•PRO-MSACTIVE evaluated ocrelizumab in patients with active RMS.•This phase IV study tended to mimic current clinical practice.•Disease activity was assessed by clinical and/or imaging ...features.•Efficacy and safety profile of ocrelizumab is confirmed in a pragmatic setting.•PRO data allowed a better understanding of MS impact on patients’ lives.
Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has been approved in Europe for the treatment of adult patients with active relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), on the basis of previous phase III studies. However, limited data were available on ocrelizumab efficacy in RMS according to the Lublin definition of activity (clinical and/or imaging features) used in the current drug label. The PRO-MSACTIVE study was thus designed to provide additional data on ocrelizumab efficacy according to this definition, and also on safety and patient reported outcomes (PROs).
PRO-MSACTIVE is a national, multicenter, open-label, single-arm phase IV French study, conducted in patients with active RMS (relapsing-remitting multiple sclerosis, RRMS, or secondary progressive multiple sclerosis, SPMS). The primary endpoint, which was assessed at week (W) 48, was defined as the proportion of patients free of disease activity (defined by no relapses and no T1 gadolinium-enhancing nor new and/or enlarging T2 lesions using brain MRI). Disease activity, disability and PROs using 6 questionnaires for disease severity, quality of life, impact on work productivity, and treatment satisfaction were described at W24 and W48. Adverse events were described until W72.
Among the 422 analyzed patients (RRMS: 376, SPMS: 46), 63.3% (95% CI 58.5%; 67.9%) were free of disease activity at W48 (RRMS: 62.2% 57.1%; 67.2%, SPMS: 71.7% 56.5%; 84.0%). A total of 358 patients (84.8%; RRMS: 84.6%, SPMS: 87.0%) were relapse-free up to W48, and the overall adjusted annualized relapse rate was 0.14 (RRMS: 0.15, SPMS: 0.09). Overall, 67.8% of patients (RRMS: 66.8%, SPMS: 76.1%) had no evidence of MRI activity (no T1 gadolinium-enhancing lesions 83.4% and no new/enlarging T2 lesions 75.1%); 58.5% of patients (RRMS: 57.7%, SPMS: 65.2%) achieved No Evidence of Disease Activity (NEDA: no relapses, no confirmed disability progression, and no MRI activity) at W48. All PRO scores were stable between the first dose of ocrelizumab and W48 and better outcomes were seen for patients having an EDSS score ≥4. Overall, 89.3% of patients reported adverse events, 62.3% adverse events assessed as related to ocrelizumab, and 8.5% serious adverse events. No serious infusion-related reactions, opportunistic infections, progressive multifocal leukoencephalopathy, nor deaths were reported. No new safety signal was identified.
These data confirm the efficacy of ocrelizumab in a pragmatic setting and its favorable benefit-risk profile in patients with RMS.
(ClinicalTrials.gov identifier: NCT03589105; EudraCT identifier: 2018-000780-91).
Objective Long bones develop through the strictly regulated process of endochondral ossification within the growth plate, resulting in the replacement of cartilage by bone. Defects in this process ...can result in skeletal abnormalities and a predisposition to degenerative joint diseases such as osteoarthritis (OA). Studies suggest that activation of the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) is an important therapeutic target in OA. To devise PPARgamma-related therapies in OA, it is critical to identify the role of this transcription factor in cartilage biology. Therefore, this study sought to determine the in vivo role of PPARgamma in endochondral ossification and cartilage development, using cartilage-specific PPARgamma-knockout (KO) mice. Methods Cartilage-specific PPARgamma-KO mice were generated using the Cre/loxP system. Histomorphometric and immunohistochemical analyses were performed to assess the patterns of ossification, proliferation, differentiation, and hypertrophy of chondrocytes, skeletal organization, bone density, and calcium deposition in the KO mice. Results PPARgamma-KO mice exhibited reductions in body length, body weight, length of the long bones, skeletal growth, cellularity, bone density, calcium deposition, and trabecular bone thickness, abnormal organization of the growth plate, loss of columnar organization, shorter hypertrophic zones, and delayed primary and secondary ossification. Immunohistochemical analyses for Sox9, 5-bromo-2'-deoxyuridine, p57, type X collagen, and platelet endothelial cell adhesion molecule 1 revealed reductions in the differentiation, proliferation, and hypertrophy of chondrocytes and in vascularization of the growth plate in mutant mice. Isolated chondrocytes and cartilage explants from mutant mice showed aberrant expression of Sox9 and extracellular matrix markers, including aggrecan, type II collagen, and matrix metalloproteinase 13. In addition, chondrocytes from mutant mice exhibited enhanced phosphorylation of p38 and decreased expression of Indian hedgehog. Conclusion The presence of PPARgamma is required for normal endochondral ossification and cartilage development in vivo. PUBLICATION ABSTRACT
Between the different anticancer treatments, radiation therapy, chemotherapies and some target therapies could have cardiac toxicity. This toxicity could be a clinical cardiac insufficiency reducing ...the global benefit of these treatments. Between the different anticancer drugs the more cardiotoxic and frequently used are anthracyclines. The combination of anthracyclines with other agents like trastuzumab or paclitaxel could improve the treatment results, but with an increasing risk of cardiac toxicity. Different strategies have been developed and evaluated concerning the prevention of cardiac toxicity induced by anthracyclines. They are: using of potentially less cardiotoxic anthracyclines but with no direct comparison in adjuvant trials; modification of anthracycline infusion not so used because of technical problems; developing therapeutic strategies who could offer the opportunity to optimize the combination of different treatment with no increasing of cardiac toxicity. Use of a cardioprotecting agent before anthracycline infusion (as dexrazoxane is) is possible. However, the indication is not well defined despite existence of efficacy results.
Few elderly cancer patients are included in clinical trials, resulting insuffisant data of the effectiveness and tolerance of anticancer drugs in this patient population. The aim of this study was to ...analyse the studies concerning the effectiveness and tolerance of chemotherapy prescribed for elderly patients treated for colorectal, breast and lung cancer. The data of this population showed that the older patients are less likely to receive chemotherapy than the younger. The age is considered as significant important factor for the decision of chemotherapy of this population. However elderly patients seem to have the same benefit as compared with younger patients. Rather than the criteria of age, comorbidities should be considered. It is necessary to develop specific geriatric assessment and development of clinical trials specifically including elderly patients remains a necessity.
Digital cooperative studio 07-08 Kubicki, Sylvain; Bignon, Jean-Claude; Elsen, Catherine ...
2008 IEEE International Technology Management Conference (ICE),
2008-June, 20080601
Conference Proceeding, Journal Article
Teaching cooperation-related issues to AEC (Architecture, Engineering and Construction) students is a major stake nowadays. There are many reasons for that: construction projects become more and more ...complex and cooperation practices are evolving in both organizational and IT-based ways. It is notably for these reasons that the issue of IT is addressed in most of the AEC-oriented schools and universities. Traditionally IT is taught to support the tasks of each specific construction field (e.g. CAD for architects, simulation tools for static engineers etc.). The Digital Cooperative Studio, presented in this article, considers IT as a support to cooperation and especially its communication and coordination dimensions. Moreover, we describe here a living lab involving students, teachers and researchers. This strong link between research and teaching allows both the students to be "analysts" of their real project situations and the researchers to experiment their development in real project situations.
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