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Spinal Diseases: HELP
Articles by Iain B. McInnes
Based on 56 articles published since 2009
(Why 56 articles?)
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Between 2009 and 2019, I. McInnes wrote the following 56 articles about Spinal Diseases.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. 2018

Smolen, Josef S / Schöls, Monika / Braun, Jürgen / Dougados, Maxime / FitzGerald, Oliver / Gladman, Dafna D / Kavanaugh, Arthur / Landewé, Robert / Mease, Philip / Sieper, Joachim / Stamm, Tanja / Wit, Maarten de / Aletaha, Daniel / Baraliakos, Xenofon / Betteridge, Neil / Bosch, Filip van den / Coates, Laura C / Emery, Paul / Gensler, Lianne S / Gossec, Laure / Helliwell, Philip / Jongkees, Merryn / Kvien, Tore K / Inman, Robert D / McInnes, Iain B / Maccarone, Mara / Machado, Pedro M / Molto, Anna / Ogdie, Alexis / Poddubnyy, Denis / Ritchlin, Christopher / Rudwaleit, Martin / Tanew, Adrian / Thio, Bing / Veale, Douglas / Vlam, Kurt de / van der Heijde, Désirée. ·Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · Health Consult, Vienna, Austria. · Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany. · Department of Rheumatology, Paris Descartes University, Paris, France. · Department of Rheumatology, St Vincent's University Hospital, Dublin, Ireland. · Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada. · Division of Rheumatology, University of California, San Diego, CA, USA. · Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands. · Division of Rheumatology Research, Swedish-Providence St. Joseph Health System, University of Washington, Seattle, WA, USA. · Department of Gastroenterology, Infectiology and Rheumatology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany. · Section for Outcomes Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. · Department of Medical Humanities, VU University Medical Centre, Amsterdam, The Netherlands. · Neil Betteridge Associates, UK. · Ghent University Hospital, Ghent, Belgium. · Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK. · Department of Medicine, University of California, San Francisco, CA, USA. · Department of Rheumatology, UPMC Univ Paris 06, GRC-UPMC 08 (EEMOIS); AP-HP, Pitié Salpêtrière Hospital, Paris, France. · Institute of Molecular Medicine, University of Leeds, Leeds, UK. · Seayn Medical, Voorschoten, The Netherlands. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · University Health Network and University of Toronto, Toronto, Ontario, Canada. · University of Glasgow, College of Medical Veterinary and Life Sciences, Glasgow, UK. · A.DI.PSO. (Associazione per la Difesa degli Psoriasici)-PE.Pso.POF (Pan European Psoriasis Patients' Organization Forum), Rome, Italy. · Centre for Rheumatology & MRC Centre for Neuromuscular Diseases, University College London, London, UK. · Division of Rheumatology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, USA. · German Rheumatism Research Centrer, Berlin, Germany. · Allergy, Immunology and Rheumatology Division, University of Rochester Medical Center Rochester, New York, NY, USA. · Division of Internal Medicine and Rheumatology, Klinikum Bielefeld, Bielefeld, Germany. · Department of Dermatology, Medical University of Vienna, Vienna, Austria. · Department of Dermatology, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands. · Department of Rheumatology, Klinikum Bielefeld, Bielefeld, Germany. · Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. ·Ann Rheum Dis · Pubmed #28684559.

ABSTRACT: Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field.

2 Guideline EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. 2017

Agca, R / Heslinga, S C / Rollefstad, S / Heslinga, M / McInnes, I B / Peters, M J L / Kvien, T K / Dougados, M / Radner, H / Atzeni, F / Primdahl, J / Södergren, A / Wallberg Jonsson, S / van Rompay, J / Zabalan, C / Pedersen, T R / Jacobsson, L / de Vlam, K / Gonzalez-Gay, M A / Semb, A G / Kitas, G D / Smulders, Y M / Szekanecz, Z / Sattar, N / Symmons, D P M / Nurmohamed, M T. ·Departments of Rheumatology, Amsterdam Rheumatology and Immunology Center, Reade & VU University Medical Center, Amsterdam, The Netherlands. · Department of Rheumatology, Preventive Cardio-Rheuma Clinic, Diakonhjemmet Hospital, Oslo, Norway. · College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. · Internal and Vascular Medicine, VU University Medical Center, Amsterdam, The Netherlands. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Department of Rheumatology, Paris Descartes University, Hôpital Cochin. Assistance Publique, Hôpitaux de Paris INSERM (U1153): Clinical epidemiology and biostatistics, PRES Sorbonne Paris-Cité, Paris, France. · Department of Internal Medicine III, Division of Rheumatology, Medical University Vienna, Vienna, Austria. · IRCCS Galeazzi Orthopedic Institute, Milan, Italy. · Institute for Regional Health Research, University of Southern Denmark, Odense, Denmark. · Sygehus Sønderjylland (Hospital of Southern Jutland), Aabenraa, Denmark. · King Christian 10's Hospital for Rheumatic Diseases, Graasten, Denmark. · Department of Public Health and Clinical Medicine/Rheumatology, University of Umeå, Umeå, Sweden. · PARE (patient research partners), Sint-Joris-Weert, Belgium. · Romanian League Against Rheumatism (Vice-President) and Board Member (General Secretary) of AGORA, the Platform of S-E organisations for patients with RMDs, Bucharest, Romania. · Oslo University Hospital, Ullevål, Center for Preventive Medicine and Medical Faculty, University of Oslo, Oslo, Norway. · Department of Rheumatology & Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg and Section of Rheumatology, Lund, Sweden. · Department of Clinical Sciences Malmö, Lund University, Lund, Sweden. · Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · University of Cantabria, IDIVAL, Santander, Spain. · Head of Research and Development, Academic Affairs Dudley Group NHS Foundation Trust, Arthritis Research UK Centre for Epidemiology, University of Manchester, Russells Hall Hospital, Clinical Research Unit, Dudley, UK. · Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, University of Debrecen, Debrecen, Hungary. · Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK. · Department of Rheumatology and Musculoskeletal Epidemiology, Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK. · Department of Rheumatology Reade, Amsterdam Rheumatology and Immunology Center, Reade & VU University Medical Center, Amsterdam, The Netherlands. ·Ann Rheum Dis · Pubmed #27697765.

ABSTRACT: Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

3 Guideline European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. 2016

Gossec, L / Smolen, J S / Ramiro, S / de Wit, M / Cutolo, M / Dougados, M / Emery, P / Landewé, R / Oliver, S / Aletaha, D / Betteridge, N / Braun, J / Burmester, G / Cañete, J D / Damjanov, N / FitzGerald, O / Haglund, E / Helliwell, P / Kvien, T K / Lories, R / Luger, T / Maccarone, M / Marzo-Ortega, H / McGonagle, D / McInnes, I B / Olivieri, I / Pavelka, K / Schett, G / Sieper, J / van den Bosch, F / Veale, D J / Wollenhaupt, J / Zink, A / van der Heijde, D. ·Sorbonne Universités, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique, GRC-UPMC 08 (EEMOIS), Paris, France Department of rheumatology, AP-HP, Pitié Salpêtrière Hospital, Paris, France. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria Second Department of Medicine, Hietzing Hospital, Vienna, Austria. · Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands. · EULAR, representing People with Arthritis/Rheumatism in Europe (PARE), London, UK. · Research Laboratory and Clinical Division of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto, Italy. · Medicine Faculty, Paris Descartes University, Paris, France Rheumatology B Department, APHP, Cochin Hospital, Paris, France. · Leeds NIHR Musculoskeletal Biomedical Research Unit, LTHT, Leeds, UK Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK. · Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology Center, Amsterdam, The Netherlands Atrium Medical Center, Heerlen, The Netherlands. · North Devon, UK. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · Rheumazentrum Ruhrgebiet, Herne and Ruhr-Universität Bochum, Herne, Germany. · Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Germany. · Arthritis Unit, Department of Rheumatology, Hospital Clínic and IDIBAPS, Barcelona, Spain. · Belgrade University School of Medicine, Belgrade, Serbia. · Department of Rheumatology, St. Vincent's University Hospital and Conway Institute, University College Dublin, Dublin, Ireland. · Section of Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden Sweden and School of Business, Engineering and Science, Halmstad University, Halmstad, Sweden. · Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Belgium Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Department of Dermatology, University Hospital Münster, Münster, Germany. · A.DI.PSO. (Associazione per la Difesa degli Psoriasici)-PE.Pso.POF (Pan European Psoriasis Patients' Organization Forum), Rome, Italy. · Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. · Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Italy. · Institute and Clinic of Rheumatology Charles University Prague, Czech Republic. · Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany. · Department of Rheumatology, Campus Benjamin Franklin, Charité, Berlin, Germany. · Ghent University Hospital, Ghent, Belgium. · Centre for Arthritis and Rheumatic Disease, Dublin Academic Medical Centre, St. Vincent's University Hospital, Dublin, Ireland. · Schoen Klinik Hamburg, Rheumatology and Clinical Immunology, Hamburg, Germany. · Department of Rheumatology and Clinical Immunology, German Rheumatism Research Centre Berlin, Charité-University Medicine Berlin, Germany. ·Ann Rheum Dis · Pubmed #26644232.

ABSTRACT: BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

4 Guideline The 2012 BSR and BHPR guideline for the treatment of psoriatic arthritis with biologics. 2013

Coates, Laura C / Tillett, William / Chandler, David / Helliwell, Philip S / Korendowych, Eleanor / Kyle, Stuart / McInnes, Iain B / Oliver, Susan / Ormerod, Anthony / Smith, Catherine / Symmons, Deborah / Waldron, Nicola / McHugh, Neil J / Anonymous440765. ·Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK. neil.mchugh@rnhrd.nhs.uk. ·Rheumatology (Oxford) · Pubmed #23887065.

ABSTRACT: -- No abstract --

5 Guideline European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. 2012

Gossec, L / Smolen, J S / Gaujoux-Viala, C / Ash, Z / Marzo-Ortega, H / van der Heijde, D / FitzGerald, O / Aletaha, D / Balint, P / Boumpas, D / Braun, J / Breedveld, F C / Burmester, G / Cañete, J D / de Wit, M / Dagfinrud, H / de Vlam, K / Dougados, M / Helliwell, P / Kavanaugh, A / Kvien, T K / Landewé, R / Luger, T / Maccarone, M / McGonagle, D / McHugh, N / McInnes, I B / Ritchlin, C / Sieper, J / Tak, P P / Valesini, G / Vencovsky, J / Winthrop, K L / Zink, A / Emery, P / Anonymous2420706. ·Paris Descartes University, Paris, France. laure.gossec@cch.aphp.fr ·Ann Rheum Dis · Pubmed #21953336.

ABSTRACT: BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.

6 Guideline EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. 2010

Peters, M J L / Symmons, D P M / McCarey, D / Dijkmans, B A C / Nicola, P / Kvien, T K / McInnes, I B / Haentzschel, H / Gonzalez-Gay, M A / Provan, S / Semb, A / Sidiropoulos, P / Kitas, G / Smulders, Y M / Soubrier, M / Szekanecz, Z / Sattar, N / Nurmohamed, M T. ·Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands. ·Ann Rheum Dis · Pubmed #19773290.

ABSTRACT: OBJECTIVES: To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR's "standardised operating procedures", the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis. RESULTS: Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk. CONCLUSIONS: Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.

7 Editorial Psoriasis, psoriatic arthritis and cardiovascular risk: are we closer to a clinical recommendation? 2015

Kristensen, Søren Lund / McInnes, Iain B / Sattar, Naveed. ·BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK Department of Cardiology, Gentofte Hospital, Copenhagen, Denmark. · BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. ·Ann Rheum Dis · Pubmed #25429028.

ABSTRACT: -- No abstract --

8 Editorial Psoriatic arthritis - expanding options, exciting times? 2014

McInnes, Iain B / Siebert, Stefan. · ·Acta Reumatol Port · Pubmed #25584617.

ABSTRACT: -- No abstract --

9 Review Psoriatic arthritis: tissue-directed inflammation? 2018

Cafaro, Giacomo / McInnes, Iain B. ·Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy. giacomo.cafaro@libero.it. · Institute of Infection Immunity and Inflammation, College of MVLS, University of Glasgow, Glasgow, G128QQ, UK. ·Clin Rheumatol · Pubmed #29476352.

ABSTRACT: The clinical picture of psoriatic arthritis (PsA) is heterogeneous, potentially involving numerous organs and tissues, such as skin and joint. From a clinical point of view, discrete tissue PsA features develop and respond to treatments apparently independently. The pathogenic events occurring in the various tissues are only partially understood. Although the vast majority of known genetic predisposing factors are shared between patients with skin psoriasis (PSO) and those affected by PsA, some tissue-specific variants have been identified. Furthermore, current data suggest that the TNF pathway and IL-23/Th17 pathways may be differentially activated in distinct tissue sites. In this review, we briefly describe current knowledge on the pathogenesis of PsA in terms of genetic predisposition, environmental factors and immunology, advancing our hypothesis to explain why a common immunologic process can express itself with significant differences in various tissues.

10 Review Psoriatic arthritis: embracing pathogenetic and clinical heterogeneity? 2016

McInnes, Iain B. ·Institute of Infection Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, U.K. iain.mcinnes@glasgow.ac.uk. ·Clin Exp Rheumatol · Pubmed #27586796.

ABSTRACT: Psoriatic arthritis (PsA) is a clinically heterogeneous condition of skin, joint, enthesis and bone that provides considerable unmet therapeutic need. Recent treatment advances have offered new opportunities to improve quality of life and long term well being for afflicted patients. It is timely therefore, to consider the underlying heterogeneity inherent in the disease from a pathologic aspect so as to best optimise the choice and order of therapeutic application over time. Herein I will discuss the various contributions made by immune pathways to discrete tissue compartments that in turn might allow a more targeted approach to the management of PsA in which different tissues express variable severity of involvement.

11 Review Therapeutic Targeting of IL-17 and IL-23 Cytokines in Immune-Mediated Diseases. 2016

Fragoulis, George E / Siebert, Stefan / McInnes, Iain B. ·Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8QQ, United Kingdom; email: Iain.McInnes@glasgow.ac.uk , Stefan.Siebert@glasgow.ac.uk. ·Annu Rev Med · Pubmed #26565676.

ABSTRACT: The discovery of the biological functions of the interleukin-23/-17 axis led to the identification of IL-23 and IL-17 as important participants in the pathogenesis of several immune-mediated diseases. Therapeutic agents targeting these cytokines and/or their receptors have now been developed as potential treatment strategies for common immune-mediated diseases. Anti-IL-17 and anti-IL-12/-23 regimens appear particularly effective in psoriasis, with promising results in spondyloarthropathies also emerging. Overall, these agents appear well tolerated, with adverse-event rates that are commensurate with those in other biologic treatment programs. The strategic utility of these new agents, however, remains uncertain, and further studies will be required to determine their place in the context of existing conventional and biologic immune-modifying agents.

12 Review Interleukin-12 and interleukin-23 inhibition in psoriatic arthritis. 2015

Johnsson, Hanna J / McInnes, Iain B. ·Institute of Infection, Immunity and Inflammation, University of Glasgow, UK. hanna.johnsson@glasgow.ac.uk. · Institute of Infection, Immunity and Inflammation, University of Glasgow, UK. ·Clin Exp Rheumatol · Pubmed #26471946.

ABSTRACT: The cytokines interleukin (IL)-12 and interleukin (IL)-23 have been implicated variously in the pathogenesis of psoriasis and psoriatic arthritis (PsA). By corollary, the IL-12/23 inhibitor, Ustekinumab has been developed as an approved therapeutic for the skin and musculoskeletal syndrome of psoriasis / PsA. This review describes briefly the role of IL-12 and IL-23 in the pathophysiology of psoriatic arthritis and evaluates trial data that support its clinical use in psoriasis and different manifestations of psoriatic arthritis. The next steps towards targeting this pathway also are discussed.

13 Review Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases. 2015

Siebert, Stefan / Tsoukas, Alexander / Robertson, Jamie / McInnes, Iain. ·Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom (S.S., J.R., I.M.); and Division of Rheumatology, McGill University Health Centre, Montreal, Quebec, Canada (A.T.) stefan.siebert@glasgow.ac.uk. · Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom (S.S., J.R., I.M.); and Division of Rheumatology, McGill University Health Centre, Montreal, Quebec, Canada (A.T.). ·Pharmacol Rev · Pubmed #25697599.

ABSTRACT: The human immune system involves highly complex and coordinated processes in which small proteins named cytokines play a key role. Cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases. Cytokines are therefore attractive therapeutic targets in these conditions. Anticytokine therapy for inflammatory diseases became a clinical reality with the introduction of tumor necrosis factor (TNF) inhibitors for the treatment of severe rheumatoid arthritis. Although these therapies have transformed the treatment of patients with severe inflammatory arthritis, there remain significant limiting factors: treatment failure is commonly seen in the clinic; safety concerns remain; there is uncertainty regarding the relevance of immunogenicity; the absence of biomarkers to direct therapy decisions and high drug costs limit availability in some healthcare systems. In this article, we provide an overview of the key efficacy and safety trials for currently approved treatments in rheumatoid arthritis and review the major lessons learned from a decade of use in clinical practice, focusing mainly on anti-TNF and anti-interleukin (IL)-6 agents. We also describe the clinical application of anticytokine therapies for other inflammatory diseases, particularly within the spondyloarthritis spectrum, and highlight differential responses across diseases. Finally, we report on the current state of trials for newer therapeutic targets, focusing mainly on the IL-17 and IL-23 pathways.

14 Review The interleukin-17 pathway in psoriasis and psoriatic arthritis: disease pathogenesis and possibilities of treatment. 2014

Frleta, Marina / Siebert, Stefan / McInnes, Iain B. ·University of Glasgow, Glasgow, UK. ·Curr Rheumatol Rep · Pubmed #24570394.

ABSTRACT: Psoriasis and psoriatic arthritis (PsA) are pathophysiological enigmas among rheumatic diseases. Substantial clinical advances have been made with new therapy targeting different components of the IL-17 and IL-23 pathways. At the same time, an increase in research on the topic has provided new insights into the potential functional effects of treatments on cell types, pathways, and tissues of interest. Here we review our knowledge of all IL-17 family members, their relationships with the IL-23 pathway, and the outcomes of relevant clinical trials in which different strategies for targeting these molecules have been tested in the treatment of moderate to severe psoriasis and PsA.

15 Review Cardiovascular comorbidities in patients with psoriatic arthritis: a systematic review. 2013

Jamnitski, Anna / Symmons, Deborah / Peters, Mike J L / Sattar, Naveed / McInnes, Iain / Nurmohamed, Michael T. ·Department of Rheumatology, Jan van Breemen Research Institute/READE, Dr Jan van Breemenstraat 2, 1056 AB Amsterdam, The Netherlands. ·Ann Rheum Dis · Pubmed #22532629.

ABSTRACT: OBJECTIVE: Data regarding cardiovascular comorbidity and cardiovascular risk factors in patients with psoriatic arthritis (PsA) are limited. To evaluate the cardiovascular risk profile, a systematic literature search was performed to provide an extensive summary of all studies available on cardiovascular risk in PsA. METHODS: Medline, EMBASE and the Cochrane library were searched from January 1966 to April 2011 for English language articles on data concerning cardiovascular diseases and cardiovascular risk factors in PsA. Review articles, case reports and studies on psoriasis alone were excluded. RESULTS: Twenty-eight articles were included in this review. Studies on all-cause mortality revealed mixed results. Available data on cardiovascular disease appeared more consistent, indicating an increased cardiovascular mortality and morbidity in PsA. Commensurate with this, surrogate markers of subclinical atherosclerosis, arterial stiffness and cardiovascular risk factors, for example hypertension, dyslipidaemia, obesity and metabolic-related factors, were more prominent in PsA compared with controls. Suppression of inflammation was linked with a favourable effect on cardiovascular surrogate markers, for example carotid intima media thickness and endothelial dysfunction, in several (un)controlled studies. CONCLUSION: Most studies point towards an increased cardiovascular risk in PsA, broadly on a par with the risk level in rheumatoid arthritis, emphasising the need for similar cardiovascular risk management in both conditions. Further studies are needed to indicate whether inflammatory suppression or modification of traditional cardiovascular risk factors, or both, will reduce cardiovascular risk.

16 Review Cardiovascular and metabolic risks in psoriasis and psoriatic arthritis: pragmatic clinical management based on available evidence. 2012

Johnsson, Hanna / McInnes, Iain B / Sattar, Naveed. ·Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK. h.johnsson@doctors.org.uk ·Ann Rheum Dis · Pubmed #22294632.

ABSTRACT: Several studies suggest that patients with psoriasis and, in particular, psoriatic arthritis (PsA) are at increased risk of cardiovascular disease. These patients are also more likely to be obese and to have diabetes and fatty liver disease. This article discusses the association between psoriasis and PsA and cardiometabolic disorders, emphasising the need for better consideration of simple lifestyle interventions. It also highlights areas for future research and proposes a simple and pragmatic test portfolio to screen for cardiovascular risk and metabolic disorders in patients at higher risk.

17 Clinical Trial Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study. 2017

McInnes, Iain B / Mease, Philip J / Ritchlin, Christopher T / Rahman, Proton / Gottlieb, Alice B / Kirkham, Bruce / Kajekar, Radhika / Delicha, Eumorphia-Maria / Pricop, Luminita / Mpofu, Shephard. ·Institute of Infection Immunity and Inflammation, University of Glasgow, Glasgow, UK. · Division of Rheumatology Clinical Research, Swedish Medical Centre and University of Washington, Seattle, WA. · Allergy/Immunology and Rheumatology Division, University of Rochester, Rochester, NY, USA. · Faculty of Medicine, Memorial University, St. John's, NL, Canada. · Department of Dermatology, New York Medical College, Valhalla, NY, USA. · Rheumatology Department, Guy's & St Thomas' NHS Foundation Trust, London, UK. · Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. · Novartis Pharma, Basel, Switzerland. ·Rheumatology (Oxford) · Pubmed #28968735.

ABSTRACT: Objectives: To assess long-term efficacy, safety and tolerability of secukinumab up to 104 weeks in patients with active PsA. Methods: Patients with PsA (n = 397) were randomized to s.c. secukinumab 300, 150 or 75 mg or placebo at baseline, weeks 1, 2, 3 and 4 and every 4 weeks thereafter. Placebo-treated patients were re-randomized to receive secukinumab 300 or 150 mg s.c. from week 16 (placebo non-responders) or week 24 (placebo responders). Exploratory endpoints at week 104 included 20, 50 and 70% improvement in ACR criteria (ACR20, 50, 70); 75 and 90% improvement in the Psoriasis Area Severity Index, 28-joint DAS with CRP, presence of dactylitis and enthesitis and other patient-reported outcomes. For binary variables, missing values were imputed; continuous variables were analysed by a mixed-effects model for repeated measures. Results: A total of 86/100 (86%), 76/100 (76%) and 65/99 (66%) patients in the secukinumab 300, 150 and 75 mg groups, respectively, completed 104 weeks. At week 104, ACR20 response rates after multiple imputation in the 300, 150 and 75 mg groups were 69.4, 64.4 and 50.3%, respectively. Sustained clinical improvements were observed through week 104 with secukinumab across other clinically important domains of PsA. Responses were sustained through week 104 regardless of prior anti-TNF-α use. Over the entire treatment period the incidence, type and severity of adverse events were consistent with those reported previously. Conclusion: Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains in patients of active PsA through 2 years of therapy. Secukinumab was well tolerated, with a safety profile consistent with that reported previously. Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01752634.

18 Clinical Trial Ustekinumab Treatment and Improvement of Physical Function and Health-Related Quality of Life in Patients With Psoriatic Arthritis. 2016

Rahman, Proton / Puig, Lluis / Gottlieb, Alice B / Kavanaugh, Arthur / McInnes, Iain B / Ritchlin, Christopher / Li, Shu / Wang, Yuhua / Song, Michael / Mendelsohn, Alan / Han, Chenglong / Anonymous70877. ·Memorial University, Newfoundland, Canada. · Hospital de la Santa Creu i Sant Pau, Universitat Autònoa de Barcelona, Barcelona, Spain. · Tufts University School of Medicine, Boston, Massachusetts. · University of California, San Diego. · University of Glasgow, Glasgow, Scotland. · University of Rochester, Rochester, New York. · Janssen Research & Development, LLC, Spring House, Pennsylvania. · Janssen Global Services, LLC, Malvern, Pennsylvania. ·Arthritis Care Res (Hoboken) · Pubmed #27483458.

ABSTRACT: OBJECTIVE: To examine the effects of ustekinumab on patient-reported outcomes (PROs) in PSUMMIT 1 and PSUMMIT 2 patients with active psoriatic arthritis (PsA) who were methotrexate (MTX) naive, MTX experienced, or anti-tumor necrosis factor (TNF) experienced. METHODS: Patients in the phase 3, PSUMMIT 1 (n = 615) and PSUMMIT 2 (n = 312) studies randomly (1:1:1) received placebo, ustekinumab 45-mg, or ustekinumab 90-mg subcutaneous injections at weeks 0, 4, 16, 28, 40, and 52. The PROs (Health Assessment Questionnaire [HAQ] disability index [DI], Dermatology Life Quality Index [DLQI], 36-Item Short Form [SF-36] health survey physical (PCS) and mental component summary scores, patient assessments of pain and disease activity, and impact of disease on productivity) were assessed at weeks 0, 24, and 52. In these post hoc analyses, outcomes were compared between the ustekinumab and placebo groups for 3 mutually exclusive antecedent-exposure populations from the combined studies: MTX/anti-TNF naive (placebo, n = 56; 45 mg, n = 58; and 90 mg, n = 66), MTX experienced, biologic agent naive (placebo, n = 192; 45 mg, n = 190; and 90 mg, n = 185), and anti-TNF experienced with or without MTX (placebo, n = 62; 45 mg, n = 60; and 90 mg, n = 58). RESULTS: At week 24, mean improvements from baseline in HAQ DI, DLQI, and SF-36 PCS scores were significantly greater in both ustekinumab groups versus placebo across antecedent-exposure groups. Greater proportions of ustekinumab-treated than placebo-treated patients (all P < 0.05) had clinically meaningful improvements in HAQ DI (≥0.3), DLQI (≥5), and SF-36 (≥5) scores at week 24, irrespective of drug exposure. Improvements in pain, disease activity, and impact of disease on productivity were similar, and benefits were maintained through week 52. CONCLUSION: Significant improvements in PROs with ustekinumab versus placebo were observed in 3 antecedent-exposure populations of PsA patients, including those with prior MTX and anti-TNF use.

19 Clinical Trial Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2). 2016

Kavanaugh, Arthur / Puig, Lluis / Gottlieb, Alice B / Ritchlin, Christopher / You, Yin / Li, Shu / Song, Michael / Randazzo, Bruce / Rahman, Proton / McInnes, Iain B. ·Division of Rheumatology, Allergy, and Immunology, University of California-San Diego, La Jolla, California, USA. · Department of Dermatology, Hospital de la Santa Creu I Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain. · Department of Dermatology, Tufts Medical Center, Boston, Massachusetts, USA. · Department of Dermatology, University of Rochester, Rochester, New York, USA. · Department of Biostatistics, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA. · Department of Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA. · Department of Immunology, Janssen Research & Development, LLC, Spring House, Pennsylvania, USA University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Dermatology, Memorial University, St. Johns, Newfoundland, Canada. · College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. ·Ann Rheum Dis · Pubmed #27098404.

ABSTRACT: OBJECTIVE: To evaluate ustekinumab efficacy and safety in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (termed the 'spondylitis subset'). METHODS: Adults with active PsA (PSUMMIT-1/PSUMMIT-2, n=615/312) were randomised to ustekinumab 45 mg, 90 mg or placebo at week 0/week 4/q12 week. At week 16, patients with <5% improvement in tender and swollen joints entered blinded early escape. A subset of patients with physician-identified spondylitis was evaluated with spondylitis-specific assessments, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score employing C reactive protein (ASDAS-CRP), through week 24. RESULTS: 256/927 (27.6%) PSUMMIT-1/PSUMMIT-2 patients (placebo/ustekinumab, n=92/164) comprised the evaluable spondylitis subset. At week 24, in this analysis subset, significantly more patients achieved BASDAI20/50/70 responses (54.8%/29.3%/15.3% vs 32.9%/11.4%/0%; p≤0.002), improvement in BASDAI question 2 concerning axial pain (1.85 vs 0.24; p<0.001) and mean per cent ASDAS-CRP improvements (27.8% vs 3.9%; p<0.001) for ustekinumab versus placebo recipients, respectively. Comparable to the overall study population, significant improvements were also achieved in psoriasis, peripheral arthritis, enthesitis, dactylitis, physical function and peripheral joint radiographs in the spondylitis subset. CONCLUSIONS: In this post-hoc analysis of PsA patients with baseline peripheral arthritis and physician-reported spondylitis, ustekinumab-treated patients demonstrated significant improvements in axial signs and symptoms through week 24. TRIAL REGISTRATION NUMBER: PSUMMIT-1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT-2 (NCT01077362, EudraCT 2009-012265-60); post-study results.

20 Clinical Trial Brief Report: Secukinumab Provides Significant and Sustained Inhibition of Joint Structural Damage in a Phase III Study of Active Psoriatic Arthritis. 2016

van der Heijde, Désirée / Landewé, Robert B / Mease, Philip J / McInnes, Iain B / Conaghan, Philip G / Pricop, Luminita / Ligozio, Greg / Richards, Hanno B / Mpofu, Shephard. ·Leiden University Medical Centre, Leiden, The Netherlands. · Robert B. Landewé, MD: Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Swedish Medical Center and University of Washington, Seattle. · Institute of Infection, Immunity, and Inflammation, University of Glasgow, Glasgow, UK. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK. · Novartis Pharmaceuticals, East Hanover, New Jersey. · Novartis Pharma AG, Basel, Switzerland. ·Arthritis Rheumatol · Pubmed #27014997.

ABSTRACT: OBJECTIVE: To assess whether secukinumab treatment in patients with active psoriatic arthritis (PsA) is associated with sustained inhibition of radiographic progression. METHODS: In this phase III, double-blind, placebo-controlled study, 606 patients with PsA were randomized to receive intravenous (IV) secukinumab at a dose of 10 mg/kg (weeks 0, 2, 4) followed by subcutaneous secukinumab at a dose of 150 mg or 75 mg (the IV→150 mg and IV→75 mg groups, respectively) or placebo. Patients were stratified according to prior anti-tumor necrosis factor (anti-TNF) exposure (71% were anti-TNF naive). At week 16, placebo-treated patients who had at least a 20% reduction in the tender and swollen joint counts (responders) continued to receive placebo until week 24; nonresponders were re-randomized to receive secukinumab at a dose of 150 mg or 75 mg. The modified total Sharp/van der Heijde score (SHS) was determined at baseline, week 16 or 24, and week 52. RESULTS: In the overall population, radiographic progression was inhibited through 52 weeks; efficacy was demonstrated for both erosion and joint space narrowing scores and in patients who switched from placebo to secukinumab at week 24. Subgroup analyses showed that secukinumab reduced radiographic progression at week 24, regardless of previous anti-TNF treatment. Among anti-TNF-naive patients, the mean changes from baseline to week 24 in the modified total SHS were 0.05 in the pooled secukinumab group and 0.57 in the placebo group; among patients with an inadequate response or intolerance to anti-TNF treatment, the mean changes were 0.16 and 0.58, respectively. Anti-TNF-naive patients showed negligible progression through week 52. Inhibition of structural damage was observed through week 52 irrespective of concomitant methotrexate use. A high proportion of patients receiving secukinumab showed no progression (change in SHS of ≤ 0.5) from baseline to week 24 (82.3% of the IV→150 mg group and 92.3% of the IV→75 mg group) and from week 24 to week 52 (85.7% of the IV→150 mg group and 85.8% of the IV→75 mg group). CONCLUSION: Secukinumab inhibited radiographic progression over 52 weeks of treatment in patients with active PsA.

21 Clinical Trial Radiographic Progression of Patients With Psoriatic Arthritis Who Achieve Minimal Disease Activity in Response to Golimumab Therapy: Results Through 5 Years of a Randomized, Placebo-Controlled Study. 2016

Kavanaugh, Arthur / van der Heijde, Désirée / Beutler, Anna / Gladman, Dafna / Mease, Philip / Krueger, Gerald G / McInnes, Iain B / Helliwell, Philip / Coates, Laura C / Xu, Stephen. ·University of California, San Diego, La Jolla. · Leiden University Medical Center, Leiden, The Netherlands. · Janssen Research & Development, Spring House, Pennsylvania. · University of Toronto, Toronto, Ontario, Canada. · Swedish Medical Center, Seattle, Washington, and University of Washington, Seattle. · University of Utah, Salt Lake City. · University of Glasgow, Glasgow, UK. · Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK. ·Arthritis Care Res (Hoboken) · Pubmed #25779603.

ABSTRACT: OBJECTIVE: To evaluate long-term outcomes in psoriatic arthritis (PsA) patients who achieved or did not achieve minimal disease activity (MDA) through 5 years of golimumab treatment in the GO-REVEAL trial. METHODS: The GO-REVEAL trial was a phase III, randomized, double-blind trial with placebo-control through week 24 followed by an open-label extension of golimumab 50/100 mg treatment up to 5 years. In these post-hoc analyses, MDA was defined by the presence of ≥5 of 7 PsA outcome measures (≤1 swollen joint, ≤1 tender joint, Psoriasis Area and Severity Index [PASI] ≤1, patient pain score ≤15, patient global disease activity score ≤20 [range 0-100], Health Assessment Questionnaire disability index [HAQ DI] ≤0.5, and ≤1 tender enthesis point). RESULTS: Treatment with golimumab yielded significantly higher MDA response rates versus patients randomized to placebo at week 14 (23.5% versus 1.0%; P < 0.0001), week 24 (28.1% versus 7.7%; P < 0.0001), and week 52 (42.4% versus 30.2%; P = 0.037). MDA was achieved at least once by ∼50% of golimumab-treated patients overall. Irrespective of treatment randomization, achievement of MDA at ≥3 and ≥4 consecutive visits was associated with significantly less radiographic progression and more improvement in MDA components allowing specific assessment of physical function (HAQ DI) and overall disease activity (patient global assessment of disease activity) at week 256 versus patients not achieving MDA. Logistic regression analyses indicated that a 1-unit higher baseline HAQ DI score yielded a significantly lower likelihood of achieving MDA at ≥3 (odds ratio 0.514 [95% confidence interval 0.321-0.824]; P = 0.006) and ≥4 (odds ratio 0.480 [95% confidence interval 0.290-0.795]; P = 0.004) consecutive visits. CONCLUSION: Among golimumab-treated PsA patients, better long-term functional improvement, patient global assessment, and radiographic outcomes were observed when patients achieved persistent MDA.

22 Clinical Trial Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. 2015

Mease, Philip J / McInnes, Iain B / Kirkham, Bruce / Kavanaugh, Arthur / Rahman, Proton / van der Heijde, Désirée / Landewé, Robert / Nash, Peter / Pricop, Luminita / Yuan, Jiacheng / Richards, Hanno B / Mpofu, Shephard / Anonymous2430844. ·From the Swedish Medical Center and the University of Washington - both in Seattle (P.J.M.) · University of Glasgow, Glasgow (I.B.M.), and Guy's and St. Thomas' NHS Foundation Trust, London (B.K.) - both in the United Kingdom · University of California, San Diego, School of Medicine, San Diego (A.K.) · Memorial University, St. John's, NL, Canada (P.R.) · Leiden University Medical Center, Leiden (D.H.), and University of Amsterdam and Atrium Medical Center, Amsterdam (R.L.) - all in the Netherlands · University of Queensland, Brisbane, Australia (P.N.) · Novartis Pharmaceuticals, East Hanover, NJ (L.P., J.Y.) · and Novartis Pharma, Basel, Switzerland (H.B.R., S.M.). ·N Engl J Med · Pubmed #26422723.

ABSTRACT: BACKGROUND: In a phase 2 study, the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis. We sought to evaluate the efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody, in such patients. METHODS: In this double-blind, phase 3 study, 606 patients with psoriatic arthritis were randomly assigned in a 1:1:1 ratio to receive intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains. RESULTS: ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for both comparisons with placebo). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks. Infections, including candida, were more common in the secukinumab groups. Throughout the study (mean secukinumab exposure, 438.5 days; mean placebo exposure, 128.5 days), four patients in the secukinumab groups had a stroke (0.6 per 100 patient-years; 95% confidence interval [CI], 0.2 to 1.5), and two had a myocardial infarction (0.3 per 100 patient-years; 95% CI, 0.0 to 1.0), as compared with no patients in the placebo group. CONCLUSIONS: Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group. The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT01392326.).

23 Clinical Trial Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. 2015

McInnes, Iain B / Mease, Philip J / Kirkham, Bruce / Kavanaugh, Arthur / Ritchlin, Christopher T / Rahman, Proton / van der Heijde, Désirée / Landewé, Robert / Conaghan, Philip G / Gottlieb, Alice B / Richards, Hanno / Pricop, Luminita / Ligozio, Gregory / Patekar, Manmath / Mpofu, Shephard / Anonymous1170835. ·Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. Electronic address: Iain.McInnes@glasgow.ac.uk. · Swedish Medical Center and University of Washington, Seattle, WA, USA. · Guy's and St Thomas' NHS Foundation Trust, London, UK. · Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, University of California San Diego School of Medicine, San Diego, CA, USA. · Allergy/Immunology and Rheumatology Division, University of Rochester, Rochester, NY, USA. · Memorial University, Newfoundland, NL, Canada. · Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands. · Amsterdam Rheumatology and Immunology Center, Amsterdam, and Atrium Medical Center, Heerlen, Netherlands. · NIHR Leeds Musculoskeletal Biomedical Research Unit and University of Leeds, Leeds, UK. · Department of Dermatology, Tufts Medical Center, Boston, MA, USA. · Novartis Pharma, Basel, Switzerland. · Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. · Novartis Healthcare, Hyderabad, India. ·Lancet · Pubmed #26135703.

ABSTRACT: BACKGROUND: Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis. METHODS: In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01752634. FINDINGS: Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6·81, 95% CI 3·42-13·56; p<0·0001), 150 mg (51 [51%] patients; 6·52, 3·25-13·08; p<0·0001), and 75 mg (29 [29%] patients; 2·32, 1·14-4·73; p=0·0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported. INTERPRETATION: Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder. FUNDING: Novartis.

24 Clinical Trial Maintenance of Clinical Efficacy and Radiographic Benefit Through Two Years of Ustekinumab Therapy in Patients With Active Psoriatic Arthritis: Results From a Randomized, Placebo-Controlled Phase III Trial. 2015

Kavanaugh, Arthur / Puig, Lluís / Gottlieb, Alice B / Ritchlin, Christopher / Li, Shu / Wang, Yuhua / Mendelsohn, Alan M / Song, Michael / Zhu, Yaowei / Rahman, Proton / McInnes, Iain B / Anonymous350834. ·University of California, San Diego, La Jolla, California. · Universitat Autònoma de Barcelona, Barcelona, Spain. · Tufts Medical Center, Boston, Massachusetts. · University of Rochester, Rochester, New York. · Janssen Research & Development, Spring House, Pennsylvania. · Memorial University, St. John's, Newfoundland and Labrador, Canada. · University of Glasgow, Glasgow, Scotland. ·Arthritis Care Res (Hoboken) · Pubmed #26097039.

ABSTRACT: OBJECTIVE: To evaluate the efficacy and safety of ustekinumab through 2 years in adult patients with active psoriatic arthritis (PsA). METHODS: A total of 615 adult patients with active PsA were randomized to placebo, ustekinumab 45 mg, or ustekinumab 90 mg, at weeks 0, 4, and every 12 weeks through week 88 (last dose). At week 16, patients with <5% improvement in both tender and swollen joint counts entered blinded early escape (placebo to 45 mg, 45 mg to 90 mg, and 90 mg to 90 mg). All remaining placebo patients crossed over to ustekinumab 45 mg at week 24. Clinical efficacy measures included American College of Rheumatology criteria for 20% improvement (ACR20), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and ≥75% improvement in the Psoriasis Area and Severity Index (PASI75). Radiographic progression was evaluated using the modified Sharp/van der Heijde score (SHS). RESULTS: At week 100, ACR20, DAS28-CRP moderate/good response, and PASI75 rates ranged from 56.7-63.6%, 71.9-76.7%, and 63.9-72.5%, respectively, across the 3 treatment groups. In both ustekinumab groups, the median percent improvement in dactylitis and enthesitis was 100% at week 100. The mean changes in SHS score from week 52 to week 100 were similar to those observed from week 0 to week 52 in the ustekinumab groups. Through week 108, 70.7% and 9.7% of patients had an adverse event (AE) or serious AE, respectively. The rates and type of AEs were similar between the dose groups. CONCLUSION: Clinical and radiographic benefits from ustekinumab treatment were maintained through week 100 in the PSUMMIT 1 study. No unexpected safety events were observed; the safety profile of ustekinumab in this population was similar to that previously observed in psoriasis patients treated with ustekinumab.

25 Clinical Trial Clinical efficacy, radiographic and safety findings through 5 years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of a randomised, placebo-controlled trial (the GO-REVEAL study). 2014

Kavanaugh, Arthur / McInnes, Iain B / Mease, Philip / Krueger, Gerald G / Gladman, Dafna / van der Heijde, Désirée / Zhou, Yiying / Lu, Jiandong / Leu, Jocelyn H / Goldstein, Neil / Beutler, Anna. ·Division of Rheumatology, Allergy, Immunology, University of California, San Diego, La Jolla, California, USA. · Institute of Infection, Immunity, and Inflammation, University of Glasgow, Glasgow, UK. · Department of Rheumatology, Swedish Medical Center, University of Washington, Seattle, Washington, USA. · Department of Dermatology, University of Utah, Salt Lake City, Utah, USA. · Toronto Western Research Institute, Toronto, Ontario, Canada. · Director of Imaging Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. · Department of Biostatistics, Janssen Research & Development, LLC., Spring House, Pennsylvania, USA. · Biologics Clinical Pharmacology, Janssen Research & Development, LLC., Spring House, Pennsylvania, USA. · Department of Immunology, Janssen Research & Development, LLC., Spring House, Pennsylvania, USA. ·Ann Rheum Dis · Pubmed #24748630.

ABSTRACT: OBJECTIVES: Assess golimumab's long-term efficacy/safety in psoriatic arthritis (PsA). METHODS: Adults with active PsA (≥3 swollen and tender joints, active psoriasis) were randomly assigned to subcutaneous placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks (q4wks) through wk20. All patients received golimumab 50 mg or 100 mg q4wks from wk24 forward. Methotrexate was allowed and taken by approximately half the patients. Findings through 5 years are reported herein. Efficacy assessments included ≥20% improvement in American College of Rheumatology (ACR20) response, C-reactive-protein-based, 28-joint-count Disease Activity Score (DAS28-CRP) response, ≥75% improvement in Psoriasis Area and Severity Index (PASI75) scores, and PsA-modified Sharp/van der Heijde scores (SHSs). RESULTS: 126/405 (31%) randomised patients discontinued treatment through wk252. Golimumab was effective in maintaining clinical improvement through year-5 (ACR20: 62.8-69.9%, DAS28-CRP: 75.2-84.9% for randomised patients; PASI75: 60.8-72.2% among randomised patients with ≥3% body surface area involvement) and inhibiting radiographic progression (mean changes in PsA-modified SHS: 0.1-0.3) among patients with radiographic data. While concomitant methotrexate did not affect ACR20/PASI75, it appeared to reduce radiographic progression. No new safety signals were identified. Antibodies-to-golimumab occurred in 1.8%/10.0% of patients with/without methotrexate). CONCLUSIONS: Long-term golimumab safety/efficacy in PsA was demonstrated through 5 years. TRIAL REGISTRATION NUMBER: NCT00265096.

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