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

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. [link removed - page archived]

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.