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Irinotecan-induced interstitial lung disease (ILD) requires accurate diagnosis, followed by prompt and appropriate treatment. This study was conducted to compile information and imaging data to define the characteristics of irinotecan-induced ILD. Searches were performed on information collected for a drug reexamination application and on data from spontaneous safety reports submitted to Daiichi Sankyo Company, Limited. These database searches revealed 153 cases of serious ILD that occurred in association with irinotecan therapy, and which were reported as adverse drug reactions. Computed tomographic findings obtained after the onset of ILD were categorized based on four typical patterns. A total of 66 patients (including 15 for whom a relationship between death and serious ILD could not be excluded; incidence of serious ILD: 0.74%; death rate of ILD: 0.17%) were detected during the postmarketing surveillance along with 87 patients (22 deaths) that were identified from spontaneous reports. Within 16 weeks of starting treatment, 80.7% of the patients developed ILD. A total of 61.3% of the cases treated using steroids responded to the steroid therapy. These results indicate that there is no specific clinical or imaging feature associated with ILD related to irinotecan and that the prognosis of ILD related to irinotecan was poor in patients with preexisting ILD. The relative risk calculated for the association between preexisting ILD and death was 2.25 (P=0.29). During irinotecan treatments, patients need to be carefully observed for symptoms, especially at 16 weeks after starting treatment. In addition, when patients are receiving this type of therapy, they also need to undergo chest imaging studies.

BackgroundTofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Efficacy and safety of tofacitinib have been shown in RA patients in global Phase 2, Phase 3 (one study included Japanese patients) and long-term extension (LTE) studies and in two Phase 2 and one LTE study in Japanese patients.ObjectivesWe evaluated the safety of tofacitinib following drug approval in Japanese patients with RA using all-case post-marketing surveillance (PMS) data.MethodsA 6-month interim analysis of safety data from an ongoing 3-year PMS study was conducted (5 Nov 2016 data-cut). All Japanese patients with RA who were treated with tofacitinib were consecutively and prospectively registered in the PMS study and were monitored for all adverse events (AEs) for 3 years. Baseline and follow-up data were collected from booklet-type survey forms. Follow-up surveillance after discontinuation of tofacitinib treatment was implemented: 12 months for serious infections and 3 years for malignancy or AEs leading to death from the date of treatment initiation with tofacitinib. AEs were coded using MedDRA/J.ResultsOverall, 2387 tofacitinib-treated patients were enrolled (1020.0 patient-years [pt-yrs] of exposure); of these, 594 patients (24.9%) discontinued treatment, mainly due to AEs (n=236; 9.9%) or lack of effectiveness (n=225; 9.4%). In total, 1793 (75.1%) patients continued treatment for 6 months. At least one AE was observed in 815 patients (34.1%), the most frequent of which was herpes zoster (n=78; 3.3%), including 12 serious cases. Serious AEs occurred in 190 patients (8.0%); the most frequent were pneumonia (n=20; 0.8%), interstitial lung disease (n=14; 0.6%) and condition aggravated (n=13; 0.5%). Infections (n=304; 12.7%) were serious in 88 patients (3.7%). Thirteen patients (0.5%) reported malignancy, including ovarian cancer (n=2; 0.1%), diffuse large B-cell lymphoma (n=2; 0.1%) and lymphoproliferative disorder (n=1, 0.04%). Sixteen (0.7%) deaths were reported.ConclusionsInterim analyses of AEs during the initial 6-month treatment period from PMS reports of tofacitinib in Japanese patients did not reveal any new or unexpected safety signals vs the tofacitinib RA clinical programme. The target sample size for the final PMS analysis is 6000 patients (4000 tofactinib-treated, 2000 control patients).AcknowledgementsThis study was sponsored by Pfizer Inc. Editorial support was provided by K Nicholson of CMC and was funded by Pfizer Inc.Disclosure of InterestT. Mimori Grant/research support from: Astellas, Ayumi, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Nippon Shinyaku, Takeda, Speakers bureau: Astellas, Bristol-Myers Squibb, Chugai, Eisai, Mitsubishi-Tanabe, M. Harigai Grant/research support from: Bristol-Myers Squibb, Eisai, Eli Lilly, Ono, Takeda, T. Atsumi Grant/research support from: Alexion, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Sanofi. Scholarship donations from: Bayer, Daiichi-Sankyo, Takeda, Speakers bureau: AbbVie, Astellas, Chugai, Eisai, Mitsubishi-...

Background and Aim The prevalence of ulcerative colitis (UC) is increasing in Japan. Validated claims‐based definitions are required to investigate the epidemiology of UC and its treatment and disease course in clinical practice. This study aimed to develop a claims‐based algorithm for UC in Japan. Methods A committee of epidemiologists, gastroenterologists, and internal medicine physicians developed a claims‐based definition for UC, based on diagnostic codes and claims for UC treatments, procedures (cytapheresis), or surgery (postoperative claims). Claims data and medical records for a random sample of 200 cases per site at two large tertiary care academic centers in Japan were used to calculate the positive predictive value (PPV) of the algorithm for three gold standards of diagnosis, defined as physician diagnosis in the medical records, adjudicated cases, or registration in the Japanese Intractable Disease Registry (IDR). Results Overall, 1139 claims‐defined UC cases were identified. Among 393 randomly sampled cases (mean age 44; 48% female), 94% had received ≥ 1 systemic treatment (immunosuppressants, tumor necrosis factor inhibitors, corticosteroids, or antidiarrheals), 7% had cytapheresis, and 7% had postoperative claims. When physician diagnosis was used as a gold standard, PPV was 90.6% (95% confidence interval [CI]: 87.7–93.5). PPV with expert adjudication was also 90.6% (95% CI: 87.7–93.5). PPVs with enrollment in the IDR as gold standard were lower at 41.5% (95% CI: 36.6–46.3) due to incomplete case registration. Conclusions The claims‐based algorithm developed for use in Japan is likely to identify UC cases with high PPV for clinical studies using administrative claims databases.

Long-term ETN treatment safety and effectiveness were sustained over 3 and 2 years, respectively.