Real-World Insurance Claims Analysis of Venous Thromboembolism in Japanese Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD), which encompasses both ulcerative colitis (UC) and Crohn's disease (CD), is a risk factor for venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). AIM: To investigate the incidence of, and risk factors for, VTE in patients with IBD in Japan. METHODS: This was a retrospective, non-interventional study in patients with IBD from the Japan Medical Data Center claims database. Incidence rates (IRs; unique patients with events per 100 patient-years) were calculated for VTE, DVT, and PE among the IBD, UC, and CD cohorts. Odds ratios of potential risk factors were calculated by univariate and multivariate analyses in a nested case-control design. RESULTS: Overall, 16 273 patients with IBD were included: 13 585 with UC and 3443 with CD. VTE events occurred in 1.3%, 1.2%, and 1.9% of patients with IBD, UC, and CD, respectively. In patients with IBD, UC, and CD, IRs of VTE were 0.45, 0.40, and 0.64, respectively, IRs of DVT were 0.42, 0.38, and 0.61, respectively, and IRs of PE were 0.07, 0.07, and 0.11, respectively. In patients with IBD, treatment history (immunomodulators), cardiovascular risk (hypertension, high-density lipoprotein or diabetes mellitus, and history of coronary artery disease or heart failure), malignancy, and undergoing major surgery were identified as potential risk factors for VTE in the multivariate analysis, with similar risk factors reported for patients with UC and CD. CONCLUSIONS: This large study provides insight into the incidence and risk factors for VTE in patients with IBD from Japan.

Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn's disease in Japanese and Korean patients: the OPERA study.

BACKGROUND/AIMS: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4ß7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn's disease (CD). METHODS: OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn's Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. RESULTS: In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating ß7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. CONCLUSIONS: In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509).

Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo-controlled phase 3 trial.

Tofacitinib is an oral Janus kinase inhibitor. These post-hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52-week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo-treated patients advanced to tofacitinib at week 16. Primary efficacy end-points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment (PGA) of "clear" or "almost clear" (PGA response) at week 16. Other end-points included: Itch Severity Item (ISI), Dermatology Life Quality Index (DLQI) score and Nail Psoriasis Severity Index (NAPSI). Adverse events (AEs) were recorded throughout the study. Overall, 58 Japanese patients were included in this analysis (tofacitinib 5 mg b.i.d., n = 22; 10 mg b.i.d., n = 24; placebo, n = 12); 29 completed the study. At week 16, significantly more patients receiving tofacitinib 5 and 10 mg b.i.d. versus placebo achieved PASI-75 (50% and 75% vs 0%, P < 0.01) and PGA response (59% and 75% vs 0%, P < 0.001). Substantial improvements in ISI, DLQI and NAPSI score were observed with both tofacitinib doses. Over 52 weeks, similar rates of AEs were reported across treatment groups; one serious AE occurred with tofacitinib 10 mg b.i.d. Herpes zoster occurred in three patients receiving tofacitinib 10 mg b.i.d. No deaths, serious infections, malignancies or gastrointestinal perforations were reported. Results were generally consistent with global analysis, suggesting sustained efficacy and a manageable safety profile, with increased herpes zoster incidence, of tofacitinib in Japanese patients with psoriasis.

[Japan phase 3 study of pegaptanib sodium in patients with diabetic macular edema].

PURPOSE: To evaluate the efficacy and safety of intravitreal injections of pegaptanib sodium in subjects with diabetic macular edema (DME). METHODS: There were 243 subjects with DME who were randomized to receive, every 6 weeks, either an intravitreal injection of pegaptanib sodium or a sham injection. The study was double-masked for the first 24 weeks, and then an open label phase continued to week 54. The primary efficacy endpoint was evaluated at week 24, and safety was assessed throughout the 54 weeks. RESULTS AND CONCLUSION: The proportion of subjects who experienced more than 10 letters improvement of visual acuity in ETDRS chart from baseline to week 24 was statistically significantly greater (p-value = 0.0003) in the pegaptanib sodium group, 20.3%, than in the sham group, 5.0%. The incidence of treatment-related adverse events was similar between the treatment groups (pegaptanib sodium group: 10.6%, sham group: 10.0%). The reported adverse events were mainly mild or moderate ophthalmic events and related to the injection procedure. During open-label phase up to 54 weeks, no new safety concerns were identified compared with the double-masked phase. However, in light of the issue concerning proper maintenance of masking of the study treatments, the study was not considered as a well-controlled, double-masked study.