Communique #48

WEEK IN REVIEW

Taskforce amends remarks for Tocilizumab in response to critical shortage
This week the Taskforce was alerted by the Therapeutic Goods Administration (TGA) to a global tocilizumab shortage for both COVID-19 treatment use and other indications. To help support the TGA’s efforts to conserve supply, the Taskforce has revised the remarks section of the tocilizumab for adults recommendation to reflect:

• the second dose of tocilizumab be considered in light of availability; and
• in patients who are receiving supplemental oxygen, but who are not mechanically ventilated, baricitinib should be considered as an alternative unless contraindicated.

For the recommendations for pregnant or breastfeeding women, and for children or adolescents, the amendment relates only to consideration of the second dose.

The Taskforce emphasises that there are no changes to the strength or direction of the recommendations.

For further information view the full recommendation and remarks for the tocilizumab recommendations and refer to the TGA statement.

Ivermectin recommendation remains ‘only in clinical trials’
The Disease-Modifying Treatment and Chemoprophylaxis Panel have incorporated the evidence from one new study (Vallejos et al.) into the body of evidence for ivermectin and concluded that there remains significant uncertainty whether ivermectin is more effective and safer than standard care in treating patients with COVID-19.

As a result of this uncertainty, the Taskforce recommendation remains:

Do not use ivermectin for the treatment of COVID-19 outside of randomised trials with appropriate ethical approval.

Evidence underpinning the current recommendation now comes from 18 randomised trials that compared ivermectin with standard care in over 2100 adults with COVID-19. Please view our Ivermectin FAQ for further information.

Updates to the Living Treatment Guideline

Version 41.3 includes:

• Convalescent plasma, Ivermectin, Bamlanivimab plus etesivmab, VTE prophylaxis — updated evidence base with no change to the strength or direction of recommendations; and
• Non-invasive ventilation, Oestrogen-containing therapies — the Evidence to decision framework has been updated based on feedback from the Consumer Panel; there were no changes to the strength or direction of recommendations.

Taskforce moves into ‘Sustain Mode’
As a natural transition into a longer term and sustained project, the Taskforce is now operating in a lower intensity ‘Sustain Mode’.

We continue daily global evidence surveillance and the evidence work is now guided by levels of priority assigned to guideline recommendations.

The Taskforce Expert Clinical Panels together with the Guidelines Leadership Group (GLG) have prioritised each recommendation as either high, medium or low:

• High priority–recommendations which we continue to responsively update in light of new evidence
• Moderate priority–recommendations for which we incorporate evidence which meets certain thresholds when approved by GLG
• Low priority–recommendations which we are unlikely to update

We continue to consider questions of high clinical importance and like the guidelines, the prioritisation list is living and may change over time.

Since moving to Sustain Mode on 1 July, we have not identified any evidence relevant to our high priority recommendations and have focused on several moderate priority recommendations including VTE prophylaxis.

The Taskforce governance and approval process remains unchanged with 100% consensus member approval required for every new or changed recommendation.

The Recommendation Prioritisation list and Sustain Mode Methods paper are available on the website.

QUICK STATISTICS

COVID-19 research pipeline

• 72,953 studies published or registered in Cochrane COVID-19 Study Register, 1,498 added this fortnight
• 3,253 randomised controlled trials registered (data from Covid-nma site), 45 added this fortnight
• 4,823 systematic reviews registered in PROSPERO, 122 added this fortnight
• 384 randomised controlled trials published (data from Covid-nma site), 15 added this fortnight

CLINICAL FLOWCHARTS

11 clinical flowcharts have been developed by the Taskforce to cover:

EVIDENCE UNDER REVIEW

We are currently reviewing evidence to develop recommendations and flowcharts to guide practice in areas including:

• Budesonide
• Canakinumab
• Corticosteroids
• Hydroxychloroquine plus azithromycin
• Imatinib
• Immunoglobulin plus methylprednisolone
• Proxalutimide
• Remdesivir
• Tocilizumab
• Care of people with Post-acute COVID-19

NEWS & EVENTS

Cochrane 

• Engaging Evidence 2021—Abstract submissions for Cochrane’s upcoming Engaging Evidence 2021 (EE21) are now open. If you’re based in Australia or New Zealand and work in evidence synthesis or implementation, you’re encouraged to submit papers, posters and/or workshops to present over the course of this three-day event. EE21 offers a chance to exchange knowledge and ideas, and hear what others are up to in the worlds of evidence and research synthesis. Submissions close 30 August & registration for the big event opens Monday 2 August. More information here.
• New systematic reviews—Cochrane recently published Ivermectin for preventing and treating COVID‐19 and consistent with the Taskforce recommendations, the authors found no evidence to support the use of ivermectin for treating or preventing COVID-19 infection, but the evidence base is limited. Similarly, their new review Vitamin D supplementation for the treatment of COVID‐19: a living systematic review, the authors concluded they are very uncertain about the effectiveness of vitamin D supplementation for participants with COVID‐19.

The full list of Cochrane Reviews and related COVID-19 content from the Cochrane Library can be found here.