Clinical features and risk factors of panitumumab-induced interstitial lung disease: a postmarketing all-case surveillance study.

BACKGROUND: Drug-induced interstitial lung disease (ILD) is one of the most serious adverse reactions associated with the molecularly targeted drugs. Panitumumab has been approved for advanced or recurrent colorectal cancer. Although there were no adverse reaction reports of ILD in panitumumab monotherapy, 4 cases in combination chemotherapy were reported prior to its approval in Japan in 2010. Several studies also reported that the incidence of drug-induced ILD was higher in Japan than in other countries. The clinical features of ILD and the associated risk factors therefore need investigation. METHODS: We analyzed the data from 3085 unresectable, advanced or recurrent colorectal cancer patients enrolled in a postmarketing all-case surveillance study of panitumumab in Japan. ILD case reports were assessed based on the clinical and radiologic findings by a committee of external experts. Multivariate analysis using Cox's hazard model identified the risk factors. RESULTS: ILD incidence (1.3 %) and mortality rates (51.3 %) were similar to those of patients receiving another anti-epidermal growth factor receptor (EGFR) monoclonal antibody in Japan. No specific onset timing was determined. Although panitumumab-specific ILD findings were not observed in computed tomography images or clinical practice, panitumumab can induce ILD with diffuse alveolar damage, as do the other anti-EGFR targeting drugs. A history/complication of ILD, male sex, poor general condition, and 65 years or older were identified as ILD risk factors, and no history of previous drug treatment was an apparent risk factor. CONCLUSION: Panitumumab-induced ILD can occur at any time after initiation, and close and regular monitoring is needed.

Impact of class-level labelling change on prescriptions of antidepressants for adolescents: An interrupted time-series study using a health insurance claims database in Japan, 2005-2013.

BACKGROUND: In October 2007, the Japanese Health Authority directed that precautions be added to antidepressants (ADs) labelling regarding suicide risk among young people. This study evaluates the impact of the labelling change on AD prescriptions and Japanese adolescent suicide rates. METHODS: We compared AD prescription rates per 100,000 population as a primary outcome. The intervention group comprised adolescents (10-24 years), while the control group comprised adults (25-64 years). We defined the pre-intervention period as January 2005 to October 2007 and post-intervention as November 2007 to February 2013. Monthly prescription rate data from a commercial claims database were triangulated with annual suicide rates in Japan. We performed segmented regression analysis for the prescription rates, using a quasi-Poisson model, and tested for level and trend changes. RESULTS: The commercial claims database included 152,686 adolescents and 195,251 adults during the pre-intervention period and 846,367 adolescents and 1,352,453 adults during post-intervention. Post-intervention, the overall AD prescription rates decreased only in adult males (-95.8 prescription per 100,000) but increased in all other groups. The mean annual suicide rate increased in adolescent males (+1.5 suicides per 100,000) but decreased in all other groups. Overall, the upward trend became moderate or inverse in all groups post-intervention but with a large difference between males and females. The suicide rates rose slightly in adolescents but began declining in adults a year post-intervention. In females, changes in level, trend, and suicide rates were very small in both adolescents and adults. CONCLUSIONS: Contrary to expectations, the mean prescription rates only decreased in adult males, but not in adolescents, regardless of gender. Downward level and trend change were clearly observed in adult males but not in adolescents, the original target of the updated warning. There were no clear temporal associations between suicide rates and the labelling change in either group.