Comparison of clinical outcomes after multivessel versus single-vessel stenting with the zotarolimus-eluting stent in the RESOLUTE Global Clinical Trial Program

2017 ◽  
Vol 12 (13) ◽  
pp. 1605-1613
Author(s):  
Ganesh Manoharan ◽  
Jorge Belardi ◽  
Zhimin Du ◽  
Michael Lee ◽  
Shubin Qiao ◽  
...  
2015 ◽  
Vol 42 (10) ◽  
pp. 1761-1766 ◽  
Author(s):  
Ronald F. van Vollenhoven ◽  
Roy M. Fleischmann ◽  
Daniel E. Furst ◽  
Stuart Lacey ◽  
Patricia B. Lehane

Objective.Final evaluation of the longterm safety of rituximab (RTX) in rheumatoid arthritis (RA) up to 11 years.Methods.Pooled observed case analysis of data from patients with moderate to severe, active RA in a global clinical trial program.Results.As of September 2012, 3595 patients received a mean of 4 courses (range 1–20) of RTX over 11 years [14,816 patient-years (PY)]. Of these, 1246 patients had > 5 years of followup (8970 PY). A pooled placebo population (n = 818) was included in the analysis. The overall serious infection event (SIE) rate was 3.76/100 PY (2.71/100 PY in patients observed for > 5 yrs) and comparable with rates reported previously at 9.5 years (3.94/100 PY and 3.26/100 PY, respectively). SIE rates continued to be similar before and during/after development of low immunoglobulin levels, and serious opportunistic infections remained rare. Rates of cardiac events remained consistent with previous analysis and with rates in the general RA population. No increased risk of malignancy over time was observed.Conclusion.This final report demonstrates that RTX remains well tolerated over time and multiple courses. No new safety risks were identified and there was no increase in the rate of any types of adverse events with prolonged exposure to RTX during 11 years of observation.


2010 ◽  
Vol 37 (3) ◽  
pp. 558-567 ◽  
Author(s):  
RONALD F. van VOLLENHOVEN ◽  
PAUL EMERY ◽  
CLIFTON O. BINGHAM ◽  
EDWARD C. KEYSTONE ◽  
ROY FLEISCHMANN ◽  
...  

Objective.To evaluate the longterm safety of rituximab in clinical trials in patients with rheumatoid arthritis (RA).Methods.Pooled analysis of safety data, including adverse events (AE) and infections, from patients treated with rituximab in combination with methotrexate in a global clinical trial program.Results.A total of 2578 patients with RA received at least 1 course of rituximab. Safety analyses were based on 5013 patient-years of rituximab exposure. The most frequent AE was infusion-related reactions (25% of patients during the first infusion of Course 1). Less than 1% of infusion-related reactions were considered serious. Rates of AE and serious AE (SAE; 17.85 events/100 patient-yrs, 95% CI 16.72, 19.06) were stable following each course. The overall serious infection rate was 4.31/100 patient-years (95% CI 3.77, 4.92). Infections and serious infections over time remained stable across 5 courses at 4–6 events/100 patient-years. Compared with other patients with RA and with the general US population, there was no increased risk of malignancy.Conclusion.In this longterm safety update in RA clinical trial patients, rituximab remained well tolerated over multiple courses. SAE and infections remained stable over time and by treatment course.


Author(s):  
Neal E. Storm ◽  
Wen Chang ◽  
Tzu-Chieh Lin ◽  
Jeff L. Lange ◽  
Brian Bradbury ◽  
...  

AbstractOn June 23, 2020, Prolia® (denosumab) was approved by the National Medical Products Administration (NMPA) in the People’s Republic of China as the first monoclonal antibody for the treatment of postmenopausal women with osteoporosis at high risk of fractures. Its brand name in Chinese is 普罗力, a transliteration from the English name “Prolia”, which has an implied meaning of “to give strength to everyone”— a suitable name for a potent anti-resorptive therapy. The approval was supported by a novel marketing authorization application (MAA) that included data from Prolia’s global clinical trial program establishing favorable efficacy and safety, augmented by results from a real-world evidence (RWE) study confirming the effectiveness and safety of Prolia in clinical practice within Taiwan and Hong Kong. Key constructs for this registration-quality RWE study included the fit-for-purpose assessment of data quality, methodology and quantitative assessment of potential biases, good practices of study conduct, and reproducibility of results. Using data from clinical practice in Taiwan and Hong Kong to evaluate the benefits versus risks of Prolia treatment in ethnic Chinese women with postmenopausal osteoporosis, the RWE study results for effectiveness were comparable to efficacy demonstrated in the global clinical trial program and results for safety were consistent with the incidence observed in global post-marketing safety studies. While RWE is often used to monitor postmarket safety of drug products, support health insurance coverage decisions, and inform clinicians on real-world use of medicines, it has not been widely used to support regulatory approval for new medicines in lieu of clinical bridging studies in countries where such studies are required. Well-conducted registrational RWE studies can play a pivotal role in complementing the totality of evidence presented in an MAA. The benefits of such an approach include avoiding the collection of additional placebo-controlled trial data in populations where adequate ethnic characterization of efficacy, effectiveness, and safety may already exist from postmarketing sources, and accelerate access for patients to innovative medicines in important regions. Here, we describe a regulatory case study of a novel MAA incorporating RWE that provided important evidence to confirm the benefit:risk of a new drug and facilitated a label expansion to a new patient population.


2021 ◽  
Vol 49 (4) ◽  
pp. 982-993
Author(s):  
Anne-Sofie Agergaard ◽  
Rene B. Svensson ◽  
Nikolaj M. Malmgaard-Clausen ◽  
Christian Couppé ◽  
Mikkel H. Hjortshoej ◽  
...  

Background: Loading interventions have become a predominant treatment strategy for tendinopathy, and positive clinical outcomes and tendon tissue responses may depend on the exercise dose and load magnitude. Purpose/Hypothesis: The purpose was to investigate if the load magnitude influenced the effect of a 12-week loading intervention for patellar tendinopathy in the short term (12 weeks) and long term (52 weeks). We hypothesized that a greater load magnitude of 90% of 1 repetition maximum (RM) would yield a more positive clinical outcome, tendon structure, and tendon function compared with a lower load magnitude of 55% of 1 RM when the total exercise volume was kept equal in both groups. Study Design: Randomized clinical trial; Level of evidence, 1. Methods: A total of 44 adult participants with chronic patellar tendinopathy were included and randomized to undergo moderate slow resistance (MSR group; 55% of 1 RM) or heavy slow resistance (HSR group; 90% of 1 RM). Function and symptoms (Victorian Institute of Sport Assessment–Patella questionnaire [VISA-P]), tendon pain during activity (numeric rating scale [NRS]), and ultrasound findings (tendon vascularization and swelling) were assessed before the intervention, at 6 and 12 weeks during the intervention, and at 52 weeks from baseline. Tendon function (functional tests) and tendon structure (ultrasound and magnetic resonance imaging) were investigated before and after the intervention period. Results: The HSR and MSR interventions both yielded significant clinical improvements in the VISA-P score (mean ± SEM) (HSR: 0 weeks, 58.8 ± 4.3; 12 weeks, 70.5 ± 4.4; 52 weeks, 79.7 ± 4.6) (MSR: 0 weeks, 59.9 ± 2.5; 12 weeks, 72.5 ± 2.9; 52 weeks, 82.6 ± 2.5), NRS score for running, NRS score for squats, NRS score for preferred sport, single-leg decline squat, and patient satisfaction after 12 weeks, and these were maintained after 52 weeks. HSR loading was not superior to MSR loading for any of the measured clinical outcomes. Similarly, there were no differences in functional (strength and jumping ability) or structural (tendon thickness, power Doppler area, and cross-sectional area) improvements between the groups undergoing HSR and MSR loading. Conclusion: There was no superior effect of exercising with a high load magnitude (HSR) compared with a moderate load magnitude (MSR) for the clinical outcome, tendon structure, or tendon function in the treatment of patellar tendinopathy in the short term. Both HSR and MSR showed equally good, continued improvements in outcomes in the long term but did not reach normal values for healthy tendons. Registration: NCT03096067 (ClinicalTrials.gov identifier)


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