11 October 2021

ATAGI covid booster recommendations leave rheumatologists with questions

COVID-19

ATAGI has recommended a third dose of covid vaccine for severely immunocompromised patients, taking effect from Monday 11 October.

UPDATE: 14 October 2021

Rheumatology Republic understands that concerns from multiple parties have been raised with ATAGI and the bodies advising it regarding several ambiguous areas in the statement.

This includes clarification on doses for methotrexate and whether JAK inhibitors are included among the therapies for which a third dose is recommended. In its rationale for the recommendations, ATAGI states: “A meta-analysis found that seroconversion can also [be] substantially impaired with the use of JAK inhibitors and abatacept (CTLA4 analog).” However, while abatacept is included in the list, JAK inhibitors are not.

Meanwhile, the ARA has updated its Covid vaccination information for patients with information about the booster dose.

In addressing questions as to whether the doses of methotrexate and azathioprine specified by ATAGI are higher than those that might be expected to have an impact on immunogenicity, ARA has stated in its public vaccination guidance that these medicines “at higher doses” might warrant a third dose, rather than the specific doses recommended by ATAGI.

Reflecting the fact that many rheumatic disease patients are on combination therapies or taking medications such as JAK inhibitors that aren’t specifically included on the list, the ARA has also included a statement suggesting clinical judgement could apply in these cases.

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The booster recommendation, which would apply to everyone over 12 with a condition or on medication leading to severe immunocompromise, is aimed at addressing the risk of suboptimal or non-response to the standard two-dose vaccination schedule.

ATAGI has nominated that an mRNA vaccine (Pfizer or Moderna) would be preferred as a third dose among this patient group over AstraZeneca.

However, AstraZeneca may be appropriate for individuals who had received AstraZeneca for their first two doses, if there were no contraindications or precautions for use, or if a significant adverse reaction (such as anaphylaxis or myocarditis) had occurred after a previous mRNA vaccine.

The optimal interval for a third dose was between two to six months after completing their two-dose schedule of vaccine. People who received their second dose more than six months should get their third dose as soon as possible.

How this affects rheumatology patients

According to the ATAGI statement, the booster is recommended when patients are on multiple immunosuppressants where the cumulative effect is considered to be severely immunosuppressive.

For rheumatology patients, the booster shot is recommended for those on the following drug regimens:

  • High dose corticosteroid treatment equivalent to >20mg/day of prednisone for ≥14 days in a month, or pulse corticosteroid therapy.
  • Selected csDMARDs, including: mycophenolate, methotrexate (>0.4 mg/kg/week), leflunomide, azathioprine (>3mg/kg/day), 6-mercaptopurine (>1.5 mg/kg/day), alkylating agents (e.g. cyclophosphamide, chlorambucil), and systemic calcineurin inhibitors (e.g. cyclosporin, tacrolimus).
  • Biologic and targeted therapies anticipated to reduce the immune response to COVID-19 vaccine including B cell depleting agents (e.g. anti-CD20 monoclonal antibodies) and abatacept.

There are certain DMARDs not included as they’re expected to have a minimal effect on vaccine response, including hydroxychloroquine and sulfasalazine when used as monotherapy, anti-TNF-α, anti-IL1, anti-IL6, anti-IL17 and anti-IL23 antibodies.

Since ATAGI’s statement was released, rheumatologists have raised questions including which patients should get the booster, which vaccine is best and what to do with patients on JAK inhibitors or SSZ/HCQ combination therapy.

Dr Daman Langguth, a clinical immunologist at The Wesley Hospital in Brisbane, was a member of the the ASCIA Covid working group on vaccination. He spoke to Rheumatology Republic about the recommendation and some of the details about the medications included.  

The group adapted documents from the American College of Rheumatology and the British guidelines as the basis for the recommendations. While some of the medications listed and their dosages seem very prescriptive, Dr Langguth said there is leeway for clinical judgement, broadly covered by the statement that the booster can be given to any patient taking immunosuppressants where the cumulative effect is considered to be severely immunosuppressive.

For example, he said, the dosage of MTX for which a booster is recommended 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. It comes down to clinical judgement and I’d just be giving it to anyone on a standard dose of oral or SC weekly methotrexate,” said Dr Langguth.

“Similarly for azathioprine, they say 3mg per kilo but no one’s on that sort of dose in rheumatology”.

JAK inhibitors haven’t been included in the list of medications for which a booster is recommended, nor in the list of those DMARDs excluded for being expected to have minimal effect on vaccine response.

“We did actually suggest JAK inhibitors, but it didn’t come through specifically. However, they would be covered by the recommendation for patients on medications considered to be severely immunosuppressive,” said Dr Langguth.

“We excluded agents that have not been shown to decrease antibody production. Sulfasalazine increases your risk of covid, but as yet we don’t have enough evidence that it decreases the effect of vaccination.”

Hard data still needed in rheuma patients

At this point there is limited data regarding booster vaccines in immunosuppressed patients, and what exists is mainly in transplant recipients.

The NIH has begun a new trial, Covid‐19 Booster Vaccine in Autoimmune Disease Non‐Responders, to look at antibody responses to a covid vaccine booster dose in patients with autoimmune disease who failed to respond to the initial vaccine regimen. Only patients taking mycophenolic acid, methotrexate or B-cell depleting drugs are included. Preliminary results are expected in November this year.

The ARA has stated it will update its guidelines later this week.

ATAGI statement on the use of a third primary dose of COVID-19 vaccine in individuals who are severely immunocompromised.