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In this article, we review the mechanism of anti-IL-6 in the treatment of RA, provide the key efficacy Via Krishan Maggon 
Krishan Maggon 's curator insight,
April 29, 2015 5:08 AM
IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and futureGW Kim, NR Lee, RH Pi, YS Lim, YM Lee… - Archives of pharmacal …, 2015 - Springer...
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The safety and efficacy profiles in clinical trials of olokizumab, sarilumab and sirukumab are similar and are consistent with those observed in RA patients treated with tocilizumab. Furthermore, the clinical efficacy of these IL-6 inhibitors is similar to that of TNF inhibitors in patients with MTX-IR and TNF-IR. Screening of biomarkers or genetics in each RA patient, for instance, baseline serum levels of TNF and/or soluble IL-6R, may help to predict the efficacy of each drug and to select patients for cytokine-oriented targeted therapies.33 However, better strategies are warranted for selecting and identifying appropriate patients earlier once bDMARDs targeting IL-6 are launched in the near future. We also need to determine whether there are important differences between the many IL-6 inhibitors and which are suitable for particular patients, otherwise companies may waste time and money in development. Via Krishan Maggon
Krishan Maggon 's curator insight,
August 8, 2014 7:03 PM
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RA patients not responding to TNF inhibitors benefit from treatment with IL6 targeting mabs and show regression of RA disease.
Ann Rheum Dis 2014;73:1595-1597 doi:10.1136/annrheumdis-2013-205002 EditorialIL-6 targeting compared to TNF targeting in rheumatoid arthritis: studies of olokizumab, sarilumab and sirukumabYoshiya Tanaka1, Emilio Martin Mola2+Author Affiliations 1The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan2Servicio de Reumatología, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Paseo de la Castellana 261, Madrid, SpainCorrespondence toProfessor Yoshiya Tanaka, The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi, Kitakyushu 807-8555, Japan; tanaka@med.uoeh-u.ac.jpReceived 31 January 2014Revised 23 April 2014Accepted 1 May 2014Published Online First 15 May 2014 |
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Abstract Objectives To evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA). Methods In this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200 mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed. Results The proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150 mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors. Conclusions Sarilumab improved signs and symptoms of RA over 12 weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III. Via Krishan Maggon
Krishan Maggon 's curator insight,
August 8, 2014 9:51 PM
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Ann Rheum Dis 2014;73:1626-1634 doi:10.1136/annrheumdis-2013-204405 Clinical and epidemiological researchExtended reportSarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trialTom W J Huizinga1, Roy M Fleischmann2, Martine Jasson3, Allen R Radin4,Janet van Adelsberg4, Stefano Fiore5, Xiaohong Huang5, George D Yancopoulos4,Neil Stahl4, Mark C Genovese6+Author Affiliations 1Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands2Division of Rheumatology, Department of Medicine, University of Texas Southwestern Medical Center and Metroplex Clinical Research Center, Dallas, Texas, USA3Department of Research and Development, Sanofi, Paris, France4Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA5Department of Research and Development, Sanofi, Bridgewater, New Jersey, USA6Department of Immunology and Rheumatology, Stanford University Medical Center, Palo Alto, California, USACorrespondence toDr TWJ Huizinga, Chairman, Department of Rheumatology, C1-41 Leiden University Medical Center, Albinusdreef 2, PO Box 9600, Leiden 2300RC, The Netherlands;T.W.J.Huizinga@lumc.nlReceived 6 August 2013Revised 23 October 2013Accepted 24 October 2013Published Online First 2 December 2013 |
