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      EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update

      research-article
      1 , 2 , , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 10 , 11 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 22 , 34 , 35 , 36
      Annals of the Rheumatic Diseases
      BMJ Publishing Group
      psoriatic arthritis, treatment, DMARDs (biologic)

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          Abstract

          Objective

          To update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA).

          Methods

          According to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined.

          Results

          The updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed.

          Conclusion

          These recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.

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          Most cited references73

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          Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis.

          To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA).
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            Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials

            Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis.
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              Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

              Objective Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients.
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                Author and article information

                Journal
                Ann Rheum Dis
                Ann. Rheum. Dis
                annrheumdis
                ard
                Annals of the Rheumatic Diseases
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0003-4967
                1468-2060
                June 2020
                20 May 2020
                : 79
                : 6
                : 700-712
                Affiliations
                [1 ] departmentInstitut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM , Sorbonne Universite , Paris, France
                [2 ] departmentAPHP.Sorbonne Universite, Rheumatology Department , Hopital Universitaire Pitie Salpetriere , Paris, France
                [3 ] departmentRuhr-Universität Bochum , Rheumazentrum Ruhrgebiet , Herne, Germany
                [4 ] departmentDivision of Rheumatology, Department of Medicine 3; 2nd Department of Medicine, Hietzing Hospital , Medical University of Vienna , Vienna, Austria
                [5 ] EULAR , Zurich, Switzerland
                [6 ] departmentInstitute of Infection, Immunity and Inflammation , University of Glasgow , Glasgow, UK
                [7 ] departmentHopital Cochin, Rheumatology , Université Paris Descartes , Paris, France
                [8 ] departmentDanish Hospital for Rheumatic Diseases , University Hospital of Southern Denmark , Sønderborg, Denmark
                [9 ] departmentDepartment of Regional Health Research , University of Southern Denmark , Odense, Denmark
                [10 ] departmentLTHT , Leeds NIHR Biomedical Research Centre , Leeds, UK
                [11 ] departmentLeeds Institute of Rheumatic and Musculoskeletal Medicine , University of Leeds , Leeds, UK
                [12 ] departmentDivision of Rheumatology, Department of Medicine 3 , Medical University of Vienna , Vienna, Austria
                [13 ] departmentResearch Center of Rheumatic Diseases, Sf Maria Hospital , Carol Davila University of Medicine and Pharmacy , Bucharest, Romania
                [14 ] department3rd Department of Rheumatology , National Institute of Rheumatology and Physiotherapy , Budapest, Hungary
                [15 ] departmentPatient Research Partner , EULAR , Oslo, Norway
                [16 ] departmentDermatology , University Hospitals of Geneva , Geneva, Switzerland
                [17 ] departmentRheumatology and Clinical Immunology , Charite University Hospital Berlin , Berlin, Germany
                [18 ] departmentArthritis Unit, Department of Rheumatology and IDIBAPS , Hospital Clinic , Barcelona, Spain
                [19 ] departmentInstitute of Rheumatology , Belgrade University School of Medicine , Belgrade, Serbia
                [20 ] departmentDepartment of Biomedicine , Aarhus University , Aarhus C, Denmark
                [21 ] departmentDepartment of Rheumatology , Aarhus Universitetshospital , Aarhus, Denmark
                [22 ] departmentRheumatology , Diakonhjemmet Hospital , Oslo, Norway
                [23 ] departmentAmsterdam Rheumatology Center , AMC , Amsterdam, The Netherlands
                [24 ] departmentRheumatology , Zuyderland MC , Heerlen, The Netherlands
                [25 ] departmentLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center , KU Leuven , Leuven, Flanders, Belgium
                [26 ] departmentRheumatology , KU Leuven University Hospitals Leuven , Leuven, Flanders, Belgium
                [27 ] departmentDepartment of Rheumatology, Infectious Diseases and Rheumatology , Charité Universitätsmedizin Berlin , Berlin, Germany
                [28 ] departmentEpidemiology , German Rheumatism Research Center Berlin , Berlin, Germany
                [29 ] departmentRheumatology , Hospital de Egas Moniz , Lisboa, Portugal
                [30 ] Universidade Nova de Lisboa Centro de Estudos de Doencas Cronicas , Lisboa, Portugal
                [31 ] departmentInternal Medicine , University of Erlangen-Nuremberg , Erlangen, Germany
                [32 ] departmentCentre for Arthritis and Rheumatic Disease, Dublin Academic Medical Centre , St Vincent’s University Hospital , Dublin, Ireland
                [33 ] departmentDepartment of Internal Medicine and Pediatrics, VIB Center for Inflammation Research , Ghent University , Gent, Belgium
                [34 ] departmentRheumatology , Leiden University Medical Center , Leiden, The Netherlands
                [35 ] departmentDivision of Rheumatology, Department of Medicine 3 , Medical University of Vienna , Vienna, Wien, Austria
                [36 ] department2nd Department of Medicine , Hietzing Hospital , Vienna, Wien, Austria
                Author notes
                [Correspondence to ] Professor Laure Gossec, Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM, Sorbonne Universite, Paris 75013, France; laure.gossec@ 123456gmail.com
                Author information
                http://orcid.org/0000-0002-4528-310X
                http://orcid.org/0000-0002-6685-8873
                http://orcid.org/0000-0002-8428-6354
                http://orcid.org/0000-0002-1049-4150
                http://orcid.org/0000-0001-7932-2632
                http://orcid.org/0000-0002-4537-6015
                http://orcid.org/0000-0002-7217-0469
                http://orcid.org/0000-0001-8740-9615
                http://orcid.org/0000-0003-2802-4971
                http://orcid.org/0000-0002-5781-158X
                Article
                annrheumdis-2020-217159
                10.1136/annrheumdis-2020-217159
                7286048
                32434812
                b1914a78-be5f-483e-bde0-029f634e1e2d
                © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 13 February 2020
                : 30 April 2020
                : 01 May 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100008741, European League Against Rheumatism;
                Categories
                Recommendation
                1506
                2430
                2311
                Custom metadata
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                Immunology
                psoriatic arthritis,treatment,dmards (biologic)
                Immunology
                psoriatic arthritis, treatment, dmards (biologic)

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