Covid antiviral’s MTX block

4 minute read

Molnupiravir is now PBS-listed, but rheum patients get left behind yet again in the race for covid protection in Australia.

The covid antiviral molnupiravir (Lagevrio, MSD) is now PBS-listed for treating covid in people who have mild-moderate disease but with risk factors for severe disease.

The streamlined authority listing took effect on 1 March and can be prescribed for people with covid confirmed by PCR or medically verified RAT and who can start treatment within five days of symptom onset. But concerns persist that many rheumatology patients will be left behind, in a repeat of last year’s covid booster vaccine DMARD dosage debacle.

People eligible for PBS-subsidised molnupiravir are those aged 65 and over with two risk factors for severe disease; aged 75 and over with one risk factor for severe disease; people with moderate to severe immunocompromise; or Aboriginal or Torres Strait Islander people aged over 50 with two risk factors for severe disease.

The list of immunocompromising conditions in the PBS eligibility criteria has been expanded to include those where the patient has taken rituximab in the last 12 months – previously it was three months.

Other eligibility criteria include immunocompromise related to the following medications taken in the last three months:

  • high-dose corticosteroids (greater than or equal to 20 mg of prednisone per day, or equivalent) for at least 14 days in a month, or pulse corticosteroid therapy
  • some ts/bDMARDs, including anti-CD20 antibodies, BTK inhibitors, JAK inhibitors and anti-CD52 antibodies
  • some csDMARDs, including mycophenolate, methotrexate (more than 0.4mg/kg/week), leflunomide, azathioprine (at least 3mg/kg/day), 6-mercaptopurine (at least 1.5mg/kg/day), alkylating agents (eg. cyclophosphamide, chlorambucil), and systemic calcineurin inhibitors (eg. cyclosporin, tacrolimus).

However, there are concerns that rheumatology patients on methotrexate could be missing out, due to the dosage criteria of more than 0.4mg/kg/week.

Speaking to Rheumatology Republic last year in the context of the ATAGI covid booster recommendations, where the same dosage criteria was in place for two weeks before advocacy led to a backflip, clinical immunologist Dr Daman Langguth pointed out that the methotrexate dosage criteria of more than 0.4mg/kg/week is very high and comes from old US data.

“That’s a lot of methotrexate and we know that doses somewhere between 10 and 15mg affect vaccination.”

Dr Langguth, who’s based at The Wesley Hospital in Brisbane, also pointed out that the azathioprine criteria of 3mg per kilo is very high, saying “no one’s on that sort of dose in rheumatology”.

ATAGI’s current criteria for ‘severely immunocompromised’ includes patients on a methotrexate dosage of 10mg per week or more and patients taking ≥ 1mg/kg day of azathioprine.

Concerns about the vulnerability of patients on methotrexate have been further raised by recent evidence from Brazil published last week in Annals of the Rheumatic Diseases, where protection from covid vaccination was not evident unless methotrexate was withheld for two weeks.

However, the improved immunogenicity in patients where methotrexate was withheld came at a price, with patients experiencing an increased rate of flares.

While some provisos in the interpretation of that study remain, including the use of the SinoVac-CoronaVac vaccine not currently used in Australia, it raises concerns for Australian methotrexate patients given that a two-week window was not recommended by any international guidelines.

A study published in the Annals of the Rheumatic Diseases showed the impact of immunosuppressive agents in 149,000 patients in Michigan, further emphasising the risk that rheumatology patients currently face.

Fully vaccinated patients taking immunosuppressive therapies – DMARDS or corticosteroids – were at greater risk of covid infection than the wider vaccinated population, although at less risk than their unvaccinated counterparts. Immunocompromised patients who’d received a third dose fared better than those who had not, emphasising the importance of the third dose.

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