ATLANTA—Rheumatologists are often asked about the safety and efficacy of various immunizations in adults with rheumatic diseases, but many have questions about which vaccines are safe to use in this population. Clifton Bingham III, MD, director of the Johns Hopkins Arthritis Center and associate professor of medicine at Johns Hopkins University in Baltimore, addressed these concerns during a presentation titled “Immunizations and Rheumatic Diseases: An Update” at the 2010 ACR/ARHP Annual Scientific Meeting here in November.
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Dr. Bingham remarked that many rheumatologists may hesitate to vaccinate patients with inflammatory and autoimmune disease for fear of triggering flares of disease or because of possible contraindications with the medications patients take. However, there are some vaccinations that are appropriate for this group.
“We know that patients with diseases such as rheumatoid arthritis [RA] and lupus have an increased risk of usual infections as well as atypical infections. We also understand that corticosteroids and immunomodulators may increase this risk and that outcomes can be more severe in this population. Immunizations can help decrease these risks,” said Dr. Bingham in the session, “Immunizations and Rheumatic Diseases: An Update.” [Editor’s note: This session was recorded and is available via ACR SessionSelect at www.rheumatology.org.]
Dr. Bingham said that studies in patients with autoimmune disease have shown a significant “underutilization and underappreciation” of immunizations.
A survey conducted by the ACR in April 2008 found a knowledge gap related to rheumatologists’ understanding of vaccines, Dr. Bingham said. For example, only 40% of those surveyed realized that yellow fever was a live vaccine; only 39% identified human papillomavirius (HPV) as an inactive vaccine.
In addition to any vaccine misunderstandings or a fear that they will worsen diseases, Dr. Bingham believes that a lack of familiarity with vaccine recommendations and a lack of communication between rheumatologists and primary care physicians also contribute to underutilization of vaccines in patients with autoimmune disease.
Although some reports in the literature have addressed a possible association between vaccinations and worsening disease, the incident rate is quite low, Dr. Bingham said. “The risk–benefit assessment shows the benefit of immunization,” he said.
Dr. Bingham believes that a lack of familiarity with vaccine recommendations and a lack of communication between rheumatologists and primary care physicians contribute to underutilization of vaccines in patients with autoimmune disease.
Which Vaccinations To Recommend
Dr. Bingham listed these vaccinations as safe for patients with autoimmune disease: diphtheria, acellular pertussis, hepatitis A/B, seasonal flu A/B (injected), injected H1N1, HPV, smallpox, inactivated polio, pneumococcal conjugate (PCV7 in children), and meningococcal conjugate.
Another group of immunizations that present carbohydrate/polysaccharide to the immune system are also acceptable for patients with immunodisease, Dr. Bingham said. These include pneumococcus, menincoccus, influenza B (Hib), and typhoid Vi injection.
However, there are a number of live and attenuated vaccines that rheumatologists should approach with extreme caution. In fact, “many of these are largely contraindicated in most immunosuppressed individuals,” Dr. Bingham said. These include varicella/zoster, the H1N1 flu mist, yellow fever, oral polio, the oral form of typhoid vaccines (Ty21a oral), vaccinia (smallpox), BCG (a vaccine for tuberculosis), rotavirus, and measles, mumps, and rubella.
“What is normally an attenuated form of the virus can become pathogenic in patients with immunosuppression,” Dr. Bingham said. Because studies have shown that patients who receive a live virus may shed live virus for up to three weeks, those who receive a live virus and live with patients with autoimmune disease should avoid close household contact after vaccinations, even though the risk is relatively low, he explained.
Role of Medications and Vaccine Administration
Dr. Bingham’s presentation addressed how common medications that patients with autoimmune disease use may affect vaccinations.
For example, he cited an earlier recommendation from the ACR based on Centers for Disease Control and Prevention (CDC) guidelines that said that it is acceptable to vaccinate patients with inflammatory disorders against zoster if they are using less than 20 mg of prednisone a day for less than two weeks or if they are using corticosteroids, topical or intraarticular corticosteroids, low-dose methotrexate (defined as < 0.4 mg/kg/week), azathioprine (< 3.0 mg/kg/day), or 6-mercaptopurine (< 1.5 mg/kg/day).
However, the zoster vaccine should not be given if the patient is using recombinant immune mediators—the guidelines specifically named adalimumab, infliximab, and etanercept, which by inference should include other tumor necrosis factor antagonists and other biologicals, according to Dr. Bingham—and high-dose corticosteroids (> 20 mg/day for more than two weeks).
In a study led by Dr. Bingham, immunization responses in RA patients treated with rituximab demonstrated that polysaccharide and primary immunizations should be administered before rituximab infusions to maximize responses. This study enrolled 103 patients with active RA who received a stable dose of methotrexate. The patients received tetanus toxoid, pneumococcal polysaccharide, keyhole limpet hemocyanin (KLH) vaccines, and a Candida albicans skin test. The patients were divided into two groups—one group received rituximab and methotrexate for 26 weeks and the other received methotrexate alone for 12 weeks. Investigators were looking for the proportion of patients with a four-fold or greater rise in antitetanus immunoglobulin G levels. Patients who had used both rituximab and methotrexate had decreased responses to the pneumococcal polysaccharide vaccine and to the KLH vaccine.
Another study outlined in the presentation focused on the use of the flu vaccinations in RA patients who had used rituximab four to eight weeks previously (11 patients who were considered the early group) or six to 10 months before (12 patients who were considered the late subgroup), 20 patients who were using methotrexate, and 29 healthy controls.2 Investigators measured the levels of antibodies against the three vaccine strains before and 28 days after vaccination. The investigators found that rituximab reduced humoral responses in RA patients, although there was a slightly better response six to 10 months after rituximab was used.
Dr. Bingham’s presentation reviewed studies regarding vaccines and their efficacy with medications such as methotrexate, hydroxychloroquine, abatacept, and others, noting that there is only scant information regarding vaccines and some of these drugs. He also cautioned that one common problem with vaccination studies is that there is rarely a control group for comparison. Additionally, “the primary endpoints may be very different, immunizations and assays used may vary, and prior exposures may also introduce variability,” he said.
Staying Up to Date
Rheumatologists and health professionals can stay up to date on vaccination guidelines, which are revised each year, on the CDC website, www.cdc.gov/vaccines/pubs/vis/default.htm. Although there is not a specific category on these guidelines for autoimmune patients, physicians might find it helpful to look at guidelines for immunocompromised patients and patients with chronic diseases such as diabetes. Rheumatologists can also find more vaccine information on the Vaccine Adverse Event Reporting System at www.vaers.hhs.gov.
Dr. Bingham concluded by sharing the recommendations published in Vaccine.3 The investigators, who took part in a Delphi process, recommend that a three- to six-month delay take place between the end of drug-related immune deficiency and the administering of live virus vaccines. They also noted that there is no contraindication in administering live virus in patients who are receiving systemic corticosteroids for less than two weeks or at a daily dose that does not exceed 10 mg of prednisone if the latter is long-term treatment.
Dr. Bingham recommended that rheumatologists and their staff include a careful immunization history and documentation as part of patient information and that communication take place with the patient and primary care provider regarding immunizations. He also recommended immunizing before immunosuppression therapy when possible and conducting ongoing reassessment of this issue.
Vanessa Caceres is a medical writer in Bradenton, Florida.
- Bingham CO 3rd, Looney RJ, Deodhar A, et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: Results from a controlled clinical trial. Arthritis Rheum. 2010;62:64-74.
- van Assen S, Holvast A, Benne CA. Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum. 2010. 62:75-81.
- Duchet-Niedziolka P, Launay O, Coutsinos Z, et al. Vaccination in adults with auto-immune disease and/or drug related immune deficiency: Results of the GEVACCIM Delphi survey. Vaccine. 2009;27:1523-1529.