Common adult vaccinations are not associated with an increased risk of developing rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

“Vaccinations are among the events which have long been postulated as inciting agents for RA, as well as for many other chronic inflammatory diseases of unknown origin,” says Camilla Bengtsson, PhD, an epidemiologist at the Institute of Environmental Medicine, Karolinska Institutet in Stockholm, Sweden, and lead investigator in the study.

“In our case-control study including incident cases of newly diagnosed RA, no increased risk of RA following immunization was observed, at least not in the five years prior to disease onset,” explains Dr. Bengtsson, noting that the study is ongoing. “This indicates that immunological provocation with commonly used vaccines in their present form carries no risk of RA in adults.”

The study is based on data from the Epidemiological Investigation of Rheumatoid Arthritis, an ongoing, population-based, case-control study in Sweden designed to investigate associations between genes as well as environmental factors and the risk of developing RA. One of the largest etiological RA studies in the world, EIRA began in 1996 and includes data from more than 8,000 subjects.

For the vaccination study, researchers compared 1,998 participants with RA who were vaccinated within the five years prior to disease onset to 2,252 participants with RA who were not. Each group was matched based on age, gender and place of residence, and all participants were between 18 and 70 years old.

Researchers found no association between vaccinations and the development of RA. Furthermore, they found no association between any specific vaccine (e.g., influenza, tetanus, diphtheria, tick-borne encephalitis, hepatitis – A, B, C together, polio, or pneumococcus) and the risk of developing RA.

The study also examined whether vaccinations have a different impact on two smaller groups of participants—those with ACPA-positive and those with ACPA-negative disease—and found that the vaccines did not increase the risk of either disease form. ACPA, or anti-citrullinated protein antibodies, are autoantibodies (antibodies directed against one or more of an individual’s own proteins) that are frequently detected in the blood of RA patients. ACPAs have proven to be powerful biomarkers of RA and ACPA testing has become a commonly accepted and crucial part of diagnosing the disease.

Finally, the researchers noted that vaccinations did not elevate the risk of RA among participants who smoke and among participants who are carriers of HLA-DRB1 SE alleles—a genotype—both of which are established risk factors of RA.

“Since RA has a hereditary component, our results are reassuring, not only for the population in general, but especially for children and other relatives of patients with RA,” Dr. Bengtsson says.

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.rheumatology.org/education. Follow the meeting on twitter by using the official hashtag: #ACR2010.

Editor’s Notes: Camilla Bengtsson, PhD will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 3:45 PM on Monday, November 8 in Room A 411. Dr. Bengtsson will be available for media questions and briefing at 8:30 AM on Monday, November 8 in the on-site press conference room, B 212.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover how the ACR Research and Education Foundation’s Within Our Reach: Finding a Cure for Rheumatoid Arthritis campaign is accelerating RA research.

Presentation Number: 645

Common Vaccinations among Adults and the Risk of Developing Rheumatoid Arthritis; Results from the Swedish EIRA Study.

Camilla Bengtsson (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden)
Meliha Kapetanovic (Institute for Clinical Sciences, Department of Rheumatology, Lund University, Lund, Sweden)
Henrik Källberg(Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden)
Berit Sverdrup (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden)
Birgitta Nordmark (Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden)
Lars Klareskog (Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden)
Lars Alfredsson (Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden)

Background: Vaccinations are among the events frequently considered as inciting agents for rheumatoid arthritis (RA), but no sufficiently powered epidemiological studies have been published addressing whether vaccinations commonly used in industrialised societies constitute risk factors for RA1.

Objectives: To investigate whether common vaccinations given to adults were associated with an increased risk of RA, and whether vaccinations have different impact on two subsets of RA, characterized by presence/absence of antibodies to citrullinated peptides (ACPA). In addition we examined potential interactions between vaccinations and smoking and between vaccinations and HLA-DRB1 SE alleles regarding risk of ACPA-positive RA.2

Methods: Data from the Swedish population-based EIRA (Epidemiological Investigation of Rheumatoid Arthritis) case-control study encompassing 1998 incident cases aged 18-70 years and 2252 randomly selected controls, matched on age, sex and residency, was analysed. All cases were diagnosed by rheumatologists according to the ACR criteria of 1987. Those vaccinated within five years prior to disease onset were compared with those not vaccinated within five years before disease onset, by calculating odds ratios (OR) with 95% confidence interval (CI). Biological interaction, defined by departure from additivity of effects was evaluated between vaccination and smoking and between vaccination and HLA-DRB1 SE alleles.

Results: In total, 31% of the cases and 31% of the controls had been vaccinated. Vaccinations did neither increase the risk of RA overall (OR=1.0 (95% CI 0.9-1.1) nor the risk of ACPA-positive or ACPA-negative disease. Furthermore, there was no association between any specific vaccine (influenza, tetanus, diphtheria, tick-borne encephalitis, hepatitis (A, B, C together), polio, pneumococcus) and the risk of RA. Finally, no interaction was found between any vaccination and smoking or between any vaccination and SE alleles regarding risk of ACPA-positive disease.

Conclusions: Our results indicate that immunological provocation with common vaccines given to adults in their present form is not a major risk factor for RA, at least not vaccines administered within five years before onset of disease. In addition, the results indicate that active immunisation does not increase the risk of RA in individuals with established risk factors, i.e smokers or those carrying HLA-DRB1 SE alleles. These findings should be implemented among clinicians and health care providers in order to encourage common vaccinations according to recommended vaccinations schedule for adults.

References: 1. Conti F, Rezai S, Valesini G. Vaccination and autoimmune rheumatic diseases. Autoimmun Rev. 2008;8:124-8. Review. 2. Klareskog L, Stolt P, Lundberg K, et al. A new model for an etiology of RA: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 2006;54:38–46.

Disclosure: Camilla Bengtsson, nothing to disclose; Meliha Kapetanovic, nothing to disclose; Henrik Källberg, nothing to disclose; Berit Sverdrup, nothing to disclose; Birgitta Nordmark, nothing to disclose; Lars Klareskog, nothing to disclose; Lars Alfredsson, nothing to disclose.

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Source:  American College of Rheumatology (ACR)