Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register.
TL;DR: In patients with active RA, anti-TNF therapy was not associated with increased risk of overall serious infection compared with DMARD treatment, after adjustment for baseline risk, but the rate of serious skin and soft tissue infections was increased, suggesting an important physiologic role of TNF in host defense in the skin andsoft tissues beyond that in other tissues.
Abstract: Objective
To determine whether the rate of serious infection is higher in anti–tumor necrosis factor (anti-TNF)–treated rheumatoid arthritis (RA) patients compared with RA patients treated with traditional disease-modifying antirheumatic drugs (DMARDs).
Methods
This was a national prospective observational study of 7,664 anti-TNF–treated and 1,354 DMARD-treated patients with severe RA from the British Society for Rheumatology Biologics Register. All serious infections, stratified by site and organism, were included in the analysis.
Results
Between December 2001 and September 2005, there were 525 serious infections in the anti-TNF–treated cohort and 56 in the comparison cohort (9,868 and 1,352 person-years of followup, respectively). The incidence rate ratio (IRR), adjusted for baseline risk, for the anti-TNF–treated cohort compared with the comparison cohort was 1.03 (95% confidence interval 0.68–1.57). However, the frequency of serious skin and soft tissue infections was increased in anti-TNF–treated patients, with an adjusted IRR of 4.28 (95% confidence interval 1.06–17.17). There was no difference in infection risk between the 3 main anti-TNF drugs. Nineteen serious bacterial intracellular infections occurred, exclusively in patients in the anti-TNF–treated cohort.
Conclusion
In patients with active RA, anti-TNF therapy was not associated with increased risk of overall serious infection compared with DMARD treatment, after adjustment for baseline risk. In contrast, the rate of serious skin and soft tissue infections was increased, suggesting an important physiologic role of TNF in host defense in the skin and soft tissues beyond that in other tissues.
Citations
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TL;DR: The biology of T NF and related family members are discussed in the context of the potential mechanisms of action of TNF antagonists in a variety of immune-mediated inflammatory diseases.
1,517 citations
Cites result from "Rates of serious infection, includi..."
...…(Listing et al., 2005; Bongartz et al., 2006; Askling et al., 2007), but some studies have found there is no overall increased risk for infections after TNF blockade as compared with the frequency in patients with RA not treated with TNF antagonists (Dixon et al., 2006; Schiff et al., 2006a)....
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TL;DR: Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient.
Abstract: Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.
1,447 citations
University of Porto1, The Catholic University of America2, Sheba Medical Center3, Rambam Health Care Campus4, University of Palermo5, Boston Children's Hospital6, University College Dublin7, University of Barcelona8, Western General Hospital9, Guy's and St Thomas' NHS Foundation Trust10, McMaster University11, Université de Montréal12, Mount Sinai Hospital13
TL;DR: The treatment of inflammatory bowel disease has been revolutionised over the past decade by the increasing use of immunomodulators, mainly azathioprine/6-mercaptopurine and methotrexate, together with the advent of biological therapy.
1,150 citations
TL;DR: Strong evidence now shows that people with RA are at a high risk for developing several comorbid disorders, that these conditions may have atypical features and thus may be difficult to diagnose, and that persons with RA experience poorer outcomes after comorbridity compared with the general population.
Abstract: Epidemiology is the study of the distribution and determinants of disease in human populations. Over the past decade there has been considerable progress in our understanding of the fundamental descriptive epidemiology (levels of disease frequency: incidence and prevalence, comorbidity, mortality, trends over time, geographic distributions, and clinical characteristics) of the rheumatic diseases. This progress is reviewed for the following major rheumatic diseases: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriatic arthritis, osteoarthritis, systemic lupus erythematosus, giant cell arteritis, polymyalgia rheumatica, gout, Sjogren's syndrome, and ankylosing spondylitis. These findings demonstrate the dynamic nature of the incidence and prevalence of these conditions – a reflection of the impact of genetic and environmental factors. The past decade has also brought new insights regarding the comorbidity associated with rheumatic diseases. Strong evidence now shows that persons with RA are at a high risk for developing several comorbid disorders, that these conditions may have atypical features and thus may be difficult to diagnose, and that persons with RA experience poorer outcomes after comorbidity compared with the general population. Taken together, these findings underscore the complexity of the rheumatic diseases and highlight the key role of epidemiological research in understanding these intriguing conditions.
798 citations
University of California, Los Angeles1, University of Toronto2, Leiden University3, Charité4, Chapel Allerton Hospital5, University of Texas Southwestern Medical Center6, Hospital for Special Surgery7, University of Erlangen-Nuremberg8, University of California, San Diego9, Guy's and St Thomas' NHS Foundation Trust10, University of Washington11, MetroHealth12, Medical University of Vienna13, Radboud University Nijmegen14, Cedars-Sinai Medical Center15, Oregon Health & Science University16
TL;DR: The consensus statement is annotated to document the credibility of the data supporting it as much as possible and the number of possible references has become so large that reviews are sometimes included; if they contain category A references, they will be referred to as category A evidence.
Abstract: As in previous years, the consensus group to consider the use of biological agents in the treatment of rheumatic diseases met during the 13th Annual Workshop on Advances in Targeted Therapies in April, 2011. The group consisted of rheumatologists from a number of universities among the continents of Europe, North America, South America, Australia and Asia.
Pharmaceutical industry support was obtained from a number of companies for the annual workshop itself, but these companies had no part in the decisions about the specific programme or about the academic participants at this conference. Representatives of the supporting sponsors participated in the initial working groups to supply factual information. The sponsors did not participate in the drafting of the consensus statement.
This consensus was prepared from the perspective of the treating physician.
In view of the new data for abatacept, B cell-specific agents, interleukin 1 (IL-1) antagonists, tocilizumab (TCZ) and tumour necrosis factor α blocking agents (TNF inhibitors), an update of the previous consensus statement is appropriate. To allow ease of updating, the 2010 (data from March 2009 to January 2010) updates are incorporated into the body of the article, while 2011 updates (February 2010–January 2011) are separated and highlighted. The consensus statement is annotated to document the credibility of the data supporting it as much as possible. This annotation is that of Shekelle et al and is described in appendix 1.1 We have modified the Shekelle annotation by designating all abstracts as ‘category D evidence’, whether they describe well-controlled trials or not, as details of the study were often not available in the abstracts. Further, the number of possible references has become so large that reviews are sometimes included; if they contain category A references, they will be referred to as category A evidence.
The rheumatologists and bioscientists who attended …
722 citations
References
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TL;DR: The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists) and are as valid as disease activity scores that include more comprehensive joint counts.
Abstract: Objective. The development and validation of Modified Disease Activity Scores (DAS) that include different 28-joint counts.
Methods. These scores were developed by canonical discriminant analyses and validated for criterion, correlational, and construct validity. The influence of disease duration on the composition of the DAS was also investigated.
Results. No influence of disease duration was found. The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists).
Conclusion. The Modified DAS are as valid as disease activity scores that include more comprehensive joint counts.
5,718 citations
"Rates of serious infection, includi..." refers background in this paper
...UK national guidelines recommend that anti-TNF agents be reserved for patients with active RA (defined as a 28-joint Disease Activity Score [DAS28] [23] 5....
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TL;DR: Infliximab is a humanized antibody against tumor necrosis factor α (TNF-α) that is used in the treatment of Crohn's disease and rheumatoid arthritis but there is no direct evidence of a protective role of TNF- α in patients with tuberculosis.
Abstract: Background Infliximab is a humanized antibody against tumor necrosis factor α (TNF-α) that is used in the treatment of Crohn's disease and rheumatoid arthritis. Approximately 147,000 patients throughout the world have received infliximab. Excess TNF-α in association with tuberculosis may cause weight loss and night sweats, yet in animal models it has a protective role in the host response to tuberculosis. There is no direct evidence of a protective role of TNF-α in patients with tuberculosis. Methods We analyzed all reports of tuberculosis after infliximab therapy that had been received as of May 29, 2001, through the MedWatch spontaneous reporting system of the Food and Drug Administration. Results There were 70 reported cases of tuberculosis after treatment with infliximab for a median of 12 weeks. In 48 patients, tuberculosis developed after three or fewer infusions. Forty of the patients had extrapulmonary disease (17 had disseminated disease, 11 lymph-node disease, 4 peritoneal disease, 2 pleural dis...
3,405 citations
TL;DR: Infliximab was well-tolerated; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group.
2,411 citations
TL;DR: The addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously every other week to long-term MTX therapy in patients with active RA provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo.
Abstract: Objective
To evaluate the efficacy and safety of adalimumab (D2E7), a fully human monoclonal tumor necrosis factor α antibody, in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite treatment with MTX.
Methods
In a 24-week, randomized, double-blind, placebo-controlled study, 271 patients with active RA were randomly assigned to receive injections of adalimumab (20 mg, 40 mg, or 80 mg subcutaneously) or placebo every other week while continuing to take their long-term stable dosage of MTX. The primary efficacy end point was the American College of Rheumatology criteria for 20% improvement (ACR20) at 24 weeks.
Results
An ACR20 response at week 24 was achieved by a significantly greater proportion of patients in the 20-mg, 40-mg, and 80-mg adalimumab plus MTX groups (47.8%, 67.2%, and 65.8%, respectively) than in the placebo plus MTX group (14.5%) (P < 0.001). ACR50 response rates with the 20-mg, 40-mg, and 80-mg adalimumab dosages (31.9%, 55.2%, and 42.5%, respectively) were significantly greater than that with placebo (8.1%) (P = 0.003, P < 0.001, and P < 0.001, respectively). The 40-mg and 80-mg doses of adalimumab were associated with an ACR70 response (26.9% and 19.2%, respectively) that was statistically significantly greater than that with placebo (4.8%) (P < 0.001 and P = 0.020). Responses were rapid, with the greatest proportion of adalimumab-treated patients achieving an ACR20 response at the first scheduled visit (week 1). Adalimumab was safe and well tolerated; comparable numbers of adalimumab-treated patients and placebo-treated patients reported adverse events.
Conclusion
The addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously every other week to long-term MTX therapy in patients with active RA provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo.
1,813 citations
TL;DR: The combination of etanercept and methotrexate was significantly better in reduction of disease activity, improvement of functional disability, and retardation of radiographic progression compared with methotRexate or etanorcept alone.
1,783 citations