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

Thermal Disparity among Fingers and Its Amelioration by CO2-Water Bathing in Connective Tissue Disease Patients

Objective. Correlation between a low finger temperature and thermal disparity among fingers was studied in connective tissue disease (CTD) patients. Whether the thermal disparity may be ameliorated by hand immersion in a warm carbon dioxide- (CO2-) water bath was analyzed. Methods. CTD patients with suspected peripheral circulation disorder underwent a thermography test. From before to 30 min after hand immersion in CO2-water (CO2 bathing; 1000 ppm CO2, 42°C, 10 min), the nailfold temperatures were measured. The mean temperature (m-Temp) and the coefficient of variation of the temperature (CV=SD/m‐Temp of one hand; the mean of CVs of both hands was adopted as the indicator of thermal disparity) were monitored. The correlation between m-Temp and CV was also analyzed. Results. Forty-seven (45 females and 2 males) patients were included, 32 of whom had Raynaud’s phenomenon. The m-Temp was 30.8±3.0°C at the baseline, increased to 35.3±1.0°C immediately after CO2 bathing, and remained significantly higher than that at the baseline until 30 min after (32.1±1.9°C). The CV was 0.0291±0.0247 at the baseline, decreased to 0.0135±0.0039 immediately after CO2 bathing, and remained significantly lower than the baseline until 30 min after (0.0163±0.0143). Between m-Temp and CV, a negative correlation was observed throughout the measurements. Conclusion. Thermal disparity was observed at baseline measurement in CTD patients. Warm CO2 bathing markedly ameliorated the disparity, and this amelioration remained until after 30 min. Throughout the observation, the lower the m-Temp, the more severe the thermal disparity among fingers

Eleven Cases of Angioedema with Eosinophilia Treated in a Single Hospital in Japan

Background: Angioedema with eosinophilia (AE) is mostly reported in Japanese patients, and only as case reports. In this study, we aimed to determine how prevalent AE cases appear, the characteristic features and the course of AE, and to evaluate whether corticosteroid therapy for AE is necessary or not. Methods: The patients whose blood samples showed an eosinophil count of ≥2,000/μL, among the samples tested for blood cell counts and differential counts between January 2006 and December 2010, in Japanese Red Cross Medical Center, were firstly included. Among these, patients with AE were extracted. Results: All of the 11 patients were Japanese young females. One patient with arthralgia showed radioisotope accumulation in the joints by bone scintigraphy. The peak peripheral blood eosinophil count was 7,839 ± 6,008 (2,130-23,170)/μL after visiting our hospital. An increase in white blood cell count was only due to an increase in eosinophil count. Serum C-reactive protein and IgE levels remained almost normal. Peripheral blood eosinophil count decreased steadily for 8 weeks, regardless of corticosteroid use. Edema in all of the patients and arthralgia in 6 patients improved within 12 weeks. As far as followed, none of the patients had a recurrence of AE. Conclusions: AE developed in Japanese young females and likely showed a single course. In AE, the count of eosinophil of 104/μL was observed. Only eosinophil count increased among leukocyte series. Serum C- reactive protein and IgE levels remained almost normal. The eosinophil count in AE patients will return to the normal level within 8 weeks even without corticosteroid therapy