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From: The Rheumatologist, February 2013

ACR/ARHP Annual Meeting 2012: Immunosuppressed Rheumatic Disease Patients Still Candidates for Vaccines

by Thomas R. Collins

WASHINGTON, D.C.—People with rheumatic diseases should be considered for flu and pneumococcal vaccines—but generally not live vaccines—even if they are on immunosuppressive drugs, an expert said during a session titled, “Immunizations in Patients with Rheumatologic Disease,” here at the 2012 ACR/ARHP Annual Meeting, held November 9–14. [Editor’s Note: This session was recorded and is available via ACR SessionSelect at]

But since immunosuppression can impair the response to these vaccines—and evidence suggests that methotrexate may be more to blame than antitumor necrosis factor therapies alone—getting patients vaccinated early on is the best course, said Gil Melmed, MD, MS, director of clinical trials at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center in Los Angeles.

“In our diseases that we treat, immunosuppression is unpredictable,” he said, referring to autoimmune disorders. “Somebody may not be on immunosuppression now, but they may require immunosuppression tomorrow. So we have them here today, let’s take advantage of the opportunity to educate them and administer the vaccines that they should get... They may actually respond less robustly tomorrow after they are on that immunosuppressive therapy.”

Taking on an Internist Role

Rheumatologists may need to assume the role of an internist, including advising patients on getting vaccines, he said. “There are many healthcare maintenance issues that we need to think about that may not necessarily be addressed appropriately by primary care providers who usually take care of healthcare maintenance,” Dr. Melmed said.

The risk of infection in rheumatologic disease or any disease treated with immunosuppressive therapies is the most common significant adverse event that doctors have to be aware of, and many of those infections are preventable with routine vaccinations.

But patients are not getting vaccinated nearly often enough. Studies have found that only 50% to 60% of patients with rheumatic diseases on immunosuppressives are up to date on flu and pneumococcal vaccines.1,2 One recent study found that a predictor of vaccination was a rheumatologist being in practice for fewer than 10 years.1

At-risk patients are generally not getting their vaccines, even when they have had recent visits to a primary care physician.

Simply finding a spot in the practice flow for a brief questionnaire—and then immediately rerouting patients to receive a vaccine or at least vaccine education—can be effective in boosting vaccine rates, Dr. Melmed said. So can assigning a nonphysician vaccination coordinator.

Disease Activity in SLE

One study found that systemic lupus erythematosus (SLE) patients with no active disease had a similar response to healthy controls when given the H1N1 vaccine.3 However, those with active disease had a lower seroconversion rate; it was even worse for those with very active disease.

“What we can see here is that disease activity in lupus patients may actually play a role in the ability of the body to respond adequately to vaccinations,” Dr. Melmed said.

Combination Therapy and Vaccines

A study at Dr. Melmed’s center found that, when they checked five of the 23 serotypes in the pneumococcal polysaccharide vaccine, those on combination therapy with methotrexate or azathioprine plus an antitumor necrosis factor (anti-TNF) agent had significantly blunted responses compared with those who were not.4

Studies have generally found that those on anti-TNF agents as monotherapy do not have an impaired response, while those on concomitant methotrexate tend to have blunted responses, he said. “It’s probably more the methotrexate or the azathioprine that’s influencing the vaccine response rather than anti-TNF drugs,” he said.


As tofacitinib is an oral drug, it opens the possibility of simply stopping the drug for a period of time when the vaccine is given. But one study—with the drug either continued or withheld for a week prior and a week after, with response measured 35 days later—found no significant differences in postvaccination responses between those groups.5 So, there may be no advantage to withholding the drug, Dr. Melmed said.

HPV Vaccine

A recent study found that the human papillomavirus vaccine seems to bring no increased risk of developing rheumatoid arthritis, lupus, Guillain-Barre Syndrome, Hashimoto’s thyroiditis, and other autoimmune diseases.6 Because this non-live vaccine protects against cancer-causing serotypes of human papillomavirus, it is recommended in women and men up to the age of 26 regardless of immunosuppression status.

Hepatitis B Vaccine and Reactivation

A study out of Spain found that that there was a 39% reactivation of latent hepatitis B vaccine among recipients of anti-TNF therapy, including four with fulminant hepatic failure, in patients who were hepatitis B surface antigen-positive. But even among those in whom the infection seemingly cleared—those who were isolated hepatitis B virus (HBV) core antibody-positive—the reactivation rate was 5%—“a not insignificant” number, Dr. Melmed said.7 Therefore, these patients should be treated for HBV or followed very closely with HBV viral loads if initiating anti-TNF therapy.

Live Vaccines

Live vaccines are generally contraindicated for those on any kind of immunosuppressive therapies, including the live attenuated influenza virus, yellow fever, bacille Calmette-Guerin (given outside the U.S), measles/mumps, rubella, varicella, and herpes zoster vaccines, although U.S. Centers for Disease Control and Prevention (CDC) guidelines say the zoster vaccine can be administered to those on low-dose immunosuppression (not biologics)—prednisone less than 20 mg, 6MP less than 1.5 mg/kg, azathioprine less than 3 mg/kg, and methotrexate less than 0.4 mg/kg/week.

But in studies reviewing hundreds of people on biologics who got the zoster vaccine accidentally, there were either no infections, or infection rates were similar for those vaccinated and not vaccinated.8,9

“I suspect we’re going to be breaking down that dogma of not using live virus vaccines in individuals who are on immunosuppressive therapy in certain cases where the risk of infection outweighs theoretical but unproven risk from vaccination with a live virus vaccine,” Dr. Melmed said.

Yellow Fever

“The CDC guidelines suggest that we should be discouraging these [immunosuppressed] individuals from going to highly endemic areas of yellow fever,” he said. “The risk from vaccination is potentially significant. There can be neurotoxic effects from yellow fever vaccination, particularly in somebody who’s immunocompromised, and yet the risk of infection in a highly endemic area is also significant. In somebody who’s immunocompromised, that infection may be even worse, or even fatal.”

Newborn Vaccination

Because of the active transport mechanism of antibodies from the mother to the fetus, increased levels of infliximab and adalimumab have been found in cord blood, so newborns should not be given live vaccinations in the first six months of life.

Thomas Collins is a freelance medical journalist based in Florida.


  1. Bridges MJ, Coady D, Kelly CA, Hamilton J, Heycock C. Factors influencing uptake of influenza vaccination in patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62:685.
  2. Desai SP, Turchin A, Szent-Gyorgyi LE, et al. Routinely measuring and reporting pneumococcal vaccination among immunosuppressed rheumatology outpatients: The first step in improving quality. Rheumatology. 2011;50:366-372.
  3. Borba EF, Pasoto SG, Calich AL, et al. Lupus disease activity severely impairs pandemic influenza A/H1N1 vaccine immune response in patients without therapy. Arthritis Rheum. 2012;64(10 Suppl.): S1109.
  4. Melmed GY, Frenck R, Barolet-Garcia C, et al. TNF blockers and immunomodulators impair antibody responses to pneumococcal polysaccharide vaccine (Ppv) in patients with inflammatory bowel disease (IBD). Gastroenterology. 2008;134(4 Suppl.):A68.
  5. Winthrop LK, Racewicz A, Lee EB, et al. Evaluation of influenza and pneumococcal vaccine responses in patients with rheumatoid arthritis receiving tofacitinib. Arthritis Rheum. 2012;64(10 Suppl.): S550.
  6. Grimaldi L, Rossignol M, Aubrun E, et al. Human papillomavirus vaccine [types 6, 11, 16, 18] (Gardasil ) and autoimmune disorders: Safety assessment using the pharmacoepidemiologic general research extension system. Arthritis Rheum. 2012;64(10 Suppl.):774.
  7. Pérez-Alvarez R, Díaz-Lagares C, García-Hernández F, et al. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: Analysis of 257 cases. Medicine. 2011;90:359-371.
  8. Zhang J, Delzell E, Xie F, et al. The use, safety, and effectiveness of herpes zoster vaccination in individuals with inflammatory and autoimmune diseases: A longitudinal observational study. Arthritis Res Ther. 2011; 13:R174.
  9. Zhang J, Xie F, Delzell E, et al. Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases. JAMA. 2012;308:43-49.


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