Background/Aims: Crohn’s disease is a chronic disorder; therefore, it is essential to investigate long-term safety and efficacy of treatments. This study assessed the safety and effectiveness of adalimumab for up to 3 years in Japanese patients with Crohn’s disease in real-world settings. Methods: This was a multicenter, single-cohort, observational study of patients with Crohn’s disease. Safety assessments included incidence of adverse drug reactions. Effectiveness assessments included clinical remission, mucosal healing, and Work Productivity and Activity Impairment (WPAI). Results: The safety and effectiveness analysis populations comprised 389 and 310 patients, respectively. Mean (standard deviation) exposure to adalimumab in the safety analysis population was 793.4 (402.8) days, with a 58.1% retention rate. A total of 105 patients (27.0%) and 43 patients (11.1%) experienced adverse drug reactions and serious adverse drug reactions, respectively, with no patient reporting tuberculosis or hepatitis B. Infections and serious infections were reported in 37 patients (9.5%) and 17 patients (4.4%), respectively. Malignancy was reported as an adverse drug reaction in 2 patients (0.5%). Remission rate increased from 37.8% (98/259) at baseline to 73.9% (167/226) at week 4 and remained > 70% over 3 years. Proportion of patients without mucosal ulcerations increased from 2.7% (2/73) at baseline to 42.3% (11/26) between years > 2 to ≤ 3. WPAI improvement started at 4 weeks, with the overall work impairment score improving from 42.7 (n = 102) at baseline to 26.9 (n = 84) at 4 weeks. Conclusions Results from this study confirm the long-term safety and effectiveness of adalimumab treatment in Japanese patients with Crohn’s disease in the real-world setting.

A 38-year-old man was admitted to our hospital with fever and skin rash, and he was diagnosed as having dermatomyositis. He was treated with anti-inflammatory steroid and immunosuppressive agents. On hospital day 48, chest computed tomography (CT) revealed a nodule measuring approximately 2 cm in size in the lower lobe of the right lung (S9). Bacterial and/or fungal infection was suspected, but there was no response to antibiotic or antifungal treatment. A week later, repeat chest CT revealed the tumor now measuring approximately 6 cm in size in the lower lobe of the right lung. We performed bronchoscopy, and bacteriological examination of the transbronchial biopsy specimen revealed pulmonary tuberculosis. Interferongamma release assay (IGRA) before the initiation of immunosuppressive treatment was negative, so we did not administer treatment for latent tuberculosis infection. He was, however, treated with isoniazid, rifampicin, ethambutol, and pyrazinamide for 9 months, following which radiological features improved gradually. Here we describe in detail this rare case of a negative IGRA result before immunosuppressive therapy in a relatively young Japanese man who went on to develop active tuberculosis with a rapidly-growing pulmonary lesion during hospitalization.

Inflammatory bowel disease (IBD) is an idiopathic, multi-etiological disease characterized by inflammation and mucosal destruction of the gastrointestinal tract. Despite the remarkable advance in immunomodulating therapies, there still remains a certain population of patients who are refractory to conventional as well as biologic therapies and fail to achieve mucosal healing. To improve the prognosis of those patients, at least 2 types of stem cells have been tested for their potential therapeutic use. Transplantation of hematopoietic stem cells or mesenchymal stem cells have been tested in several clinical studies, but their beneficial effect still remains controversial. In this review, we would like to overview the recent clinical challenges of stem cell-based therapies in IBD and also introduce our new therapeutic plan of intestinal stem cell transplantation for IBD, based on our ex vivo intestinal organoid culture technique.
Biological Therapy ; Culture Techniques ; Gastrointestinal Tract ; Hematopoietic Stem Cells ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Mesenchymal Stromal Cells ; Organoids ; Prognosis ; Stem Cell Transplantation ; Stem Cells

BACKGROUND/AIMS: An interim analysis of post-marketing surveillance of CT-P13, an infliximab biosimilar, was performed to evaluate its safety and efficacy in Japanese patients with inflammatory bowel disease.METHODS: Patients were prospectively enrolled between November 2014 and March 2017, after the launch of CT-P13 in Japan, and case report forms of patients followed for at least 4 months were analyzed as of July 2018.RESULTS: Of 523 patients in the analysis set, 372 remained on CT-P13 therapy, while 54 (20.2%) of 267 patients with Crohn’s disease, and 97 (37.9%) of 256 patients with ulcerative colitis were withdrawn during follow-up. A total of 144 adverse drug reactions (ADRs) were reported in 106 patients (20.3%). Infusion reaction was the most frequent ADR observed in 49 patients (9.4%). Efficacy parameters decreased immediately after the start of treatment in naïve patients to anti-tumor necrosis factor-α antibody. In the patients switched from originator infliximab for nonmedical reasons, the decreased parameters due to proceeded treatment with the originator were maintained in low ranges, and the treatment continuation rate was high with low ADR incidence. In contrast, in patients switched for medical reasons such as adverse event or loss of response, the incidence of ADRs was high. However, the efficacy parameters were improved, and the treatment continuation rate was not significantly different from that of the naïve patient group.CONCLUSIONS: In this interim analysis, CT-P13 was comparable to the originator infliximab with respect to ADRs and efficacy, and is therefore considered to be a cost-efficient interchangeable biosimilar for Japanese patients with inflammatory bowel disease.
Asian Continental Ancestry Group ; Colitis, Ulcerative ; Drug-Related Side Effects and Adverse Reactions ; Follow-Up Studies ; Humans ; Incidence ; Inflammatory Bowel Diseases ; Infliximab ; Japan ; Necrosis ; Prospective Studies

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.
Asian Continental Ancestry Group ; Colectomy ; Colitis, Ulcerative ; Colorectal Neoplasms ; Consensus ; Crohn Disease ; Disease Management* ; Disease Progression ; Early Intervention (Education) ; Epidemiology ; Expert Testimony ; Gastrointestinal Tract ; Hospitalization ; Humans ; Inflammatory Bowel Diseases* ; Japan* ; Prevalence ; Prognosis

No abstract available.
Crohn Disease* ; Food, Formulated* ; Humans ; Infliximab*

[Background] Although we have demonstrated the clinical effect of acupuncture therapy with epidermal stimulation by needle penetration, its neurophysiological mechanisms are unclear. To investigate the clinical effects of epidermal stimulation by needle penetration on muscle tone, we tested the Hoffmann's reflex (Hreflex) of the soleus muscle during epidermal needle stimulation.
[Methods] Eighteen healthy participants were recruited. We tested the soleus H-reflex elicited by tibial nerve stimulation before and after epidermal stimulation by needle penetration. Epidermal stimulation was performed at several points on the Achilles tendon by needle penetration. We analyzed the amplitude ratio of H/M obtained from the waveforms of the soleus muscle before and after epidermal stimulation.
[Results] The amplitude ratio of H/M was significantly decreased during stimulation when compared with ratio during rest (p < 0.05). Each participant demonstrated a decrease in soleus muscle amplitude ratio of H/M during epidermal stimulation by needle penetration as compared with the ratio during rest.
[Discussion] Epidermal stimulation of the muscle by needle penetration activated the inhibitory interneurons of the dermatome at the stimulation site. Therefore, epidermal stimulation by needle penetration was considered as a possible method to induce muscle relaxation.
[Conclusion] It is suggested that epidermal stimulation by needle penetration for 2 minutes for the insertion of the Achilles tendon results in an inhibitory effect by stimulating the spinal cord neural mechanisms that correspond to the soleus muscle.

BACKGROUND/AIMS: Anti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines. METHODS: This cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines. RESULTS: Thirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (P =0.037). CONCLUSIONS: Exposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion.
Adalimumab ; Abortion, Spontaneous ; Asia ; Asian Continental Ancestry Group ; Congenital Abnormalities ; Cross-Sectional Studies ; Female ; Humans ; Incidence ; Infliximab ; Infant, Low Birth Weight ; Infant, Newborn ; Inflammatory Bowel Diseases* ; Japan* ; Live Birth ; Necrosis* ; Pregnancy ; Pregnancy Outcome* ; Pregnancy*

This paper presents diagnostic criteria for Meniere's disease jointly formulated by the Classification Committee of the Barany Society, The Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology, the Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery, and the Korean Balance Society. The classification includes two categories: definite Meniere's disease and probable Meniere's disease. The diagnosis of definite Meniere's disease is based on clinical criteria and requires the observation of an episodic vertigo syndrome associated with low- to medium- frequency sensorineural hearing loss and fluctuating aural symptoms (hearing, tinnitus and/or fullness) in the affected ear. Duration of vertigo episodes is limited to a period between 20 minutes and 12 hours. Probable Meniere's disease is a broader concept defined by episodic vestibular symptoms (vertigo or dizziness) associated with fluctuating aural symptoms occurring in a period from 20 minutes to 24 hours.
Classification ; Diagnosis ; Ear ; Hearing Loss, Sensorineural ; Japan ; Meniere Disease ; Neck ; Neurotology ; Otolaryngology ; Tinnitus ; Vertigo