Efficacy of Long-Term Treatment with Once-Daily Baricitinib 2 mg in Patients with Active Rheumatoid Arthritis: Post Hoc Analysis of Two 24-Week, Phase III, Randomized, Controlled Studies and One Long-Term Extension Study

Background: Patients with immune thrombocytopenia (ITP) are at risk of bleeding and, paradoxically, thromboembolic events (TEEs), irrespective of thrombocytopenia. The risk of thrombosis is increased by advanced age, obesity, and prothrombotic comorbidities: cancer, hyperlipidemia, diabetes, hypertension, coronary artery disease, and chronic kidney disease, among others. Certain ITP treatments further increase the risk of TEE, especially splenectomy and thrombopoietin receptor agonists. Spleen tyrosine kinase (SYK) is a key signaling molecule common to thromboembolic and hemostatic (in addition to inflammatory) pathways. Fostamatinib is an orally administered SYK inhibitor approved in the USA and Europe for treatment of chronic ITP in adults. Methods: The phase III and extension studies included heavily pretreated patients with long-standing ITP, many of whom had risk factors for thrombosis prior to initiating fostamatinib. This report describes long-term safety and efficacy of fostamatinib in 146 patients with up to 5 years of treatment, a total of 229 patient-years, and assesses the incidence of thromboembolic events (by standardized MedDRA query). Results: Platelet counts ⩾50,000/µL were achieved in 54% of patients and the safety profile was as described in the phase III clinical studies with no new toxicities observed over the 5 years of follow-up. The only TEE occurred in one patient (0.7%, or 0.44/100 patient-years), who experienced a mild transient ischemic attack. This is a much lower rate than might be expected in ITP patients. Conclusion: This report demonstrates durable efficacy and a very low incidence of TEE in patients receiving long-term treatment of ITP with the SYK inhibitor fostamatinib. identifiers: NCT02076399, NCT02076412, and NCT02077192.

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Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial

British Journal of Dermatology ◽

10.1111/j.1365-2133.2006.07685.x ◽

2007 ◽

Vol 156 (3) ◽

pp. 492-498 ◽

Cited By ~ 105

Author(s):

I. Buraczewska ◽

B. Berne ◽

M. Lindberg ◽

H. Törmä ◽

M. Lodén

Keyword(s):

Randomized Controlled Trial ◽

Barrier Function ◽

Controlled Trial ◽

Skin Barrier ◽

Term Treatment ◽

Skin Barrier Function ◽

Randomized Controlled ◽

Long Term Treatment

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Glucosamine Long-Term Treatment and the Progression of Knee Osteoarthritis: Systematic Review of Randomized Controlled Trials

Annals of Pharmacotherapy ◽

10.1345/aph.1e576 ◽

2005 ◽

Vol 39 (6) ◽

pp. 1080-1087 ◽

Cited By ~ 59

Author(s):

Nalinee Poolsup ◽

Chutamanee Suthisisang ◽

Patchareeya Channark ◽

Wararat Kittikulsuth

Keyword(s):

Knee Osteoarthritis ◽

Disease Progression ◽

Term Treatment ◽

Glucosamine Sulfate ◽

Controlled Trials ◽

Efficacy And Safety ◽

Knee Oa ◽

Randomized Controlled ◽

Long Term Treatment

OBJECTIVE: To investigate the structural and symptomatic efficacy and safety of glucosamine in knee osteoarthritis (OA). DATA SOURCES: Clinical trials of glucosamine were identified through electronic searches (MEDLINE, EMBASE, BIOSIS, EMB review, the Cochrane Library) using the key words glucosamine, osteoarthritis, degenerative joint disease, degenerative arthritis, osteoarthrosis, gonarthrosis, knee, disease progression, and clinical trial. The bibliographic databases were searched from their respective inception dates to August 2004. We also hand-searched reference lists of relevant articles. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they were double-blind, randomized, controlled trials that evaluated oral glucosamine long-term treatment in knee OA; lasting at least one year; and reporting as outcome measures the symptom severity and disease progression as assessed by joint space narrowing. Two authors interpreted data independently. Disagreements were resolved through discussion. DATA SYNTHESIS: Glucosamine sulfate was more effective than placebo in delaying structural progression in knee OA. The risk of disease progression was reduced by 54% (pooled RR 0.46; 95% CI 0.28 to 0.73; p = 0.0011). The number-needed-to-treat was 9 (95% CI 6 to 20). The pooled effect sizes for pain reduction and improvement in physical function were 0.41 (95% CI 0.21 to 0.60; p < 0.0001) and 0.46 (95% CI 0.27 to 0.66; p < 0.0001), respectively, in favor of glucosamine sulfate. Glucosamine sulfate caused no more adverse effects than placebo. CONCLUSIONS: The available evidence suggests that glucosamine sulfate may be effective and safe in delaying the progression and improving the symptoms of knee OA. Due to the sparse data on structural efficacy and safety, further studies are warranted.

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139 Early Response with Valbenazine and Long-Term Symptom Reduction in Patients with Tardive Dyskinesia: Post Hoc Analysis of the KINECT 3 Study

CNS Spectrums ◽

10.1017/s1092852920000553 ◽

2020 ◽

Vol 25 (2) ◽

pp. 288-289

Author(s):

Stanley N. Caroff ◽

Jean-Pierre Lindenmayer ◽

Stephen R. Marder ◽

Stewart A. Factor ◽

Khodayar Farahmand ◽

...

Keyword(s):

Tardive Dyskinesia ◽

Early Response ◽

Term Treatment ◽

Score Change ◽

Double Blind ◽

Early Improvement ◽

Long Term Treatment ◽

Post Hoc ◽

Improvement Score

Abstract:Study Objective:Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from a long-term study (KINECT 3; NCT02274558), the effects of once-daily valbenazine (40 mg, 80 mg) on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS) in participants who were early responders based on subjective measures, including patient self-report (Patient Global Impression of Change [PGIC]) or clinician judgment (Clinical Impression of Change-Tardive Dyskinesia [CGI-TD]).Methods:Data from KINECT 3 (6-week double-blind, placebo-controlled [DBPC] period; 42-week double-blind extension) were analyzed post hoc. Long-term outcomes included mean change from baseline to Week 48 in AIMS total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48. These AIMS outcomes were assessed in participants who achieved early improvement, defined as a PGIC or CGI-TD score of ≤3 (“minimally improved” or better) at Week 2 (first post-baseline visit of the DBPC period). Participants who initially received placebo were not included in the analyses.Results:In participants who received only valbenazine (40 or 80 mg) during KINECT 3 and had available Week 2 assessment, 50% (72/143) had early PGIC improvement (score ≤3) and 43% (61/142) had early CGI-TD improvement (score ≤3). Baseline characteristics were generally similar between participants who achieved early PGIC or CGI-TD improvement and those who did not. Based on available assessments at Week 48, mean AIMS total score change from baseline in participants with early PGIC improvement was similar to those who did not reach the early PGIC improvement threshold (-4.1 [n=35] vs -3.5 [n=41]). Mean AIMS total score change from baseline in participants with early CGI-TD improvement was similar to those who did not achieve early CGI-TD improvement (-4.2 [n=31] vs -3.5 [n=45]). AIMS response at Week 48 was also similar in those who achieved early PGIC and CGI-TD improvement (40% and 42%, respectively) compared to those who did not achieve early PGIC and CGI-TD improvement (39% and 38%, respectively).Conclusions:Results from this long-term valbenazine trial indicate that many participants achieved at least minimal patient- and clinician-reported improvement at Week 2. AIMS outcomes at Week 48 demonstrated long-term reductions in TD severity regardless of early response. More research is needed to understand the association between early improvement and long-term treatment effects, but early non-improvement based on subjective measures may not be predictive of long-term treatment failure.Presented:International Congress of Parkinson’s Disease and Movement Disorders; September 22-26, 2019; Nice, France.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

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