Newswise — Anti tumor necrosis factor therapy for rheumatoid arthritis appears to increase a patient’s risk of developing septic arthritis, which is the infection of a joint, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Philadelphia, Pa.
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. Septic arthritis is a serious condition that can be life threatening, and it is more likely to occur in patients with rheumatoid arthritis.
TNF-antagonists (anti-TNF therapy; among drugs called biologics) are a class of drugs that have been used since 1998; overall, they have been given to more than 600,000 people worldwide. These drugs are given to lessen inflammation by interfering with biologic substances that cause or worsen inflammation.
Using the British Society for Rheumatology Biologics Register—a registry that tracks the progress of patients with severe rheumatoid arthritis and other rheumatic conditions who are taking anti-TNF therapy—researchers recently looked at the association between anti-TNF therapy and septic arthritis.
Researchers studied 11,757 people with RA who were undergoing anti-TNF therapy and compared them to 3,515 patients who were undergoing treatment with disease-modifying antirheumatic drugs. They began recruiting patients in October of 2001 and continued to monitor them until December 31, 2008, the end of their follow up to treatment, or their death. A patient’s health was monitored through questionnaires filled out by the patients and their physicians. A case of septic arthritis was attributable to anti-TNF therapy if it was diagnosed while the patient was on the therapy or within 90 days of his or her last dose.
During the study, 246 cases of septic arthritis were identified. Of these cases, 229 were among patients taking anti-TNF therapy and 17 were among the patients on disease-modifying antirheumatic drugs (commonly called DMARDs). Staphylococci (commonly called staph) were the most common infection among both groups of patients. Septic arthritis was twice as likely to occur in patients with rheumatoid arthritis who were taking anti-TNF therapy than in patients who were not on these drugs.
"It has previously been shown that patients exposed to TNF-antagonists have an increased risk of serious infections as a whole,” explains James Galloway, MD; clinical research fellow; BSR Biologics Register; ARC unit; University of Manchester, Manchester, United Kingdom, and lead investigator in the study. “This study adds to this knowledge confirming that septic arthritis in particular is associated with TNF inhibition."
Dr. Galloway also mentions that, as many patients do not realize that replaced joints are still at risk for infection, it is important to note that the risk of infection is increased in joints that have already been replaced as well as in original joints.
Patients with RA need to be carefully monitored for the development of septic arthritis. Appropriate medical evaluation and treatment, including reducing—and even stopping—immunosuppressive therapy is essential to the management of septic arthritis. Patients should talk to their rheumatologists to determine their best course of treatment.
The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see www.rheumatology.org/annual.
Editor’s Notes: Dr. Galloway will present this research during the ACR Annual Scientific Meeting at the Pennsylvania Convention Center at 11:45 AM on Wednesday, October 21 in Room 108 B. Deborah Symmons, MD will be available for media questions and briefing at 8:30 AM on Sunday, October 18 in the on-site press conference room, 109 A.
Presentation Number: 2060
Risk of Septic Arthritis in Patients with Rheumatoid Arthritis Treated with Anti-TNF Therapy: Results From the BSR Biologics Register (BSRBR)
J. B. Galloway, arc Epidemiology Unit, University of Manchester, Manchester, United Kingdom K. L. Hyrich, arc Epidemiology Unit, University of Manchester, Manchester, United Kingdom L. K. Mercer, arc Epidemiology Unit, University of Manchester, Manchester, United Kingdom W. G. Dixon, arc Epidemiology Unit, University of Manchester, Manchester, United Kingdom A. P. Ustianowski, Infectious Diseases, North Manchester General Hospital, Manchester, United Kingdom K. D. Watson, arc Epidemiology Unit, University of Manchester, Manchester, United Kingdom M. Lunt, arc Epidemiology Unit, University of Manchester, Manchester, United Kingdom D. P. Symmons, arc Epidemiology Unit, University of Manchester, Manchester, United Kingdom On behalf of the BSRBR, arc Epidemiology Unit, University of Manchester, Manchester, United Kingdom
Purpose: Rheumatoid arthritis (RA) is associated with an increased risk of septic arthritis (SA). Clinical trials of anti-TNF therapy have not suggested an increased risk of SA, but there have been case reports suggesting a potential association.
Method: Consecutive RA patients treated with anti-TNF therapy recruited between 10/01 and 5/08 by the BSRBR were followed 6 monthly via consultant and patient questionnaires until 12/31/08, end of follow up or death. A comparison cohort with active RA on disease modifying anti-rheumatic drugs (DMARD) was recruited and followed up in the same way. Incident cases of SA were identified from follow-up questionnaires and verified via medical records. SA was attributed to anti-TNF if it was diagnosed while on anti-TNF or within 90 days of the last dose. SA event rates in the anti-TNF and DMARD cohorts were compared using Cox proportional hazard ratio estimates adjusted for age, gender, disease severity, prior joint replacement, co-morbidity and steroid use. Missing baseline data were replaced using multiple imputations.
Results: 246 cases of SA were reported during the follow up period: 229/11757 in the anti-TNF cohort and 17/3515 in the comparison cohort. 179 cases could be attributed to anti-TNF using the “on drug plus 90 day” model. Incident rates were 5.0/1000 pyrs (95% CI 4.3, 5.8) in the anti-TNF cohort and 1.9/1000 pyrs (1.1, 3.0) in the controls. At least 51% of the SA in patients on anti-TNF occurred in native joints (Table). Patients on anti-TNF therapy were twice as likely to develop SA as controls (adjusted HR 2.0, 95% CI 1.1, 3.5). The individual anti-TNF drug adjusted results were etanercept HR 2.3, (CI 1.2, 4.4), infliximab HR 1.6, (CI 0.8, 3.2), and adalimumab HR 1.8, (CI 1.0, 3.5). Staphylococci were the most common organisms in both cohorts (DMARD 50%; anti-TNF 75%). 5 cases of intracellular infection (2 Listeria, 3 Salmonella) and 11 cases of Streptococcal SA (including 4 Streptococcus pyogenes) were reported (all in the anti-TNF cohort).
Conclusion: Exposure to TNF inhibitor therapy is associated with an increased risk of SA in patients with RA. Careful vigilance for joint infections remains important with awareness of the potential range of pathogens. Antibiotic guidelines should incorporate this information.
Table (View the press release with full abstract at www.rheumatolgy.org
Disclosure: J. B. Galloway, None; K. L. Hyrich, British Society for Rheumatology, 2 ; L. K. Mercer, None; W. G. Dixon, None; A. P. Ustianowski, None; K. D. Watson, None; M. Lunt, None; D. P. Symmons, British Society for Rheumatology, 2 ; O. behalf of the BSRBR, BSR BR, 2 .
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