Economic impact of adalimumab treatment in Japanese patients with rheumatoid arthritis from the adalimumab non-interventional trial for up-verified effects and utility (ANOUVEAU) study.

OBJECTIVES: The objective of this study is to evaluate the economic impact of adalimumab (ADA) on Japanese rheumatoid arthritis (RA) patients. METHODS: ANOUVEAU was a 48-week multicenter, prospective, observational, single-cohort study. Work-related outcomes including absenteeism, presenteeism, overall work impairment (OWI), and activity impairment (AI) were evaluated using the RA-related work productivity and activity impairment (WPAI/RA). The amount of productivity loss was estimated via multiplication of absenteeism, presenteeism and OWI by the national average occupational wage for paid worker (PW) and part time worker (PTW), and via multiplication of AI by the estimated wage for domestic work for home maker (HM). RESULTS: In this analysis, 1196 patients were included. At week 48, measures of productivity loss due to absenteeism, presenteeism, OWI, and AI were significantly improved by administrating ADA to RA patients in all employment types (PW, PTW, and HM), compared to baseline (p < .01). Productivity loss of Japanese society by RA disease was estimated to be $9.80 billion. The annual decrease in productivity loss through ADA administration to Japanese RA patients was estimated to be $3.76 billion. CONCLUSIONS: The socioeconomic burden of RA is high, but ADA treatment may reduce productivity loss related to RA.

Case of Large Cecoureterocele with Contralateral Renal Rupture in Neonate.

A cecoureterocele is a rare form of ectopic ureterocele that the orifice of the affected ureter is within the bladder, but the cavity of the ureterocele extends beyond the bladder neck into the urethra. We present a case of a newborn boy with a large cecoureterocele with contralateral renal rupture. He required an emergency transurethral incision of the ureterocele for the treatment of acute renal failure and respiratory disorder.

Relapsed urachal carcinoma responding to first-line chemotherapy with capecitabine-oxaliplatin plus bevacizumab.

Introduction: Advanced urachal carcinoma has a poor prognosis; however, a standard systemic treatment has not been established. We treated a patient with relapsed urachal carcinoma with capecitabine-oxaliplatin plus bevacizumab, a standard regimen for colon cancer, and obtained favorable responses. Case presentation: A 47-year-old woman presented with hematuria. Under the diagnosis of non-metastatic urachal carcinoma, an extended partial cystectomy was performed. Histopathological examination revealed adenocarcinoma with negative surgical margins and lymph nodes. Thirty-two months postoperatively, lung metastases and local recurrence were confirmed, along with elevated carcinoembryonic antigen levels, and nine chemotherapy cycles were administered. Subsequently, the recurrent lesion regressed, and tumor marker levels normalized. Fourteen months after treatment discontinuation, the disease remained stable without progression. Conclusion: This is the first report of advanced urachal carcinoma treated with capecitabine-oxaliplatin plus bevacizumab, demonstrating the potential of this treatment as first-line chemotherapy for this disease.

Altered association of interleukin-6 with sex steroids in lipid metabolism disorder in men with prostate cancer receiving androgen deprivation therapy.

BACKGROUND: Interleukin-6 produced in adipose tissue plays a role in lipid metabolism, and also interacts with sex steroids. This study was performed to elucidate the mechanism of lipid metabolism disorder during androgen deprivation therapy (ADT) in terms of the association of interleukin-6 with sex steroids. METHODS: Seventy-two patients with localized prostate cancer were prospectively studied based on their body-composition and blood samples before and after ADT for 6 months. RESULTS: Before ADT, serum interleukin-6 levels were inversely correlated with serum total-testosterone (rs = -0.305, P = 0.009) and dihydrotestosterone (rs = -0.380, P = 0.006) concentrations, but not correlated with adrenal androgen or estradiol levels. Pretreatment interleukin-6 levels were positively correlated with %body fat (rs = 0.349, P = 0.003) and %visceral fat (rs = 0.384, P = 0.001). After ADT, %body fat increased (P < 0.001) and lean body mass decreased (P = 0.036). After ADT, in contrast to the pretreatment relationship, interleukin-6 levels were positively correlated with total-testosterone concentrations (rs = 0.343, P = 0.003), and were positively correlated also with levels of androstenedione (rs = 0.351, P = 0.002) and estoradiol (rs = 0.335, P = 0.004). Interleukin-6 levels were equivalent between before and after ADT (2.02 vs. 2.16 pg/ml, P = 0.205), but the positive correlation between interleukin-6 levels and %body or %visceral fat noted before ADT disappeared after ADT. CONCLUSIONS: Posttreatment interleukin-6 levels had a strong positive correlation with total-testosterone, androstenedione, and estradiol levels, suggesting that a regulation loop may emerge between these sex steroids and interleukin-6 during ADT. The altered association between interleukin-6 and sex steroids is possibly involved in ADT-related lipid metabolism disorder with unchanged interleukin-6 levels despite increased %body fat.

Impact of Adalimumab on Work Productivity and Activity Impairment in Japanese Patients with Rheumatoid Arthritis: Large-Scale, Prospective, Single-Cohort ANOUVEAU Study.

INTRODUCTION: The Adalimumab Non-interventional Trial for Up-verified Effects and Utility (ANOUVEAU) was a large-scale, multicenter, prospective, observational, single-cohort study that evaluated the effects of adalimumab (ADA) on rheumatoid arthritis (RA)-related work productivity and activity impairment (RA-related WPAI) and disease activity in routine rheumatology care in Japan. METHODS: Patients with RA were categorized as paid workers (PWs, ≥35 h/week), part-time workers (PTWs, <35 h/week), or homemakers (HMs, unemployed) and were administered the WPAI for RA (WPAI/RA) questionnaire. All patients who received ADA were followed for 48 weeks to evaluate safety and effectiveness. RESULTS: Of the 1808 patients analyzed, 825, 243, and 740 patients were PWs, PTWs, and HMs, respectively. WPAI/RA domain scores significantly improved at weeks 12, 24, and 48 in all groups, with maximum improvement observed for PWs (p < 0.05). Additionally, remission rates (according to Disease Activity Score 28, erythrocyte sedimentation rate, Simplified Disease Activity Index, or Health Assessment Questionnaire-Disability Index scores) and EuroQol 5-Dimension 3-Level scores significantly increased from baseline to 48 weeks in all groups (p < 0.0001). Analysis of patient subgroups revealed better WPAI/RA outcomes for patients who were biologic-naïve, treated with concomitant methotrexate, or with RA duration of ≤2 years (p < 0.05). The rate of serious adverse events over 48 weeks of ADA treatment was 5.23%. CONCLUSIONS: Treatment with ADA provided sustained improvement in WPAI and had an acceptable safety profile in patients with RA. FUNDING: AbbVie GK and Eisai Co., Ltd. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01346488.

Effect of Methotrexate Plus Adalimumab on the Achievement of Rheumatoid Arthritis Therapeutic Goals: Post Hoc Analysis of Japanese Patients (MELODY Study).

INTRODUCTION: There is insufficient evidence regarding the appropriate dose of methotrexate (MTX) required to achieve specific treatment goals in patients with rheumatoid arthritis (RA) receiving biologic drugs in Japan. The present study aimed to assess the dose-response effect of MTX in combination with adalimumab (ADA) to achieve low disease activity (LDA) and/or remission at 24 weeks in RA patients. METHODS: This analysis used data of the ADA all-case survey in Japan (n = 7740), and 5494 patients who received ADA and MTX were classified into five groups by weighted average MTX dose (>0-<4, 4-<6, 6-<8, 8-< 10, and ≥10 mg/week). Of the 5494 patients, 3097 with baseline 28-joint disease activity score based on erythrocyte sedimentation rate >3.2 were analyzed for effectiveness by MTX dose. RESULTS: In biologic-naïve patients (n = 1996/3097), LDA/remission rates increased with MTX up to 6-<8 mg/week and then plateaued at higher doses (LDA, p = 0.0440; remission, p = 0.0422). In biologic-exposed patients (n = 1101/3097), LDA/remission rates increased with MTX dose (LDA, p = 0.0009; remission p = 0.0143). The incidences of serious adverse drug reactions (ADRs) and serious infections did not differ by MTX dose, but total ADRs and infections were significantly higher (p < 0.05) with increased MTX doses. CONCLUSION: The appropriate MTX doses in combination with ADA to achieve LDA and/or remission at week 24 were different between biologic-naïve and biologic-exposed patients with RA, suggesting that 8 mg/week of MTX would be enough for biologic-naïve patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01076959. FUNDING: AbbVie and Eisai Co., Ltd.

Evaluation of magnetic resonance imaging-based prostate-specific antigen density of the prostate in the diagnosis of prostate cancer.

OBJECTIVES: We evaluated prostate-specific antigen (PSA) density of the prostatic volume (PSAD) estimated using transrectal ultrasonography (TRUS; TRUS-based PSAD), magnetic resonance imaging (MRI; MRI-based PSAD), and PSA density of the transition zone (TZ) volume (PSATZD) estimated using MRI (MRI-based PSATZD) in the diagnosis of prostate cancer (PCa). METHODS: One hundred and twenty patients, who were suspected to have PCa based on PSA, ranged between 4.1 and 20.0 ng/mL were enrolled in this study. RESULTS: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI by 11.4% in the patients with PSA levels ranging 4.1-20.0 ng/mL, 7.2% in those 4.1-10.0 ng/mL, and 15.7% in those 10.1-20.0 ng/mL, respectively. PSA levels were correlated with the prostatic volume estimated using TRUS and MRI, and TZ volume estimated using MRI in the patients without PCa; however, the level was not correlated with them in the patients with PCa. The area under the receiver operating characteristic curve of MRI-based PSAD was higher than that of TRUS-based PSAD; however, there was no statistical difference. Stepwise logistic regression analysis for the prediction of PCa by using PSA-related parameters confirmed that MRI-based PSATZD was the most significant predictor in patients with PSA levels in the range of 4.1-20.0 ng/mL (P < 0.001), the range of 4.1-10.0 ng/mL (P = 0.002), and the range of 10.1-20.0 ng/mL (P < 0.001), respectively. CONCLUSIONS: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI. MRI-based PSATZD is the most significant predictor in the four parameters.

Primitive neuroectodermal tumor of the adrenal gland.

We report a rare case of primitive neuroectodermal tumor arising from adrenal gland in adulthood, diagnosed preoperatively as having non-functional adrenocortical adenoma. Laparoscopic adrenalectomy was performed. Immunohistological examination revealed the definite diagnosis as primitive neuroectodermal tumor of the adrenal gland. Although primitive neuroectodermal tumor is a highly malignant neoplasm, there is no evidence of local recurrence and distant metastasis 16 months after surgery.

Skin tests of a novel nicotine patch, PHK-301p, in healthy male volunteers: phase I, placebo-controlled study.

Major local adverse reactions in the nicotine patches are skin reactions. To assess the skin reaction of PHK-301p, a newly developed nicotine patch, we conducted a phase I study that consisted of 2 parts: a skin irritation test (48-h closed patch test) and a photosensitivity test (24-h closed patch test + Ultraviolet A irradiation). Twenty healthy men were treated with PHK-301p and placebo. Both preparations were punched out to a circle of 6-mm diameter and were applied simultaneously to each participant. Skin irritation and photosensitivity were assessed by a physician who was kept unaware of the treatment. In the skin irritation test, moderate and mild erythemas were observed in each participant 72 h after application (24 h after removal) for PHK-301p. Mild erythema was observed in one participant 49 h after application (1 h after removal) for placebo. The skin irritation index, which was calculated based on the skin reactions of participants, was 7.5 for PHK-301p and 2.5 for placebo. In the photosensitivity test, one participant had mild erythema (+/-) approximately 25 and 72 h after application of PHK-301p. No solar urticaria was observed. From these results, we concluded that PHK-301p is an acceptable product as a nicotine patch.