ACR Guidance on Timing of 3rd Dose Booster with Immunomodulatory Drugs Save

The American College of Rheumatology has issued an updated version of its COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases following recent recommendations from the CDC that certain immunocompromised patients receive a third dose of an available mRNA vaccine. Based on evidence published to date, the task force continues to feel the benefits of the COVID-19 vaccine outweigh the potential for vaccine harm for most rheumatology patients.

The updated recommendations include guidance on timing third vaccine doses and immunomodulatory medications, a preference for the use of mRNA vaccines in patients who have not yet been vaccinated, and a notation of the FDA emergency use authorization (EUA) for post-exposure prophylaxis with monoclonal antibody treatment for patients who are exposed to COVID-19, including most vaccinated rheumatology patients.

Key recommendations include:

• A third dose of Pfizer-BioNTech COVID-19 vaccine (age 12 years and older) or Moderna COVID-19 vaccine (age 18 years and older) is recommended at least 28 days after the second dose of an mRNA vaccine for patients on immunosuppressive or immunomodulatory therapy, except for hydroxychloroquine. Attempts should be made to match the additional mRNA dose type to the type given in the mRNA primary series; however, if that is not feasible, using the alternative mRNA vaccine is permitted. 
• Providers should counsel their patients to hold certain immunomodulatory or immunosuppressive medications for one to two weeks after booster vaccination if disease activity allows. Exceptions to this guidance were made for glucocorticoids and anti-cytokine therapies, which would include most biologic agents. The task force did not achieve consensus on whether anti-cytokine medications such as tumor necrosis factor (TNF) inhibitors and others including IL-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists meaningfully impair vaccine response that would warrant their temporary interruption. For that reason, no recommendation was made as to whether to temporarily hold or to continue these treatments at the time of booster vaccination until additional evidence accrues. 
• Patients on rituximab or other anti-CD20 medications should discuss the optimal timing with their rheumatology provider before receiving a third dose. Some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, the recommendation is to provide the third dose two to four weeks before the next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients who receive rituximab every six months).

Given current uncertainties regarding the safety of providing supplemental dose(s) of an mRNA vaccine to patients who already have received the single-dose J&J vaccine, the task force did not achieve consensus regarding recommending supplemental dose(s) of the mRNA vaccine to patients who previously received the single-dose J&J vaccine.

In a modification to previous guidance that expressed no preference for one type of vaccine over another for rheumatology patients who have yet to be vaccinated, the task force recommended they receive either of the two mRNA vaccines over the single-dose Johnson & Johnson (J&J) vaccine. The preference for the mRNA vaccines was partially driven by the fact that a supplemental dose is now authorized for the mRNA vaccines. This issue may be revisited if a supplemental dose strategy becomes authorized and recommended for patients who received the single dose vaccine.

Because of uncertainties in the interpretation of lab testing following vaccination as it would impact clinical decision-making, the task force felt it was important to reaffirm its stance that healthcare providers should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post-vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.

The guidance also notes the August 2021 Emergency Use Authorization by the FDA authorizing REGEN-COV monoclonal antibody treatment for emergency use as post-exposure prophylaxis (preventative) measure for COVID-19 in adults and pediatric individuals (12 years of age and older weighing at least 40 kg) who are at high risk for developing severe COVID-19. This at-risk group includes rheumatology patients and those receiving immunosuppressive or immunomodulatory therapy other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should ask their provider whether this treatment would be beneficial as an additional precautionary measure. Prophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19.

The guidance also maintained that rheumatology patients should continue to follow all public health guidelines regarding physical distancing and other preventive measures following vaccination. For the average rheumatology patient, the panel did not recommend that they exceed preventive health measures currently recommended by public health authorities.

“I’m tremendously pleased that the ACR COVID-19 Vaccine Clinical Guidance Task Force was able to quickly mobilize and respond to the new CDC guidance surrounding supplemental dosing against COVID-19. The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said Dr. Jeffrey Curtis, Chair of the ACR COVID-19 Vaccine Guidance Task Force and Professor of Medicine, Epidemiology and Computer Science at the University of Alabama at Birmingham.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution. We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The updated recommendations can be found on the ACR website. Bold text signifies areas that have been revised, updated, or added to the most current version of the document. Changes are also summarized in the appendix table on page seven. Providers with questions about the guidance can email COVID@rheumatology.org for support.