Comparison of two biosimilarity studies of FKB327 with the adalimumab reference product: randomized phase 1 studies of single-blind, single-dose subcutaneous injection in healthy Japanese male participants

Background FKB327 has been developed as a biosimilar of the adalimumab reference product (RP). We compared the pharmacokinetics (PK), safety, and immunogenicity of FKB327 with those of the adalimumab RP after a single dose by subcutaneous (SC) injection in Japanese male participants. Methods Two randomized, single-blind, single-dose studies were conducted in healthy Japanese male participants to compare PK characteristics between FKB327 and the RP. Study 1 included 130 participants who were randomized in a 1:1 ratio to receive a subcutaneous injection of 40 mg of either FKB327 or the RP into the abdomen. In Study 2, another 130 subjects were randomized in a 1:1 ratio to receive either drug as in Study 1, but the drug administration site was changed to the thigh. The primary PK endpoints of both studies were area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and maximum serum concentration; area under the concentration-time curve from time zero to 360 h was also evaluated as one of the primary endpoints in Study 1. Biosimilarity in terms of pharmacokinetics was determined if the 90% confidence interval of the mean difference in geometric mean ratio of all primary PK parameters was within the prespecified equivalence criteria (0.80–1.25). Immunogenicity and safety were also evaluated as secondary endpoints. Results The serum concentration-time profiles were comparable between the FKB327 and the RP treatment groups in both studies. Primary PK parameters were within the prespecified bioequivalence range in Study 2, although AUC0-t was slightly outside the upper side of the range in Study 1. No differences in safety profile were observed in these studies. The incidence of anti-drug antibodies (ADAs) and impact of ADAs on PK profile were similar among the treatment groups in both studies. Conclusion Biosimilarity between FKB327 and the RP after a single 40-mg SC injection was confirmed in healthy Japanese male participants by modifying the study design. Trial registration jRCT2071200058 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200058, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200058) and jRCT2071200057 (https://jrct.niph.go.jp/en-latest-detail/jRCT2071200057, https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2071200057). Retrospectively registered 25/11/2020.

The ‘Oh, Mistake’ Incident and Juvenile Delinquency in Defeated Japan

This article explores the moral panic that erupted in Japan in 1950 over a robbery committed by a Japanese male teenager during the Allied occupation. Labeled by the press as an example of ‘after-war,’ the specific details of the ‘Oh, Mistake’ Incident and the varied public reactions it generated reveals the many ways Japanese people ascribed particular understandings of war, defeat, and occupation through the prism of juvenile delinquency. A close examination of the public outcry illuminates deep-seated Japanese anxieties over not only the future of juveniles traumatized by war and defeat, but also how some of them were able to construct new forms of hybrid identities and even language through Nisei impersonation and broken English during the tumultuous setting of defeated Japan.

Association between 24 h Urinary Sodium and Potassium Excretion and Dietary Intake in Japanese Male Adolescent Football Players

High urinary sodium-to-potassium ratio is considered a strong risk factor for hypertension. This study aimed to evaluate urinary excretion of sodium and potassium, and we analyzed these levels associated with dietary intake in Japanese adolescent football players. This cross-sectional study included 120 Japanese male adolescent football players. Over 24 h, urine was collected and measured for creatinine, sodium, and potassium levels. A dietary assessment was performed using a self-administered diet history questionnaire. The study analyzed 79 participants. The mean urinary sodium was 143.2 mmol/day, urinary potassium was 42.8 mmol/day, and the mean urinary sodium-to-potassium ratio was 3.6. Compared with the Japanese Dietary Reference Intakes, the estimated salt intake was 73.4% for the participants who exceeded the sodium intake, and the estimated potassium intake was 73.4% for the participants who did not satisfy it. Multiple regression analysis revealed that milk and dairy product intake was independently and positively associated with urinary potassium (β = 0.252) and independently and negatively associated with the urinary sodium-to-potassium ratio (β = −0.254). Adolescent football players had a high-sodium and low-potassium diet, well above the Japanese Dietary Reference Intakes recommendations. Milk and dairy products could be effective for increasing urinary potassium and decreasing the urinary sodium-to-potassium ratio.

Case Report: A Variety of Immune-Related Adverse Events Triggered by Immune Checkpoint Inhibitors in a Subject With Malignant Melanoma: Destructive Thyroiditis, Aseptic Meningitis and Isolated ACTH Deficiency

Recently, immune checkpoint inhibitors have been drawing much attention as cancer immunotherapy, but it has been shown that various immune-related adverse events (irAEs) are induced by immune checkpoint inhibitors in various organs, which has become one of the serious issues at present. A 58-year-old Japanese male with malignant melanoma was treated with nivolumab and/or ipilimumab. During the period of treatment, he suffered from various irAEs. Firstly, about 1 month after starting nivolumab monotherapy, destructive thyroiditis was induced, and so we started replacement therapy with levothyroxine. Secondly, about 1 month after starting nivolumab and ipilimumab combination therapy, aseptic meningitis was induced. We stopped both drugs and started steroid therapy with prednisolone. Finally, about 9 months after restarting nivolumab, isolated adrenocorticotropic hormone (ACTH) deficiency was induced, and so we started replacement therapy with hydrocortisone. Taken together, we should bear in mind the possibility of a variety of irAEs when we use immune checkpoint inhibitors.

Scalp Microbiome and Sebum Composition in Japanese Male Individuals with and without Androgenetic Alopecia

The skin microbiome and sebum may be associated with inflammation-related diseases of the scalp. To assess the pathogenesis and progression of androgenetic alopecia (AGA), we analyzed the composition of sebum and the bacterial and fungal microbiomes of the scalps of 118 Japanese male individuals with and without AGA, then discussed their roles in the pathogenesis of AGA. Sebum triglyceride and palmitic acid contents were higher in the AGA group than in the non-AGA group. Malassezia restricta, a lipophilic fungus that consumes palmitic acid, was abundant on the scalps of patients with AGA. Cutibacterium, Corynebacterium, and Staphylococcus were the most common genera in both groups, and patients with AGA exhibited scalp dysbiosis (increased abundance of Cutibacterium and decreased abundance of Corynebacterium). Our findings suggest that both sebum and the bacterial and fungal microbiomes of the scalp may be involved in the development of AGA.

The Development of Primary Effusion Lymphoma-Like Lymphoma in a Patient with Preexisting Essential Thrombocythemia

A 71-year-old Japanese male was diagnosed with essential thrombocythemia (ET) with the JAK2 V617F mutation variation, in April 2011. He was mainly treated with hydroxyurea following which the number of platelets was maintained within the normal limit. At age 80, he was hospitalized due to cardiac tamponade. Computed tomography showed no evidence of tumor masses or lymphadenopathy. Pericardial drainage was performed, and cytopathologic examination of the fluid revealed atypical lymphoid cells consistent with an effusion lymphoma of B cell lineage. The pericardial effusion was completely drained, and complete remission was achieved. Ultimately, the patient was diagnosed with primary effusion lymphoma-like lymphoma (PEL-LL). To the best of our knowledge, this is the first report of PEL-LL following ET.