Article

Time-dependent increased risk for serious infection from continuous use of tumor necrosis factor antagonists over three years in patients with rheumatoid arthritis.

Tokyo Medical and Dental University, Japan.
Arthritis care & research 03/2012; 64(8):1125-34. DOI: 10.1002/acr.21666
Source: PubMed

ABSTRACT To investigate associations between continuous treatments with tumor necrosis factor (TNF) antagonists and risk for developing serious infections (SIs) over 3 years in Japanese patients with rheumatoid arthritis (RA) enrolled in the Registry of Japanese RA Patients for Long-Term Safety (REAL) database.
We analyzed 727 RA patients who had started either infliximab or etanercept (the anti-TNF group; 1,480.1 patient-years [PY]) and 571 RA patients who had started conventional nonbiologic disease-modifying antirheumatic drugs (the unexposed group; 1,104.1 PY) at the time of enrollment in the REAL. We assessed the occurrence of SIs within a 3-year observation period, including the period after switching to other TNF antagonists, and all SIs, unlimited to the first one in each patient as reported in other studies, to evaluate the real safety of TNF antagonists in daily practice.
The incidence rate of SIs per 100 PY was 5.54 (95% confidence interval [95% CI] 4.44-6.84) in the anti-TNF group and 2.72 (95% CI 1.87-3.83) in the unexposed group. Poisson regression analysis revealed that the relative risk (RR) of continuous use of TNF antagonists for SIs after adjusting for baseline and time-dependent covariates was significantly elevated both overall (1.97, 95% CI 1.25-3.19) and for the first year (2.40, 95% CI 1.20-5.03), but not for the second and third years combined (1.38, 95% CI 0.80-2.43). The adjusted RR for SIs of etanercept compared to infliximab was not significantly elevated.
Continuous anti-TNF therapy was significantly associated with increased risks for developing SIs during, but not after, the first year.

2 Bookmarks
 · 
115 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: A post-marketing surveillance (PMS) program was implemented to assess the safety and effectiveness of tacrolimus (TAC) in Japanese rheumatoid arthritis (RA) patients and to identify risk factors related to adverse drug reactions (ADRs). METHODS: Patients were registered centrally and monitored for all adverse events (AEs) for 24 weeks. Effectiveness was evaluated using the Disease Activity Score 28-CRP (DAS28-CRP). RESULTS: Data from 3,172 patients (mean age 62.2 years) were evaluated in the safety analysis. Of the safety population, 78.5 %were female and 25.9 % were in Steinbrocker's functional class 3 or 4. TAC was prescribed as monotherapy in 52.5 % and the most common concomitant disease modifying antirheumatic drug (DMARD) was methotrexate, used in 28.9 % of the patients. The incidence of AEs, serious AEs (SAEs), ADRs and serious ADRs were 41.2, 6.4, 36.0, and 4.9 %, respectively. The most frequent serious ADR category was infections and infestations. Age ≥65 years, concurrent renal dysfunction, and concurrent diabetes mellitus were identified as significant risk factors for ADR. Based on EULAR response criteria, 65.4 % of the patients showed moderate or good response. CONCLUSIONS: The results demonstrate that TAC is well tolerated by Japanese patients with active RA, including those receiving concomitant methotrexate, in the real world.
    Modern Rheumatology 05/2013; · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: TNF blockers have demonstrated efficacy in inflammatory rheumatic diseases (IRDs). The drugs are associated with a moderate but definite risk of bacterial infection, but risk of viral infection is not clearly known. To assess the risk of herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA) receiving TNF blockers as compared with DMARDs. A systematic search of literature up to March 2013 was performed, in MEDLINE, EMBASE, the Cochrane library and abstracts from the ACR and EULAR congresses from 2008 to 2011. Studies were included if they reported the incidence of HZ, respectively, in patients receiving anti-TNF and conventional DMARDs. The literature search identified 3446 articles and 88 congress abstracts; a manual search retrieved seven articles. Finally, 26 articles and nine abstracts were included; six articles and one abstract were of meta-analyses estimating the relative risk of HZ in patients with RA with a total follow-up of 163,077 patient-years. From the meta-analyses of data for seven registries, the pooled risk ratio for HZ with TNF blockers was 1.61 [95%CI 1.16-2.23] (P=0.004). Proportions of severe HZ ranged from 4.9% to 20.9% with TNF-blockers and from 2.0% to 5.5% with conventional DMARDs, in the different registries. This meta-analysis revealed a significantly increased risk of HZ, up to 61%, in patients with IRD receiving TNF blockers. These data raise the issue of systematic prophylactic treatment with known history of HZ or vaccination without this history.
    Joint, bone, spine: revue du rhumatisme 08/2013; · 2.25 Impact Factor
  • Clinical Rheumatology 05/2013; · 2.04 Impact Factor

Full-text (2 Sources)

View
1 Download
Available from
Oct 8, 2014