scholarly journals Safety profile of anifrolumab in patients with active SLE: an integrated analysis of phase II and III trials

2021 ◽  
Vol 8 (1) ◽  
pp. e000464
Author(s):  
Raj Tummala ◽  
Gabriel Abreu ◽  
Lilia Pineda ◽  
M Alex Michaels ◽  
Rubana N Kalyani ◽  
...  
Keyword(s):  
Phase Ii ◽  
Safety Profile ◽  
Human Monoclonal Antibody ◽  
Pooled Analysis ◽  
Incidence Rates ◽  
Risk Difference ◽  
Integrated Analysis ◽  
Type I ◽  
Tract Infections ◽  
Phase Ii And Iii

ObjectiveIn phase II and III trials, anifrolumab, a human monoclonal antibody that binds type I interferon receptor subunit 1, has shown efficacy in adults with moderate to severe SLE. We evaluated the safety and tolerability of anifrolumab using data pooled from these trials to more precisely estimate the rate and severity of adverse events (AEs).MethodsData were pooled from patients receiving monthly intravenous anifrolumab 300 mg or placebo in MUSE, TULIP-1 and TULIP-2. Key safety endpoints included percentages and exposure-adjusted incidence rates (EAIRs) of patients who experienced AEs, serious AEs (SAEs), AEs leading to discontinuation and AEs of special interest.ResultsDuring treatment, 86.9% of patients receiving anifrolumab 300 mg (n=459) experienced AEs (≥1) versus 79.4% receiving placebo (n=466), and 4.1% versus 5.2% experienced an AE leading to discontinuation of investigational product. SAEs (≥1) were experienced by 11.8% and 16.7% of patients receiving anifrolumab and placebo, respectively (EAIR risk difference (95% CI) −7.2 (−12.5 to –1.9)), including lupus exacerbations classified as SAEs (1.5% and 3%, respectively). Infections occurred in 69.7% and 55.4% of patients receiving anifrolumab and placebo, respectively; difference in reported rates was driven by herpes zoster (HZ) and mild and moderate respiratory (excluding pneumonia) infections. The risk of HZ was increased with anifrolumab versus placebo (6.1% vs 1.3%, respectively; EAIR risk difference (95% CI) 5.4 (2.8 to 8.4)); most HZ events were mild or moderate, cutaneous and resolved without treatment discontinuation. Serious infections occurred in 4.8% and 5.6% of patients receiving anifrolumab and placebo, respectively.ConclusionsIn this pooled analysis of 925 patients with moderate to severe SLE, monthly intravenous anifrolumab 300 mg was generally well tolerated over 52 weeks with an acceptable safety profile. Anifrolumab was associated with an increased incidence of HZ and respiratory tract infections and lower reported rate of SLE worsening as SAEs.

scholarly journals Pharmacoethnicity of docetaxel-induced severe neutropenia: integrated analysis of published phase II and III trials

2011 ◽  
Vol 18 (1) ◽  
pp. 96-104 ◽  
Author(s):  
Ryoichi Yano ◽  
Aya Konno ◽  
Kyohei Watanabe ◽  
Hitoshi Tsukamoto ◽  
Yuichiro Kayano ◽  
...  
Keyword(s):  
Phase Ii ◽  
Severe Neutropenia ◽  
Integrated Analysis ◽  
Phase Ii And Iii

Evolution of statistical methodology and design of phase II/III clinical trials in non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7108-7108 ◽  
Author(s):  
R. K. Bagai ◽  
A. Dowlati
Keyword(s):  
Clinical Trials ◽  
Survival Time ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Iii ◽  
Type I ◽  
Phase Ii Trials ◽  
Improvement In Survival ◽  
Phase Ii And Iii ◽  
Phase Iii Studies

7108 Background: A significant heterogeneity exists in the design and reporting of phase II and III therapeutic clinical trials in NSCLC. This has led to difficulty in interpretation of these trials leading to over- or underestimation of therapeutic efficacy. We set out to investigate the statistical methodology and design reporting of chemotherapeutic trials in NSCLC published in the Journal of Clinical Oncology (JCO) over 20 years. Methods: We identified all phase II and III NSCLC chemotherapy trials published in the JCO from January 1983 to August 2005. All manuscripts were reviewed to evaluate components of statistical design that were reported, including: sample size calculation, power, type I error, single or multiple drug trials, relative response sought in phase II trials and improvement in survival time or response rate sought in phase III trials. Results: One hundred forty eight trials were identified. 52% of studies were phase III and 48% were phase II. The majority (78%) were conducted in advanced stage NSCLC. Sample size calculations were reported for only 58% of phase III studies and 31% of phase II studies. Power was reported in 66% of phase III studies and 13% of phase II trials. Type I error was reported in 47% of phase III studies and 17% in phase II studies. 60% of phase III trials defined endpoints (percentage improvement in survival time, improvement in survival time in months or increase in response rate). 41% of phase II trails defined the target response rate, ranging from response rates of 15% to 70%. The frequency of adequate reporting of statistical design was shown to increase from 31% in 1990–1995 to 64% in 2000–2005 ( table ). Conclusions: Significant heterogeneity exists in trial design and reporting of phase II and III trials in NSCLC. This impacts the ability to adequately interpret these studies. More widespread application of statistical methods in planning and reporting of lung cancer clinical trials are necessary to increase reliability of data. [Table: see text] No significant financial relationships to disclose.

SAFETY PROFILE OF BELATACEPT IN KIDNEY TRANSPLANT RECIPIENTS FROM A POOLED ANALYSIS OF PHASE II AND PHASE III STUDIES

2010 ◽  
Vol 90 ◽  
pp. 156 ◽  
Author(s):  
J. Grinyo ◽  
B. Charpentier ◽  
J. O.M. Pestana ◽  
Y. Vanrenterghem ◽  
F. Vincenti ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Phase Ii ◽  
Safety Profile ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Phase Iii Studies

Secukinumab long-term safety experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis

2016 ◽  
Vol 75 (1) ◽  
pp. 83-98.e4 ◽  
Author(s):  
Peter C.M. van de Kerkhof ◽  
Christopher E.M. Griffiths ◽  
Kristian Reich ◽  
Craig L. Leonardi ◽  
Andrew Blauvelt ◽  
...  
Keyword(s):  
Phase Ii ◽  
Plaque Psoriasis ◽  
Clinical Studies ◽  
Pooled Analysis ◽  
Severe Plaque Psoriasis ◽  
Phase Ii And Iii

scholarly journals Effect of race and ethnicity on vildagliptin efficacy: A pooled analysis of phase II and III studies

2017 ◽  
Vol 19 (3) ◽  
pp. 429-435 ◽  
Author(s):  
Plamen Kozlovski ◽  
Marilia Fonseca ◽  
Viswanathan Mohan ◽  
Valentina Lukashevich ◽  
Masato Odawara ◽  
...  
Keyword(s):  
Phase Ii ◽  
Race And Ethnicity ◽  
Pooled Analysis ◽  
Phase Ii And Iii

scholarly journals New Calcipotriol/Betamethasone Dipropionate Foam Formulation for the Treatment of Psoriasis: An Overview

2018 ◽  
Vol 76 (1) ◽  
pp. 53-64
Author(s):  
Tiago Torres ◽  
Paulo Filipe
Keyword(s):  
Plaque Psoriasis ◽  
Safety Profile ◽  
Topical Treatment ◽  
Clinical Studies ◽  
Therapeutic Option ◽  
Pooled Analysis ◽  
Tolerability Profile ◽  
Foam Formulation ◽  
New Formulation ◽  
Phase Ii And Iii

Psoriasis is a chronic, inflammatory, immune-mediated, potentially disfiguring and disabling skin disorder, affecting over 100 million individuals worldwide. Calcipotriol plus betamethasone fixed-combination (0.005% Cal/0.064% BD) is the recommended topical treatment for psoriasis. However, topical treatments are associated to lack of efficacy and low adhesion rates due to poor cosmetic characteristics’ formulations, and vehicle issues. To answer the need for improving patients’ acceptability and adherence, an innovative Cal/BD aerosol foam formulation was developed for the topical treatment of adults with plaque psoriasis. Phase II and III clinical trials have consistently shown that the two-compound formulation is more effective and safer than its individual ingredients in the same vehicle. Cal/BD aerosol foam formulation has proved higher efficacy in clinical studies, and a pooled analysis of the main clinical studies has demonstrated that this does not occur at the safety profile expense. Furthermore, Cal/BD aerosol foam has shown a significantly improved efficacy compared with more traditional formulations, such as ointments, gels, and lotions. The improved efficacy and safety profile of this new formulation, together with the once-daily treatment, a more acceptable tolerability profile, and an early and rapid response, offers improved convenience and better acceptance over the twice- -daily applications required for the respective monotherapies, which may improve adherence to treatment, leading to faster and greater improvements in HR-QoL, representing a useful therapeutic option to the management of patients with plaque psoriasis. Further clinical investigations to explore the possibility of Cal/BD aerosol foam treatment ability to provide long-term psoriasis’ management are required.

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