The largest study of respiratory syncytial virus (RSV) infection outcomes in people with systemic autoimmune rheumatic diseases (SARDs) to date found that more than half were hospitalized with the disease, indicating the need for people in this group to consider vaccination with one of the three RSV vaccines approved by the FDA since 2023.

In the single-center, retrospective study, patients with frailty had nearly five times the odds of hospitalization compared with those considered robust, Justine P. Enns, MD, of Massachusetts General Hospital in Boston, and her colleagues reported in Seminars in Arthritis and Rheumatism. Other risk factors for hospitalization included having a concurrent infection and having a higher number of comorbidities.

“Clinicians who take care of people with SARDs should consider these findings when discussing and recommending age-appropriate RSV vaccination with their patients and when reviewing related prevention strategies such as pneumococcal, COVID, and influenza vaccinations,” the authors wrote.

“This study confirms what we have all feared — that RSV causes significant morbidity and mortality in our rheumatology patients taking immunosuppressive drugs,” Christopher R. Palma, MD, ScM, an associate professor of medicine and director of the Clinical Research Center at the University of Rochester Clinical and Translational Science Institute, told Medscape Medical News. Palma was not involved with the study but said the findings strongly suggest the need for the American College of Rheumatology (ACR) to urgently update their vaccine guidelines.

“All physicians taking care of persons that are immunosuppressed should be routinely discussing RSV vaccination,” Palma said. “This includes rheumatologists as well as primary care physicians, nephrologists, pulmonologists, dermatologists, transplant specialists, hematologists, oncologists, etc.”

The study also showed a signal for greater risk for hospitalization among those taking CD20 inhibitors, but it did not reach statistical significance.

“It will be important to reassess outcomes and monitor data regarding risks of severe outcomes of RSV infection in the setting of vaccination, particularly among those with SARDs, to determine how to best provide recommendations moving forward,” Naomi J. Patel, MD, MPH, senior author of the study and a rheumatologist at Harvard Medical School and Massachusetts General Hospital, told Medscape Medical News.

The CDC recommends RSV vaccination in adults aged 75 years or older and in those aged 50-74 years who are at an increased risk for severe infection.

“Having a SARD in and of itself does not qualify someone for the RSV vaccine at age 50, though moderate or severe immunocompromised individuals 50 [or] over are recommended to receive the vaccine,” Patel said. “This includes individuals who are on high-dose glucocorticoids and most conventional synthetic and biologic disease-modifying antirheumatic drugs [DMARDs].”

High Morbidity in Patients With SARDs

The researchers’ retrospective review included 188 patients with SARDs who were seen for a confirmed RSV infection in the Mass General Brigham healthcare system between 2015 and 2023. Most patients were White (74%), women (75.5%), with a median age of about 69 years. None had been vaccinated against RSV.

Just over half had rheumatoid arthritis or another inflammatory arthritis (52%), 19% had lupus or another connective tissue disease, and 10% had polymyalgia rheumatica and/or giant cell arteritis.

About two thirds of patients (68%) were taking a DMARD, including 52% taking conventional synthetic DMARDs, 2% taking targeted synthetic DMARDs, 44% taking oral glucocorticoids, and 24% taking biologic DMARDs, including TNF inhibitors or CD20 inhibitors.

Half the patients (51%) were hospitalized, and 22% had a concurrent viral, bacterial, or fungal infection based on imaging, lab testing, or clinical diagnosis. The average age of those hospitalized vs nonhospitalized patients was 72 vs 66 years, initially resulting in significantly greater odds of hospitalization for older patients (odds ratio [OR], 1.03 per year; 95% CI, 1.01-1.05). But adjustment for age, sex, smoking status, frailty, and comorbidities barely removed statistical significance (adjusted OR, 1.02 per year; 95% CI, 0.996-1.04).

Odds of hospitalization were over four times greater for patients with a Claims-Based Frailty Index over 0.25 (adjusted OR, 4.8; 95% CI, 2.3-9.9) and more than double for those with a concurrent infection (adjusted OR, 2.52; 95% CI, 1.1-5.9). Patients with a higher Charlson Comorbidity Index also had 16% greater odds of hospitalization (adjusted OR, 1.16 per point; 95% CI, 1.04-1.31).

Over half the hospitalized patients needed oxygen (56%); 12 died within 90 days of admission, making up 12.5% of those hospitalized and 6% of those with RSV. Most who died (92%) had preexisting cardiovascular or pulmonary comorbidities; a third had moderate-to-severe chronic kidney disease.

Overall, 74% of all those with preexisting interstitial lung disease (ILD) were hospitalized. Patients who had preexisting ILD had higher odds of hospitalization than those who did not (adjusted OR, 2.23; 95% CI, 0.76-6.50), but it did not reach significance. Because this was a small group, there may have been insufficient power for significance, Patel suggested. But among patients who were hospitalized due to RSV infection, there was a significant association with ILD (adjusted OR, 3.63; 95% CI, 1.27-10.34).

Use of CD20 inhibitors vs conventional synthetic DMARDs did not quite reach statistical significance for higher odds of hospitalization (adjusted OR, 3.84; 95% CI, 0.99-15.20).

“CD20 inhibitors are one of the most strongly immunosuppressive medications we use in rheumatology, and a robust B-cell response is important in RSV infection,” Patel said. “CD20 inhibitors also impair the response to vaccination and can have an impact on breakthrough infection, though our study period was prior to the widespread availability of RSV vaccines.”

RSV Vaccination Management

The most recent ACR guidelines for vaccinating people with SARDs recommends flu, COVID, and pneumococcal vaccines, but its release in 2022 predates the FDA’s 2023 approval of three RSV vaccines.

“While there are not specific ACR guidelines for RSV vaccines, we extrapolate guidelines from other vaccines and from the SARS-CoV-2 vaccines to guide management around immunosuppressive medications,” Patel said. “All management is individualized.”

Those on high-dose glucocorticoids could consider deferring vaccination until they are tapered to a lower dose, if feasible, and sometimes, methotrexate and other conventional synthetic DMARDs could be held for 1-2 weeks after vaccination, Patel said. But “these decisions involve a discussion of the risks and benefits of holding medications based on the status of the individual’s underlying SARD and other comorbidities,” she said.

Bibi Ayesha, MBBS, associate professor of rheumatology and director of the Vasculitis Clinic at Montefiore Medical Center and Albert Einstein College of Medicine in Bronx, New York, agreed that management varies by patient.

“Given the risk of flare of the autoimmune disease, it is a clinician’s judgment call if the clinician wants to hold it,” Ayesha told Medscape Medical News. “Clinicians will decide based on the disease activity of the patient, and every patient is different and every disease is different. More studies are needed to see the immune responses, at least in the stable patients whose diseases are well-controlled, and how they responded to these medications.”

Without those data, Ayesha emphasized the need to “make sure the underlying autoimmune disease is well controlled prior to introducing any vaccine.”

Kevin Winthrop, MD, MPH, a professor of public health at Oregon Health & Science University in Portland, Oregon, told MedscapeMedical News this was an important study with a group of patients in whom there’s currently a dearth of data related to RSV.

It reaffirms that these individuals are at a higher risk for poor outcomes with RSV, he said, “and it reiterates the idea that we should focus on these people for vaccination to have the possibility of preventing some pretty serious disease.”

Although data from flu and COVID immunization show poor antibody responses in people taking CD20 inhibitors, some do show a cell-mediated response, which is important for RSV, Winthrop said.

“We need to study how those drugs affect [RSV] vaccine response, and if they do negatively affect it, how best to give the vaccine, seeing if holding those drugs makes a difference,” he said. Ideally, based on data with other vaccines, patients taking CD20 inhibitors should receive the vaccine as far from the previous infusion as possible, followed by at least a 2-week delay of the next infusion, he said. But more research could help guide vaccination and medication management with abatacept, JAK inhibitors, methotrexate, and other immunosuppressants.

Palma, however, follows a different strategy with vaccinating patients on immunosuppressants, saying he doesn’t “let perfection be the enemy of the good.”

“While there is high-quality evidence that holding [DMARDs and other immunosuppressive drugs] improves vaccine response and this would be reasonable to extrapolate to other vaccines, I always worry that giving more complex instructions to a patient reduces the likelihood that they actually receive a vaccine,” Palma said. “It can also give the impression that the vaccine is unsafe to receive if they are taking methotrexate, which is not at all the case. In the current climate of extensive, intentional disinformation around vaccines, I am greatly simplifying my messaging to patients and simply encouraging them to receive a vaccine that I think will benefit them without any additional complications as far as medication management.”

Currently available RSV vaccines include two inactivated ones (Abrysvo and Arexvy) and an mRNA one (mResvia), but because none of these are live vaccines, there does not appear to be any reason to give preference to one over another or to consider different dosing schedules based on the specific RSV vaccine type, Ayesha and Palma said.

The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the authors reported receiving grants from the National Institutes of Health, the Rheumatology Research Foundation, the Arthritis Foundation, the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Gordon and Llura Gund Foundation.

Patel reported receiving consulting fees from FVC Health, Arrivo Bio, Alosa Health, and Guidepoint Consulting and grant support from Amgen. One author reported being an employee at Massachusetts General Hospital at the time the study was conducted but reported now being an employee and stockholder of Amgen. Another author reported receiving consulting and/or research support from AbbVie, Amgen, Anaptys, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius Kabi, Gilead, GSK, Inova Diagnostics, Invivyd, Johnson & Johnson, Merck, MustangBio, Novartis, Optum, Pfizer, Recor, Sana, Sobi, Sonoma Biotherapeutics, and UCB.

Winthrop reported receiving research grants and/or scientific consulting around vaccines from GSK. Ayesha and Palma had no relevant disclosures.

Tara Haelle is a science/health journalist based in Dallas.