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

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

Safety and effectiveness of switching from infliximab to etanercept in patients with rheumatoid arthritis: results from a large Japanese postmarketing surveillance study

Finding an effective treatment strategy for rheumatoid arthritis (RA) patients who have not benefited from previous tumor necrosis factor–α antagonist treatment is important for minimizing RA disease activity and improving patient outcomes. The aim of this study was to compare the safety and effectiveness of etanercept in patients with and without infliximab (IFX) treatment experience. Patients (n = 7,099) from a large postmarketing observational study of etanercept use in Japan were divided into 2 cohorts based on previous IFX use (pre-IFX and non-IFX). Baseline characteristics were assessed in each cohort. Adverse events (AEs) and European League Against Rheumatism (EULAR) responses were monitored every 4 weeks for 24 weeks. At baseline, pre-IFX patients were younger and had fewer comorbidities and a shorter RA duration than non-IFX patients. During the study, pre-IFX patients received concomitant methotrexate more often than non-IFX patients. The incidence of AEs and serious AEs were significantly lower in pre-IFX patients, as was the percentage of patients who discontinued treatment. Both cohorts had significant improvement (P < 0.001) in EULAR responses at the end of the treatment period. This study demonstrated that etanercept was effective and well tolerated in active RA patients with and without prior IFX treatment

Safety and effectiveness responses to etanercept for rheumatoid arthritis in Japan: a sub-analysis of a post-marketing surveillance study focusing on the duration of rheumatoid arthritis

The aim is to investigate the relationship of duration of rheumatoid arthritis (RA) with safety and effectiveness of etanercept (ETN) in Japan. Post-marketing surveillance data for 7,099 patients treated with ETN were analyzed. Baseline characteristics, treatment effectiveness, incidence of adverse events (AEs), and serious AEs (SAEs) in relation to duration of RA were studied. At baseline, patients with RA for longer duration were older, weighed less, had more comorbidities, allergies, and corticosteroid use, but smoked less and had less morning stiffness. By 2–5 years with RA, more than half of the patients had advanced to Steinbrocker radiographic stage III or IV. Methotrexate (MTX) was the most commonly used pre-treatment disease-modifying antirheumatic drug; however, concomitant MTX use and its dose were lower among patients with longer duration of RA. Remission rates (26.6%) were greatest among patients having RA for <2 years. Less AEs and SAEs were observed among patients with shorter duration of RA. These results suggest that RA treatment in Japan in the era pre-biologics may not have been adequate to control disease activity and prevent joint destruction. Patients with shorter duration of RA may have better physical status which allows the opportunity to treat more intensively putting a higher percentage of patients in remission and possibly decreasing exposure to SAEs

Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients

Objective: An interim analysis of an all-patient postmarketing surveillance programme in Japan to investigate the safety of tocilizumab for the treatment of rheumatoid arthritis (RA) in the real world. Methods: This analysis included 3881 patients. Patients received 8 mg/kg of tocilizumab every 4 weeks, and were observed for 28 weeks. Data on baseline characteristics and adverse events (AE) were collected. Results: Total and serious AE were reported as 167 and 27 events/100 patient-years, respectively. The most frequent AE and serious AE were infections. Logistic regression analysis identified the following risk factors for the development of serious infection: concurrent or medical history of respiratory disorders; prednisolone dose at baseline ≥ 5 mg/day; and age ≥ 65 years. Twenty-five patients died, and the standardised mortality ratio, with the Japanese general population in 2008 as reference, was 1.66, similar to the results from the Japanese cohort study for RA patients. Conclusions: Tocilizumab is acceptably safe in the real clinical setting. Tocilizumab needs to be used with consideration of the benefit-risk balance to avoid serious infections in elderly patients and those on high doses of corticosteroids or with a concurrent or medical history of respiratory disorders

Effect of Methotrexate Plus Adalimumab on the Achievement of Rheumatoid Arthritis Therapeutic Goals : Post Hoc Analysis of Japanese Patients (MELODY Study)

Introduction: There is insufficient evidence regarding the appropriate dose of methotrexate (MTX) required to achieve specific treatment goals in patients with rheumatoid arthritis (RA) receiving biologic drugs in Japan. The present study aimed to assess the dose-response effect of MTX in combination with adalimumab (ADA) to achieve low disease activity (LDA) and/or remission at 24 weeks in RA patients. Methods: This analysis used data of the ADA all-case survey in Japan (n = 7740), and 5494 patients who received ADA and MTX were classified into five groups by weighted average MTX dose (>0-3.2 were analyzed for effectiveness by MTX dose. Results: In biologic-naive patients (n = 1996/3097), LDA/remission rates increased with MTX up to 6-<8 mg/week and then plateaued at higher doses (LDA, p = 0.0440; remission, p = 0.0422). In biologic-exposed patients (n = 1101/3097), LDA/remission rates increased with MTX dose (LDA, p = 0.0009; remission p = 0.0143). The incidences of serious adverse drug reactions (ADRs) and serious infections did not differ by MTX dose, but total ADRs and infections were significantly higher (p < 0.05) with increased MTX doses. Conclusion: The appropriate MTX doses in combination with ADA to achieve LDA and/or remission at week 24 were different between biologic-naive and biologic-exposed patients with RA, suggesting that 8 mg/week of MTX would be enough for biologic-naive patients

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

Objective: To perform a postmarketing surveillance study evaluating the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis (RA). Methods: Safety and effectiveness data were collected for all RA patients (at 772 sites) treated with intravenous abatacept between September 2010 and June 2011. Patients were treated by the approved dosing regimen according to the package insert. Treatment effectiveness was evaluated at baseline and at weeks 4, 12, and 24 using Disease Activity Score 28 (DAS28) according to erythrocyte sedimentation rate or serum C-reactive protein concentrations. Results: Overall, 3882 and 3016 abatacept-naive RA patients were included in safety and effectiveness analyses, respectively. Adverse drug reactions (ADRs) were reported for 15.66% of patients and serious ADRs were detected for 2.52% of patients. The incidence of serious infections was 1.03% and these were mainly attributed to different types of bacterial pneumonia. Disease activity improved significantly over 6 months. Separate multivariate analysis identified predictors of severe ADR, and severe infections and factors predictive of clinically meaningful DAS28 improvement after 6 months of treatment with abatacept. Conclusions: Abatacept was efficacious and well tolerated in a clinical setting. No new safety concerns were detected