DOCSLIB.ORG

Long-Term Safety and Efficacy of Sirukumab for Patients with Rheumatoid Arthritis Who Previously Received Sirukumab in Randomise

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Long-Term Safety and Efficacy of Sirukumab for Patients with Rheumatoid Arthritis Who Previously Received Sirukumab in Randomise Rheumatoid arthritis RMD Open: first published as 10.1136/rmdopen-2020-001465 on 1 February 2021. Downloaded from ORIGINAL RESEARCH Long-­term­safety­and­efficacy­of­ sirukumab for patients with rheumatoid arthritis­who­previously­received­ sirukumab­in­randomised­controlled­ trials (SIRROUND- LTE) Daniel Aletaha ,1 Clifton O Bingham,2 George Athanasios Karpouzas ,3 Tsutomu Takeuchi,4 Carter Thorne,5,6 Androniki Bili,7 Prasheen Agarwal,8 Benjamin Hsu,7 Ravi Rao,9 Kurt Brown,10 Yoshiya Tanaka 11 To cite: Aletaha D, Bingham CO, ABSTRACT Karpouzas GA, et al. Long- Objective Interleukin (IL)-6 is a pleiotropic cytokine Key messages term safety and efficacy of involved in the pathophysiology of rheumatoid arthritis sirukumab for patients with (RA). Sirukumab is a human monoclonal antibody that What is already known about this subject? rheumatoid arthritis who binds to IL-6 with high affinity and specificity. ► Inhibition of interleukin (IL)-6 receptor (IL- 6R) is an previously received sirukumab Methods This long- term extension (LTE) study of the established, effective and safe approach for treat- in randomised controlled trials ment of rheumatoid arthritis (RA). (SIRROUND- LTE). RMD Open SIRROUND- D and SIRROUND- T studies assessed long- term ► The IL-6 cytokine inhibitor sirukumab has been 2021;7:e001465. doi:10.1136/ safety and efficacy of sirukumab in adults with moderate- studied in a pivotal trial programme, and has been rmdopen-2020-001465 to- severe RA refractory to conventional disease- modifying antirheumatic drug therapy or antitumor necrosis shown to be of comparable efficacy and safety to factor agents. Patients received sirukumab 100 mg existing IL-6R inhibitors. Received 29 September 2020 subcutaneously (SC) every 2 weeks (q2w) or sirukumab 50 What does this study add? Revised 5 January 2021 mg SC every 4 weeks (q4w). ► The long- term extension (LTE) study of sirukumab Accepted 9 January 2021 http://rmdopen.bmj.com/ Results 1820 patients enrolled in the LTE; median confirms that reductions in RA signs and symp- exposure was 2.34 and 2.07 years in sirukumab 50 mg toms and improvements in physical function were q4w and 100 mg q2w groups, respectively. Adverse maintained. events (AEs) occurred in similar proportions between ► The safety profile of sirukumab in the LTE remained groups, with the exception of major adverse cardiovascular consistent with that reported in pivotal SIRROUND-D events (MACE), which were more common in the 50 mg and SIRROUND-T trials. q4w versus 100 mg q2w group (2.2% vs 1.0%), and injection- site reactions, more common in the 100 mg How might this impact on clinical practice? q2w group versus 50 mg q4w group (7.5% vs 3.7%). ► Sirukumab has not reached real- life clinical appli- The most common serious AEs were infections (10% of cation, but the current evaluation of the long-term on September 29, 2021 by guest. Protected copyright. the patients); 32 (1.8%) patients died during the study efficacy and particular safety of an IL-6 cytokine in- (primarily from serious infection and MACE). Malignancies hibitor in patients with RA is informative and relevant were reported in 24 (1.3%) patients. Gastrointestinal in a highly dynamic therapeutic field. perforations, hepatobiliary abnormalities and changes in ► The data provided here may serve to further our un- laboratory parameters were rare. Reductions in RA signs derstanding of different modes of action in RA. and symptoms and improvements in physical function were maintained throughout the LTE. © Author(s) (or their Conclusions The safety profile of sirukumab in the TEL employer(s)) 2021. Re- use remained consistent with that reported in SIRROUND- D includes disease- modifying antirheumatic permitted under CC BY- NC. No and SIRROUND- T and efficacy was maintained. drugs (DMARDs), to which many patients do commercial re- use. See rights Trial registration number NCT01856309. 1 and permissions. Published not respond or become intolerant. There- by BMJ. fore, compounds specifically involved in syno- For numbered affiliations see vial inflammation such as tumour necrosis end of article. factor (TNF) and other proinflammatory INTRODUCTION pathway targets have been examined. Correspondence to Professor Daniel Aletaha; Rheumatoid arthritis (RA) is a chronic condi- Interleukin (IL)-6 is a pleiotropic cyto- daniel. aletaha@ meduniwien. tion associated with high rates of pain, disa- kine with proinflammatory functions, which ac. at bility and comorbidity.1 Traditional treatment include differentiation of B and helper T Aletaha D, et al. RMD Open 2021;7:e001465. doi:10.1136/rmdopen-2020-001465 1 RMD Open RMD Open: first published as 10.1136/rmdopen-2020-001465 on 1 February 2021. Downloaded from cells, and is involved in maintaining chronic inflamma- anti- TNF agents or other biologics for RA within the past tion in RA.2 Increased levels of IL-6, IL-1 and TNF have 3 months. been observed in synovial fluid and serum in patients with RA.3 4 Treatments Sirukumab is a human monoclonal antibody directed In SIRROUND- D and SIRROUND- T, patients were against the IL-6 cytokine that inhibits IL-6- mediated randomised 1:1:1 to sirukumab 50 mg every 4 weeks signal transduction.5 6 In two phase III, randomised, (q4w), sirukumab 100 mg every 2 weeks (q2w) or placebo double- blind, placebo- controlled, multicenter studies, delivered subcutaneously (SC). Patients in the placebo sirukumab reduced signs and symptoms of RA, improved group were rerandomised at week 18 (early escape), physical function and health status and inhibited radio- week 24 (crossover in SIRROUND-T only), week 40 (late graphic progression in patients with moderately to escape in SIRROUND-D) or at the crossover at week 52 severely active RA refractory to DMARDs (through 104 (SIRROUND- D only).6 8 Eligible patients from primary weeks; SIRROUND- D)6 7 or anti-TNF agents (through 52 studies remained on their blinded treatment, either weeks; SIRROUND- T).8 In SIRROUND- D, where radio- sirukumab 100 mg SC q2w or sirukumab 50 mg SC q4w graphic progression was examined, sirukumab also inhib- (with q4w placebo injections in between). Treatments ited radiographic progression.6 7 were blinded until: (1) week 52 database lock occurred Since the sirukumab development programme was in SIRROUND- D, (2) week 24 database lock occurred not further pursued based on a strategic decision by the in SIRROUND- T and (3) the last autoinjector usability sponsor, data from these studies and their extension will substudy patient completed week 16 or was terminated likely be the only evidence for long-term efficacy and from the study. Patients in the LTE study randomised in safety of an IL-6 cytokine inhibitor. The primary objective SIRROUND- D remained blinded until all three condi- of this study therefore was to assess and make available the tions occurred. Thereafter, the LTE became open-label; long- term safety of sirukumab in patients with active RA placebo injections were discontinued in the sirukumab refractory or intolerant to DMARDs or anti- TNF agents. 50 mg SC treatment group. Patients treated with siru- kumab 100 mg q2w were offered the option to reduce the dose to 50 mg q4w during the open-label period, after METHODS discussion with their treating rheumatologist. Adverse Study design events (AEs) occurring after patients had switched from This was a multicenter, parallel-group, long- term exten- the 100 mg q2w to the 50 mg q4w group were attributed sion (LTE) study of the SIRROUND- D and SIRROUND- T to the 100 mg q2w group. studies monitoring safety and efficacy of patients with The maximum duration of participation in this study moderately to severely active RA. The full methods and was to be 208 weeks of treatment, followed by approx- results of these studies have been published.6–8 Prior to imately 16 weeks of safety and efficacy follow- up after http://rmdopen.bmj.com/ early study termination, the original intention was to the administration of the final injection of sirukumab. follow enrolled patients for 208 weeks. This study also However, due to the sponsor’s decision to discontinue included a substudy to assess usability of the SmartJect the sirukumab RA programme, the LTE was terminated prefilled syringe autoinjector. early. Patients were scheduled for a final safety follow- up visit at study termination (31 December 2017). Patients For inclusion in this study, patients completed the Evaluations final study agent administrations from the primary Safety was based on reported AEs, clinical laboratory on September 29, 2021 by guest. Protected copyright. studies (week 104 in SIRROUND-D and week 52 in tests, vital sign measurements and physical examina- SIRROUND- T) and provided informed consent. Patients tions. An independent review committee assessed cases were excluded if they had active diverticulitis or any of major adverse cardiovascular events (MACE), and condition that would compromise the well-being of the an independent gastroenterologist reviewed potential patient or preclude protocol- specified assessments. gastrointestinal perforation events. Documentation of For enrolment in SIRROUND- D and SIRROUND- T, events was subject based and not event based. Therefore, patients were ≥18 years of age with moderately to severely the main presentation of AEs is as per cent of subjects active RA.6 8 For SIRROUND-D, patients were refrac- with event from enrolment in the LTE to last observation. tory to single- agent or combination DMARD therapy, However, to put the observed number of subjects with including methotrexate or sulfasalazine, due to lack AEs in context and to allow comparison to other IL6- of benefit after ≥12 weeks as assessed by the treating targeted compounds, we also calculated incidence rates physician. For SIRROUND- T, patients were refrac- per 100 patient- years (PY) for key treatment- emergent tory to previous anti-TNF agents due to an absence of adverse event (TEAE) using the overall exposure time of benefit with ≥1 anti- TNF or documented intolerance to each subject (ie, from first dose to last observation or first 1 anti- TNF.
Load more

Recommended publications
  • (COVID-19) in the Era of Cardiac Vigilance: a Systematic Review
    Journal of Clinical Medicine Review Repurposing Immunomodulatory Therapies against Coronavirus Disease 2019 (COVID-19) in the Era of Cardiac Vigilance: A Systematic Review Courtney M. Campbell 1,* , Avirup Guha 2 , Tamanna Haque 3, Tomas G. Neilan 4 and Daniel Addison 1,5 1 Cardio-Oncology Program, Division of Cardiology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, OH 43210, USA; [email protected] 2 Harrington Heart and Vascular Institute, Case Western Reserve University, Cleveland, OH 44106, USA; [email protected] 3 Division of Hematology/Oncology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, OH 43210, USA; [email protected] 4 Cardio-Oncology Program, Division of Cardiology, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA 02144, USA; [email protected] 5 Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43210, USA * Correspondence: [email protected] Received: 23 July 2020; Accepted: 8 September 2020; Published: 11 September 2020 Abstract: The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in efforts to identify therapies to ameliorate adverse clinical outcomes. The recognition of the key role for increased inflammation in COVID-19 has led to a proliferation of clinical trials targeting inflammation. The purpose of this review is to characterize the current state of immunotherapy trials in COVID-19, and focuses on associated cardiotoxicities, given the importance of pharmacovigilance. The search terms related to COVID-19 were queried in ClinicalTrials.gov. A total of 1621 trials were identified and screened for interventional trials directed at inflammation.
    [Show full text]
  • As a Group, Anti- Inflammatories Will
    THERAPEUTIC FOCUS Sandoz’s Zarxio in March opened the door The inflammatory disease space exalts the for an established regulatory pathway here. approval of moderate-to-severe plaque Zarxio is biosimilar to Amgen’s neutrope- psoriasis treatment Cosentyx (secukinu- nia drug Neupogen (filgrastim), originally mab). “This is the first drug in the last 10 licensed in 1991. years with published studies showing clear According to Lindqvist, the US entry of superiority to the current standard of treat- biosimilars will dent the sales of a number ment,” observes Marcin Ernst, MD, VP of of individual branded biologic franchises, clinical development at INC Research (see Autoimmune but the impact is likely to pale in compari- “Clinical Corner,” p. 52). son to the generic competition for “white Eli Lilly’s ixekizumab and AstraZeneca/ pill” small-molecule drugs. Looking ahead, “As a group, anti- Amgen’s brodalumab, both of which target Biosimilars are threatening to chip away at established blockbusters. Industry giants are N+1 Singer analysts believe the biolog- inflammatories will the IL-17A cytokine, are expected to elbow battling to devise better therapies for celiac, Crohn’s and lupus even as they work around ics market will reach about $300 billion in their way into the picture. Both companies annual global sales by 2020, including about continue to top the plan regulatory submissions for psoriasis the clock to protect their turf in RA and psoriasis. Welcome to the autoimmune category— $50 billion from biosimilars. best-selling drug list. this year. in which, Rebecca Mayer Knutsen explains, there’s never a dull moment But the regulatory pathway for biosimilars These drugs are high- A few companies are jockeying to bring is murky, Buthusiem says.
    [Show full text]
  • Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis
    REVIEW published: 09 July 2021 doi: 10.3389/fimmu.2021.686155 Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis † † Jie Huang 1 , Xuekun Fu 1 , Xinxin Chen 1, Zheng Li 1, Yuhong Huang 1 and Chao Liang 1,2* 1 Department of Biology, Southern University of Science and Technology, Shenzhen, China, 2 Institute of Integrated Bioinfomedicine and Translational Science (IBTS), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both Edited by: existing and emerging targets, including the proteins, small molecular metabolites, and Trine N. Jorgensen, epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that Case Western Reserve University, result in inflammation and the development of new drugs for blocking the various United States modulators in RA. Reviewed by: Åsa Andersson, Keywords: rheumatoid arthritis, targets, proteins, small molecular metabolites, epigenetic regulators Halmstad University, Sweden Abdurrahman Tufan, Gazi University, Turkey *Correspondence: INTRODUCTION Chao Liang [email protected] Rheumatoid arthritis (RA) is classified as a systemic poly-articular chronic autoimmune joint † disease that primarily affects hands and feet.
    [Show full text]
  • Tables-Of-Phase-3-Mabs.Pdf
    Table 3. Monoclonal antibodies in Phase 2/3 or 3 clinical studies for cancer indications Most advanced Primary sponsoring company INN or code name Molecular format Target(s) phase Phase 3 indications Therapeutic area Janssen Research & Development, LLC JNJ-56022473 Humanized mAb CD123 Phase 2/3 Acute myeloid leukemia Cancer Murine IgG1, Actinium Pharmaceuticals Iomab-B radiolabeled CD45 Phase 3 Acute myeloid leukemia Cancer Humanized IgG1, Seattle Genetics Vadastuximab talirine ADC CD33 Phase 3 Acute myeloid leukemia Cancer TG Therapeutics Ublituximab Chimeric IgG1 CD20 Phase 3 Chronic lymphocytic leukemia Cancer Xencor XMAB-5574, MOR208 Humanized IgG1 CD19 Phase 2/3 Diffuse large B-cell lymphoma Cancer Moxetumomab Murine IgG1 dsFv, AstraZeneca/MedImmune LLC pasudotox immunotoxin CD22 Phase 3 Hairy cell leukemia Cancer Humanized scFv, Viventia Bio Oportuzumab monatox immunotoxin EpCAM Phase 3 Bladder cancer Cancer scFv-targeted liposome containing Merrimack Pharmaceuticals MM-302 doxorubicin HER2 Phase 2/3 Breast cancer Cancer MacroGenics Margetuximab Chimeric IgG1 HER2 Phase 3 Breast cancer Cancer Gastric cancer or gastroesophageal junction Gilead Sciences GS-5745 Humanized IgG4 MMP9 Phase 3 adenocarcinoma; ulcerative colitis (Phase 2/3) Cancer; Immune-mediated disorders Depatuxizumab Humanized IgG1, AbbVie mafodotin ADC EGFR Phase 2/3 Glioblastoma Cancer AstraZeneca/MedImmune LLC Tremelimumab Human IgG2 CTLA4 Phase 3 NSCLC, head & neck cancer, bladder cancer Cancer NSCLC, head & neck cancer, bladder cancer, breast AstraZeneca/MedImmune
    [Show full text]
  • The Two Tontti Tudiul Lui Hi Ha Unit
    THETWO TONTTI USTUDIUL 20170267753A1 LUI HI HA UNIT ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2017 /0267753 A1 Ehrenpreis (43 ) Pub . Date : Sep . 21 , 2017 ( 54 ) COMBINATION THERAPY FOR (52 ) U .S . CI. CO - ADMINISTRATION OF MONOCLONAL CPC .. .. CO7K 16 / 241 ( 2013 .01 ) ; A61K 39 / 3955 ANTIBODIES ( 2013 .01 ) ; A61K 31 /4706 ( 2013 .01 ) ; A61K 31 / 165 ( 2013 .01 ) ; CO7K 2317 /21 (2013 . 01 ) ; (71 ) Applicant: Eli D Ehrenpreis , Skokie , IL (US ) CO7K 2317/ 24 ( 2013. 01 ) ; A61K 2039/ 505 ( 2013 .01 ) (72 ) Inventor : Eli D Ehrenpreis, Skokie , IL (US ) (57 ) ABSTRACT Disclosed are methods for enhancing the efficacy of mono (21 ) Appl. No. : 15 /605 ,212 clonal antibody therapy , which entails co - administering a therapeutic monoclonal antibody , or a functional fragment (22 ) Filed : May 25 , 2017 thereof, and an effective amount of colchicine or hydroxy chloroquine , or a combination thereof, to a patient in need Related U . S . Application Data thereof . Also disclosed are methods of prolonging or increasing the time a monoclonal antibody remains in the (63 ) Continuation - in - part of application No . 14 / 947 , 193 , circulation of a patient, which entails co - administering a filed on Nov. 20 , 2015 . therapeutic monoclonal antibody , or a functional fragment ( 60 ) Provisional application No . 62/ 082, 682 , filed on Nov . of the monoclonal antibody , and an effective amount of 21 , 2014 . colchicine or hydroxychloroquine , or a combination thereof, to a patient in need thereof, wherein the time themonoclonal antibody remains in the circulation ( e . g . , blood serum ) of the Publication Classification patient is increased relative to the same regimen of admin (51 ) Int .
    [Show full text]
  • Plivensia, INN-Sirukumab
    14 September 2017 EMA/CHMP/576037/2017 Committee for Medicinal Products for Human Use (CHMP) Withdrawal assessment report Plivensia International non-proprietary name: sirukumab Procedure No. EMEA/H/C/004165/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Recommendation ..................................................................................... 5 2. Executive summary ................................................................................. 6 2.1. Problem statement ............................................................................................... 6 2.1.1. Disease or condition ........................................................................................... 6 2.1.2. Epidemiology .................................................................................................... 6 2.1.3. Biologic features; aetiology and pathogenesis ....................................................... 6 2.1.4. Clinical presentation, diagnosis and prognosis ....................................................... 6 2.1.5. Management ....................................................................................................
    [Show full text]
  • (INN) for Biological and Biotechnological Substances
    INN Working Document 05.179 Update 2013 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) INN Working Document 05.179 Distr.: GENERAL ENGLISH ONLY 2013 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) International Nonproprietary Names (INN) Programme Technologies Standards and Norms (TSN) Regulation of Medicines and other Health Technologies (RHT) Essential Medicines and Health Products (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) © World Health Organization 2013 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int ) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected] ). Requests for permission to reproduce or translate WHO publications – whether for sale or for non-commercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html ). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]
  • 13-400 Phrma Stateclinicaltrials MN 120913.Indd
    Research in Your Backyard Developing Cures, Creating Jobs PHARMACEUTICAL CLINICAL TRIALS IN Dots show locations of clinical trials in the state. MINNESOTA Executive Summary Clinical Trials in Minnesota “ Advancements in medicine would not be • Biopharmaceutical research companies have possible without individuals willing to volunteer conducted more than 2,900 clinical trials of new their time to participate in clinical studies. medicines since 1999 in collaboration with the The Minnesota Clinical Research Association state’s local research institutions, including the Clinical Research Institute in Minneapolis and (MCRA) is a collaboration of Minnesota based Plymouth, Twin Cities Clinical Research/ research institutions and professionals who are Prism Clinical Research in Brooklyn Center, committed to objectively informing the general Prism Clinical Research in St. Paul, MAPS public to the benefits and risks involved in Applied Research Center in Edina, Minnesota clinical research far beyond international and Diet Research Center/Frestedt Inc. in St. Louis domestic regulations. MCRA members believe Park, Mercy Hospital in Coon Rapids, St. Mary’s that a fully informed participant is critical to Duluth Clinic in Duluth, St. Cloud Hospital in successful clinical research outcomes.” St. Cloud, St. Paul’s Heart Clinic in St. Paul, the — Jeff Cosgrove, President University of Minnesota School of Medicine in Prism Clinical Research Minneapolis and the Mayo Clinic in Rochester. • The trials have been aimed at a wide array of diseases and medical conditions, ranging from • MCRA provides important clinical research the most debilitating chronic diseases, including education at a time when it is a challenge for cancer, pain, heart disease, obesity and diabetes, to biopharmaceutical and device companies and bothersome allergies, sinusitis, chronic obstructive local research collaborators to recruit volunteers, pulmonary disease (COPD), migraine headaches, and patients often don’t know about trials of pneumonia and rare diseases affecting small new drugs.
    [Show full text]
  • WO 2018/234879 Al 27 December 2018 (27.12.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/234879 Al 27 December 2018 (27.12.2018) W !P O PCT (51) International Patent Classification: c/o Novartis Pharmaceuticals Corporation, One Health C07K 16/24 (2006.01) A61K 39/00 (2006.01) Plaza, East Hanover, New Jersey 07936 (US). THUREN, Tom; c/o Novartis Pharmaceuticals Corporation, One (21) International Application Number: Health Plaza, East Hanover, New Jersey 07936 (US). R - PCT/IB20 18/053096 KER, Paul; c/o The Brigham and Women's Hospital, 75 (22) International Filing Date: Francis Street, Boston, Massachusetts 021 15 (US). LIB- 03 May 2018 (03.05.2018) BY, Peter; c/o The Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 021 15 (US). OT- (25) Filing Language: English TEWELL, Penelope; c/o The Medical School, Beech Hill (26) Publication Langi English Road, Sheffield South Yorkshire S10 2RX (GB). LAU, Yi Yang; c/o Novartis Pharmaceuticals Corporation, One (30) Priority Data: Health Plaza, East Hanover, New Jersey 07936 (US). 62/523,458 22 June 2017 (22.06.2017) US DUGAN, Margaret; c/o Novartis Pharmaceuticals Corpo 62/529,5 15 07 July 2017 (07.07.2017) US ration, One Health Plaza, East Hanover, New Jersey 07936 62/550,307 25 August 2017 (25.08.2017) US (US). 62/550,325 25 August 2017 (25.08.2017) US 62/596,054 07 December 20 17 (07. 12.20 17) US (81) Designated States (unless otherwise indicated, for every 62/649,63 1 29 March 2018 (29.03.2018) US kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (71) Applicant: NOVARTIS AG [CH/CH]; Lichtstrasse 35, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 4056 Basel (CH).
    [Show full text]
  • Biologicals in Rheumatoid Arthritis: Current and Future
    Rheumatoid arthritis RMD Open: first published as 10.1136/rmdopen-2015-000127 on 5 August 2015. Downloaded from REVIEW Biologicals in rheumatoid arthritis: current and future Ali Berkant Avci,1 Eugen Feist,2 Gerd-R Burmester2 To cite: Avci AB, Feist E, ABSTRACT Key messages Burmester G-R. Biologicals in The aim of the review is to highlight the current rheumatoid arthritis: current knowledge about established and new biologicals and ▸ and future. RMD Open Biological disease-modifying antirheumatic to summarise recent advances by focusing on 2015;1:e000127. drugs (DMARDs) have translated the knowledge doi:10.1136/rmdopen-2015- comparative efficacy, safety and possible on molecular pathways into targeted therapies 000127 discontinuation of treatment in patients with and are increasingly used in patients with rheumatoid arthritis (RA). Up to now, comparative rheumatoid arthritis (RA) with excellent efficacy analyses showed only minor differences with respect to ▸ Prepublication history for and acceptable safety. efficacy and safety among the established biologicals. this paper is available online. ▸ Head-to-head studies confirm comparable effi- To view these files please Studies confirmed the excellent drug retention rate as cacy of different biological DMARDs in RA treat- visit the journal online well as efficacy and safety of approved biologicals ment, however, with respect to adalimumab (http://dx.doi.org/10.1136/ including their use in monotherapy. Tapering and in monotherapy the results are favourable for rmdopen-2015-000127). some instances discontinuation of biologicals is tocilizumab. possible in disease remission. In case of relapse, ▸ Discontinuation studies show that patients with Received 24 May 2015 patients usually show full response after reintroduction RA in sustained remission can successfully Revised 16 July 2015 of the same compound.
    [Show full text]
  • Radiographic Progression in Clinical Trials in Rheumatoid Arthritis: a Systemic Literature Review of Trials Performed by Industry
    Rheumatoid arthritis RMD Open: first published as 10.1136/rmdopen-2020-001277 on 15 July 2020. Downloaded from ORIGINAL RESEARCH Radiographic progression in clinical trials in rheumatoid arthritis: a systemic literature review of trials performed by industry Yune-Jung Park ,1,2 Ana Maria Gherghe,3 Desirée van der Heijde 4 To cite: Park Y-J, Gherghe AM, ABSTRACT van der Heijde D. Radiographic Objectives To summarise radiographic data in Key messages progression in clinical trials in randomised controlled trials (RCTs) as part of the rheumatoid arthritis: a systemic radiographic inhibition claim of disease-modifying What is already known about this subject? literature review of trials ► Radiographic progression has been an important antirheumatic drugs (DMARDs) approved for patients with performed by industry. RMD outcome assessment in rheumatoid arthritis rheumatoid arthritis (RA). Open 2020;6:e001277. randomised controlled trials (RCTs). doi:10.1136/rmdopen-2020- Methods A systemic literature review was performed 001277 using the Medline database from 1994 to February 2020. What does this study add? The results were grouped based on the scoring methods ► This is a systematic literature review of the available ► Additional material is (Sharp, Genant modification, van der Heijde modification) published online only. To view published information on demographic features, please visit the journal online and RA patient populations. radiographic scoring methods, statistical analyses (http://dx.doi.org/10.1136/rmdo Results One hundred sixty-eight publications were and detailed radiographic data. pen-2020-001277). selected. After detailed assessment, 52 RCTs (7 methotrexate (MTX)-naive, 23 MTX inadequate response How might this impact on clinical practice? Received 24 April 2020 (IR), 9 DMARDs IR and 3 tumour necrosis factor-alpha ► This systematic literature review will help the design Revised 28 May 2020 inhibitors (TNFi) IR studies) were finally included.
    [Show full text]
  • INN Working Document 05.179 Update 2011
    INN Working Document 05.179 Update 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) INN Working Document 05.179 Distr.: GENERAL ENGLISH ONLY 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Essential Medicines and Pharmaceutical Policies (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) © World Health Organization 2011 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]