Analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis using the Japanese Adverse Drug Event Report database

Abstract

BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions associated with fatal disorders. Although many causes of SJS/TEN have been proposed, the time-to-onset for SJS/TEN and the relationship between aging and SJS/TEN are still not clear. Therefore, the aim of this study was to determine the relationship between aging and SJS/TEN using the Japanese Adverse Drug Event Report (JADER) database and analyze the time-to-onset profile of SJS/TEN.MethodsWe analyzed reports of SJS/TEN recorded in the JADER database between 2004 and 2015 using an adjusted reporting odds ratio (ROR). We also used Weibull proportional hazards models for each drug to examine the expression patterns of SJS/TEN. We selected the drugs according to the number of the reports associated with SJS/TEN.ResultsThe JADER contained 330,686 reports from April 2004 to April 2015. The adjusted RORs for patients in the 0–19-, 20–39-, 60–79-, and ≥ 80-year-old groups from all data extracted from the JADER database were 1.33 (95 % confidence interval [CI], 1.21–1.45), 1.78 (95 % CI, 1.65–1.93), 0.71 (95 % CI, 0.66–0.75), and 0.72 (95 % CI, 0.66–0.79), respectively. The adjusted ROR tended to be higher in patients aged 0–19 years, particularly in patients using antipyretic analgesics, such as loxoprofen or acetaminophen. More than half of the cases of SJS/TEN onset following administration of loxoprofen and acetaminophen occurred within 4 days of the initiation of treatment. The median times-to-onset were 3 days for loxoprofen and 2 days for acetaminophen. The scale parameter α values of loxoprofen and acetaminophen were 9.44 and 6.17, respectively. The upper 95 % CIs of shape parameter β values for the drugs were all less than 1, with the exceptions of those for carbamazepine, ACE inhibitors, and corticosteroids.ConclusionsOur results suggested that monitoring of younger patients who frequently use antipyretic analgesics is important. These drugs should be used and monitored within the first 2–3 days of treatment in the Japanese population.

Analysis of Time-to-onset of Interstitial Lung Disease after the Administration of Small Molecule Molecularly-targeted Drugs

“…Abe et al reported that any interpretation of data from small sample sizes (notably, less than 100 case reports) should be performed cautiously. 17) Thus, it should be noted that there were less than 100 case reports for ALK TKI (alectinib), Bcr-Abl TKI (dasatinib and nilotinib), ErbB family TKI (lapatinib), EGFR TKI (osimertinib), and JAK inhibitor (tofacitinib) found in JADER in our current study. Therefore, due to the small number of samples, the variance of the regression line that was estimated by the Weibull analysis would be increased.…”

Evaluation of Drug-Induced Photosensitivity Using the Japanese Adverse Drug Event Report (JADER) Database

“…Analysis of time-toonset using the Weibull shape parameter (WSP) has recently been proposed to detect the signals for AEs by utilizing timeto-event data without requiring a reference population. [17][18][19][20] The WSP can describe the varying incidence of AEs and can * To whom correspondence should be addressed. e-mail: mnakamura@gifu-pu.ac.jp evaluate hazard functions for detecting AEs.…”

Factorial Analysis of Hepatitis B Virus Reactivation-Induced Hepatitis B Using JADER

“…Statistical Analysis The safety signal index, ROR, was calculated from the 2×2 contingency table 7,8) (Table 1). When the lower limit of the 95% confidence interval (Cl) exceeded 1, the drug was regarded as signal-positive.…”

“…Most of these are disequilibrium analyses relatively comparing the reporting frequency, and the reporting odds ratio (ROR) is the representative method with high sensitivity capable of detecting signals at an early stage with a few case reports. 7,8) In addition, time information from drug administration to the development of adverse events is described in JADER, enabling time-to-event analysis using the Weibull distribution. [9][10][11][12][13] In this study, using JADER, the sex, age, outcome, drug, and onset time were surveyed in patients who developed hepatitis B as an adverse event, and the ROR and Weibull distribution were calculated.…”