Vaccination guidelines vary for immunocompromised patients

Key takeaways:

• Influenza, pneumococcal, zoster and COVID-19 vaccines all are recommended for immunocompromised patients.
• Vaccines may be less effective when patients get them during immunosuppressive treatment.

Patients who are immunocompromised still can receive a variety of vaccinations based on their specific needs, Cassandra Calabrese, DO, said during her presentation at Updates in Primary Immunodeficiency 2025.

“Immunocompromised patients are a very heterogenous population,” Calabrese, assistant professor of medicine, department of rheumatologic and immunologic disease, Cleveland Clinic Lerner College of Medicine, said. “This is an individualized approach.”

Care in scheduling

Between 3% and 6% of people in the United States are immunocompromised, Calabrese said, but age, sex, social determinants of health, stress and lifestyle make uniform guidelines for vaccination challenging to develop.

“And addressing vaccines with patients during our visits becomes increasingly difficult with time constraints,” Calabrese added. “But this is important.”

Calabrese advised physicians to review each patient’s history of vaccinations and infections as well as any travel plans that they may have. Patients who are not current for their age-appropriate vaccinations should be brought up-to-date, she continued.

These vaccines include pneumococcal pneumonia, influenza and herpes zoster as well as HPV for those patients up to aged 45 years. Live vaccines should be administered at least 4 weeks before any immunosuppression the patient has scheduled.

When patients require more than one vaccine, they could be administered during a single day, if they are not live vaccines, but that should still follow discussions with the patient.

“It really depends on the patient and their desires and health beliefs,” Calabrese said. “But generally, I advise against this, especially if patients have any degree of vaccine hesitancy or wariness, or if their arms are just going to hurt a lot more or they’re going to feel a lot more crummy the next day. It can help with future vaccine uptake to space them out.”

Cassandra also noted the impact of timing vaccinations for patients with immune-mediated inflammatory diseases (IMIDs) who may be taking concomitant immunosuppressive drugs such as disease-modifying antirheumatic drugs.

For example, she said, vaccinations for influenza, pneumococcal, tetanus and SARS-CoV-2 are less effective when patients are taking rituximab (Rituxan, Genentech).

“If you give someone a vaccine within a few months after rituximab, they will have very little response,” Calabrese said. “The recommendation is to wait as long as possible after their last infusion, and then 2 to 4 weeks before their next dose.”

Methotrexate, which also has a negative impact on vaccine efficacy, should be held for 4 weeks before and for 4 weeks after administration of a live virus. Abatacept (Orencia, Bristol Myers Squibb) should be held for one dosing interval before and for 4 weeks after administration of a live virus.

In fact, she said, patients with rheumatoid arthritis who hold off on their methotrexate dose for 2 weeks after influenza or COVID-19 vaccination will have better vaccine response with no increase in rheumatoid arthritis flares. Similar patients who get non-live vaccinations do not have to skip their methotrexate at all.

“We do have discussions with our patients on methotrexate during flu season to hold a dose if they feel comfortable, if they’re doing well,” Calabrese said. “There aren’t any really firm recommendations to hold any of our other immunosuppressive drugs around the flu or COVID vaccine.”

Calabrese called prednisone “a big culprit” in reducing vaccine efficacy at any dose and said that physicians should taper doses of 20 mg daily or more if they plan on giving their patients the influenza vaccination.

“If you can wait until they’re on a little bit less prednisone, they’ll have a better response,” she said. “Defer to them if you can.”

Overall, Calabrese said, “there is a paucity of data to guide recommendations on administering live vaccines in the setting of iatrogenic immunosuppression, for obvious reasons,” and the recommendations that are available are cautious and generous.

However, cytokine inhibitors and many biologics used for atopic conditions such as dupilumab (Dupixent; Sanofi, Regeneron) and mepolizumab (Nucala, GSK) do not have any negative impact on vaccine responses, Cassandra said, which is important to share with patients.

Influenza, pneumococcal vaccines

Patients with primary immunodeficiencies should still get the influenza vaccine every year, even if they are aged as young as 6 months, Calabrese said.

“The only true contraindication to getting a flu vaccine is if you have a significant allergy to a component of the flu vaccine,” she continued.

Patients with egg allergy can still get the influenza vaccine, even if it uses an egg-based formulation, Calabrese said.

Patients between aged 2 to 49 years can receive an intranasal formulation of the influenza vaccine, she added. Patients aged 65 years and older with solid organ transplants can receive high-dose, recombinant and adjuvanted influenza vaccines as well.

“And there are data to show that patients with immune-mediated inflammatory diseases such as rheumatoid arthritis have a better response to high-dose flu vaccine when given younger than 65,” Calabrese said.

Also, Calabrese noted that Streptococcus pneumoniae is the primary bacterial cause of pneumonia, meningitis and sepsis, with mortality rates ranging from 5% to 32% and increased risk for immunocompromised patients.

“We know from experience in our IMIDs patients that vaccines are protective and safe,” Calabrese said, although patients with cryopyrin-associated periodic syndromes have very severe reactogenicity with vaccines for pneumonia, so caution is required.

Calabrese also said that the 15-valent (PCV15), 20-valent (PCV20), and 21-valent (PCV21) pneumococcal conjugate vaccines are indicated for all PCV-naïve adults aged 50 years and older and for adults aged 19 to 64 years with underlying medical conditions

But recent updates in pneumococcal guidance are “confusing,” with reports that the polysaccharide vaccine probably will be phased out, she said.

“If you receive a 20-valent pneumococcal conjugate vaccine or the 21-valent PCV, you don’t need the polysaccharide vaccine at all,” Calabrese said. “However, if you receive a PCV15, you still need the polysaccharide vaccine, and these cover more serotypes that are implicated in a greater proportion of invasive streptococcal infections.”

Zoster vaccines

Noting that the risk for herpes zoster is high but preventable among immunocompetent individuals, Calabrese said that it is important for physicians to discuss vaccine status with their patients.

“Once someone has zoster, available antivirals do not fully protect you from complications, such as post-herpetic neuralgia, which is a big source of morbidity,” Calabrese said. “And this treatment is complicated and not overly successful. Prevention is preferable.”

Zoster incidence rates per 1,000 patient-years in the U.S. include two to three among all adults, four among adults aged 50 years and older, 10 among patients with rheumatoid arthritis and 11 among adults aged 80 and older.

“That’s almost tripled,” Calabrese said. “That’s comparable to patients with IMIDs across all ages.”

Incidence rates also include a range from six to 32 for patients with systemic lupus erythematosus, 39 for patients with rheumatoid arthritis who use tofacitinib (Xeljanz, Pfizer), 45 for patients with granulomatosis with polyangiitis and 69 for patients who use anifrolumab (Saphnelo, AstraZeneca).

“[Janus kinase (JAK)] inhibitors are very strongly associated with increased risk for zoster,” Calabrese said.

Immunocompromised adults can be vaccinated against zoster with the non-live recombinant zoster vaccine (Shingrix, GSK), which Calabrese called “a very potent adjuvant” that is “over 90% effective at preventing zoster” in more than 7 years of follow-up.

The two shots in the series are administered 2 to 6 months apart, she said, adding that reactogenicity counseling also is important since one in 10 patients had significant local or systemic reactogenicity.

“It can be helpful, I think, to share that information with patients to increase serious completion,” Calabrese said. “I encourage them not to get it the day before a vacation or they’re going to a wedding or have something important to do.”

Calabrese also advised patients who received the live zoster vaccine (Zostavax, Merck) in the past, which grew less effective over time and has since been phased out in the U.S., to get Shingrix.

Patients with autoimmune diseases who contract herpes zoster are at particular risk for stroke, Calabrese continued, including a 36% increased risk overall and a 76% increased risk for patients who have cranial nerve complications within 90 days of infection.

“There’s significant increased risk of stroke, especially within 30 days after zoster, which is attenuated by a vaccine and attenuated by rapid start of antivirals,” Calabrese said.

Further, Calabrese said that patients may be hesitant to get the vaccine because of anecdotes about poor reactions heard from others who have already received it.

“It’s also important to discuss the reactogenicity so patients don’t take that reactogenicity they might experience as an adverse event,” she said. “Let them know it’s their immune system at work. This is good, and it will be gone in 24 hours, and it will very much help with vaccine acceptance.”

Patients with immune-mediated rheumatic disease may experience flares triggered by the vaccine, Calabrese said, but these flares do not happen often, and when they do, they are mild and manageable.

“We do avoid giving our IMID patients recombinant zoster vaccine when they are in a flare or having a hard time with their disease or on a prednisone taper,” she said. “We try to wait until things are quiet.”

Calabrese added that she prioritizes patients who are on JAK inhibitors and anifrolumab for vaccination, as well as patients who already have had zoster and who are at risk for getting it again.

“Patients who are 40 years old on a TNF inhibitor and/or methotrexate can probably wait until they’re 50 to get the zoster vaccine,” she said.

RSV, COVID-19 vaccines

Further, Calabrese noted the hospitalization burdens that come with RSV, including up to 160,000 adults aged 65 years and older and 80,000 children aged 5 years and younger each year in the U.S.

The CDC recommends RSV vaccines for all adults aged 75 years and older and adults aged 60 to 74 years with risk factors including being immunocompromised. Arexvy (GSK) is approved for all adults aged 50 years and older, and Abrysvo (Pfizer) is approved for all adults including women who are between weeks 32 and 36 in pregnancy.

The ongoing Monet trial of Abrysvo among immunocompromised and other at-risk patients, including rheumatology patients and patients with chronic kidney disease, has shown some favorable and effective results, Calabrese said.

“However, several months ago, both vaccines received a black box warning for Guillain-Barré syndrome,” Calabrese said. “This is significant and something to be aware of.”

CDC and WHO recommendations for COVID-19 vaccines targeting circulating omicron subvariants include additional doses for patients with primary immunodeficiencies who face greater risks for severe outcomes, Calabrese said.

“Who is still at risk for severe disease and hospitalization?” Calabrese said. “That’s largely B cell deleted patients, specifically iatrogenically B cell depleted patients on rituximab and other B cell blocking drugs.”

Yet studies have shown that patients with primary immunodeficiencies including patients receiving intravenous immunoglobulin (IVIG) treatment who have been vaccinated against COVID-19 experience increases in neutralizing antibodies, she said.

“Patients on immunoglobulin replacement now do have a decent amount of protection,” Cassandra said.

In addition to COVID-19 vaccines, she said, patients receiving IVIG treatment should have protective titers for the MMR, pneumococcus, Haemophilus influenza and meningococcus vaccines. These patients also experienced increasing levels of neutralizing antibodies against SARS-CoV-2 as the pandemic continued.

“But if someone on IVIG does get a live vaccine, there are some timing considerations,” Calabrese added.

Pemivibart (Pemgarda, Invivyd) pre-exposure prophylaxis (PrEP) is available for patients aged 12 years and older with primary immunodeficiencies at risk for severe COVID-19 who may not have an adequate response with COVID-19 vaccination, Calabrese said.

“It is a long-acting IV formulation of anti-spike protein that lasts for 3 months and then recommended for another dose,” she said.

Patients who use rituximab and other anti-CD20 drugs, who have received a solid organ transplant or hematopoietic stem cell transplantation, or who are on active chemotherapy should be prioritized for PrEP, Calabrese said, as should those with immunosuppression and significant comorbidities.

Other patients who should be prioritized include those on anifrolumab, cyclophosphamide or mycophenolate, she continued, as well as those on combination therapies including high-dose steroids and those with a concomitant common variable immunodeficiency or other inborn error of immunity.

Pemivibart has emergency use authorization from the FDA.

“We want to treat you and get you PrEP if we can,” Calabrese said.

Talking to patients

Calabrese cited the importance of communication in improving vaccination rates among immunocompromised patients, noting that physician recommendations have the greatest impact in increasing vaccine uptake.

“Take a few moments to talk to your patients about vaccines,” she said. “Take a moment to assess vaccine status.”

Some patients may say that they do not want to get vaccinated, she added.

“I just say, ‘Tell me more about that,’ and go from there. If they don’t want to talk about it, move on,” she said. “But you’ll find that you can convince some patients to change their minds.”

For more information:

Cassandra Calabrese, DO, can be reached at allergy@healio.com.