Long-Term Safety and Efficacy of Belimumab in Japanese Patients with SLE: a 7-Year Open-Label Continuation Study

Abstract Objectives Evaluate long-term safety, tolerability and efficacy of belimumab in Japanese patients with systemic lupus erythematosus (SLE). Methods This was a subgroup analysis of Japanese patients who completed studies BEL113750 or BEL112341 and were enrolled in a Phase 3, open-label extension study (BEL114333; NCT01597622). Eligible patients received intravenous belimumab 10 mg/kg every 28 days for ≤7 years. Primary endpoint: safety and tolerability. Secondary endpoints included SLE responder index (SRI)-4 response rate, SRI-4 components, severe SLE flare, use of corticosteroids/other SLE-related treatments. Analyses were based on observed data from first parent or current study belimumab dose through to study end. Results Of 71 Japanese patients enrolled, 69.0% completed the study. Overall, 98.6% patients had adverse events (AEs); 32.4% had serious AEs. The proportion of SRI-4 responders increased progressively (Year 1, Week 24: 40.9% [27/66]; Year 7, Week 48: 84.6% [11/13]) as did the proportion of SELENA-SLEDAI responders. The proportion of patients with no worsening in PGA (91.2−100.0%) and no new organ damage (92.6−100.0%) remained stable over time. Severe SLE flare was experienced by 11.3% (8/71) of patients. Corticosteroid and immunosuppressant use decreased over time. Conclusion : Favorable safety profile and treatment responses with belimumab were maintained for ≤7 years in Japanese patients with SLE.

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134 Long-Term Deutetrabenazine Treatment Is Associated with Sustained Treatment Response in Tardive Dyskinesia: Results from an Open-Label Extension Study

CNS Spectrums ◽

10.1017/s1092852920000504 ◽

2020 ◽

Vol 25 (2) ◽

pp. 284-285 ◽

Cited By ~ 1

Author(s):

Robert A. Hauser ◽

Hadas Barkay ◽

Hubert H. Fernandez ◽

Stewart A. Factor ◽

Joohi Jimenez-Shahed ◽

...

Keyword(s):

Adverse Events ◽

Percentage Change ◽

Extension Study ◽

Total Daily Dose ◽

Open Label ◽

Daily Dose ◽

Open Label Extension ◽

The Mean ◽

Over Time

Abstract:Background:In the 12-week ARM-TD and AIM-TD studies evaluating deutetrabenazine for the treatment of tardive dyskinesia (TD), the percentage of patients achieving ≥50% response was higher in the deutetrabenazine-treated group than in the placebo group. These studies also showed low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The current open-label study evaluated the long-term efficacy and safety of deutetrabenazine in patients with TD.Methods:Patients with TD who completed ARM-TD or AIM-TD could enroll in this open-label, single-arm extension study, titrating up over 6 weeks to a maximum total daily dose of deutetrabenazine 48 mg/day on the basis of dyskinesia control and tolerability. The proportion of Abnormal Involuntary Movement Scale (AIMS; items 1-7) responders was assessed based on response rates for achieving ≥50% improvement from baseline in the open-label extension study. AlMS score was assessed by local site raters for this analysis.Results:343 patients enrolled in the extension study. At Week 54 (n=249; total daily dose [mean ± standard error]: 38.6±0.66 mg), the mean percentage change from baseline in AIMS score was –40%; 48% of patients achieved a ≥50% response and 59% of those had already achieved a ≥50% response at Week 15. Further, 34% of those who had not achieved a ≥50% response at Week 15 achieved a ≥50% response at Week 54. At Week 106 (n=169; total daily dose: 39.6±0.77 mg), the mean percentage change from baseline in AIMS score was –45%; 55% of patients achieved a ≥50% response, 59% of those patients had already achieved a ≥50% response at Week 15, and 41% of those who had not achieved a ≥50% response at Week 15 but who reached Week 106 achieved a ≥50% response. At Week 132 (n=109; total daily dose: 39.7±0.97 mg), the mean percentage change from baseline in AIMS score was –61%; 55% of patients achieved a ≥50% response, 61% of those patients had already achieved a ≥50% response at Week 15, and 43% of those who had not achieved a ≥50% response at Week 15 but who reached Week 132 achieved a ≥50% response. Completer analysis suggests that long-term efficacy was not due to dose increases over time. Treatment with deutetrabenazine was generally well tolerated. There were 623 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) of adverse events of special interest were 0.01 for akathisia and restlessness, 0.07 for somnolence and sedation, 0.04 for parkinsonism, and 0.05 for depression.Conclusions:Patients who received long-term treatment with deutetrabenazine achieved response rates that were indicative of clinically meaningful long-term benefit. Results from this open-label trial suggest the possibility of increasing benefit over time with individual dose titration of deutetrabenazine.Funding Acknowledgements:This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.

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Long‐term (52‐week) efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: An uncontrolled, open‐label extension of a phase III study

Journal of Diabetes Investigation ◽

10.1111/jdi.13181 ◽

2020 ◽

Vol 11 (3) ◽

pp. 662-671

Author(s):

Kohei Kaku ◽

Hiroyuki Isaka ◽

Taishi Sakatani ◽

Junko Toyoshima

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Japanese Patients ◽

Phase Iii ◽

Efficacy And Safety ◽

Open Label ◽

Open Label Extension ◽

Phase Iii Study

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The efficacy and long-term safety of a triple combination of 80 mg telmisartan, 5 mg amlodipine and 12.5 mg hydrochlorothiazide in Japanese patients with essential hypertension: a randomized, double-blind study with open-label extension

Hypertension Research ◽

10.1038/hr.2016.100 ◽

2016 ◽

Vol 40 (1) ◽

pp. 51-60 ◽

Cited By ~ 5

Author(s):

Jitsuo Higaki ◽

Issei Komuro ◽

Kosuke Shiki ◽

Hiroyuki Ugai ◽

Atsushi Taniguchi ◽

...

Keyword(s):

Essential Hypertension ◽

Japanese Patients ◽

Blind Study ◽

Double Blind Study ◽

Triple Combination ◽

Open Label ◽

Double Blind ◽

Open Label Extension

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Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the REGAIN open-label extension study

Journal of the Neurological Sciences ◽

10.1016/j.jns.2019.08.004 ◽

2019 ◽

Vol 407 ◽

pp. 116419 ◽

Cited By ~ 2

Author(s):

Hiroyuki Murai ◽

Akiyuki Uzawa ◽

Yasushi Suzuki ◽

Tomihiro Imai ◽

Hirokazu Shiraishi ◽

...

Keyword(s):

Myasthenia Gravis ◽

Subgroup Analysis ◽

Japanese Patients ◽

Extension Study ◽

Efficacy And Safety ◽

Open Label ◽

Term Efficacy ◽

Open Label Extension

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Long‐term safety of brodalumab in Japanese patients with plaque psoriasis: An open‐label extension study

The Journal of Dermatology ◽

10.1111/1346-8138.15343 ◽

2020 ◽

Vol 47 (6) ◽

pp. 569-577 ◽

Cited By ~ 3

Author(s):

Yukie Yamaguchi ◽

Nobumichi Takatsu ◽

Kenji Ootaki ◽

Hidemi Nakagawa

Keyword(s):

Plaque Psoriasis ◽

Japanese Patients ◽

Extension Study ◽

Open Label ◽

Open Label Extension

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Long-term safety and efficacy of lanreotide treatment in Japanese patients with neuroendocrine tumors: Final analysis of a phase II open-label extension study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.621 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 621-621

Author(s):

Tetsuhide Ito ◽

Seiichi Hisamatsu ◽

Akihiro Nakajima ◽

Akira Shimatsu

Keyword(s):

Neuroendocrine Tumors ◽

Phase Ii ◽

Phase Ii Study ◽

Final Analysis ◽

Japanese Patients ◽

Extension Study ◽

Open Label ◽

Safety And Efficacy ◽

Open Label Extension

621 Background: Lanreotide autogel 120mg (lanreotide) was approved in Japan in July 2017 for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs) based on the results from an international phase III study (CLARINET study) and a Japanese single-arm phase II study. The CLARINET extension study demonstrated long-term efficacy and safety of lanreotide treatment; however, no Japanese patients were included in the study. To describe the safety and efficacy of long-term lanreotide treatment for NETs in Japanese patients, the final analysis of the Japanese phase II study and its extension study was performed. Methods: This open-label extension study (Study 002, JapicCTI-142698) enrolled patients who completed 48 weeks of treatment with 4-weekly subcutaneous lanreotide in an open-label phase II study in Japanese patients with NETs (Study 001, JapicCTI-132375). Study 002 had the same design as Study 001. Results: Of the 32 patients who started treatment with lanreotide, 17 completed Study 001 and enrolled in Study 002. In the safety analysis set (n = 17), 16 patients (94.1%) developed adverse events (AEs) that were considered drug-related (adverse drug reactions; ADRs), most commonly faeces pale (n = 5; 29.4%), injection site induration (n = 4; 23.5%), flatulence and diabetes mellitus (both n = 3; 17.6% each). No patient permanently discontinued lanreotide or died as a result of an AE. Four patients had a total of eight serious AEs; of these, two events of bile duct stones were considered to be ADRs. In the efficacy analysis set (n = 28), the median lanreotide exposure over Studies 001 and 002 was 52.7 weeks (range: 12–181 weeks). The best overall response was partial response in 2 patients (7.1%; reached at 60 and 108 weeks), stable disease in 20 patients (71.4%) and progressive disease in 6 patients (21.4%). Conclusions: No unexpected serious AEs developed during prolonged use of lanreotide. Lanreotide was effective over long-term treatment in Japanese patients with NETs. Clinical trial information: JapicCTI-132375, JapicCTI-142698.

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