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Objectives To assess the real-world safety and effectiveness of canakinumab in patients in Japan with tumour necrosis factor receptor-associated periodic syndrome (TRAPS) or mevalonate kinase deficiency/hyperimmunoglobulinaemia D with periodic fever syndrome (MKD/HIDS). Methods All patients with TRAPS or MKD/HIDS who received canakinumab following drug approval in Japan were registered in a post-marketing all-patient surveillance with a 2-year observation period. Herein, the interim results are reported. Results Fifteen patients with TRAPS and seven with MKD/HIDS were included in the safety and effectiveness analysis set. Adverse drug reactions were reported in 26.67% (n = 4) and 42.86% (n = 3) of TRAPS and MKD/HIDS patients, respectively. Most common adverse drug reactions were upper respiratory tract inflammation (13.33%, n = 2) and pyrexia (42.86%, n = 3) in TRAPS and MKD/HIDS patients, respectively. No serious adverse drug reactions were observed in either TRAPS or MKD/HIDS patients. The proportion of responders was 46.67% and 14.29% in the TRAPS and MKD/HIDS groups, respectively; 72.73% and 66.67% achieved clinical remission, while 90.91% and 66.67% achieved serological remission by Week 4 in the TRAPS and MKD/HIDS groups, respectively. Conclusions These interim results provide the first evidence of the real-world effectiveness of canakinumab in patients with TRAPS or MKD/HIDS in Japan. No new safety concerns were identified.

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% ( p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.

Aims LIK066 (licogliflozin) is a dual sodium glucose co-transporter 1/2 inhibitor with potential benefits in weight loss. This study evaluated the efficacy, tolerability and safety of licogliflozin in Japanese adults with obesity. Materials and methods This study was a randomized, double-blind, placebo-controlled, dose-finding study to evaluate the effect of licogliflozin (2.5, 10, 25 and 50 mg once daily) in 126 Japanese patients with obesity. The primary objective was to examine the dose-response relationship of licogliflozin treatment in body weight reduction relative to placebo at 12 weeks. The secondary objectives included assessment of responder rates, change in parameters related to complications, visceral and subcutaneous fat area, and safety during 12 weeks of treatment. Results The placebo-subtracted least square mean percentage change in body weight from baseline at week 12 was -1.99 (95% confidence interval -2.92, -0.21), -3.00 (-4.15, -1.70), -3.54 (-4.54, -2.26) and - 3.91% (-5.01, -2.77) in licogliflozin 2.5, 10, 25 and 50 mg once-daily dose groups, respectively. The proportion of responders with ≥3% reduction in body weight in the licogliflozin 2.5, 10, 25 and 50 mg once-daily dose groups were 15.8%, 55.6%, 50.0% and 56.7%, respectively, versus placebo [7.1%; P ≤0.002 for all except the 2.5 mg once-daily group (P = 0.39)]. Dose-dependent reductions were observed significantly in haemoglobin A1c, uric acid, fasting plasma glucose and potentially in the waist circumference, diastolic blood pressure and visceral fat area. Conclusion Dual inhibition of SGLT1/2 with licogliflozin treatment induced a dose-dependent reduction in body weight in Japanese patients with obesity. Treatment with licogliflozin was safe and well tolerated in this study. The study is registered with ClinicalTrials.gov (NCT03320941).

Background: Vildagliptin is a dipeptidyl peptidase-4 inhibitor that reduces glycemia in patients with type 2 diabetes mellitus (T2DM). When approved in 2013, data on vildagliptin combined with >750...

Background: Vildagliptin is indicated for type 2 diabetes mellitus (T2DM); however, the onset and exacerbation of diabetic complications in Japanese T2DM patients treated with vildagliptin is unknown. Research design and methods: This 2-year post-marketing surveillance (PMS) assessed the real-world safety and efficacy of vildagliptin therapy in 19,218 Japanese T2DM patients. The relationship between the incidence of macro- and microvascular complications with patient characteristics and changes in glycemic control (HbA1c) were evaluated. Results: The incidences of macro- and microvascular diseases were 1.14% and 3.09%, respectively. Patients with HbA1c ≥8.4% had a higher odds ratio (OR) for micro- and macrovascular disease (OR: 2.02 and 1.90) compared with patients with HbA1c Conclusions: Vildagliptin elicited no increases/exacerbations of diabetic complications; this PMS suggested that the incidence of diabetic complications tends to be low in subjects with good HbA1c control.

Introduction To assess the efficacy and safety of vildagliptin as add-on therapy in Japanese patients with type 2 diabetes mellitus (T2DM), inadequately controlled on stable long-acting, intermediate-acting, or pre-mixed insulin, with or without concomitant metformin. Methods In this 12-week placebo-controlled study, patients were randomized to receive either vildagliptin 50 mg twice daily (bid) or placebo treatment in a 1:1 ratio. The primary endpoint was change in glycated hemoglobin A1c (HbA1c) from baseline to 12-week endpoint. Secondary endpoints included proportion of patients achieving pre-defined HbA1c targets of ≤6.5%

Background A 6-month phase 2 study of fingolimod demonstrated efficacy and safety in Japanese patients with relapsing-remitting multiple sclerosis (MS). Here we report a 6-month observational extension that evaluated efficacy and safety in patients who received fingolimod continuously for 12 months or who switched from placebo to fingolimod. Methods Of 147 patients who completed the 6-month core study, 143 entered the extension. Those originally randomized to placebo were re-randomized to fingolimod 1.25 mg or 0.5 mg. During the extension, all patients were switched to open-label fingolimod 0.5 mg. Results Magnetic resonance imaging (MRI) and relapse outcomes were maintained or improved in patients treated with fingolimod for 12 months versus those treated for 6 months. No new safety events were reported over 12 months of treatment. Infections occurred in similar proportions of continuously treated and switched patients, while cardiac and liver adverse events occurred in fewer continuously treated than switched patients. Four patients were aquaporin-4 (AQP4) antibody-positive, three of whom showed rapid disease exacerbations within 10 days of fingolimod initiation. Conclusion Continuous fingolimod treatment for up to 12 months was associated with maintained or improved efficacy and a manageable safety profile, consistent with that previously seen. Results in a small number of patients suggest lack of benefit in AQP4 antibody-positive patients. Meaningful statistical interpretation was limited by the small sample size in each treatment group, owing to the number of patients who completed the core study. Trial registration ClinicalTrials.gov NCT00670449

Background The low level of disease activity and manageable safety profile seen with fingolimod versus placebo in a 6-month, phase 2, randomized controlled trial in Japanese patients with relapsing multiple sclerosis (MS; ClinicalTrials.gov Identifier NCT00537082) were maintained in the initial 6-month observational study extension. Here, we report long-term safety and efficacy results of the 3-year follow-up to the phase 2 study extension. Methods The 6-month core study was completed by 147 patients, of whom 143 entered the extension and took at least one dose of fingolimod. Those originally randomized to placebo were re-randomized to fingolimod 1.25 mg (n = 23) or 0.5 mg (n = 27). During the extension, the patients taking fingolimod 1.25 mg (n = 46) were switched to open-label fingolimod 0.5 mg, and those originally randomized to fingolimod 0.5 mg (n = 47) continued with open-label fingolimod 0.5 mg. Results Continuous fingolimod treatment was associated with a sustained low level of MRI and relapse activity for the duration of the extension phase; 75–100% (range across all assessment time points up to end of study) of patients remained free of Gd-enhanced T1 lesions, 88–100% remained free of new/newly enlarged T2 lesions, and 45–62% remained relapse-free. In patients who switched to the active treatment, a 79.5% decrease in annualized relapse rate (ARR; from 1.131 before switch to 0.232 6-months after switch) was observed in the first 6 months of the extension phase and thereafter remained low until the end of study (0.16–0.31 across all assessment time points after switch up to end of study). The mean number of Gd-enhanced T1 and new/newly enlarged T2 lesions decreased up to month 9 and thereafter remained low until the end of study (0.0–0.1 and 0.0–0.3, respectively, across all assessment time points after switch up to end of study). Fingolimod was generally well-tolerated and the safety profile was consistent with the core and 6-month extension. Serious adverse events were reported in 13.3% of patients during the extension study, with the range in the continuous fingolimod and placebo-fingolimod switch groups (3.7–21.7%) being similar to that reported in the core study for the placebo and fingolimod groups (5.3–20.4%). Conclusion Continuous fingolimod treatment over 36 months was associated with maintained efficacy and a manageable safety profile with no new safety signals. These results indicate that fingolimod provides long-term treatment benefit for Japanese patients with relapsing MS. Trial registration ClinicalTrials.gov NCT00670449 (April 28, 2008). Electronic supplementary material The online version of this article (doi:10.1186/s12883-017-0794-5) contains supplementary material, which is available to authorized users.