The American College of Rheumatology (ACR) held a special session at the ACR Convergence in Philadelphia on November 12 to announce the forthcoming publication of its “ACR Guideline for Vaccination in Patients with Rheumatic and Musculoskeletal Diseases.”

According to project leader Anne Bass, MD, professor of Clinical Science at Weill Cornell Medicine—Hospital for Special Surgery, “This guideline applies across diseases. We created this guideline based on epidemiology and vaccine availability in the United States, but it is applicable across much broader populations.”

In announcing its planned publication, ACR noted that patients with rheumatic and musculoskeletal diseases (RMDs) are at increased risk for vaccine-preventable infections, particularly if they are treated with immunosuppressive medications. In addition, these diseases and the medications that treat them can also affect the immunogenicity and safety of vaccines.

ACR’s recommendations are complementary to other guidelines from the Advisory Committee on Immunization Practices and the Centers for Disease Control and Prevention (ACIP/CDC), as well as the American Academy of Pediatrics (AAP), the organization announced. The new guideline includes expanded vaccine recommendations specific for RMDs, as well as guidance on management of medications for patients receiving both nonlive-attenuated and live-attenuated vaccines.

The College has expanded indications for influenza, pneumococcus, recombinant varicella zoster (VZV), and human papillomavirus (HPV) vaccination in patients with RMDs who are on immunosuppression. ACR also recommends that all patients with RMDs who are older than 65 and those between 18 and 65 who receive immunosuppressive medications should receive high-dose or adjuvanted influenza vaccine rather than regular-dose influenza vaccine, if possible.

The ACR strongly recommends pneumococcal vaccination for patients with RMDs who are younger than 65 on any immunosuppressive medication, as well as those who are older than 65, as do the general CDC-ACIP recommendations.

The Shingrix vaccine for herpes zoster is also strongly recommended RMD patients older than 18 who are on immunosuppressive medication. These patients are at higher risk of developing shingles than are adults 50 and older for whom vaccination is broadly recommended.

Herpes papilloma virus (HPV) vaccination is conditionally recommended for patients with RMDs between 26 and 45 years of age who receive immunosuppressive medications and have not previously been vaccinated. Dr. Bass noted the recommendation applies to all RMD patients, as do CDC-ACIP recommendations for universal HPV vaccination before beginning sexual activity.

Because the ACR has already issued its COVID-19 vaccine guidance— because the disease continues to evolve rapidly—this vaccine was not included in the overall vaccination guidance. The ACR’s goal is to eventually bring COVID-19 vaccines into this guideline. 

The guidance also includes recommendations for managing immune-suppressing medications near or at the time of vaccination. If these medications are withheld there is increased risk of a disease flare, but these drugs may reduce vaccine immunogenicity.

“Methotrexate is known to reduce response to pneumococcal, flu, and other vaccines,” said Kevin L. Winthrop, MD, MPH, professor of infectious diseases and public health at Oregon Health and Science University.

“For influenza vaccination, you should hold methotrexate for two weeks after vaccination, but you should continue rituximab and other immunosuppressive medications other than methotrexate,” he said. “Whenever possible, vaccinations should be given before initiating rituximab.”

For other non-live-attenuated vaccines, methotrexate should be continued. Among patients treated with rituximab, vaccination should be timed to coincide with the due date for the next rituximab dose; rituximab should then be held for at least 2 weeks after vaccination. Other immunosuppressive medications should be continued as usual.

Patients taking less than 20 mg prednisone daily should have their influenza and other nonlive-attenuated vaccines as scheduled. For patients taking 20 mg or more prednisone daily, the influenza vaccine should be given as scheduled, but other nonlive-attenuated vaccines should be delayed until glucocorticoids are tapered to less than 20 mg daily prednisone equivalent, the ACR stated.

Patients on immunosuppressive medications should defer live-attenuated vaccines. Immunosuppressive medications should be held before live-attenuated virus vaccination and for 4 weeks after.

There are no known issues with tumor necrosis factor (TNF) inhibitors and live-attenuated varicella zoster (Zostavax). JAK inhibitors pose a potential risk of vaccine-associated varicella infection in the approximately 2 percent of the U.S. population that is seronegative to varicella.

The ACR guideline follows the CDC advice on delaying live-attenuated vaccines for 8 to 11 months after receiving Intravenous immunoglobulin (IVIG) treatment, due to the potential for IVIG to reduce efficacy. However, Dr Bass said, “there are clearly situations where earlier vaccination is preferred, such as during a measles outbreak, where some immunity is preferred over none.”

Live-attenuated vaccination after prenatal exposure to DMARDs has also raised questions. Dr Bass noted that observational studies have found no clear signals of adverse events among infants exposed in utero to TNFis. Therefore, ACR recommends that infants receive the live-attenuated rotavirus vaccine within the first 6 months of life with second- and/or third-trimester antenatal exposure to TNF inhibitors is conditionally recommended.

However, delaying live-attenuated rotavirus until 6 months of age is conditionally recommended for neonates with second and/or third trimester antenatal exposure to rituximab, which is associated with low or absent B lymphocyte levels in newborns.

“It is important that you, as a provider, give your recommendations (for rotavirus vaccination after in utero exposure) to the pregnant rheumatic disease patient before delivery,” Dr. Bass said. “Let that patient know this is something they should share with their pediatrician-to-be.”

—Rebecca Mashaw