Postmarketing surveillance of safety and effectiveness of etanercept in Japanese patients with rheumatoid arthritis

Abstract

Our aim was to evaluate real-world safety and effectiveness in a 6-month postmarketing surveillance study covering all Japanese patients with rheumatoid arthritis (RA) who received etanercept during a 2-year period. Data for 13,894 patients (1334 sites) enrolled between March 2005 and April 2007 were collected. Adverse events (AEs) and serious adverse events (SAEs) were reported in 4336 (31.2%) and 857 (6.2%) patients, respectively. The most frequent AEs were injection site reactions (n = 610, 4.4%) and rash (n = 339, 2.4%), whereas pneumonia (n = 116, 0.8%) and interstitial lung disease (n = 77, 0.6%) were the most frequent SAEs. Significant improvement in the proportion of patients with a good European League Against Rheumatism (EULAR) response was observed from week 4 (17.6%) to week 24 (31.6%) (p < 0.001); 84.3% of patients had good or moderate EULAR responses at week 24. The percentage of patients achieving remission increased significantly from week 4 (9.3%) to week 24 (18.9%) (p < 0.001). Patients with early moderate RA were less likely to experience SAEs and were more likely to achieve remission compared with patients with more severe disease. The safety and effectiveness of etanercept was demonstrated in Japanese patients in one of the largest observational trials conducted thus far in RA patients treated with biologics.

Immune-mediated adverse effects of biologicals used in the treatment of rheumatic diseases

“…Post-marketing surveillance studies in Japan indicated that the frequencies of drug-related ILD in Japanese RA patients treated with infliximab or etanercept were 0.5% and 0.6%, respectively [24,77]. In accordance with findings in TNF antagonist-naïve RA patients, men were twice as frequently affected by ILD as women [77].…”

“…According to a systematic review by the Spanish Study Group of Autoimmune Diseases (the BIOGEAS project), 14 of 1842 (0.76%) patients enrolled in clinical trials of TNF antagonists developed drug-induced lupus (DIL) [74]. Post-marketing surveillance yielded lower incidence rates [74,77]. In the pivotal trials examining the efficacy and safety of abatacept in the treatment of RA, SLE and a lupus-like syndrome occurred at markedly lower rates than during TNF blockade (0.05/100 PY and 0.01/100 PY, respectively) [25].…”

Clinical Manifestations and Prognostic Factors of <b><i>Pneumocystis jirovecii</i></b> Pneumonia without HIV

“…The mortality of patients with non-HIV PCP is diverse and ranges from 0 to 70% [1,4,5,6,7,8,9], compared with the mortality of HIV-infected PCP patients which ranges from 10 to 20% [1,10]. The higher mortality among non-HIV patients has been attributed to severe lung inflammation [1,5], although the exact etiologies responsible for the differences in mortality have not yet been determined.…”

“…There is no culture method for determining the presence of P. jirovecii [4], so microscopic findings such as Grocott or Diff-Quik staining are commonly used. Although Diff-Quik is specific and useful, it requires high expertise and has a low sensitivity in the diagnosis of non-HIV PCP [37].…”

“…Over the past decade, a paradigm shift in the treatment of autoimmune diseases such as rheumatoid arthritis (RA) [4,5] and inflammatory bowel disease (IBD) has been brought about by the introduction of biologics [6,7,8]. While the emergence of innovative biologic agents targeted at specific molecules and pathways in the immune system has altered the clinical course of patients with an autoimmune disease, improving their quality of life and social outcomes, an increasing incidence of non-HIV PCP has also been noticed [4,5,6,7,8]. In the field of solid-organ transplant recipients and malignancies, the emergence of a new generation of immunosuppressive agents like rituximab and also cytotoxic agents could be the cause of this more frequent occurrence of non-HIV PCP [9,10,11,12].…”