Slide set should, if possible, not exceed 20 Slides 2016 update of the ASAS-EULAR management recommendations for axial SpondyloArthritis

Slide 1: Target population/question Health care professionals taking care of patients with axSpA Patients to be educated for informed shared decision-making Pharmaceutical industry, drug agencies, policy makers, health insurance companies 07/04/2019

Methods/methodical approach 2 Systematic literature reviews (SLRs) since 2009 non-pharmacological treatment (Andrea Regel) pharmacological treatment (Alexandre Sepriano) SLR on the use of ASDAS vs. BASDAI to define disease activity for the start and continuation of bDMARDs One-day meeting of the task force presentation of the findings of the SLRs rewording of 2010 overarching principles and recommendations new recommendations formulated voting on each new overarching principle/recommendation by all task force members in maximal 3 rounds (first round ≥75%, second round ≥67%, third round ≥50%) After the meeting Addition of the level of evidence for each recommendation (LoE) and Grade of Recommendation Addition of level of agreement by the task force members by anonymous voting from 0 (I do not agree at all) to 10 (I fully agree) (LoA, mean (SD), %≥8) 07/04/2019

Overarching prinicples Axial Spondyloarthritis (axSpA) is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist. The primary goal of treating the patient with axSpA is to maximize health related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalisation of function and social participation. 07/04/2019

Overarching prinicples The optimal management of patients with axSpA requires a combination of non-pharmacological and pharmacological treatment modalities Treatment of axSpA should aim at the best care and must be based on a shared decision between the patient and the rheumatologist axSpA incurs high individual, medical and societal costs, all of which should be considered in its management by the treating rheumatologist 07/04/2019

Recommendation 1: General treatment The treatment of patients with axSpA should be individualised according to the current signs and symptoms of the disease (axial, peripheral, extra-articular manifestations) and the patient characteristics including comorbidities and psychosocial factors. 07/04/2019

Recommendation 2: Disease monitoring Disease monitoring of patients with axSpA should include patient reported outcomes, clinical findings, laboratory tests and imaging, all with the appropriate instruments and relevant to the clinical presentation The frequency of monitoring should be decided on an individual basis depending on symptoms, severity, and treatment 07/04/2019

Recommendation 3: Treatment target Treatment should be guided according to a predefined treatment target 07/04/2019

Recommendation 4: Non-pharmacological therapy Patients should be educated about axSpA and encouraged to exercise on a regular basis and stop smoking Physical therapy should be considered 07/04/2019

Recommendation 5: NSAIDs Patients suffering from pain and stiffness should use an NSAID as first line drug treatment up to the maximum dose, taking risks and benefits into account For patients who respond well to NSAIDs continuous use is preferred if symptomatic otherwise 07/04/2019

Recommendation 6: Analgesics Analgesics, such as paracetamol and opioid-(like) drugs, might be considered for residual pain after previously recommended treatments have failed, are contraindicated, and/or poorly tolerated 07/04/2019

Recommendation 7: Corticosteroids Glucocorticoid injections directed to the local site of musculoskeletal inflammation may be considered Patients with axial disease should not receive long-term treatment with systemic glucocorticoids 07/04/2019

Recommendation 8: DMARDs Patients with purely axial disease should normally not be treated with csDMARDs Sulfasalazine may be considered in patients with peripheral arthritis 07/04/2019

Recommendation 9: Biological therapy bDMARDs should be considered in patients with persistently high disease activity despite conventional treatments (box1) Current practice is to start with TNFi therapy 07/04/2019

Rheumatologist’s diagnosis of axial SpA ASAS-EULAR Recommendations for the Treatment of axSpA Patients with bDMARDs (box 1) Rheumatologist’s diagnosis of axial SpA Failure of standard treatment: all patients at least 2 NSAIDs over 4 weeks (in total) patients with predominant peripheral manifestations one local steroid injection if appropriate normally a therapeutic trial of sulfasalazine High disease activity: ASDAS ≥ 2.1 or BASDAI ≥ 4 Positive rheumatologist’s opinion and Elevated CRP and/or positive MRI and/or Radiographic sacroiliitis 07/04/2019

ASAS-EULAR Recommendations for the continuation of bDMARDs ASDAS improvement ≥ 1.1 or BASDAI improvement ≥ 2 (0-10) and Positive rheumatologist‘s opinion to continue Consider to continue bDMARDs if after at least 12 weeks of treatment 07/04/2019

Recommendation 10: TNFi failure If TNFi therapy fails, switching to another TNFi or IL17i therapy should be considered 07/04/2019

Recommendation 11: bDMARD tapering If a patient is in sustained remission, tapering of a bDMARD can be considered 07/04/2019

Recommendation 12: Surgery Total hip arthroplasty should be considered in patients with refractory pain or disability and radiographic evidence of structural damage, independent of age Spinal corrective osteotomy in specialised centres may be considered in patients with severe disabling deformity 07/04/2019

Recommendation 13: Changes in the disease course If a significant change in the course of the disease occurs, causes other than inflammation, such as a spinal fracture, should be considered and appropriate evaluation, including imaging, should be performed 07/04/2019

Oxford table 07/04/2019 Overarching principles LoE GoR LoA 1 9.9 (0.31) 100% ≥8 2 9.8 (0.47) 100% ≥8 3 9.8 (0.45) 100% ≥8 4 9.5 (0.91) 100% ≥8 5 9.3 (1.17) 97% ≥8 Recommendations D 9.7 (0.65) 100% ≥8 9.6 (0.78) 100% ≥8 Treatment should be guided according to a predefined treatment target. 8.9 (1.45) 93% ≥8 Patients should be educated* about axSpA and encouraged to exercise* on a regular basis and stop smoking#; physical therapy^ should be considered. *2 ^1a #5 *B ^A #D Patients suffering from pain and stiffness should use an NSAID as first line drug treatment up to the maximum dose, taking risks and benefits into account. For patients who respond well to NSAIDs continuous use is preferred if symptomatic otherwise. 1a A 9.4 (0.94) 100% ≥8 6 Analgesics, such as paracetamol and opioid-(like) drugs, might be considered for residual pain after previously recommended treatments have failed, are contraindicated, and/or poorly tolerated. 8.8 (0.94) 100% ≥8 7 Glucocorticoid injections* directed to the local site of musculoskeletal inflammation may be considered. Patients with axial disease should not receive long-term treatment with systemic glucocorticoids#. *2 #5 *B #D 9.4 (0.78) 100% ≥8 8 Patients with purely axial disease should normally not be treated with csDMARDs1; Sulfasalazine^ may be considered in patients with peripheral arthritis. ^1a 9.2 (0.78) 100% ≥8 9 bDMARDs should be considered in patients with persistently high disease activity despite conventional treatments (box1); current practice is to start with TNFi therapy 1a (TNFi); 1b (IL17i) 9.6 (1.09) 93% ≥8 10 If TNFi therapy fails, switching to another TNFi* or IL17i” therapy should be considered. *2 “1b *B “A 9.6 (0.95) 97% ≥8 11 If a patient is in sustained remission, tapering of a bDMARD can be considered. B 9.1 (1.57) 97% ≥8 12 Total hip arthroplasty should be considered in patients with refractory pain or disability and radiographic evidence of structural damage, independent of age; spinal corrective osteotomy in specialised centres may be considered in patients with severe disabling deformity C 9.4 (0.82) 100% ≥8 13 If a significant change in the course of the disease occurs, causes other than inflammation, such as a spinal fracture, should be considered and appropriate evaluation, including imaging, should be performed. 9.9 (0.31) 97% ≥8 07/04/2019

Summary of Recommendations 2016 management recommendations are better worded as recommendations integrate the previous management and TNFi-therapy recommendations cover the entire spectrum of axSpA emphasize the usefulness of nonpharmacological management NSAIDs remain the first-line drug starting of bDMARDs is integrated for patients with radiographic and nonradiographic axSpA ASDAS as well as BASDAI can be used as disease activity measure discontinuation of bDMARDs is reworded as continuation TNFi therapy is the currently preferred bDMARD after failure of TNFi therapy a switch to either a second TNFi or IL17i therapy is recommended tapering of bDMARDs is included in the recommendations 07/04/2019

Summary of Recommendations in Lay format 07/04/201907/04/201907/04/201907/04/201907/04/201907/04/201907/04/201907/04/201907/04/201907/04/2019 Summary of Recommendations in Lay format The new ASAS-EULAR recommendations are applicable to all patients with axial SpondyloArthritis (axSpA). This includes patients with nonradiographic axSpA (normal joints on the pelvis radiograph) and patients with radiographic axSpA (with abnormalities on the pelvis radiographs). There are five overarching principles dealing with good practice such as Optimal treatment requires a combination of non-pharmacological and pharmacological treatment modalities shared decision making The primary goal of treating the patient with axSpA is to maximize health related quality of life. This should be done by control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalisation of function and social participation. Thirteen recommendations are formulated The first three deal with individualised treatment based on current signs and symptoms and patient characteristics; disease monitoring; and the definition of a treatment target. The next five recommendations describe the use of non-pharmacological treatment, anti-inflammatory painkillers (‘NSAIDs’), painkillers, corticosteroids and other nonbiological antirheumatic drugs. Only non-pharmacological management and NSAIDs play an important role in the treatment of axSpA.

Summary of Recommendations in Lay format 07/04/201907/04/201907/04/201907/04/201907/04/201907/04/201907/04/201907/04/201907/04/201907/04/2019 Summary of Recommendations in Lay format Recommendations 9-11 describe the use of biological antirheumatic drugs. These are prescribed when there is persistent high disease activity despite other treatment. Also the continuation in full dose and possibly tapering is discussed. The final two recommendations are on surgery and unexpected changes in the disease course.

Acknowledgements Steering committee Additional task force members Victoria Navarro-Compán Salih Özgöcmen Fernando Pimentel dos Santos John Reveille Martin Rudwaleit Percival Sampaio-Barros Jochen Sieper Irene van der Horst-Bruinsma Floris van Gaalen Dieter Wiek (PP) Steering committee Désirée van der Heijde (convenor) Jürgen Braun (co- convenor) Sofia Ramiro (methodologist) Alexandre Sepriano (fellow) Andrea Regel (fellow) Xenofon Baraliakos Robert Landewé Filip van den Bosch Additional task force members Adrian Ciurea Hanne Dagfinrud (HP) Maxime Dougados Pál Géher Robert Inman Merryn Jongkees (PP) Uta Kiltz Tore Kvien Pedro Machado Helena Marzo-Ortega Anna Moltó 07/04/2019