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      Drug retention, inactive disease and response rates in 1860 patients with axial spondyloarthritis initiating secukinumab treatment: routine care data from 13 registries in the EuroSpA collaboration

      research-article
      1 , 2 , 3 , , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 3 , 12 , 13 , 14 , 15 , 16 , 17 , 5 , 18 , 19 , 20 , 21 , 3 , 12 , 22 , 23 , 15 , 24 , 25 , 26 , 1 , 1 , 1 , 1 , 27 , 1 , 27
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      BMJ Publishing Group
      Spondyloarthritis, DMARDs (biologic), Outcomes research

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          Abstract

          Objectives

          To explore 6-month and 12-month secukinumab effectiveness in patients with axial spondyloarthritis (axSpA) overall, as well as across (1) number of previous biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), (2) time since diagnosis and (3) different European registries.

          Methods

          Real-life data from 13 European registries participating in the European Spondyloarthritis Research Collaboration Network were pooled. Kaplan-Meier with log-rank test, Cox regression, χ² and logistic regression analyses were performed to assess 6-month and 12-month secukinumab retention, inactive disease/low-disease-activity states (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <2/<4, Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3/<2.1) and response rates (BASDAI50, Assessment of Spondyloarthritis International Society (ASAS) 20/40, ASDAS clinically important improvement (ASDAS-CII) and ASDAS major improvement (ASDAS-MI)).

          Results

          We included 1860 patients initiating secukinumab as part of routine care. Overall 6-month/12-month secukinumab retention rates were 82%/72%, with significant (p<0.001) differences between the registries (6-month: 70–93%, 12-month: 53–86%) and across number of previous b/tsDMARDs (b/tsDMARD-naïve: 90%/73%, 1 prior b/tsDMARD: 83%/73%, ≥2 prior b/tsDMARDs: 78%/66%). Overall 6-month/12-month BASDAI<4 were observed in 51%/51%, ASDAS<1.3 in 9%/11%, BASDAI50 in 53%/47%, ASAS40 in 28%/22%, ASDAS-CII in 49%/46% and ASDAS-MI in 25%/26% of the patients. All rates differed significantly across number of previous b/tsDMARDs, were numerically higher for b/tsDMARD-naïve patients and varied significantly across registries. Overall, time since diagnosis was not associated with secukinumab effectiveness.

          Conclusions

          In this study of 1860 patients from 13 European countries, we present the first comprehensive real-life data on effectiveness of secukinumab in patients with axSpA. Overall, secukinumab retention rates after 6 and 12 months of treatment were high. Secukinumab effectiveness was consistently better for bionaïve patients, independent of time since diagnosis and differed across the European countries.

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          Most cited references29

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          2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis

          To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6–8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
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            A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index.

            Disease status, in terms of disease activity, disease progression and prognosis is difficult to define in ankylosing spondylitis (AS). No gold standard exists. Therefore, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a self-administered instrument, has been developed as a new approach to defining disease activity in patients with AS. The index, designed by a multidisciplinary team with input from patients, consists of six 10 cm horizontal visual analog scales to measure severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness (both qualitative and quantitative). The final BASDAI score has a range of 0 to 10. The index was distributed to a cross section of patients, including inpatients receiving 3 weeks of intensive physiotherapy treatment and hospital outpatients. BASDAI was completed by a total of 154 patients. Validation of the new instrument was achieved through analysis of user friendliness, reliability (consistency), score distribution and sensitivity to change. Comparisons were made with a previous Bath disease activity index (DAI) and the Newcastle Enthesis Index. The BASDAI was found by patients to be quick and simple to complete (mean: 67 s). Test-retest reliability was good (r = 0.93; p < 0.001), as was the distribution of scores across the scale (score range: 0.5-10; mean: 4.31). BASDAI was sensitive to change, reflecting a 16% (mean) improvement in inpatient scores after 3 weeks of treatment. It is superior to the DAI in terms of construct and content validity and to the Enthesis Index in all aspects. In summary, BASDAI is user friendly, reliability, sensitive to change and reflects the entire spectrum of disease. It is a comprehensive self-administered instrument for assessing disease activity in AS.
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              Axial spondyloarthritis.

              The term axial spondyloarthritis covers both patients with non-radiographic and radiographic axial spondyloarthritis, which is also termed ankylosing spondylitis. The disease usually starts in the third decade of life with a male to female ratio of two to one for radiographic axial spondyloarthritis and of one to one for non-radiographic axial spondyloarthritis. More than 90% heritabilty has been estimated, the highest genetic association being with HLA-B27. The pathogenic role of HLA-B27 is still not clear although various hypotheses are available. On the basis of evidence from trials the cytokines tumour necrosis factor (TNF)-α and interleukin-17 appear to have a relevant role in pathogenesis. The mechanisms of interaction between inflammation and new bone formation is still not completely understood but clarification will be important for the prevention of long-term structural damage of the bone. The development of new criteria for classification and for screening of patients with axial spondyloarthritis have been crucial for the early indentification and treatment of such patients, with MRI being the most important existing imaging method. Non-steroidal anti-inflammatory drugs and TNF blockers are effective therapies. Blockade of interleukin-17 is a new and relevant treatment option.
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                Author and article information

                Journal
                RMD Open
                RMD Open
                rmdopen
                rmdopen
                RMD Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2056-5933
                2020
                21 September 2020
                : 6
                : 3
                : e001280
                Affiliations
                [1 ] departmentCopenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopedics, Rigshospitalet Glostrup , Copenhagen, Denmark
                [2 ] departmentDivision of Rheumatology, Department of Medicine , Hospital of Southern Norway Trust , Kristiansand, Norway
                [3 ] departmentDepartment of Rheumatology , Diakonhjemmet Hospital , Oslo, Norway
                [4 ] departmentDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden
                [5 ] University of Medicine and Pharmacy "Carol Davila" , Bucharest, Bucharest, Romania
                [6 ] departmentDepartment of Rheumatology, University Hospital Zurich , Zurich, Switzerland
                [7 ] Institute of Rheumatology , Prague, Czech Republic
                [8 ] departmentDANBIO Registry, Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet Glostrup , Copenhagen, Denmark
                [9 ] departmentDepartment of Rheumatology, Aarhus University Hospital , Aarhus, Denmark
                [10 ] departmentRheumatology Service , Hospital Clinico Universitario , Santiago De Compostela, Spain
                [11 ] departmentTURKBIO Registry, Division of Rheumatology, Dokuz Eylul University School of Medicine , Izmir, Turkey
                [12 ] departmentbiorx.si and the Department of Rheumatology , University Medical Centre Ljubljana , Ljubljana, Slovenia
                [13 ] departmentReuma.pt Registry and Instituto De Medicina Molecular, Faculdade De Medicina, Universidade De Lisboa , Lisboa, Lisboa, Portugal
                [14 ] departmentGISEA Registry, Rheumatology Unit - DETO, University of Bari , Bari, Italy
                [15 ] departmentROB-FIN Registry, Helsinki University and Helsinki University Hospital , Helsinki, Finland
                [16 ] departmentCentre for Rheumatology Research (ICEBIO), University Hospital and Faculty of Medicine, University of Iceland , Reykjavik, Iceland
                [17 ] departmentClinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet , Stockholm, Sweden
                [18 ] departmentDepartment of Rheumatology , Geneva University Hospital , Geneve, Switzerland
                [19 ] departmentInstitute of Rheumatology and Department of Rheumatology, 1st Faculty of Medicine , Charles University , Prague, Czech Republic
                [20 ] departmentResearch Unit , Spanish Society of Rheumatology , Madrid, Spain
                [21 ] departmentDepartment of Rheumatology , Izmir Kâtip Çelebi University , Izmir, Turkey
                [22 ] Reuma.pt registry and Instituto Português de Reumatologia , Lisbon, Portugal
                [23 ] departmentRheumatology Unit, CHIMOMO, Azienda Policlinico of Modena , University of Modena , Modena, Italy
                [24 ] departmentDepartment of Rheumatology , Landspitali University Hospital , Reykjavik, Iceland
                [25 ] departmentEpidemiology Group, School of Medicine, Medical Science and Nutrition, University of Aberdeen , Aberdeen, UK
                [26 ] Amsterdam University Medical Centres, VU University Medical Centre, Department Rheumatology & Immunology Center (ARC) , Amsterdam, Netherlands
                [27 ] departmentDepartment of Clinical Medicine, University of Copenhagen , Copenhagen, Denmark
                Author notes
                Correspondence to Brigitte Michelsen; brigitte.michelsen@ 123456regionh.dk

                MLH and MØ contributed equally

                Author information
                http://orcid.org/0000-0003-0103-2840
                http://orcid.org/0000-0002-2250-9348
                http://orcid.org/0000-0002-7870-7132
                http://orcid.org/0000-0002-8441-3093
                http://orcid.org/0000-0002-7946-1365
                http://orcid.org/0000-0002-3734-1242
                http://orcid.org/0000-0002-1790-5610
                Article
                rmdopen-2020-001280
                10.1136/rmdopen-2020-001280
                7539854
                32950963
                135ecd90-db58-47fa-9167-e62e93b8b4c3
                © 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
                : 20 April 2020
                : 02 July 2020
                : 21 August 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004336, Novartis;
                Categories
                Spondyloarthritis
                Original research

                spondyloarthritis,dmards (biologic),outcomes research

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