Decision to widen access to tocilizumab for treatment of moderate to severe COVID-19

Medicines Decision

We’re widening funded access to tocilizumab (Actemra) from 1 October 2021 to include the treatment of moderate to severe COVID-19.

What we’re doing

We’re widening funded access to tocilizumab (Actemra) from 1 October 2021 to include the treatment of moderate to severe COVID-19, subject to access criteria.

This means prescribers will not have to make applications to use tocilizumab to treat Covid-19 for individual patients, as they have been doing up until now.

To date, applications for tocilizumab for treatment of COVID-19 have been assessed via our exceptional circumstances funding pathway (Named Patient Pharmaceutical Assessment; NPPA). Clinicians should continue to apply via this pathway if treatment is needed prior to 1 October 2021. 

Supply of tocilizumab

Roche has advised Pharmac of an expected out-of-stock for tocilizumab from October 2021. Roche is the global supplier of tocilizumab. Roche has said it expects to be able to re-supply New Zealand in January 2022.

Based on current use, stocks of tocilizumab are expected to run out in October. We want to make sure people who need tocilizumab have supply for as long as possible.

The clinical advice, and consultation feedback we have received indicates tocilizumab stock should be preserved for priority patients with the greatest health need who are at high mortality risk without treatment and have no funded alternative treatment. This includes hospitalised moderate to severe COVID-19 patients and various rheumatological and other conditions. We have sought clinical advice on alternative treatments for uses other than COVID-19 and how we can preserve the stock we currently have. An alternative treatment, upadacitinib, will be funded from 1 October 2021 for patients currently using tocilizumab for rheumatoid arthritis.

Further details about upadacitinib for rheumatoid arthritis is available on our website.

Pharmac will continue to work closely with Roche and DHB hospitals to manage tocilizumab supplies to enable continued use for people who are at high risk without treatment, including those in hospital with COVID-19.

Further details about supply of tocilizumab for uses other than COVID-19 is available on our website.

Any changes to the original proposal?

We consulted in August 2021 directly with DHBs, Ministry of Health, Medsafe, Roche and Health Care Professionals involved in the treatment of COVID-19.

Following consultation feedback, the eligibility criteria have been amended to clarify the description of inflammatory markers required to be eligible for treatment. In addition, we have changed the wording related to the diagnosis to align with Ministry of Health terminology.

Detail about this decision

Funded access to tocilizumab will be widened in Part II of Section H of the Pharmaceutical Schedule from 1 October 2021 to include the treatment of moderate to severe COVID-19 in patients who meet the following access criteria:

Restricted

Indication – moderate to severe COVID-19*

Therapy limited to 1 dose

All of the following: 

  1. Patient has confirmed (or probable) COVID-19; and
  2. Oxygen saturation of <92% on room air, or requiring supplemental oxygen; and
  3. Patient has significantly increased laboratory markers of systemic inflammation (eg CRP, PCT or ferritin); and
  4. Patient is receiving adjunct systemic corticosteroids, or systemic corticosteroids are contraindicated; and
  5. Tocilizumab is to be administered at doses no greater than 8mg/kg IV for a maximum of one dose.

Note: Indications marked with * are unapproved indications.

Similar criteria will apply in Section B of the Pharmaceutical Schedule where tocilizumab is listed as a PCT only pharmaceutical, to enable claiming.

There are no changes to other existing Special Authority criteria or hospital uses for tocilizumab.  

Clinicians should continue to apply via our exceptional circumstances funding pathway (Named Patient Pharmaceutical Assessment; NPPA) if treatment with tocilizumab for COVID-19 is needed prior to 1 October 2021.

Tocilizumab is Medsafe approved for the treatment of moderate-severe rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA), polyarticular juvenile idiopathic arthritis and giant cell arteritis. Tocilizumab is not currently Medsafe approved for use in the treatment of COVID-19.

This means that tocilizumab needs to be prescribed and used in accordance with Section 25 of the Medicines Act 1981 when used for this unapproved use.(external link)

We understand tocilizumab for use in the treatment of COVID-19 received FDA emergency use authorisation(external link) in June 2021. The European Medicines Agency is currently assessing this medicine. Roche NZ intends to submit an application to Medsafe in September 2021.

Our response to what you told us

We’re really grateful for the time people took to respond to this consultation. A summary of the main themes raised in feedback, our responses to the feedback received, and changes we have made after listening to you, are set out in the table below.

Theme

Pharmac Comment

General support. Tocilizumab has a significant effect on mortality and morbidity for people with COVID-19. Eligibility criteria are consistent with those used in the REMAP-CAP and RECOVERY trials.

We acknowledge the support received for the funding of tocilizumab for the treatment of COVID-19.

These trials were reviewed by our expert clinical advisors (the ad hoc Tocilizumab Advisory Group) and formed the basis of the access criteria.

Concerns regarding the health benefit and cost-effectiveness of the treatment. The clinical trial data may not suggest a meaningful impact on overall mortality rates.

We acknowledge that the trials show a modest reduction in mortality, but also show some evidence of other health benefits such as reduced progression to ICU and earlier discharges.

We note there is a confidential pricing arrangement that applies to tocilizumab and therefore the true cost differs to that of the publicly visible price.

Evidence for the use of tocilizumab in COVID-19 continues to emerge and will need to be reviewed to ensure funding remains appropriate and that tocilizumab is targeted to the most appropriate patients.

Concerns regarding ongoing supply of tocilizumab for both COVID-19 treatment and rheumatology use. Supply should be considered for those at greatest risk of mortality.

The clinical advice, and consultation feedback we received indicates tocilizumab stock should be preserved for priority patients  with the greatest health need with no funded alternative treatment; including hospitalised moderate to severe COVID-19 patients and various rheumatological conditions.

We have sought advice on alternative treatments for uses other than COVID-19 and how we can preserve the stock we currently have. Pharmac will continue to work closely with Roche and DHB hospitals to manage tocilizumab supplies to enable continued use for people who are at high risk without treatment, including those in hospital with COVID-19.

Further details about supply of tocilizumab for uses other than COVID-19 is available on our website.

Consideration should be given to the use of a second dose to be administered 12 or 24 hours later if the patient’s condition has not improved.

Our clinical advisors considered that there was insufficient evidence at present to recommend the use of a second dose. We would welcome further information should it become available in the future to help us further assess the benefit of a second dose.

Some guidelines, such as WHO and UK NICE say total dose should not exceed 800 mg. The Australian Guideline suggested dose is dependent on body weight.

Our clinical advisors recommended dosing based on body weight, consistent with the evidence they reviewed. At this time, we do not intend to limit the dose to 800mg.

The Special Authority criteria require doses not to exceed 8mg/kg; there is nothing in the criteria that limits the total dose to 800 mg, as per the Australian guideline. Clinicians can use their clinical judgement in determining the total dose given provided it does not exceed 8mg/kg.

The criteria should specify that the patient does not have evidence of concomitant bacterial or fungal infection.

 

The eligibility criteria are for funding purposes; we expect clinicians to use clinical judgement regarding concomitant bacterial or fungal infections, alongside all other clinical contraindications and cautions, within their scope of practice.

The Ministry of Health COVID-19 Technical Advisory Group have developed clinical guidelines, available on the MoH website.(external link)

Various suggestions around eligibility criteria related to inflammatory markers and oxygen saturation levels.

The clinical advice we received indicated that the eligibility criteria used in the RECOVERY trial, including oxygen saturation and inflammatory markers, were appropriate to use in the funding criteria. There is nothing in the criteria that prohibits use for those on non-invasive ventilation or mechanical ventilation, including ECMO.

We have amended the Special Authority criteria to clarify the intent, with new wording using the “significantly increased markers of inflammation” wording of the US NIH COVID-19 Treatment Guidelines for Interleukin-6 Inhibitors as at 21 April 2021.(external link)

The criteria for access to tocilizumab should be re-reviewed in 12 months in light of new data from 6-month follow-up of the RECOVERY trial patients and any more recently published studies

We acknowledge that the evidence for the use of tocilizumab in COVID-19 continues to emerge and would need to reviewed in the future to ensure funding remains appropriate and that tocilizumab is targeted to the most appropriate patients.

In order to maximise the cost-benefit of tocilizumab, exclude patients who have a pre-existing life-expectancy of less than one year, as estimated by the treating physician

The clinical advice we received indicated that that the extent of overall benefit from treatment may be less in some patient populations such as the very frail elderly, cognitive or neurologically impaired and in palliative settings, and that treatment by way of escalation of care in these patient groups should be carefully considered by physicians. We expect clinicians to use their own clinical judgement when considering treatment for their patients in these circumstances.

The Ministry of Health COVID-19 Technical Advisory Group have developed clinical guidelines, available on the MoH website.(external link)

Eligibility criteria make no reference to children. Consider the proposed funding restrictions should include a requirement for consultation with a multidisciplinary paediatrician team to use tocilizumab in children and young people <16yrs

The eligibility criteria are for funding purposes, we expect clinicians would use their clinical judgement with regards to consulting with the appropriate multidisciplinary team. We note there is nothing in the criteria to prohibit funded access for children.

The description in the criteria relating to the diagnosis should align with MoH terminology.

We have amended the Special Authority criteria accordingly.

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.