

Infliximab is a monoclonal antibody that is funded for a range of chronic inflammatory diseases(external link). Infliximab works by binding to and inhibiting the activity of a protein called tumor necrosis factor-alpha (TNF-α), which is a pro-inflammatory molecule produced by immune cells during periods of inflammation. By inhibiting the production of TNF-α, anti-TNF agents such as adalimumab and infliximab interrupt the inflammatory processes which cause IBD and IBD-associated arthritis. Infliximab would be funded alongside adalimumab(external link) for those patients who have not responded to prior treatment with conventional therapies and meet certain eligibility criteria.  

A funding application to widen access to infliximab to treat inflammatory bowel disease-associated arthritis (IBD-A) has been reviewed by PTAC and the Rheumatology Subcommittee of PTAC. Most recently, in February 2015 [PDF, 498 KB] PTAC recommended infliximab for IBD-A be funded with a medium priority. More information on this application, including links to the relevant clinical advice records, can be found in the Application Tracker(external link). 

This proposal would mean that from 1 February 2023, people with IBD-A would have access to alternative funded biologic treatment. Infliximab is given by intravenous infusion and can be administered at Te Whatu Ora hospitals or by outpatient providers or Te Whatu Ora infusion services. We estimate that about 30 people would benefit from this proposal in the first year of funding. 

Our advisors have told us that funding infliximab would provide health benefits to patients with IBD-A in terms of a reduction of both intestinal and arthritic symptoms. We are proposing to fund infliximab for IBD-A now as we have reached a provisional agreement with the supplier, Janssen, that includes a price reduction on infliximab that has enabled us to progress this proposal. 

Details about our proposal

The criteria for funded access to infliximab (Remicade) would be amended in Section B and Part II of Section H of the Pharmaceutical Schedule from 1 February 2023 to include people with IBD-A (proposed new criteria shown only):

Initial application — (inflammatory bowel arthritis – axial) from any relevant practitioner. Approvals valid for 6 months for applications meeting the following criteria:

All of the following

  1. Patient has a diagnosis of active ulcerative colitis or active Crohn’s disease; and
  2. Patient has axial inflammatory pain for six months or more; and
  3. Patient is unable to take NSAIDs; and
  4. Patient has bilateral sacroiliitis demonstrated by radiological imaging; and
  5. Patient has not responded adequately to prior treatment consisting of at least 3 months of an exercise regime supervised by a physiotherapist; and
  6. A BASDAI of at least 6 on a 0‑10 scale completed after the 3 month exercise trial, but prior to ceasing any previous pharmacological treatment 

Renewal — (inflammatory bowel arthritis – axial) from any relevant practitioner. Approvals valid for 2 years where treatment has resulted in an improvement in BASDAI of 4 or more points from pre-treatment baseline on a 10 point scale, or an improvement in BASDAI of 50%, whichever is less. 

Initial application — (inflammatory bowel arthritis – peripheral) from any relevant practitioners. Approvals valid for 6 months for applications meeting the following criteria:

All of the following:

  1. Patient has a diagnosis of active ulcerative colitis or active Crohn’s disease; and
  2. Patient has active arthritis in at least four joints from the following: hip, knee, ankle, subtalar, tarsus, forefoot, wrist, elbow, shoulder, sternoclavicular; and
  3. Patient has tried and not responded to at least three months of methotrexate or azathioprine at a maximum tolerated dose; and
  4. Patient has tried and not responded to at least three months of sulfasalazine at a maximum tolerated dose; and
  5. Any of the following:
    1. Patient has a CRP level greater than 15 mg/L measured no more than one month prior to the date of this application; or
    2. Patient has an ESR greater than 25 mm per hour measured no more than one month prior to the date of this application; or
    3. ESR and CRP not measured as patient is currently receiving prednisone therapy at a dose of greater than 5 mg per day and has done so for more than three months. 

Renewal — (inflammatory bowel arthritis – peripheral) from any relevant practitioner. Approvals valid for 2 years for applications meeting the following criteria:Either:

  1. Following initial treatment, patient has at least a 50% decrease in active joint count from baseline and a clinically significant response to treatment in the opinion of the physician; or
  2. Patient demonstrates at least a continuing 30% improvement in active joint count from baseline in the opinion of the treating physician.  

Other changes as a part of this proposal  

Amendments to the Special Authority criteria for infliximab 

As a part of this proposal, we would also align features of the Special Authority criteria for infliximab with other funded anti-TNF agents (ie adalimumab) for Crohn’s disease and ulcerative colitis. This would include the addition of the Harvey Bradshaw Index to determine disease activity, alongside Crohn’s disease activity index (CDAI). 

Contractual amendments 

The Remicade brand of infliximab was awarded Hospital Supply Status with a 5% DV limit from 1 September 2020 until 30 June 2024 as a result of a request for proposals. 

As a part of this proposal, Pharmac would exercise its option to extend the Hospital Supply Status for Remicade for a further 12 months until 1 July 2025. 

From 1 February 2023, the net price of infliximab 100 mg injection would reduce via a confidential rebate. There would also be a reduction to the price and subsidy in the Pharmaceutical Schedule from 1 February 2023 as follows: 

Chemical Formulation Brand Pack size Current price and subsidy Proposed price and subsidy
Infliximab Inj 100 mg vial Remicade per 1 $806.00 $428.00
Infliximab Inj 1 mg for ECP Baxter 1 mg $8.29 $4.40

Price support would be provided by the supplier to support the change in list price. 

To provide feedback

Send us an email: consult@pharmac.govt.nz by 4pm on Wednesday, 26 October 2022.

All feedback received before the closing date will be considered by Pharmac’s Board (or its delegate) prior to making a decision on this proposal. 

Feedback we receive is subject to the Official Information Act 1982 (OIA). Please be aware that we may need to share your feedback, including your identity, in response to an OIA request. This applies to anyone providing feedback, whether they are providing feedback themselves or for an organisation, in a personal or professional capacity. 

We can only keep feedback confidential as allowed under the OIA and other related laws. If you want any part of your feedback treated as confidential, you need to tell us. Please let us know if you want to keep part of your feedback confidential, and why. Is it commercially sensitive, confidential or proprietary, or personal information? Clearly state this and tell us which parts of your feedback you want to keep confidential for these reasons. We will consider your request under our OIA requirements.