Vaccines & Biologic Medicines

Simply having a rheumatic disease increases your risk for infection, and treatments that suppress your immune system, such as biologic medications and steroids, can increase this risk even more. Consequently, vaccines to prevent illnesses are an important part of treatment for rheumatoid arthritis (RA). However, many questions still surround our understanding of how vaccines, RA medications, and the disease itself interact.

“Depending on which specific disease we are talking about, the increase in risk for infection compared to the general population can be as much as three times,” says Jeffrey Curtis, MD, William J. Koopman, Endowed Professor in Rheumatology and Immunology at the University of Alabama at Birmingham. “Is this because of a disordered immune system that can’t fight off infection, or because of the steroid and biologic medications we use? Either way, this makes vaccinations relevant for those with autoimmune conditions.”

Controversies

In fact, the use of vaccines continues to be controversial, especially for individuals using biologic medications. Several questions persist, including whether biologics hamper the immune response, and whether this in turn can influence how well the vaccines work.

“A few of these drugs have been around for a relatively short period of time,” says Professor David Isenberg from the Centre for Rheumatology at the University College of London in the United Kingdom. “While it isn’t completely a data-free area, there is still a very restricted amount of information out there. There are some published recommendations on vaccines for those on steroids and immune suppression drugs but currently none for vaccinating patients treated with biologics.”

To address some of these issues, Dr. Isenberg and Isabel Ferriera, MD, Hospital Professor Doutor Fernando Fonseca in Amadora Portugal, undertook a review of the available studies on the subject. They published their findings early in 2014 in the Annals of Rheumatic Disease.

“There have been case reports that vaccinations may very rarely induce flares in some patients,” says Dr. Isenberg. “Because of this, it can be recommended that vaccinations should only be given when the disease is stable.”

Timing is important

Isenberg and Ferriera’s review found that timing of the vaccinations can be very important and can change depending on the medications being used. For example, vaccinations with anti-tumor necrosis factor agents such as infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), and golimumab (Simponi) can be given at any time during treatment.

On the other hand, the studies Dr. Isenberg reviewed suggest that any necessary vaccines should be administered before Rituximab (Rituxan) is started. If this can’t be done, your doctor may recommend vaccination be delayed until at least six months after you start and four weeks before the next course of Rituximab is due.

Thus, understanding your current vaccination status before starting any medication that has an immunosuppressive effect becomes very important. Ask your primary care physician for an updated list of any vaccinations you have had or should have in the near future, and then discuss the list with both your primary care doctor and your rheumatologist to determine which vaccinations should be given before you start taking medications that might result in suppression of the immune system.

In the article, Isenberg and Ferriera noted that a pre-injection workup is important. They suggested personalized vaccination plans based on pre-vaccination tests that show the level of antibodies already in the blood, the drugs being prescribed, and the likelihood that a given vaccine will be beneficial.

Live, attenuated vaccines

Live, attenuated vaccines are made from live organisms that have been modified to make them inactive. These vaccines are close to a natural infection, which makes them good “teachers” of the immune system. They include:

• MMR (measles, mumps, rubella)

• Rubella

• Rotavirus

• Varicella-Zoster

• Yellow Fever

• BCG for tuberculosis

• Oral typhoid

However, individuals whose immune systems already have been compromised by rheumatic disease or medications may fail to respond, and a full-blown infection can occur. Consequently, most professional groups for physicians, along with the Centers for Disease Control and Prevention (CDC), say that those who are immunocompromised should never receive a live, attenuated vaccine.

Most people in North America have access to adequate substitutes for live, attenuated vaccines (except for those against the Zoster virus that causes shingles), but Yellow Fever could be a concern for those traveling to certain areas outside of the United States. Talk to your doctor about the risks and benefits of getting vaccinated before you leave the country.

Some researchers, however, suggest that this may not be as big a concern as originally thought. “The edict against live vaccines in this population has no real evidence to support it,” says Dr. Curtis. “The current prohibition is largely the result of the CDC being appropriately conservative because it could be dangerous.”

Dr. Curtis is involved with a study funded by the American College of Rheumatology and the National Institutes of Health that is aimed at quantifying the risks involved. However, he says that until more information from clinical trials is available, live, attenuated vaccines should not be given to people receiving biologic medications.

Different responses?

Experts also voice concern about the lack of good information from studies on how (or if) patients on biologics react differently to vaccines than the general population. Does an immune system that is repressed by both medications and rheumatic disease require a different schedule of vaccinations?

“An even more important question would be how long do these vaccines actually last?” says Dr. Curtis. “That is another area with a lack of usable evidence to guide both patients and their physicians. Should we stay with the guidelines for the general population, or do we need to give at least some of the vaccines more often?”

There are reasons for concern. Current practice for those taking a TNF inhibitor is to revaccinate after five years, but one study reported in Arthritis Research and Therapy showed pre-vaccination levels of antibodies to the pneumococcal bacteria in the blood 1.5 years after individuals received the vaccine. The unanswered question is whether those people were effectively unprotected during those last 3.5 years.

In fact, it’s not completely clear whether the vaccines are actually doing what they are supposed to be doing. Most studies look at “seroprotection,” which is usually defined as antibody levels above a certain point in the blood. However, studies have not been done to see if seroprotection actually results in fewer infections in a given population.

Which physician is responsible for vaccinations?

Vaccines have long been the focus and responsibility of the primary care physician—you go to your family doctor, who takes care of giving shots to those who need them in the entire family. However, the drugs given (and better understood) by the rheumatologist are the ones causing the concerns.

“As the complexity of treatment options for rheumatic diseases increases, the recommendations for vaccines have also become more complicated [for those patients] compared to those who are totally healthy,” says Leonard H. Calabrese, DO, professor of medicine at the Cleveland Clinic, Lerner College of Medicine, Case Western Reserve University. “This can lead to physicians’ lack of confidence in knowing what their patients actually need.” The confidence concerns may lead doctors to decide not to vaccinate until these issues become clearer.

There may also be hesitancy on the part of both your rheumatologist and your family physician to give you vaccines because of a split in care. The rheumatologist may think the family doctor is handling the vaccinations. The family doctor, on the other hand, may think the rheumatologist is taking care of this issue since it relates to the medications he or she is prescribing.

“The gap is two-fold,” says Dr. Calabrese. “The first is that vaccinations are a complex area that doesn’t fall obviously into the purview of the rheumatologist. The second is that vaccinology has traditionally been in the domain of the primary care physician. It isn’t that anybody is doing a bad thing; it’s just complicated.”

It often falls to you to coordinate with both physicians regarding whether you need vaccinations and which ones are indicated, and then actually getting them. If you don’t do it, it may not get done; studies of quality of care indicators consistently show that patients with rheumatic diseases are undervaccinated.

“One of the important things that a person should be asking their physician is what vaccines should I be getting?” says Dr. Curtis. “Looking at the large population studies, most rheumatic patients don’t get vaccinated like they are supposed to. Yet it should be even more important that we make vaccination a priority in these patients.”

Many questions remain unanswered in the discussions about vaccinations for those prescribed biologic medications. Keep asking your doctor about the vaccines you need and when you need them.

Kurt Ullman has been a medical writer for 30 years. He is based in Indiana.

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