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

Medicines Decision

What we’re doing

We're pleased to announce a decision to fund ustekinumab for inflammatory bowel disease and to widen access to infliximab for people with inflammatory bowel disease-associated arthritis. In summary: 

  • ustekinumab (brand name Stelara) will be funded for the treatment of people with inflammatory bowel disease (ulcerative colitis or Crohn’s disease) that has not responded to prior biologic therapies (ie adalimumab, infliximab, or vedolizumab), from 1 February 2023. 
  • infliximab (brand name Remicade) will be funded for people with inflammatory bowel disease-associated arthritis that has not responded to conventional therapies, from 1 February 2023. 

As a part of the supply agreement with Janssen-Cilag Pty Ltd (Janssen), there will be a reduction of both the list and confidential net price for Remicade, as well as a 12-month extension to the current sole supply period. 

As a part of this decision, we have also made a number of changes to the Special Authority criteria for biologic therapies used in the treatment of Crohn’s disease and ulcerative colitis to better align the criteria across agents. 

Further details about this decision can be found below. 

Ustekinumab for inflammatory bowel disease

What does this mean for people?

From 1 February 2023 ustekinumab (Stelara) will 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 decision to fund ustekinumab is in addition to another decision we recently notified of; to fund vedolizumab for people with IBD. The clinical advice we have received is that funding both of these agents will make a significant contribution to addressing the unmet health need for people with IBD in Aotearoa New Zealand. 

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

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

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

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 

Any changes to the original proposal

This decision was subject to a consultation dated 11 October 2022, which closed on 26 October 2022. 

We would like to thank everybody who took the time to provide us with their feedback. Responses were generally supportive of this proposal, with some requests for changes to the proposed funding criteria, wider access, and funding of additional treatments. More details of the feedback and our responses can be found at the end of this notification. 

After carefully considering the consultation feedback we have made some changes to the proposed Special Authority criteria for ustekinumab. These changes were made to clarify the population group intended for funding and to remove any unnecessary barriers to access. 

We are also going to temporarily add a criterion to enable people who have already commenced treatment with ustekinumab to receive funded treatment from 1 February 2023, if they had met the remaining funding criteria at the commencement of treatment. This will remain in place until 31 August 2023. 

Details about this decision

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

Chemical Formulation Brand Pack size Price
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) will 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 will apply to all presentations of ustekinumab (Stelara) that will reduce the net price to the Funder. Stelara will have protection from delisting and subsidy reduction until 31 January 2027. 

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

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

Either:

  1. Patient is currently on treatment with ustekinumab commenced prior to 1 February 2023 and met all remaining criteria (criterion 2) below at the time of commencing treatment; or
  2. Both;
    1. Patient has active Crohn’s disease; and
    2. Either;
      1. Patient has had an initial approval for prior biologic therapy for Crohn’s disease and has experienced intolerable side effects or insufficient benefit to meet renewal criteria; or
      2. Both;
        1. Patient meets the initiation criteria for prior biologic therapies for Crohn’s disease; and
        2. Other biologics for Crohn’s disease are contraindicated

Renewal – (Crohn’s disease – adults) from any relevant practitioner. Approvals valid for 12 months for applications 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 biologic therapy; 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 be administered at a dose no greater than 90 mg every 8 weeks.

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

Either:

  1. Patient is currently on treatment with ustekinumab commenced prior to 1 February 2023 and met all remaining criteria (criterion 2) below at the time of commencing treatment; or
  2. Both:
    1. Patient has active Crohn’s disease; and
    2. Either;
      1. Patient has had an initial approval for prior biologic therapy and has experienced intolerable side effects or insufficient benefit to meet renewal criteria; or
      2. Both;
        1. Patient meets the initiation criteria for prior biologic therapies for Crohn’s disease; and
        2. Other biologics for Crohn’s disease are contraindicated

Note: Indication marked with * is an unapproved indication 

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

Both:

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

Note: Indication marked with * is an unapproved indication 

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

Either:

  1. Patient is currently on treatment with ustekinumab commenced prior to 1 February 2023 and met all remaining criteria (criterion 2) below at the time of commencing treatment; or
  2. Both:
    1. Patient has active ulcerative colitis; and
    2. Either;
      1. Patient has had an initial approval for prior biologic therapy for ulcerative colitis and has experienced intolerable side effects or insufficient benefit to meet renewal criteria; or
      2. Both;
        1. Patient meets the initiation criteria for prior biologic therapies for ulcerative colitis; and
        2. Other biologics for ulcerative colitis are contraindicated 

Renewal – (ulcerative colitis) from any relevant practitioner. Approvals valid for 12 months for applications 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 biologic therapy; or
    2. PUCAI score has reduced by 10 points or more from the PUCAI score since initiation on biologic therapy*; and
  2. Ustekinumab will be used at a dose no greater than 90 mg intravenously every 8 weeks.

Note: Criterion marked with * is for an unapproved indication

Infliximab for inflammatory bowel disease associated-arthritis

What does this mean for people?

This decision will mean that from 1 February 2023, people with inflammatory bowel disease associated-arthritis (IBD-A) will have access to an alternative funded biologic treatment alongside adalimumab. 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. 

Our advisors have told us that funding infliximab will provide health benefits to people with IBD-A in terms of a reduction of both intestinal and arthritic symptoms. 

We estimate that about 30 people will benefit from this proposal in the first year of funding. 

Who we think will be interested

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

Any changes to the original proposal

After carefully considering the consultation feedback we have made small changes to the proposed Special Authority criteria for infliximab for the treatment of IBD-A, including:

  • The removal of the requirement for patients to present bilateral sacroiliitis; and
  • The addition of MRI as a valid diagnostic tool for sacroiliitis. 

These changes were made to clarify the population intended for funding and to remove any unnecessary barriers to access. 

Details about this decision

The criteria for funded access to infliximab (Remicade) will 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 (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 unequivocal sacroiliitis demonstrated by radiological imaging or MRI; and
  5. Patient’s disease has not responded adequately to prior treatment consisting of at least 3 months of an exercise regime supervised by a physiotherapist; and
  6. Patient has 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 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 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 experienced a response to at least three months of methotrexate or azathioprine at a maximum tolerated dose (unless contraindicated); and
  4. Patient has tried and not experienced a response to at least three months of sulfasalazine at a maximum tolerated dose (unless contraindicated); 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 experienced 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 has experienced 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 IBD-biologics 

In response to consultation feedback, we have amended features of the Special Authority criteria for all biologics used for the treatment of IBD (adalimumab, infliximab, vedolizumab, and, ustekinumab) to ensure consistency across therapies and funding indications from 1 February 2023. This will include: 

  • the alignment of the paediatric ulcerative colitis activity index (PUCAI) score with the simple clinical colonic severity index (SCCAI) for all biologics
  • the addition of the Harvey Bradshaw Index to determine disease activity, alongside the Crohn’s disease activity index (CDAI)
  • the removal of the requirement for ulcerative colitis to be histologically confirmed
  • the removal of severity descriptors regarding Crohn’s disease or ulcerative colitis.
  • an increase to the initiation period of six months across IBD funding indications.
  • an increase to the renewal period to two years across first-line IBD biologics and indications
  • the inclusion of complex peri-anal fistula in the fistulising Crohn’s disease criteria for infliximab 

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 current decision, Pharmac has exercised its option to extend the Hospital Supply Status for Remicade for a further 12 months until 30 June 2025. 

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

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

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

Our response to what you told us

We’re really grateful for the time people took to respond to this consultation. The feedback we received was strongly supportive. A summary of the main themes raised in feedback, and our responses to the feedback received, are set out in the table below.  

Theme

Pharmac Comment

Ustekinumab

Responders requested consideration of alternative funded agents for the treatment of Crohn’s and ulcerative colitis, namely upadacitinib.

In providing this feedback, responders noted the preference for an oral method of administration, as well as their views that there is superior evidence of efficacy in TNF-experienced patients. 

We understand there remains a clinical need for additional treatment options for people living with IBD.

We have received a funding application for upadacitinib for IBD. We recently sought clinical advice from our Gastrointestinal Advisory Committee. The records from this meeting are in due to be finalised and once published will be available from the Application tracker(external link).

Responders requested a mechanism for enabling those who are currently accessing ustekinumab to apply for a waiver if they met the criteria prior to receiving access. Respondents told us that this should apply to those self-funding at significant cost, those on early access programmes, and those who have been enrolled in clinical trials. 

We have incorporated a temporary Special Authority criterion to enable patients who met the rest of the criteria at the commencement of treatment to transition to publicly-funded access.

Some responders noted that there would be an initial increase in clinician (gastroenterologists, registrars, IBD nurses, and pharmacists) time to set up the initial approval, initial infusion, education of subcutaneous injections, and ongoing Special Authority renewals.

We are mindful that there will likely be some increase in the utilisation of health sector resources following this decision. We consider over the longer term the subcutaneous method of administration will significantly reduce the burden on infusion centres, while better disease control will reduce the demand on secondary and tertiary care.

Responders considered that the clinical disease activity scores reflected in the Special Authority criteria should be amended to enable access for patients with moderate Crohn’s disease.

Specifically, responders requested lowering the Crohn’s Disease Activity Index (CDAI) from 300 to 220 and the Harvey Bradshaw Index (HBI) from 10 to 8

 

We acknowledge that there are health benefits associated with initiating biologic therapy at a lower level of disease activity.

We consider the request to fund earlier access to ustekinumab needs to be considered across all funded biologics for IBD. We have received a funding application to widen access to adalimumab for people with moderate Crohn’s disease. Full details about the application are available from the Application tracker(external link). We recently sought clinical advice from our Gastrointestinal Advisory Committee at its August 2022 meeting. The records from this meeting are in draft and once published will be available from the Application tracker(external link).

The paediatric disease activity (PUCAI) score in the Special Authority for ulcerative colitis should be aligned with mild-to-moderate disease, as it is for the adult population.

We have sought further clinical advice with regards to aligning the paediatric funding criteria for ulcerative colitis to the adult funding and have lowered the PUCAI score for initiation from 65 to 20. We have also lowered the required PUCAI score improvement for renewal from 30 to 10. These changes will apply to all IBD-related biologics.

Responders considered that access should include the option of dose escalation for ustekinumab, alongside infliximab and vedolizumab.

Our clinical advisors, the Pharmacology and Therapeutics Advisory Committee (PTAC) and the Gastrointestinal Advisory Committee, recommended funding ustekinumab with a dose restriction of 90mg per 8 weeks.

Evidence to support dose escalation of ustekinumab in this population group will need to be reviewed in full. We welcome a funding application for consideration of dose escalation. Information on how to submit a funding application is on the Pharmac website(external link).

We have received a funding application for dose escalation of infliximab for people with IBD. We are currently undertaking additional assessment of the proposal considering the impact of the decision to fund vedolizumab and ustekinumab. More details about the funding application for dose escalation of infliximab can be found in the application tracker(external link)

Responders requested a number of additional changes to the ustekinumab Special Authority criteria, including:

  • a renewal period of two years.
  • to enable use as a second-line agent if a patient has trialled alternatives.
  • to remove the requirement for histologically confirmed ulcerative colitis
  • to remove the severe descriptor from the Crohn’s criteria
  • to remove the requirement for patients to have tried immunomodulators and/or corticosteroids previously
  • to include a provision for patients contraindicated to prior therapies.

 

Renewal period

We are mindful of the impact that Special Authority renewal requirements can have on outpatient services and hospital pharmacy resource. We have increased the renewal period to 12 months to help alleviate some of this administrative burden. We have also increased the renewal periods for all first line agents to two years (adalimumab, infliximab and vedolizumab). 

Second-line biologic agent

We have simplified the criteria so that it is clear that ustekinumab is funded for people with active IBD who have experienced an inadequate response to other biologics, regardless of their severity index score at the time of treatment review.

Removal of histological confirmation of UC

We have amended the criteria to remove the requirement of histological confirmation given that the SCCAI index is a validated symptom-based severity index.

Removal of ‘severe’ descriptor

We have removed the ‘severe’ descriptor from active Crohn’s disease criteria, to align the criteria to those of vedolizumab.

Requirement for immunomodulators and/or corticosteroids

The criteria are based on the clinical advice we have received, that patients who have tried immunomodulators and/or corticosteroids are the group most likely to benefit with the highest health need. More information, including links to the Advisory Committee records can be found in the Application record for vedolizumab for Crohn’s disease(external link) and Ulcerative Colitis(external link). We welcome any new information/evidence, that has not been considered previously, to support earlier treatment in these population groups.

Contraindications to prior therapies

The intent of the criterion is to include funded access for people where prior treatments are contraindicated. We have clarified the criteria to reflect this intent.

Responders commented that the criterion relating to surgery should be removed altogether on the basis that it is providing clinical guidance rather than targeting funding.

We have considered this feedback and consider it appropriate to remove this particular criterion.

Proposals to change criteria for all IBD biologics to distinguish disease activity from disease severity to enable clinical decisions to be made based on the disease trajectory. This could include objective measures of disease activity.

We are considering this feedback further and will work with our clinical advisors and the New Zealand Society of Gastroenterology on our assessment of these requests.

Infliximab for IBD-A

Responders considered that the criteria should be amended to include IBD-associated axial spondyloarthritis occurring in one sacroiliac joint confirmed via imaging.

Given the very small number of patients that will have unequivocal unilateral sacroiliitis and meet the remainder of the Special Authority criteria, we have amended the criteria in line with this feedback for both adalimumab and infliximab.

Responders noted that MRI is a more sensitive imaging modality for the diagnosis of active sacroiliitis and should be included in the criteria.

We have amended the criteria to include MRI alongside radiological evidence.

Responders considered that patients should not be required to trial previous therapies if these are not tolerated or are contraindicated.

We have amended the criteria to enable access to patients for whom previous lines of therapy are contraindicated.

 

If you have any questions about this decision, you can email us at enquiry@pharmac.govt.nz; or call our toll free number (9 am to 5 pm, Monday to Friday) on 0800 660 050.