Efficacy of perampanel by etiology in Japanese patients with epilepsy-subpopulation analysis of a prospective post-marketing observational study.

OBJECTIVE: To examine the efficacy and safety of perampanel (PER) in patients with post-stroke epilepsy (PSE), brain tumor-related epilepsy (BTRE), and post-traumatic epilepsy (PTE) using Japanese real-world data. METHODS: The prospective post-marketing observational study included patients with focal seizures with or without focal to bilateral tonic-clonic seizures who received PER combination therapy. The observation period was 24 or 52 weeks after the initial PER administration. The safety and efficacy analysis included 3716 and 3272 patients, respectively. This post hoc analysis examined responder rate (50% reduction in seizure frequency), seizure-free rate (proportion of patients who achieved seizure-free), and safety in patients included in the post-marketing study who had PSE, BTRE, and PTE in the 4 weeks prior to the last observation. RESULTS: Overall, 402, 272, and 186 patients were included in the PSE, BTRE, and PTE subpopulations, and 2867 controls in the "Other" population (etiologies other than PSE, BTRE, or PTE). Mean modal dose (the most frequently administered dose) values at 52 weeks were 3.38, 3.36, 3.64, and 4.04 mg/day for PSE, BTRE, PTE, and "Other," respectively; PER retention rates were 56.2%, 54.0%, 52.6%, and 59.7%, respectively. Responder rates (% [95% confidence interval]) were 82% (76.3%-86.5%), 78% (70.8%-83.7%), 67% (56.8%-75.6%), and 50% (47.9%-52.7%) for PSE, BTRE, PTE, and "Other," respectively, and seizure-free rates were 71% (64.5%-76.5%), 62% (54.1%-69.0%), 50% (40.6%-60.4%), and 28% (25.8%-30.1%), respectively. Adverse drug reactions tended to occur less frequently in the PSE (14.7%), BTRE (16.5%), and PTE (16.7%) subpopulations than in the "Other" population (26.3%). SIGNIFICANCE: In real-world clinical conditions, efficacy and tolerability for PER combination therapy were observed at low PER doses for the PSE, BTRE, and PTE subpopulations. PLAIN LANGUAGE SUMMARY: To find out how well the medication perampanel works and whether it is safe for people who have epilepsy after having had a stroke, brain tumor, or head injury, we used information from real-life medical situations in Japan. We looked at the data of about 3700 Japanese patients with epilepsy who were treated with perampanel. We found that perampanel was used at lower doses and better at controlling seizures, and had fewer side effects for patients with epilepsy caused by these etiologies than the control group.

Effect of Psychoeducational Intervention on Donepezil Retention Rate and Analysis of Reasons for the Discontinuation in Patients with Alzheimer's Dementia: A Randomized Study.

PURPOSE: Medication discontinuation for patients with Alzheimer's dementia (AD) influences treatment efficacy. This study aimed to evaluate the effect of psychoeducational intervention (PI) on donepezil retention rates and identify the factors associated with donepezil continuation in patients with AD. PATIENTS AND METHODS: One hundred and seventeen patients with AD were randomly allocated to the PI (n = 58) or standard care (SC; n = 59) groups. All patients were prescribed donepezil for 48 weeks. Primary endpoints were the 48-week donepezil retention rate and the reasons for donepezil discontinuation in the PI and SC groups. The secondary endpoint was the predictive factors, among the baseline clinical variables, for donepezil continuation in all patients. RESULTS: The donepezil retention rate was 62.1% (36/58) in the PI group and 66.1% (39/59) in the SC group. The most common reason for discontinuation in both groups was adverse events (PI, 12.1%; SC, 10.2%). Logistic regression analysis revealed that the results of the pentagon copying test in the Mini-Mental State Examination administered at baseline was a significant predictor of donepezil continuation for all patients in both the groups (odds ratio: 0.359; 95% confidence interval: 0.154-0.839). CONCLUSION: There was no significant difference between the PI and SC groups concerning donepezil retention rate in patients with AD. Our results demonstrate that the pentagon copying test can significantly predict donepezil continuation in patients with AD, indicating that impaired visuospatial and executive functions may reflect medication discontinuation. TRIAL REGISTRATION: UMIN-CTR:UMIN000012617.

Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study.

BACKGROUND: This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). METHODS: Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn's disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn's Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. RESULTS: A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 µg/ml at week 0, 15.5 ± 7.7 µg/ml at week 12, 15.7 ± 9.6 µg/ml at week 24, and 14.5 ± 6.8 µg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). CONCLUSIONS: Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

Effect of adalimumab on axial manifestations in Japanese patients with psoriatic arthritis: a 24 week prospective, observational study.

OBJECTIVES: PsA is characterized by enthesitis, synovitis and osseous involvement in the peripheral and axial joints. Few studies have examined axial involvement in PsA using imaging techniques. Here we examined axial involvement in PsA patients using MRI. In addition, we determined the efficacy of 24 week adalimumab treatment in improving the MRI findings of spondylitis and sacroiliitis. METHODS: This was a prospective, open-label, single-arm study in patients with PsA. Adalimumab was administered to patients for a total of 24 weeks. MRI examinations were conducted at baseline and at week 24 of adalimumab treatment. RESULTS: Thirty-seven patients with PsA were included in this study. Spondylitis was observed in at least one site of the positive scan in 91% (n = 31) of patients with PsA. The number of arthritic sites in the cervical, thoracic and lumbar regions of the spine was 48, 67 and 53, respectively. All patients had MRI-determined sacroiliitis of grade ≥1 severity while 28 patients (82%) had grade ≥2 sacroiliitis in at least one sacroiliac region. Sacroiliac arthritis was statistically more severe on the right side than on the left side (P < 0.05). In 34 patients with PsA, the thoracic spine was the most common site of spondylitis. In addition, 24 week adalimumab treatment led to an improvement in the mean number of spondylitis sites and the mean grade of sacroiliitis. CONCLUSION: Treatment with adalimumab for 24 weeks resulted in improvement in spondylitis and sacroiliitis.

Efficacy and safety of adalimumab in Japanese patients with psoriatic arthritis and inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs): A prospective, observational study.

Objectives: To evaluate the efficacy and safety of adalimumab in psoriatic arthritis (PsA) patients in Japan.Methods: In this open-label, single-arm study conducted at six sites from October 2014 to June 2016 (UMIN000016543), PsA patients (≥20 years old) with inadequate response to nonsteroidal anti-inflammatory drugs received adalimumab subcutaneously (80 mg initially, then 40 mg every other week; 24 weeks total). Primary endpoint was American College of Rheumatology 20% improvement (ACR20) response rate at week 12.Results: Of 42 enrolled patients, 37 were treated (mean (SD) age, 56.2 (13.0) years; male, 27 (73.0%)). ACR20, ACR50, and ACR70 response rates were 40.5%, 24.3%, and 16.2% at week 12 and increased to 45.9%, 37.8%, and 21.6% at week 24, respectively. Psoriasis Area and Severity Index (PASI) 50 response rates were unchanged at weeks 12 and 24 (73%), but PASI75 and PASI90 increased from 40.5% and 21.6% to 59.5% and 40.5%, respectively. Other indices such as Physician's Global Assessment score, C-reactive protein-based disease activity score in 28 joints, Bath Ankylosing Spondylitis Disease Activity Index, and serum biomarker levels were significantly improved. No unexpected adverse events were reported.Conclusion: Similar to the global population, adalimumab was efficacious and well tolerated in Japanese treatment-experienced PsA patients.

Native collagen hydrogel nanofibres with anisotropic structure using core-shell electrospinning.

Collagen hydrogel is a popular extracellular matrix (ECM) material in regenerative medicine and has an isotropic structure. In contrast, native ECM has an anisotropic structure. Electrospinning of collagen dissolved in organic solvents is widely used for fabricating anisotropic collagen nanofibres; however, such fibres are water-soluble and require cross-linking before use as scaffolds for cell culture. Herein, electrospinning using a core-shell nozzle was employed to spin an aqueous acidic solution of collagen and encapsulate it within a shell of polyvinylpyrrolidone (PVP). Subsequently, the core collagen was gelled, and the shell PVP was washed away using a basic ethanol solution to yield anisotropic collagen hydrogel nanofibres. Immunostaining and Fourier transform infrared spectroscopy revealed that the obtained fibres were composed of collagen, and surface PVP was removed completely. Circular dichroism measurements confirmed that the fibres exhibited the triple helical structure characteristic of collagen. Human umbilical vein endothelial cells cultured on the collagen hydrogel fibres were oriented along the fibre direction. Hence, this method is suitable for fabricating fibrous anisotropic collagen hydrogels without chemical and thermal cross-linking, and can facilitate the development of safe medical materials with anisotropy similar to that of native ECM.

Effect of chondroitin sulfate and hyaluronic acid on gene expression in a three-dimensional culture of chondrocytes.

The effect of glycosaminoglycan addition on a three-dimensional (3D) culture of porcine chondrocyte cells was investigated with a view to use in cartilage regenerative medicine. Chondroitin sulfate C increased the mRNA expression of type 2 collagen, while chondroitin sulfate A did not. Hyaluronic acid of high molecular weight markedly decreased the mRNA expression of both aggrecan and type 2 collagen, although hyaluronic acid of low molecular weight showed no apparent effect.