scholarly journals Special issue—before translational medicine: laboratory clinic relations lost in translation? Cortisone and the treatment of rheumatoid arthritis in Britain, 1950–1960

2019 ◽  
Vol 41 (4) ◽  
Author(s):  
Michael Worboys ◽  
Elizabeth Toon

Abstract Cortisone, initially known as ‘compound E’ was the medical sensation of the late 1940s and early 1950s. As early as April 1949, only a week after Philip Hench and colleagues first described the potential of ‘compound E’ at a Mayo Clinic seminar, the New York Times reported the drug’s promise as a ‘modern miracle’ in the treatment of rheumatoid arthritis (RA). Given its high profile, it is unsurprising that historians of medicine have been attracted to study the innovation of cortisone. It arrived at the end of a decade of ‘therapeutic revolutions’, kicked off by penicillin transforming the treatment of bacterial infections and ending with hopes of a revolution in the treatment of non-infectious, chronic inflammatory diseases. Despite these studies of cortisone’s introduction, few historians have taken the story forward and considered how cortisone was adopted and adapted into clinical practice. This article tells the longer of how the drug and its derivatives were taken from research laboratories and integrated into clinical practice; what has in recent decades become known as translational medicine (TM). In exploring cortisone’s first decade in Britain, we focus specifically on its role in the treatment of RA. Our approach is always to consider cortisone’s use in the context of other treatments available to clinicians, and at local and national institutional settings. We do not discuss the many other therapeutic uses of cortisone, which ranged for topical applications for skin diseases to the management of cancers, especially childhood leukaemia, nor do we discuss its close analogue ACTH—AdenoCorticoTropic Hormone. We think there are lessons in our study for TM policies today.

2016 ◽  
Vol 9 ◽  
pp. LPI.S37450 ◽  
Author(s):  
Jonathan T. Davies ◽  
Spencer F. Delfino ◽  
Chad E. Feinberg ◽  
Meghan F. Johnson ◽  
Veronica L. Nappi ◽  
...  

Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, are commonly administered to treat atherosclerotic cardiovascular disease. Statin use may expand considerably given its potential for treating an array of cholesterol-independent diseases. However, the lack of conclusive evidence supporting these emerging therapeutic uses of statins brings to the fore a number of unanswered questions including uncertainties regarding patient-to-patient variability in response to statins, the most appropriate statin to be used for the desired effect, and the efficacy of statins in treating cholesterol-independent diseases. In this review, the adverse effects, costs, and drug–drug and drug–food interactions associated with statin use are presented. Furthermore, we discuss the pleiotropic effects associated with statins with regard to the onset and progression of autoimmune and inflammatory diseases, cancer, neurodegenerative disorders, strokes, bacterial infections, and human immunodeficiency virus. Understanding these issues will improve the prognosis of patients who are administered statins and potentially expand our ability to treat a wide variety of diseases.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1452.1-1452
Author(s):  
G. Lukina ◽  
E. Koltsova ◽  
E. Shmidt ◽  
K. Lytkina ◽  
E. Zhilyaev

Background:The introduction of perspective anti-rheumatic biologic agents into clinical practice has not only increased therapy efficacy and improved medical prognosis in patients with rheumatoid arthritis (RA), but also resulted in a dramatic increase in treatment cost and, therefore, in a reduced accessibility of the innovative treatment for patients. For this reason, over the last years, there has been a huge interest towards developing biosimilars [1,2].Objectives:To assess the effectiveness and safety of switching from reference rituximab (RTXref) to rituximab biosimilar (RTXbs) BCD-020 in patients with RA in real clinical practice according to the data from MUAR.Methods:Patients with RA who treated by RTXrefat the onset and then switched to RTXbs(BCD-020) were enrolled in the study. For all patients were performed: swollen and tender joints count, ESR, CRP, biochemistry and immunologic blood analyses. Assessment of dynamic of DAS28, RAPID3, HAQ-DI was performed. The great attention was given to the therapy safety assessment. RTXrefeffectiveness and safety profile was assessed at the moment of switching; data for RTXbs(BCD-020) were collected not earlier than 6 months after switching.Results:46 patients with RA were enrolled, 80.5% were women; the mean age was 59.5±12.2 years; 91.3% were RF-positive, 63% - ACCPA-positive, the disease activity at the moment of switching was moderate, the mean DAS28 was 3.5. The duration of RTXreftherapy until switching was 36.8 ± 26.8 months; the duration of the follow-up period for BCD-020 biosimilar was 12.1 ± 6.18 months. In 43.5% of patients, previously inefficiency or intolerance of other biologics was discovered. The proportion of patients who received concomitant therapy with glucocorticoids or methotrexate (MTX) was 45.7% and 43.5%, respectively. The mean MTX dose was 13.6 mg/wk. The mean dose of RTXref/BCD-020 was 1000 mg. The stability dynamic of clinical parameters was retained after switching to biosimilar (Tab.1) without significant difference between the rituximab products (р>0.05).Table 1.Comparison of Efficiency Parameters for the Reference Rituximab and Biosimilar BCD-020ParameterReference rituximabBiosimilar BCD-020DAS28 (ESR)3.393.34HAQ-DI1.481.44RAPID312.912.6The safety profile of RTXrefand RTXbs(BCD-020) was also similar. None of the patients discontinued BCD-020 therapy for reasons related to safety or inefficiency.Conclusion:Within the framework of routine clinical practice, switching from reference rituximab to BCD-020 biosimilar is not accompanied by a change in efficiency and safety profile of the therapy and does not pose a risk of discontinuation, which is coherent with the results of the registration clinical trial for BCD-020. [3]References:[1]Edwards CJ, et al. Switching to biosimilars: current perspectives in immune-mediated inflammatory diseases. Expert Opin Biol Ther. 2019 Oct;19(10):1001-1014. doi: 10.1080/14712598.2019.1610381. Epub 2019 May 6.[2]Dörner T, et al. The changing landscape of biosimilars in rheumatology. Ann Rheum Dis 2016;75:974–982. doi:10.1136/annrheumdis-2016-209166[3]Nasonov EL, et al. The results of a phase III comparative clinical trial of rituximab (Acellbia and MabThera) in rheumatoid arthritis (the BIORA study). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(5):510-519 (In Russ.). doi:http://dx.doi.org/10.14412/1995-4484-2016-510-519Disclosure of Interests:Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Ekaterina Koltsova: None declared, Evgeniya Shmidt Speakers bureau: MSD, Novartis, Pfizer, Karine Lytkina Speakers bureau: Novartis, Eli Lilly, Pfizer, UCB, Abbvie, Biocad, MSD, Jonson&Jonson, Evgeniy Zhilyaev Speakers bureau: Novartis, UCB, Pfizer, Biocad, Abbvie, MSD, Roche


2007 ◽  
Vol 67 (4) ◽  
pp. 462-465 ◽  
Author(s):  
A Mor ◽  
C O Bingham ◽  
M Kishimoto ◽  
P M Izmirly ◽  
J D Greenberg ◽  
...  

Objectives:Reactivation of Mycobacterium tuberculosis (TB) is a significant problem with all available tumour necrosis factor (TNF) antagonists when used to treat rheumatoid arthritis (RA), psoriatic arthritis, psoriasis and other inflammatory diseases. Concerns have been raised regarding the appropriate management of patients with latent TB (LTB) exposure (or active TB infection) before initiating TNF antagonists as the safety data of combined treatment with two potentially hepatotoxic medications, methotrexate (MTX) and isoniazid (INH), is lacking. The goal of this study was to investigate the toxicity of MTX and INH treatment in patients with RA before initiating TNF antagonists.Methods:To investigate the toxicity of MTX and INH treatment in patients with RA we performed a retrospective chart review of patients seen at the Bellevue Hospital Arthritis Clinic in New York City between 2002 and 2006. Forty-four patients who were concomitantly treated with both drugs were included. The primary outcome investigated was increase in liver function tests (LFT).Results:Transient increases in LFT were seen in 11% of patients, but in no case was this more than twice the upper limit of normal values. All abnormal LFT resolved spontaneously without intervention. In addition, no patient has developed signs or symptoms of TB reactivation.Conclusions:The use of INH for LTB was well tolerated in patients with RA on a background regimen of MTX. While the risks and benefits of all treatment must always be considered, in our experience the additive risk of INH to MTX in terms of hepatotoxicity was low. None the less it is prudent to follow LFT closely on patients taking this combination.


2003 ◽  
Vol 15 (3) ◽  
pp. 98-105 ◽  
Author(s):  
Mark Galliker ◽  
Jan Herman
Keyword(s):  
New York ◽  

Zusammenfassung. Am Beispiel der Repräsentation von Mann und Frau in der Times und in der New York Times wird ein inhaltsanalytisches Verfahren vorgestellt, das sich besonders für die Untersuchung elektronisch gespeicherter Printmedien eignet. Unter Co-Occurrence-Analyse wird die systematische Untersuchung verbaler Kombinationen pro Zähleinheit verstanden. Diskutiert wird das Problem der Auswahl der bei der Auswertung und Darstellung der Ergebnisse berücksichtigten semantischen Einheiten.


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