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Recommendation
EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis
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  1. Ioannis Parodis1,2,3,
  2. Charlotte Girard-Guyonvarc’h4,5,
  3. Laurent Arnaud6,
  4. Oliver Distler7,
  5. Andrea Domján8,
  6. Cornelia H M Van den Ende9,10,
  7. Kim Fligelstone11,
  8. Agnes Kocher12,
  9. Maddalena Larosa13,
  10. Martin Lau14,
  11. Alexandros Mitropoulos15,
  12. Mwidimi Ndosi16,
  13. Janet L Poole17,
  14. Anthony Redmond18,
  15. Valentin Ritschl19,20,
  16. Helene Alexanderson1,21,
  17. Yvonne Sjöberg22,
  18. Gunilla von Perner22,
  19. Till Uhlig23,
  20. Cecilia Varju24,
  21. Johanna E Vriezekolk9,
  22. Elisabet Welin25,
  23. René Westhovens26,
  24. Tanja A Stamm19,20,
  25. Carina Boström21,27
  1. 1 Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  2. 2 Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  3. 3 Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
  4. 4 Division of Rheumatology, Department of Medicine, University Hospital of Geneva, Geneve, Switzerland
  5. 5 Faculty of Medicine, University of Geneva, Geneva, Switzerland
  6. 6 Department of Rheumatology, Hôpitaux Universitaires de Strasbourg, Centre National de Référence (RESO), INSERM UMR-S 1109, Strasbourg, France
  7. 7 Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
  8. 8 Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  9. 9 Department of Research, Sint Maartenskliniek, Nijmegen, The Netherlands
  10. 10 Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands
  11. 11 Federation of European Scleroderma Associations (FESCA), Brussels, Belgium
  12. 12 Institute of Nursing Science, Faculty of Medicine, University of Basel, Basel, Switzerland
  13. 13 Rheumatology Unit, Department of Medical Specialties, ASL3, Genoa, Italy
  14. 14 Arthritis Action, London, UK
  15. 15 Department of Nursing and Midwifery, College of Health Wellbeing and Life Science, Sheffield Hallam University, Sheffield, UK
  16. 16 School of Health and Social Wellbeing, University of the West of England, Bristol, UK
  17. 17 Occupational Therapy Graduate Program, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA
  18. 18 Leeds Institute for Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
  19. 19 Section for Outcomes Research, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
  20. 20 Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria
  21. 21 Department of Occupational Therapy and Physiotherapy, Karolinska University Hospital, Stockholm, Sweden
  22. 22 Swedish Rheumatism Association, Stockholm, Sweden
  23. 23 Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo, Norway
  24. 24 Department of Rheumatology and Immunology, Medical School of University of Pécs, Pécs, Hungary
  25. 25 School of Health Sciences, Örebro University, Örebro, Sweden
  26. 26 Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium
  27. 27 Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to Dr Ioannis Parodis, Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm 171 76, Stockholm, Sweden; ioannis.parodis{at}ki.se

Abstract

Objective To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc).

Methods A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale A–D, A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0–10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting.

Results Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc.

Conclusions The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician–patient communication and improved outcomes.

  • Systemic Lupus Erythematosus
  • Systemic Sclerosis
  • Patient perspective
  • Patient Reported Outcome Measures
  • Patient Care Team

https://doi.org/10.1136/ard-2023-224416

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    Video Abstract

    Disclaimer: this video summarises a scientific article published by BMJ Publishing Group Limited (BMJ). The content of this video has not been peer-reviewed and does not constitute medical advice. Any opinions expressed are solely those of the contributors. Viewers should be aware that professionals in the field may have different opinions. BMJ does not endorse any opinions expressed or recommendations discussed. Viewers should not use the content of the video as the basis for any medical treatment. BMJ disclaims all liability and responsibility arising from any reliance placed on the content.

    What is already known about this subject?

    • Non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is helpful but unstandardised and often underused in current clinical practice.

    What does this study add?

    • We developed recommendations to provide guidance for non-pharmacological management of people living with SLE and SSc.

    • In this work, we present evidence to support common and disease-specific non-pharmacological interventions for SLE and SSc.

    • We generated a research agenda as well as an educational agenda to support non-pharmacological management of people with SLE and SSc.

    How might this impact on clinical practice?

    • These recommendations will provide guidance on non-pharmacological interventions in the management of SLE and SSc in clinical practice and promote their use alongside pharmacotherapy to improve the overall quality of care.

    Introduction

    Systemic lupus erythematosus (SLE) is a chronic, inflammatory, autoimmune disease that predominantly affects women and is characterised by multisystem involvement.1 SLE can affect all organs or tissues, including the skin, joints, kidneys, central and peripheral nervous system, lungs, heart, white blood cells and platelets.1 2 Despite advances in pharmacotherapy during the last decades, patients with SLE still experience poor health-related quality of life (HRQoL).3 Systemic sclerosis (SSc), also known as scleroderma, is another rheumatic autoimmune disease that is characterised by vasculopathy and fibrosis of the skin and visceral organs.4 SSc is coupled with a high morbidity burden and has a major impact on patients’ HRQoL.4 New therapies hold promise regarding prevention or even improvement of skin and lung fibrosis, as well as disease manifestations such as renal crisis, pulmonary arterial hypertension (PAH), digital ulcerations and gastro-oesophageal reflux, yet premature death remains a concern, pointing to the urgent need for further optimisation of the disease management.4

    Non-pharmacological management and self-management strategies are progressively substantiated through growing evidence.5 While a substantial use of non-pharmacological interventions is generally seen, the usage, content, delivery methods and access to such interventions are not always optimised, or even suitable. Importantly, no standardised European Alliance of Associations for Rheumatology (EULAR)-endorsed guidance has been developed for the non-pharmacological management of people with SLE and SSc. The absence of proper guidance hinders the widespread adoption of non-pharmacological interventions, representing a missed opportunity to enhance patient care to its fullest potential.

    Hence, a EULAR task force convened to develop recommendations for the non-pharmacological management of SLE and SSc. Successful implementation of the recommendations is likely to result in improved quality of care for people with SLE and SSc across Europe and worldwide.

    Methods

    Steering committee and task force

    Following the EULAR standard operating procedure (SOP) for the development of EULAR-endorsed recommendations,6 the convener (CB; physiotherapist) formed the steering committee and task force. The steering committee included the convener, a methodologist (TS; outcomes researcher, health scientist, occupational therapist), a deputy methodologist (CG-G; rheumatologist) and a postdoctoral fellow within rheumatology who also was an Emerging EULAR network (EMEUNET) representative and rheumatologist (IP; rheumatologist). In addition to the steering committee members, the task force comprised five rheumatologists (one representing EMEUNET), four nurses, two physiotherapists, two occupational therapists, two psychologists, one exercise psychologist, one dietician, one podiatrist and three patient research partners. All healthcare professionals in the task force were experienced in managing patients with SLE and/or SSc. Many had also participated in clinical trials, observational studies, outcome research and research deriving from quality registries. All task force members declared potential conflicts of interest prior to commencement of the task and updated those before submitting the manuscript.

    Target audience

    In compliance with the 2014 update of EULAR SOP for the development of EULAR-endorsed recommendations,6 the main target audience of the recommendations presented herein is healthcare providers (health professionals in rheumatology and physicians) as well as people living with SLE or SSc. Nevertheless, the recommendations and the accompanying research and educational agenda derived by the task force also highlight important unmet needs, thus targeting policymakers and health insurance companies.

    Definitions

    On proposals by the steering committee, the task force agreed on definitions and uniform nomenclature concerning non-pharmacological management and its goals as well as the patient population for a subsequent systematic literature review (SLR). These were discussed and amended until consensus during the first task force meeting, which was held remotely in December 2020.

    The task force defined non-pharmacological management as all management that is not classified as pharmacological by the Directive 2001/83/EC of the European Parliament and the Council of the European Union (6 November 2001) on the Community code relating to medicinal products for human use, that is, any substance or combination of substances, which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.7 8 In addition, non-registered pharmaceuticals under current investigation, for example, in clinical trials, were not considered non-pharmacological management. However, the task force included dietary substitutes, pre and probiotics and faecal microbiota transplants as non-pharmacological interventions, unless they are pharmaceuticals licensed by drug regulatory authorities.

    Non-pharmacological management of connective tissue diseases (CTDs) may be invasive and non-invasive, and includes, but is not limited to patient education,9 self-management,10 physical exercise,11 lifestyle or behaviour interventions (eg, photoprotection or smoking cessation),12 13 psychological counselling,14 cognitive behavioural therapy,15 relaxation or yoga,16 17 dietary, nutritional or microbiome interventions,18 19 stretching,20 massage,21 hand and foot interventions, assistive technology and devices,22 mouth exercise therapy,23 dental health and hygiene,24 modalities such as paraffin baths,25 shockwave therapy,26 acupuncture27 and transcutaneous electrical nerve stimulation,28 hydrotherapy and manual lymph drainage (MLD).29 Furthermore, it may include skin and wound care, ulcer management (eg, debridement),30 minor surgical procedures such as calcinosis removal and detection and management of malnutrition.31

    Non-pharmacological management can be provided as a single intervention or a combination of several non-pharmacological interventions, and alone or adjunct to pharmaceutical treatment.20 32 Non-pharmacological management should not substitute pharmaceutical treatment when the latter is required.33 34

    The goals of non-pharmacological management of CTDs include but are not limited to optimisation of body function and structures, increased activities and participation11 as well as implementation of favourable environmental and personal factors as defined by the International Classification of Functioning nomenclature.35 In this context, environmental factors include working and living conditions, health promotion services, access to insurance and treatments, housing and transportation and social support. Personal factors include well-being, social integration, expectations, capacity to act and lifestyle, for example, physical and intellectual activity, eating and drinking habits, and smoking.

    To mention some examples, non-pharmacological management in CTDs aims for amelioration of disease symptoms,36 improvement of HRQoL37 as well as prevention of disease progression, organ damage accrual,38 comorbidities (eg, cardiovascular disease) and adverse events.36 Additional aims include contribution to increased patient knowledge of the disease through structured patient education9 and optimisation of psychosocial functioning,15 for example, distress abatement, increased coping ability, alleviation of maladaptive illness perceptions and fear for disease progression, increased adherence to treatment, optimised care use and improvement of work capacity.

    While several aspects of non-pharmacological management may be generic or apply to more than one CTD, this task force focused on two CTDs that is, SLE and SSc, and particularly adult patients. This decision was made to ensure feasibility and facilitate in-depth analysis within the given scope.

    Research questions and SLR

    The task force formulated nine research questions to be addressed during the SLRs and that should steer the development of the recommendation statements. Those comprised (1) what non-pharmacological management should aim for, (2) which non-pharmacological interventions have been used, (3) which non-pharmacological interventions have been shown to be efficacious, (4) which instruments have been used to assess the outcome of non-pharmacological management, (5) when the outcome of non-pharmacological management should be assessed, (6) within which health-related domains or organ systems non-pharmacological management should be assessed, (7) SLE and SSc patients’ needs, expectations and preferences with regard to non-pharmacological management, (8) the educational needs for healthcare providers and patients regarding non-pharmacological management and (9) identification of facilitators and barriers for the use of non-pharmacological management of SLE and SSc.

    Subsequently, one SLR was performed about SLE and one about SSc, by the fellow (IP) and colleagues, under the supervision of the methodologists (TS, CG), in compliance with the 2014 update of the EULAR SOP.6 The search strategies were designed in collaboration with an expert librarian from the Karolinska Institutet, Stockholm, Sweden. The MEDLINE, EMBASE, Web of Science and CINAHL databases were searched for content published between January 2000 and June 2021. For each SLR, a two-block search was conducted including the diagnosis of interest and a list of non-pharmacological management strategies. Case series of less than five individuals were excluded, as were articles in languages other than English, Spanish or Swedish. Due to the diverse nature of the research questions, we did not exclude articles based on study design. Two independent reviewers screened the identified titles and abstracts for final selection. Disagreements between reviewers were discussed until consensus; the discussions were guided by the fellow (IP) and the convener (CB). All selected papers underwent risk of bias (RoB) assessment and were deemed robust, intermediate or weak, using the Joanna Briggs Institute critical appraisal (CA) checklists.39 The detailed process and results of the SLR are reported elsewhere.40

    Formulation of overarching principles and recommendation statements

    Based on the results from the SLR and mainly driven by the overall CA, but also expert opinion, overarching principles and recommendation statements were proposed by the steering committee and were presented and discussed with the task force members at four consecutive online meetings in May and June 2022. In these meetings, 23, 20, 17 and 16 of 25 task force members participated, respectively.

    On discussion and amendment of the overarching principles and recommendation statements, a voting process was applied for each statement. In the first round of this voting process, a majority of at least 75% was required to adopt the respective statement. If this was not reached, the statement was discussed and amended further. Subsequently, a second voting round was applied, where a majority of at least 66% was required for adoption of the rephrased statement. If this was not reached, the statement was discussed and amended further to next be subjected to a third voting round. In this third round, a majority of at least 50% was required for adoption of the rephrased statement. If this was not reached, the statement was discarded.

    The voting process was supported by preformulated motivational texts summarising results of the SLR, including the result of the RoB and level of evidence (LoE) assessment, the latter based on the 2011 Oxford Centre for Evidence-Based Medicine LoE 2 system.41 After the meetings, final LoE and strength of recommendation (scale A–D, with A comprising consistent LoE 1 studies and D comprising LoE 4 or inconsistent studies) assessment was performed following the 2011 Oxford Centre for Evidence-Based Medicine LoE 2 system41 and the EULAR SOP.6 The agreed on overarching principles and recommendation statements were distributed to all task force members through the Research Electronic Data Capture system. Level of agreement (LoA) with each statement was scored in a pseudonymous manner on a scale from 0 (complete disagreement) to 10 (complete agreement). Results from the LoA scoring are presented in table 1 as mean, SD and range.

    View this table:
    Table 1

    Recommendations for the non-pharmacological management of SLE and SSc

    Additionally, the task force proposed a research agenda based on identified needs (box 1) as well as an educational agenda for providers of non-pharmacological management of people with SLE and SSc (box 2).

    Box 1

    Research agenda

    1. Randomised controlled trials of non-pharmacological management of people with SLE and SSc with blinding strategies detailed in the study protocols are encouraged.

    2. Identification of patients’ needs for non-pharmacological management is essential, and strategies for identification of such needs should be implemented.

    3. Studies assessing outcomes of non-pharmacological management over a longer term are needed.

    4. Investigation of the efficacy of psychosocial interventions in patients with SSc is required.

    5. Investigation of the efficacy of skin and wound management strategies is required, particularly for people with SSc.

    6. Investigation of the efficacy of different dietary programmes is encouraged.

    7. Further identification of barriers for the implementation of non-pharmacological management of SLE and SSc, as well as means to alleviate those barriers, is warranted.

    • SLE, systemic lupus erythematosus; SSc, systemic sclerosis.

    Box 2

    Educational agenda for providers of non-pharmacological management of SLE and SSc

    1. Regular training for providers of non-pharmacological management of SLE and SSc is advised to ensure the best possible quality of services and patient outcomes.

    2. Increased awareness and education on how to facilitate and evaluate patient education and self-management for people with SLE and SSc should be reinforced among healthcare professionals.

    3. Educational programmes within EULAR and EMEUNET dedicated to the non-pharmacological management of people with SLE and SSc are advocated, both for healthcare providers and patients. This could be done in collaboration with the EULAR School of Rheumatology.

    • EULAR, European Alliance of Associations for Rheumatology; EMEUNET, Emerging EULAR network; SLE, systemic lupus erythematosus; SSc, systemic sclerosis.

    Results

    Twelve recommendations for the non-pharmacological management of people with SLE and SSc were developed based on evidence and expert opinion within the task force, emanating the derivation of four overarching principles, as detailed in table 1. The recommendations were grouped into five generic recommendation statements applicable to people with SLE and people with SSc, four recommendation statements applicable to people with SLE and three recommendation statements applicable to people with SSc. Examples of studies supporting each statement are provided.

    Recommendations for the non-pharmacological management of SLE and SSc

    Non-pharmacological management should be directed towards improving HRQoL in people with SLE (LoE: 1–3) and SSc (LoE: 2–4)

    Physical exercise42 and psychological interventions43 were found in meta-analyses of RCTs (two and three RCTs, respectively)42 43 (LoE: 1) to improve HRQoL in patients with SLE. Furthermore, non-pharmacological management in the form of physical exercise was proven efficacious in improving fatigue in patients with SLE based on two meta-analyses, one of an RCT and a quasi-experimental study (LoE: 3) and one of two RCTs and one quasi-experimental study (LoE: 1),44 45 and psychological interventions were found to improve anxiety in patients with SLE based on a meta-analysis of three RCTs46 (LoE: 1); these studies were assessed as robust in RoB assessment.

    In patients with SSc, improvements in HRQoL were noted after occupational therapy provided for improving upper extremity function in a quasi-experimental study47 (LoE: 4). RCTs encompassing patients with SSc assessed as intermediate in CA found rehabilitative treatment of the hands48 (LoE: 2) and home-based aerobic exercise49 (LoE: 2) to improve HRQoL.

    People with SLE and SSc should be offered patient education and self-management support (LoE: 2–4)

    RCTs assessed as intermediate in RoB assessment employed patient education as a part of physical exercise programmes. The addition of patient education was efficacious in improving aerobic capacity in an RCT of SLE50 (LoE: 2) and mouth opening as compared with the same physical exercise programme (mouth stretching) in an RCT of SSc51 (LoE: 2). Qualitative assessments of multidisciplinary patient education programmes52 (LoE: 4) and group education on disease management53 (LoE: 4) found these strategies to be beneficial for patients with SLE in terms of improving HRQoL52 (LoE: 4) as well as for implementing favourable lifestyle changes53 (LoE: 4); these studies were assessed as robust. In patients with SSc, internet-based self-management programmes could improve self-efficacy and fatigue54 (LoE: 4), and patient education as a complement to occupational therapy improved functional abilities over a longer term (ie, 24 weeks)55 (LoE: 3); these two quasi-experimental studies were deemed robust.

    In people with SLE (LoE: 3) and SSc (LoE: 4), smoking habits should be assessed, and cessation strategies should be implemented

    In the general population, tobacco smoking is an established risk factor for cardiovascular disease, cancer, osteoporosis and chronic obstructive pulmonary disease, among other conditions that constitute relevant comorbidities for patients with SLE and SSc.1 4 A meta-analysis of nine case–control studies found that current smokers had an approximately 50% increased risk for SLE compared with non-smokers (OR: 1.49; 95% CI 1.06 to 2.08; p=0.02)56 (LoE: 3; CA: robust). Moreover, among patients with SLE, smoking has been associated with reduced treatment efficacy. A meta-analysis of 10 observational studies found smoking to be negatively associated with the response of cutaneous SLE to antimalarial therapy (OR: 0.53; 95% CI 0.31 to 0.93; p=0.002),56 while prospective cohort studies have reported reduced overall belimumab efficacy in smokers compared with non-smokers in a Swedish57 (LoE: 3; CA: robust) and an Italian SLE population58 (LoE: 3; CA: robust) as well as reduced belimumab efficacy in mucocutaneous disease activity59 (LoE: 3; CA: robust).

    In the SSc population, a cross-sectional study of 101 patients found that current smokers were more likely to require intravenous vasodilators (OR: 3.8; 95% CI 1.1 to 12.9) and digital debridement (OR: 4.5; 95% CI 1.1 to 18.3) for digital vascular disease compared with non-smokers60 (LoE: 4; CA: robust). Similarly, in a cohort study using the European Scleroderma Trials and Research (EUSTAR) database, heavy smokers (>25 pack-years) had an increased risk for digital ulcers (OR: 1.6; 95% CI 1.1 to 2.3) compared with non-smokers, although no differences were observed in skin fibrosis or gastrointestinal symptoms across different smoking status groups61 (LoE: 4; CA: robust). In the Canadian Scleroderma Research Group cohort, smoking was found to have a negative impact on vascular, gastrointestinal and respiratory outcomes, while cessation was associated with reduced severity of Raynaud’s phenomenon62 (LoE: 4; CA: robust).

    Despite the lack of interventional studies specifically assessing the efficacy of smoking cessation strategies in the SLR performed to inform the recommendations, it was consensual among the task force members that smoking cessation should be encouraged and facilitated in smokers with SLE and SSc based on the above evidence and expert opinion. Nevertheless, cost-effectiveness aspects should be accounted for, and there should be awareness that literature is inconsistent regarding the effect of smoking on vascular outcomes.63

    In people with SLE (LoE: 5) and SSc (LoE: 4), avoidance of cold exposure should be considered for the prevention of Raynaud’s phenomenon. In people with SSc, this is of particular importance for the mitigation of severe Raynaud’s phenomenon (LoE: 4)

    Raynaud’s phenomenon constitutes one of the most frequent and troublesome manifestations of SSc.64 Although less frequent, Raynaud’s phenomenon also impacts negatively on SLE patients’ hand function and performance of daily activities.65 Cold exposure and sudden temperature changes trigger episodes of Raynaud’s phenomenon acknowledged by healthcare providers and patients. In a qualitative study, patients with SSc identified cold as the main exacerbating factor for Raynaud’s phenomenon66 (LoE: 4; CA: robust). In a cross-sectional study, SSc patients reported more frequent and longer Raynaud’s phenomenon exacerbations during winter compared with summer67 (LoE: 4; CA: intermediate). Consistently, cold challenge induces delayed reperfusion as evidenced by imaging techniques in people suffering from Raynaud’s phenomenon68 (LoE: 4; CA: robust). Finally, the task force argued that practical advice to people with SSc suffering from Raynaud’s phenomenon may include the use of gloves and heating devices for the hands, avoidance of direct contact with cold surfaces and a thorough drying of the skin, as recommended by the Arthritis Research and Collaboration Hub study group.5 A recent RCT corroborated that gloves decrease the burden of Raynaud’s phenomenon, but silver fibre gloves yielded no difference compared with conventional ones69 (LoE: 2; CA: robust).

    Physical exercise should be considered for people with SLE (LoE: 1–3) and SSc (LoE: 2–4)

    For both diseases, exercise and promotion of physical activity were among the most studied intervention strategies and were found to improve patient outcomes in several studies. Physical exercise was found to be a viable management strategy in improving fatigue in adult patients with SLE based on two meta-analyses, one of one RCT and one quasi-experimental study (LoE: 3) and one of two RCTs and one quasi-experimental study (LoE: 1),44 45 and in improving aerobic capacity, based on one meta-analysis of seven RCTs44 (LoE: 1); both studies were deemed as robust in overall CA. In adult patients with SSc, an RCT found improvements in mouth opening after application of an oral exercise programme23 (LoE: 2; CA: intermediate). Physiotherapy was found to improve functional impairment in a quasi-experimental study70 (LoE: 4; CA: robust).

    The task force felt that it is important to underline that the patient’s health status, cardiorespiratory status in particular, potential risks or medical contraindications should always be considered before commencing physical exercise programmes, and such programmes should be provided or suggested based on risk and benefit ponderation. Moreover, it is important that physical exercise programmes are tailored to each individual patient, based not only on the risk/benefit ratio but also on the patient’s individual needs, expectations and preferences.

    Recommendations for the non-pharmacological management of SLE

    In people with SLE, patient education and self-management support should be considered for improving physical exercise outcomes (LoE: 2) and HRQoL (LoE: 2–4) and could be considered for enhancing self-efficacy (LoE: 3)

    An RCT employed patient education and self-management support as parts of a supervised aerobic exercise programme and found the intervention to be efficacious in improving aerobic capacity and mental health as compared with usual care in an RCT of SLE50 (LoE: 2; CA: intermediate). Furthermore, an RCT that investigated web-based patient education and counselling14 (LoE: 3; CA: weak) and a quasi-experimental study that examined an educational programme for enhancing self-management in patients with SLE71 (LoE: 3; CA: intermediate) found these interventions to be efficacious in improving self-efficacy. A pilot RCT that investigated an internet-based coping skill training programme in patients with SLE revealed benefit in HRQoL72 (LoE: 3; CA: weak), as did a qualitative study of multidisciplinary patient education52 (LoE: 4; CA: robust).

    In people with SLE, photoprotection should be advised for the prevention of flares (LoE: 4)

    Ultraviolet (UV) radiation is a well-acknowledged triggering factor of cutaneous and systemic lupus flares.73 74 Quasi-experimental studies have shown that broad-spectrum sunscreens prevent cutaneous lesions on photo-provocation (LoE: 4; CA: robust75 and LoE: 4; CA: weak76). Based on this evidence and expert opinion within the task force, people with SLE should avoid direct sun exposure, especially during days with high UV index, use physical barriers such as hats, sunglasses and long-sleeved shirts and pants, and use of broad-spectrum sunscreen; assessment of the need for vitamin D supplements should be done when indicated.1 73

    In people with SLE, psychosocial interventions should be considered for improving HRQoL (LoE: 1–2), anxiety (LoE: 1) and depressive symptoms (LoE: 1)

    In SLRs with meta-analyses that were assessed as robust in overall CA, psychological interventions in the form of cognitive behavioural therapy (CBT), group therapy and psychoeducational programmes were shown to be an efficacious management strategy for improving HRQoL in adults with SLE based on a meta-analysis of two RCTs42 (LoE: 2) and a meta-analysis of three RCTs43 (LoE: 1). Counselling, CBT and supported psychotherapy improved anxiety based on a meta-analysis of three RCTs46 (LoE: 1). CBT and psychoeducational self-management support ameliorated depressive symptoms based on a meta-analysis of three RCTs43 (LoE: 1). Counselling and psychoeducational programmes were led by different healthcare providers, including social workers, psychologists, and nurses, whereas psychotherapeutic interventions were delivered by certified psychotherapists. Which healthcare providers deliver different psychoeducational programmes may differ considerably across countries, depending on local legislation as well as access to and use of resources.

    In people with SLE, aerobic exercise should be considered for increasing aerobic capacity (LoE: 1) and for reducing fatigue (LoE: 1–3) and depressive symptoms (LoE: 3)

    An SLR with meta-analyses from 2017 found that aerobic exercise increased aerobic capacity in patients with SLE (based on a meta-analysis of two RCTs and three quasi-experimental studies; LoE: 1), while decreasing fatigue (based on a meta-analysis of one RCT and one quasi-experimental study; LoE: 3), and depressive symptoms (based on a meta-analysis of two RCTs and one quasi-experimental study; LoE: 3)44 and was assessed as robust in CA. Another meta-analysis of two RCTs and one quasi-experimental study assessed as robust in CA found that aerobic physical exercise was effective in managing fatigue in patients with SLE45 (LoE: 1). Moreover, aerobic exercise improved functional performance as assessed using the 6 min walk distance (6MWD) test in an RCT deemed as intermediate in CA77 (LoE: 2).

    Recommendations for the non-pharmacological management of SSc

    In people with SSc, patient education and self-management support should be considered for improving hand function (LoE: 2–4), mouth-related outcomes (LoE: 2), HRQoL (LoE: 2–4) and ability to perform daily activities (LoE: 2–3)

    An RCT found self-administered hand exercises effective in improving hand mobility78 (LoE: 2; CA: intermediate). Another RCT demonstrated the efficacy of face-to-face training in improving the outcomes of orofacial exercise51 (LoE: 2; CA: intermediate). An RCT assessed as intermediate in CA found that home-based exercise comprising aerobic exercise on a stationary bike, muscular endurance training of the upper limb and stretching exercises for the hands, following a physiotherapist-supported educational programme, was effective in improving SSc patients’ HRQoL and functional ability49 (LoE: 2). Individualised rehabilitation programmes were found to improve hand mobility and HRQoL79 (LoE: 3) while psychoeducational group programmes ameliorated feelings of helplessness80 (LoE: 4) in quasi-experimental studies of patients with SSc assessed as robust in overall CA. Another robust in CA quasi-experimental study found patient education as a complement to occupational therapy to improve functional abilities as assessed with the Health Assessment Questionnaire (HAQ) and the Evaluation of Daily Activity Questionnaire (EDAQ)55 (LoE: 3). A home-based self-management programme for hand exercise was found to improve hand function in a quasi-experimental study81 that was also deemed as robust in CA (LoE: 4).

    In people with SSc, orofacial, hand and aerobic and resistance exercise should be considered for improving microstomia (LoE: 2–4), hand function (LoE: 2–4) and physical capacity (LoE: 2–4), respectively

    Microstomia and hand function emerged as major targets of non-pharmacological management, especially in studies evaluating physical exercise. RCTs assessed as intermediate in CA found mouth exercise to be efficacious in improving microstomia23 (LoE: 2) and hand exercise in improving hand function78 (LoE: 2), while body exercise increased the 6MWD49 (LoE: 2). The favourable effects of rehabilitation programmes were discussed. Quasi-experimental studies assessed as robust in CA found that rehabilitative exercise programmes were efficacious in improving hand function and HRQoL, for example, programmes comprising warm-up and cool-down exercises, training of motor functions and respiratory exercises79 (LoE: 3), mouth stretching and oral augmentation exercises ameliorated microstomia82 (LoE: 4), thermal modalities (eg, baths), tissue mobilisation and hand mobility exercises improved hand function47 (LoE: 4) and combined resistance and aerobic exercise enhanced aerobic capacity83 (LoE: 4) in patients with SSc.

    In people with SSc and puffy hands, MLD could be considered for improving hand function (LoE: 2)

    One RCT examined the effect of 5 weekly sessions of MLD compared with usual care in SSc patients with oedematous hands and found that MLD improved hand function measured using the Hand Mobility in Scleroderma index and SSc patients’ perception of upper extremity function assessed using visual analogue scales84 (LoE: 2; CA: robust). The improvements in these outcomes were maintained up to 9 weeks after treatment discontinuation. Improvements were also noted in HAQ and 36-item Short Form health survey scores at the end of treatment, although these improvements were not fully sustained at the 9-week follow-up. The findings from this study and expert opinion within the task force supported the endorsement of this recommendation statement.

    Research agenda

    Box 1 details the research agenda proposed by the task force. This was based on areas of limited or weak evidence as well as identified needs. The overarching principles should be applied when addressing the proposed research topics.

    In brief, while the SLR identified, several RCTs dealing with the non-pharmacological management of SLE and SSc, design details were not always clearly indicated, especially the blinding strategies, which limited their LoE. Identification of patients’ needs is essential, and strategies for identification of such needs should be implemented, for example, as suggested by the James Lind Alliance Priority Setting Partnerships.85 86 The majority of interventional studies had a limited follow-up time of 4–12 weeks, seldom longer. Hence, studies assessing outcomes of non-pharmacological management over a longer term are needed.

    While the efficacy of diverse psychological interventions was investigated in several studies encompassing people with SLE, it has yet to be explored within SSc. Dietary therapy was not thoroughly explored in either of the two diseases. Adherence to a Mediterranean diet was associated with a lower cardiovascular risk, lower disease activity levels and protection against organ damage in a cross-sectional study of SLE assessed as robust in CL36 (LoE: 3), but no conclusions regarding causality can be drawn from this study.

    Moreover, recommendations about wound management could not be derived based on current evidence, indicating a need for further studies within this area, which is particularly important for patients with SSc. Finally, further identification of barriers for the implementation of non-pharmacological management of SLE and SSc, as well as means to alleviate those barriers, is warranted.

    Educational agenda for providers of non-pharmacological management of SLE and SSc

    Box 2 details the educational agenda proposed by the task force for providers of non-pharmacological management of people with SLE and SSc. The purpose of this agenda is to enhance the healthcare professionals’ skills and competencies as well as the confidence needed for providing these services.

    Discussion

    Increasing awareness of the importance of non-pharmacological management and self-management strategies for people living with SLE and SSc necessitated the development of overarching principles and recommendations by a group of experts, to be used as a guide in the identification of needs, implementation and evaluation of non-pharmacological management. Hence, a multidisciplinary EULAR task force convened and formulated the overarching principles and recommendations presented herein following the EULAR SOPs.6 An SLR preceded to inform the recommendations. Along with recommendations regarding lifestyle behaviours87 as well as recommendations for physical activity,88 patient education89 and implementation of self-management strategies in inflammatory arthritis,90 the statements presented herein intend to not only guide non-pharmacological management but also increase awareness of the importance of patient involvement in the management of their disease, encourage interprofessional and multidisciplinary teams to tackle clinical challenges and prompt orchestrated research for addressing remaining important questions that form a research agenda, as determined by the task force.

    The heterogeneity in study design and conduct limited the LoE and strength of recommendation in several instances. Data in the literature were scarce even for well-established non-pharmacological strategies such as photoprotection for patients with SLE, which is not surprising considering the known contribution of sun exposure to disease precipitation, imposing ethical limitations for the conduct of RCTs on such interventions. The same could be argued for the contribution of assistive devices to enhancing mobility or improving accessibility, which is rather self-evident. Nonetheless, the rarity of SLE and SSc necessitates global collaborative efforts in the design of studies, especially investigator-initiated endeavours that deserve better funding.

    Moderate to strong evidence existed in the literature for the benefits of physical activity and exercise for SLE and SSc patients, including documented benefits regarding HRQoL, fatigue and cardiovascular burden.33 91–104 Despite sparse evidence regarding smoking cessation for improving disease activity and treatment outcomes and avoidance of cold exposure for the prevention of Raynaud’s phenomenon, the task force agreed on the crucial importance of these two recommendations. The task force also agreed that cost-effectiveness aspects should be accounted for; to illustrate why, proper modelling of the effect of smoking has been shown to be essential in studies of vascular outcomes within rheumatic diseases, SSc in particular, resulting in rather insipid evidence.63

    It is important to underscore that concomitant conditions such as fibromyalgia or other syndromes causing chronic pain, as well as established irreversible organ damage, pose challenges when evaluating the effectiveness of non-pharmacological management. Together with the complexity of SLE and SSc in terms of heterogeneity of disease manifestations, the multidimensionality of non-pharmacological interventions and sparsity of high-quality data and RCTs, especially RCTs meeting their predetermined endpoints, is not unexpected. These factors also form incentives for large-scale collaborative efforts to determine patient needs and priorities, identify barriers and means for overcoming them and investigate the efficacy of psychosocial interventions, different dietary schemes and skin and wound management. Also, efforts should be applied in educating healthcare professionals and patients on the potentiality of different non-pharmacological strategies, which in turn is expected to facilitate person-centredness in non-pharmacological management, accounting for the heterogeneity of SLE and SSc. While implementation of the recommendations will be conducted at various phases according to Loza et al,105 a first step will be a survey-based investigation of SLE and SSc patients’ and healthcare professionals’ perception of whether the recommendations and overarching principles align with current management praxis across different countries as well as their views on facilitators and barriers they foresee for their implementation. This will provide an important mapping of the current practice patterns and highlight needs for the implementation. Further steps will include determination of implementation strategies at a centre, national or international levels such as educational activities designed for patients and for healthcare professionals, and evaluation of the implementation.

    In summary, results from an SLR, RoB assessment and expert opinion within the task force resulted in the formulation of overarching principles and a comprehensive set of recommendations for the non-pharmacological management of people living with SLE and SSc. The overarching principles and recommendations presented herein promote holistic and multidisciplinary approaches in SLE and SSc patient management, patient involvement in their care and individually tailored strategies towards optimised outcomes. Despite a sparsity in high-quality evidence, the recommendations presented herein may be seen as a useful guide for healthcare providers and patients with SLE and SSc when setting up individual disease management strategies, with non-pharmacological constituents as integral components. Last but not least, the task force developed a research agenda to guide future endeavours in the field.

    Ethics statements

    Patient consent for publication

    Ethics approval

    Not applicable.

    Acknowledgments

    The task force expresses gratitude to Alvaro Gomez, Alexander Tsoi, Jun Weng Chow and Denise Pezzella for contributions to the SLR performed to inform the recommendations, as well as the EULAR Secretariat for assistance during the entire process. We would also like to thank Emma-Lotta Säätelä, librarian at the KI Library, for her help with the search strategy for the SLRs.

    References

    1. ↵
      2. Kaul A ,
      3. Gordon C ,
      4. Crow MK , et al
      . Systemic lupus erythematosus. Nat Rev Dis Primers 2016;2:16039. doi:10.1038/nrdp.2016.39
      OpenUrl
    2. ↵
      2. Anders HJ ,
      3. Saxena R ,
      4. Zhao MH , et al
      . Lupus nephritis. Nat Rev Dis Primers 2020;6:7. doi:10.1038/s41572-019-0141-9
      OpenUrl
    3. ↵
      2. Gomez A ,
      3. Qiu V ,
      4. Cederlund A , et al
      . Adverse health-related quality of life outcome despite adequate clinical response to treatment in systemic lupus erythematosus. Front Med (Lausanne) 2021;8:651249. doi:10.3389/fmed.2021.651249
    4. ↵
      2. Denton CP ,
      3. Khanna D
      . Systemic sclerosis. Lancet 2017;390:1685–99. doi:10.1016/S0140-6736(17)30933-9
      OpenUrlCrossRefPubMed
    5. ↵
      2. Stöcker JK ,
      3. Schouffoer AA ,
      4. Spierings J , et al
      . Evidence and consensus-based recommendations for non-pharmacological treatment of fatigue, hand function loss, Raynaud’s phenomenon and Digital ulcers in patients with systemic sclerosis. Rheumatology 2022;61:1476–86. doi:10.1093/rheumatology/keab537
      OpenUrl
    6. ↵
      2. van der Heijde D ,
      3. Aletaha D ,
      4. Carmona L , et al
      . Update of the EULAR standardised operating procedures for EULAR-endorsed recommendations. Ann Rheum Dis 2015;74:8–13. doi:10.1136/annrheumdis-2014-206350
      OpenUrlAbstract/FREE Full Text
    7. ↵
      2. Cramp F ,
      3. Hewlett S ,
      4. Almeida C , et al
      . Non-pharmacological interventions for fatigue in rheumatoid arthritis. Cochrane Database Syst Rev 2013;23. doi:10.1002/14651858.CD008322.pub2
    8. ↵
      Directive 2001/83/EC of the European parliament and the council of the European Union (November 6 otCcrtmpfhu). Available: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/directive-2001/83/ec-european-parliament-council-6-november-2001-community-code-relating-medicinal-products-human-use_en.pdf [Accessed 11 Oct 2022].
    9. ↵
      2. Samuelson UK ,
      3. Ahlmén EM
      . Development and evaluation of a patient education program for persons with systemic sclerosis (scleroderma). Arthritis Care Res 2000;13:141–8. doi:10.1002/1529-0131(200006)13:3<141::AID-ANR3>3.0.CO;2-M
      OpenUrlPubMed
    10. ↵
      2. Poole JL ,
      3. Skipper B ,
      4. Mendelson C
      . Evaluation of a mail-delivered, print-format, self-management program for persons with systemic sclerosis. Clin Rheumatol 2013;32:1393–8. doi:10.1007/s10067-013-2282-7
      OpenUrlCrossRefPubMed
    11. ↵
      2. Keramiotou K ,
      3. Anagnostou C ,
      4. Kataxaki E , et al
      . The impact of upper limb exercise on function, daily activities and quality of life in systemic lupus erythematosus: a pilot randomised controlled trial. RMD Open 2020;6:e001141. doi:10.1136/rmdopen-2019-001141
    12. ↵
      2. Xu D ,
      3. You X ,
      4. Wang Z , et al
      . Chinese systemic lupus erythematosus treatment and research group registry VI: effect of cigarette smoking on the clinical phenotype of Chinese patients with systemic lupus erythematosus. PLoS ONE 2015;10:e0134451. doi:10.1371/journal.pone.0134451
    13. ↵
      2. Zahn S ,
      3. Graef M ,
      4. Patsinakidis N , et al
      . Ultraviolet light protection by a Sunscreen prevents interferon-driven skin inflammation in cutaneous lupus erythematosus. Exp Dermatol 2014;23:516–8. doi:10.1111/exd.12428
      OpenUrl
    14. ↵
      2. Kankaya H ,
      3. Karadakovan A
      . Effects of web-based education and counselling for patients with systemic lupus erythematosus: self-efficacy, fatigue and assessment of care. Lupus 2020;29:884–91. doi:10.1177/0961203320928423
      OpenUrl
    15. ↵
      2. Navarrete-Navarrete N ,
      3. Peralta-Ramírez MI ,
      4. Sabio-Sánchez JM , et al
      . Efficacy of cognitive behavioural therapy for the treatment of chronic stress in patients with lupus erythematosus: a randomized controlled trial. Psychother Psychosom 2010;79:107–15. doi:10.1159/000276370
      OpenUrlCrossRefPubMed
    16. ↵
      2. Saoji AA ,
      3. Das P ,
      4. Devi NS
      . Yoga therapy as an adjunct to conventional management of systemic sclerosis: a case series. J Ayurveda Integr Med 2021;12:705–9. doi:10.1016/j.jaim.2021.06.013
      OpenUrl
    17. ↵
      2. Middleton KR ,
      3. Haaz Moonaz S ,
      4. Hasni SA , et al
      . Yoga for systemic lupus erythematosus (SLE): clinician experiences and qualitative perspectives from students and yoga instructors living with SLE. Complement Ther Med 2018;41:111–7. doi:10.1016/j.ctim.2018.09.001
      OpenUrl
    18. ↵
      2. Minami Y ,
      3. Sasaki T ,
      4. Arai Y , et al
      . Diet and systemic lupus erythematosus: a 4 year prospective study of Japanese patients. J Rheumatol 2003;30:747–54.
      OpenUrlAbstract/FREE Full Text
    19. ↵
      2. Frech TM ,
      3. Khanna D ,
      4. Maranian P , et al
      . Probiotics for the treatment of systemic sclerosis-associated gastrointestinal bloating/ distention. Clin Exp Rheumatol 2011;29:S22–5.
      OpenUrlPubMed
    20. ↵
      2. Mugii N ,
      3. Hasegawa M ,
      4. Matsushita T , et al
      . The efficacy of self-administered stretching for finger joint motion in Japanese patients with systemic sclerosis. J Rheumatol 2006;33:1586–92.
      OpenUrlAbstract/FREE Full Text
    21. ↵
      2. Vannajak K ,
      3. Boonprakob Y ,
      4. Eungpinichpong W , et al
      . The short-term effect of Gloving in combination with traditional Thai massage, heat, and stretching exercise to improve hand mobility in scleroderma patients. J Ayurveda Integr Med 2014;5:50–5. doi:10.4103/0975-9476.128859
      OpenUrl
    22. ↵
      2. Murphy SL ,
      3. Barber M ,
      4. Huang S , et al
      . Intensive and app-delivered occupational therapy to improve upper extremity function in early diffuse cutaneous systemic sclerosis: a pilot two-arm trial. Rheumatology (Oxford) 2021;60:5002–11. doi:10.1093/rheumatology/keab339
      OpenUrl
    23. ↵
      2. Cüzdan N ,
      3. Türk İ ,
      4. Çi̇ftçi̇ V , et al
      . The effect of a home-based orofacial exercise program on oral aperture of patients with systemic sclerosis: a single-blind prospective randomized controlled trial. Arch Rheumatol 2021;36:176–84. doi:10.46497/ArchRheumatol.2021.8295
      OpenUrl
    24. ↵
      2. Poole J ,
      3. Conte C ,
      4. Brewer C , et al
      . Oral hygiene in scleroderma: the effectiveness of a multi-disciplinary intervention program. Disability and Rehabilitation 2010;32:379–84. doi:10.3109/09638280903171527
      OpenUrlCrossRefPubMed
    25. ↵
      2. Mancuso T ,
      3. Poole JL
      . The effect of paraffin and exercise on hand function in persons with scleroderma: a series of single case studies. J Hand Ther 2009;22:71–7. doi:10.1016/j.jht.2008.06.009
      OpenUrlPubMed
    26. ↵
      2. Saito S ,
      3. Ishii T ,
      4. Kamogawa Y , et al
      . Extracorporeal shock wave therapy for digital ulcers of systemic sclerosis: a phase 2 pilot study. Tohoku J Exp Med 2016;238:39–47. doi:10.1620/tjem.238.39
      OpenUrl
    27. ↵
      2. Greco CM ,
      3. Kao AH ,
      4. Maksimowicz-McKinnon K , et al
      . Acupuncture for systemic lupus erythematosus: a pilot RCT feasibility and safety study. Lupus 2008;17:1108–16. doi:10.1177/0961203308093921
      OpenUrlCrossRefPubMedWeb of Science
    28. ↵
      2. Sallam H ,
      3. McNearney TA ,
      4. Doshi D , et al
      . Transcutaneous electrical nerve stimulation (TENS) improves upper GI symptoms and balances the sympathovagal activity in scleroderma patients. Dig Dis Sci 2007;52:1329–37. doi:10.1007/s10620-006-9257-3
      OpenUrlCrossRefPubMedWeb of Science
    29. ↵
      2. Bongi SM ,
      3. Del Rosso A ,
      4. Passalacqua M , et al
      . Manual lymph drainage improving upper extremity edema and hand function in patients with systemic sclerosis in edematous phase. Arthritis Care Res 2011;63:1134–41. doi:10.1002/acr.20487
      OpenUrlCrossRef
    30. ↵
      2. Hassanien M ,
      3. Rashad S ,
      4. Mohamed N , et al
      . Non-invasive oxygen-ozone therapy in treating digital ulcers of patients with systemic sclerosis. Acta Reumatol Port 2018;43:210–6.
      OpenUrl
    31. ↵
      2. Doerfler B ,
      3. Allen TS ,
      4. Southwood C , et al
      . Medical nutrition therapy for patients with advanced systemic sclerosis (MNT PASS): a pilot intervention study. JPEN J Parenter Enteral Nutr 2017;41:678–84. doi:10.1177/0148607115597883
      OpenUrlPubMed
    32. ↵
      2. Horváth J ,
      3. Bálint Z ,
      4. Szép E , et al
      . Efficacy of intensive hand physical therapy in patients with systemic sclerosis. Clin Exp Rheumatol 2017;35 Suppl 106:159–66.
      OpenUrlPubMed
    33. ↵
      2. Fangtham M ,
      3. Kasturi S ,
      4. Bannuru RR , et al
      . Non-pharmacologic therapies for systemic lupus erythematosus. Lupus 2019;28:703–12. doi:10.1177/0961203319841435
      OpenUrlPubMed
    34. ↵
      2. Gordon C ,
      3. Amissah-Arthur M-B ,
      4. Gayed M , et al
      . The British society for rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology (Oxford) 2018;57:1502–3. doi:10.1093/rheumatology/key170
      OpenUrl
    35. ↵
      2. Jiménez Buñuales MT ,
      3. González Diego P ,
      4. Martín Moreno JM
      . International classification of functioning, disability and health (ICF) 2001. Rev Esp Salud Publica 2002;76:271–9. doi:10.1590/s1135-57272002000400002
      OpenUrlPubMed
    36. ↵
      2. Pocovi-Gerardino G ,
      3. Correa-Rodríguez M ,
      4. Callejas-Rubio J-L , et al
      . Beneficial effect of Mediterranean diet on disease activity and cardiovascular risk in systemic lupus erythematosus patients: a cross-sectional study. Rheumatology (Oxford) 2021;60:160–9. doi:10.1093/rheumatology/keaa210
      OpenUrlCrossRef
    37. ↵
      2. Carvalho M de ,
      3. Sato EI ,
      4. Tebexreni AS , et al
      . Effects of supervised cardiovascular training program on exercise tolerance, aerobic capacity, and quality of life in patients with systemic lupus erythematosus. Arthritis Rheum 2005;53:838–44. doi:10.1002/art.21605
      OpenUrlCrossRefPubMedWeb of Science
    38. ↵
      2. Alvarez-Nemegyei J ,
      3. Bautista-Botello A ,
      4. Dávila-Velázquez J
      . Association of complementary or alternative medicine use with quality of life, functional status or cumulated damage in chronic rheumatic diseases. Clin Rheumatol 2009;28:547–51. doi:10.1007/s10067-008-1082-y
      OpenUrlCrossRefPubMed
    39. ↵
      2. Aromataris E ,
      3. Munn Z
      , eds. JBI manual for evidence synthesis. 2020. Available: https://synthesismanual.jbi.global
    40. ↵
      2. Parodis I ,
      3. Gomez A ,
      4. Tsoi A , et al
      . n.d. Systematic literature review informing the EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis. RMD Open doi:10.1136/rmdopen-2023-003297
    41. ↵
      1. OCEBM Levels of Evidence Working Group
      . Oxford centre for evidence-based medicine: the Oxford levels of evidence 2. 2011. Available: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence [Accessed 14 Jun 2022].
    42. ↵
      2. da Hora TC ,
      3. Lima K ,
      4. Maciel R
      . The effect of therapies on the quality of life of patients with systemic lupus erythematosus: a meta-analysis of randomized trials. Adv Rheumatol 2019;59:34. doi:10.1186/s42358-019-0074-8
      OpenUrl
    43. ↵
      2. Liang H ,
      3. Tian X ,
      4. Cao L-Y , et al
      . Effect of psychological intervention on Healthrelated quality of life in people with systemic lupus erythematosus: a systematic review. Int J Nurs Sci 2014;1:298–305. doi:10.1016/j.ijnss.2014.07.008
      OpenUrl
    44. ↵
      2. O’Dwyer T ,
      3. Durcan L ,
      4. Wilson F
      . Exercise and physical activity in systemic lupus erythematosus: a systematic review with meta-analyses. Semin Arthritis Rheum 2017;47:204–15. doi:10.1016/j.semarthrit.2017.04.003
      OpenUrlCrossRefPubMed
    45. ↵
      2. Wu M-L ,
      3. Yu K-H ,
      4. Tsai J-C
      . The effectiveness of exercise in adults with systemic lupus erythematosus: a systematic review and meta-analysis to guide evidence-based practice. Worldviews Evid Based Nurs 2017;14:306–15. doi:10.1111/wvn.12221
      OpenUrlPubMed
    46. ↵
      2. Zhang J ,
      3. Wei W ,
      4. Wang CM
      . Effects of psychological interventions for patients with systemic lupus erythematosus: a systematic review and meta-analysis. Lupus 2012;21:1077–87. doi:10.1177/0961203312447667
      OpenUrlCrossRefPubMed
    47. ↵
      2. Murphy SL ,
      3. Barber MW ,
      4. Homer K , et al
      . Occupational therapy treatment to improve upper extremity function in individuals with early systemic sclerosis: a pilot study. Arthritis Care Res (Hoboken) 2018;70:1653–60. doi:10.1002/acr.23522
      OpenUrl
    48. ↵
      2. Bongi SM ,
      3. Del Rosso A ,
      4. Galluccio F , et al
      . Efficacy of connective tissue massage and MC Mennell joint manipulation in the rehabilitative treatment of the hands in systemic sclerosis. Clin Rheumatol 2009;28:1167–73. doi:10.1007/s10067-009-1216-x
      OpenUrlCrossRefPubMedWeb of Science
    49. ↵
      2. Filippetti M ,
      3. Cazzoletti L ,
      4. Zamboni F , et al
      . Effect of a tailored home-based exercise program in patients with systemic sclerosis: a randomized controlled trial. Scand J Med Sci Sports 2020;30:1675–84. doi:10.1111/sms.13702
      OpenUrlPubMed
    50. ↵
      2. Boström C ,
      3. Elfving B ,
      4. Dupré B , et al
      . Effects of a one-year physical activity programme for women with systemic lupus erythematosus - a randomized controlled study. Lupus 2016;25:602–16. doi:10.1177/0961203315622817
      OpenUrlCrossRefPubMed
    51. ↵
      2. Uras C ,
      3. Mastroeni S ,
      4. Tabolli S , et al
      . A comparison between two educational methods in the rehabilitation of the microstomia in systemic sclerosis: a randomized controlled trial. Clin Rehabil 2019;33:1747–56. doi:10.1177/0269215519858395
      OpenUrlPubMed
    52. ↵
      2. Miljeteig K ,
      3. Graue M
      . Evaluation of a multidisciplinary patient education program for people with systemic lupus erythematosus. J Nurs Healthc Chronic Illn 2009;1:87–95. doi:10.1111/j.1365-2702.2008.01010.x
      OpenUrl
    53. ↵
      2. Brown SJ ,
      3. Somerset ME ,
      4. McCabe CS , et al
      . The impact of group education on participants' management of their disease in lupus and scleroderma. Musculoskeletal Care 2004;2:207–17. doi:10.1002/msc.72
      OpenUrlCrossRefPubMed
    54. ↵
      2. Poole JL ,
      3. Mendelson C ,
      4. Skipper B , et al
      . Taking charge of systemic sclerosis: a pilot study to assess the effectiveness of an internet self-management program. Arthritis Care Res (Hoboken) 2014;66:778–82. doi:10.1002/acr.22192
      OpenUrl
    55. ↵
      2. Zanatta E ,
      3. Rodeghiero F ,
      4. Pigatto E , et al
      . Long-term improvement in activities of daily living in women with systemic sclerosis attending occupational therapy. Br J Occup Ther 2017;80:417–22. doi:10.1177/0308022617698167
      OpenUrl
    56. ↵
      2. Parisis D ,
      3. Bernier C ,
      4. Chasset F , et al
      . Impact of tobacco smoking upon disease risk, activity and therapeutic response in systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun Rev 2019;18:102393. doi:10.1016/j.autrev.2019.102393
      OpenUrlPubMed
    57. ↵
      2. Parodis I ,
      3. Sjöwall C ,
      4. Jönsen A , et al
      . Smoking and pre-existing organ damage reduce the efficacy of Belimumab in systemic lupus erythematosus. Autoimmunity Reviews 2017;16:343–51. doi:10.1016/j.autrev.2017.02.005
      OpenUrlPubMed
    58. ↵
      2. Gatto M ,
      3. Saccon F ,
      4. Zen M , et al
      . Early disease and low baseline damage as predictors of response to Belimumab in patients with systemic lupus erythematosus in a real-life setting. Arthritis Rheumatol 2020;72:1314–24. doi:10.1002/art.41253
      OpenUrl
    59. ↵
      2. Parodis I ,
      3. Gomez A ,
      4. Frodlund M , et al
      . Smoking reduces the efficacy of belimumab in mucocutaneous lupus. Expert Opinion on Biological Therapy 2018;18:911–20. doi:10.1080/14712598.2018.1494719
      OpenUrl
    60. ↵
      2. Harrison BJ ,
      3. Silman AJ ,
      4. Hider SL , et al
      . Cigarette smoking as a significant risk factor for digital vascular disease in patients with systemic sclerosis. Arthritis Rheum 2002;46:3312–6. doi:10.1002/art.10685
      OpenUrlCrossRefPubMedWeb of Science
    61. ↵
      2. Jaeger VK ,
      3. Valentini G ,
      4. Hachulla E , et al
      . Brief report: smoking in systemic sclerosis: a longitudinal European scleroderma trials and research group study. Arthritis Rheumatol 2018;70:1829–34. doi:10.1002/art.40557
      OpenUrl
    62. ↵
      2. Hudson M ,
      3. Lo E ,
      4. Lu Y , et al
      . Cigarette smoking in patients with systemic sclerosis. Arthritis Rheum 2011;63:230–8. doi:10.1002/art.30071
      OpenUrlCrossRefPubMed
    63. ↵
      2. Hudson M ,
      3. Lo E ,
      4. Baron M , et al
      . Modeling smoking in systemic sclerosis: a comparison of different statistical approaches. Arthritis Care Res 2011;63:570–8. doi:10.1002/acr.20416
      OpenUrl
    64. ↵
      2. Bassel M ,
      3. Hudson M ,
      4. Taillefer SS , et al
      . Frequency and impact of symptoms experienced by patients with systemic sclerosis: results from a Canadian national survey. Rheumatology (Oxford) 2011;50:762–7. doi:10.1093/rheumatology/keq310
      OpenUrlCrossRefPubMedWeb of Science
    65. ↵
      2. Malcus Johnsson P ,
      3. Sandqvist G ,
      4. Nilsson J-Å , et al
      . Hand function and performance of daily activities in systemic lupus erythematosus: a clinical study. Lupus 2015;24:827–34. doi:10.1177/0961203314565690
      OpenUrlCrossRefPubMed
    66. ↵
      2. Pauling JD ,
      3. Domsic RT ,
      4. Saketkoo LA , et al
      . Multinational qualitative research study exploring the patient experience of Raynaud’s phenomenon in systemic sclerosis. Arthritis Care Res (Hoboken) 2018;70:1373–84. doi:10.1002/acr.23475
      OpenUrl
    67. ↵
      2. Pauling JD ,
      3. Reilly E ,
      4. Smith T , et al
      . Factors influencing Raynaud condition score diary outcomes in systemic sclerosis. J Rheumatol 2019;46:1326–34. doi:10.3899/jrheum.180818
      OpenUrlAbstract/FREE Full Text
    68. ↵
      2. Wilkinson JD ,
      3. Leggett SA ,
      4. Marjanovic EJ , et al
      . A multicenter study of the validity and reliability of responses to hand cold challenge as measured by laser speckle contrast imaging and Thermography: outcome measures for systemic sclerosis-related Raynaud’s phenomenon. Arthritis Rheumatol 2018;70:903–11. doi:10.1002/art.40457
      OpenUrl
    69. ↵
      2. Liem SIE ,
      3. Hoekstra EM ,
      4. Bonte-Mineur F , et al
      . The effect of silver fibre gloves on Raynaud's phenomenon in patients with systemic sclerosis: a double-blind randomized crossover trial. Rheumatology (Oxford) 2023;62:SI74–81. doi:10.1093/rheumatology/keac243
      OpenUrl
    70. ↵
      2. Brignoli E ,
      3. Frassanito P ,
      4. Vercesi E , et al
      . Rehabilitation in systemic sclerosis: proposed personalised rehabilitation programme. G Ital Med Lav Ergon 2018;40:248–56.
      OpenUrl
    71. ↵
      2. Sohng KY
      . Effects of a self-management course for patients with systemic lupus erythematosus. J Adv Nurs 2003;42:479–86. doi:10.1046/j.1365-2648.2003.02647.x
      OpenUrlCrossRefPubMedWeb of Science
    72. ↵
      2. Allen KD ,
      3. Beauchamp T ,
      4. Rini C , et al
      . Pilot study of an internet-based pain coping skills training program for patients with systemic lupus erythematosus. BMC Rheumatol 2021;5:20. doi:10.1186/s41927-021-00191-6
    73. ↵
      2. Barbhaiya M ,
      3. Costenbader KH
      . Ultraviolet radiation and systemic lupus erythematosus. Lupus 2014;23:588–95. doi:10.1177/0961203314530488
      OpenUrlCrossRefPubMed
    74. ↵
      2. Ahluwalia J ,
      3. Marsch A
      . Photosensitivity and photoprotection in patients with lupus erythematosus. Lupus 2019;28:697–702. doi:10.1177/0961203319839486
      OpenUrl
    75. ↵
      2. Stege H ,
      3. Budde MA ,
      4. Grether-Beck S , et al
      . Evaluation of the capacity of sunscreens to photoprotect lupus erythematosus patients by employing the photoprovocation test. Photodermatol Photoimmunol Photomed 2000;16:256–9. doi:10.1034/j.1600-0781.2000.160604.x
      OpenUrlCrossRefPubMedWeb of Science
    76. ↵
      2. Herzinger T ,
      3. Plewig G ,
      4. Röcken M
      . Use of sunscreens to protect against ultraviolet-induced lupus erythematosus. Arthritis Rheum 2004;50:3045–6. doi:10.1002/art.20426
      OpenUrlCrossRefPubMedWeb of Science
    77. ↵
      2. Abrahão MI ,
      3. Gomiero AB ,
      4. Peccin MS , et al
      . Cardiovascular training vs. resistance training for improving quality of life and physical function in patients with systemic lupus erythematosus: a randomized controlled trial. Scand J Rheumatol 2016;45:197–201. doi:10.3109/03009742.2015.1094126
      OpenUrlPubMed
    78. ↵
      2. Gokcen N ,
      3. Badak SO ,
      4. Sarpel T , et al
      . The efficacy of a home-based, self-administered hand exercise program for patients with systemic sclerosis: a randomized controlled, evaluator-blind, clinical trial. J Clin Rheumatol 2022;28:e422–9. doi:10.1097/RHU.0000000000001752
      OpenUrl
    79. ↵
      2. Antonioli CM ,
      3. Bua G ,
      4. Frigè A , et al
      . An individualized rehabilitation program in patients with systemic sclerosis may improve quality of life and hand mobility. Clin Rheumatol 2009;28:159–65. doi:10.1007/s10067-008-1006-x
      OpenUrlPubMed
    80. ↵
      2. Kwakkenbos L ,
      3. Bluyssen SJM ,
      4. Vonk MC , et al
      . Addressing patient health care demands in systemic sclerosis: pre-post assessment of a psycho-educational group programme. Clin Exp Rheumatol 2011;29:S60–5.
      OpenUrlPubMed
    81. ↵
      2. Landim SF ,
      3. Bertolo MB ,
      4. Marcatto de Abreu MF , et al
      . The evaluation of a home-based program for hands in patients with systemic sclerosis. J Hand Ther 2019;32:313–21. doi:10.1016/j.jht.2017.10.013
      OpenUrlPubMed
    82. ↵
      2. Pizzo G ,
      3. Scardina GA ,
      4. Messina P
      . Effects of a nonsurgical exercise program on the decreased mouth opening in patients with systemic scleroderma. Clin Oral Investig 2003;7:175–8. doi:10.1007/s00784-003-0216-5
      OpenUrlCrossRefPubMed
    83. ↵
      2. Pinto ALS ,
      3. Oliveira NC ,
      4. Gualano B , et al
      . Efficacy and safety of concurrent training in systemic sclerosis. J Strength Cond Res 2011;25:1423–8. doi:10.1519/JSC.0b013e3181d6858b
      OpenUrlPubMed
    84. ↵
      2. Bongi SM ,
      3. Del Rosso A ,
      4. Passalacqua M , et al
      . Manual lymph drainage improving upper extremity edema and hand function in patients with systemic sclerosis in edematous phase. Arthritis Care Res (Hoboken) 2011;63:1134–41. doi:10.1002/acr.20487
      OpenUrl
    85. ↵
      2. Jongsma K ,
      3. van Seventer J ,
      4. Verwoerd A , et al
      . Recommendations from a James LIND alliance priority setting partnership - a qualitative interview study. Res Involv Engagem 2020;6:68. doi:10.1186/s40900-020-00240-3
    86. ↵
      2. Levelink M ,
      3. Voigt-Barbarowicz M ,
      4. Brütt AL
      . Priorities of patients, caregivers and health-care professionals for health research - a systematic review. Health Expect 2020;23:992–1006. doi:10.1111/hex.13090
      OpenUrlPubMed
    87. ↵
      2. Gwinnutt JM ,
      3. Wieczorek M ,
      4. Balanescu A , et al
      . EULAR recommendations regarding lifestyle Behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Ann Rheum Dis 2023;82:48–56. doi:10.1136/annrheumdis-2021-222020
      OpenUrlAbstract/FREE Full Text
    88. ↵
      2. Rausch Osthoff A-K ,
      3. Niedermann K ,
      4. Braun J , et al
      . EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis. Ann Rheum Dis 2018;77:1251–60. doi:10.1136/annrheumdis-2018-213585
      OpenUrlCrossRefPubMed
    89. ↵
      2. Zangi HA ,
      3. Ndosi M ,
      4. Adams J , et al
      . EULAR recommendations for patient education for people with inflammatory arthritis. Ann Rheum Dis 2015;74:954–62. doi:10.1136/annrheumdis-2014-206807
      OpenUrlAbstract/FREE Full Text
    90. ↵
      2. Nikiphorou E ,
      3. Santos EJF ,
      4. Marques A , et al
      . EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis. Ann Rheum Dis 2021;80:1278–85. doi:10.1136/annrheumdis-2021-220249
      OpenUrlAbstract/FREE Full Text
    91. ↵
      2. Alexanderson H ,
      3. Boström C
      . Exercise therapy in patients with idiopathic inflammatory myopathies and systemic lupus erythematosus - a systematic literature review. Best Pract Res Clin Rheumatol 2020;34:101547. doi:10.1016/j.berh.2020.101547
      OpenUrl
    92. ↵
      2. Basta F ,
      3. Fasola F ,
      4. Triantafyllias K , et al
      . Systemic lupus erythematosus (SLE) therapy: the old and the new. Rheumatol Ther 2020;7:433–46. doi:10.1007/s40744-020-00212-9
      OpenUrl
    93. ↵
      2. Choi MY ,
      3. Hahn J ,
      4. Malspeis S , et al
      . Association of a combination of healthy lifestyle behaviors with reduced risk of incident systemic lupus erythematosus. Arthritis Rheumatol 2022;74:274–83. doi:10.1002/art.41935
      OpenUrl
    94. ↵
      2. Gwinnutt JM ,
      3. Wieczorek M ,
      4. Rodríguez-Carrio J , et al
      . Effects of physical exercise and body weight on disease-specific outcomes of people with rheumatic and musculoskeletal diseases (RMDs): systematic reviews and meta-analyses informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs. RMD Open 2022;8:e002167. doi:10.1136/rmdopen-2021-002167
    95. ↵
      2. Kawka L ,
      3. Schlencker A ,
      4. Mertz P , et al
      . Fatigue in systemic lupus erythematosus: an update on its impact, determinants and therapeutic management. J Clin Med 2021;10:3996. doi:10.3390/jcm10173996
    96. ↵
      2. Kostopoulou M ,
      3. Nikolopoulos D ,
      4. Parodis I , et al
      . Cardiovascular disease in systemic lupus erythematosus: recent data on epidemiology, risk factors and prevention. Curr Vasc Pharmacol 2020;18:549–65. doi:10.2174/1570161118666191227101636
      OpenUrlCrossRefPubMed
    97. ↵
      2. Legge A ,
      3. Blanchard C ,
      4. Hanly JG
      . Physical activity, sedentary behaviour and their associations with cardiovascular risk in systemic lupus erythematosus. Rheumatology (Oxford) 2020;59:e153–4. doi:10.1093/rheumatology/keaa486
      OpenUrl
    98. ↵
      2. Lu MC ,
      3. Koo M
      . Effects of exercise intervention on health-related quality of life in patients with systemic lupus erythematosus: a systematic review and meta-analysis of controlled trials. Healthcare (Basel) 2021;9:1215. doi:10.3390/healthcare9091215
    99. ↵
      2. Pettersson H ,
      3. Alexanderson H ,
      4. Poole JL , et al
      . Exercise as a multi-modal disease-modifying medicine in systemic sclerosis: an introduction by the global fellowship on rehabilitation and exercise in systemic sclerosis (G-Forss). Best Pract Res Clin Rheumatol 2021;35:101695. doi:10.1016/j.berh.2021.101695
      OpenUrl
    100. ↵
      2. Ritschl V ,
      3. Ferreira RJO ,
      4. Santos EJF , et al
      . Suitability for E-health of non-pharmacological interventions in connective tissue diseases: scoping review with a descriptive analysis. RMD Open 2021;7:e001710. doi:10.1136/rmdopen-2021-001710
    101. ↵
      2. Rodríguez Huerta MD ,
      3. Trujillo-Martín MM ,
      4. Rúa-Figueroa Í , et al
      . Healthy lifestyle habits for patients with systemic lupus erythematosus: a systemic review. Semin Arthritis Rheum 2016;45:463–70. doi:10.1016/j.semarthrit.2015.09.003
      OpenUrlPubMed
    102. ↵
      2. Sharif K ,
      3. Watad A ,
      4. Bragazzi NL , et al
      . Physical activity and autoimmune diseases: get moving and manage the disease. Autoimmun Rev 2018;17:53–72. doi:10.1016/j.autrev.2017.11.010
      OpenUrlCrossRefPubMed
    103. ↵
      2. Sieczkowska SM ,
      3. Smaira FI ,
      4. Mazzolani BC , et al
      . Efficacy of home-based physical activity interventions in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis. Semin Arthritis Rheum 2021;51:576–87. doi:10.1016/j.semarthrit.2021.04.004
      OpenUrl
    104. ↵
      2. Gwinnutt JM ,
      3. Wieczorek M ,
      4. Rodríguez-Carrio J , et al
      . Smoking, alcohol consumption and disease-specific outcomes in rheumatic and musculoskeletal diseases (RMDs): systematic reviews informing the 2021 EULAR recommendations for lifestyle improvements in people with RMDs. RMD Open 2022;8:e002167. doi:10.1136/rmdopen-2021-002167
    105. ↵
      2. Loza E ,
      3. Carmona L ,
      4. Woolf A , et al
      . Implementation of recommendations in rheumatic and musculoskeletal diseases: considerations for development and uptake. Ann Rheum Dis 2022;81:1344–7. doi:10.1136/ard-2022-223016
      OpenUrlAbstract/FREE Full Text

    Footnotes

    • Handling editor Mary K Crow

    • X @IoannisParodis, @kocheragnes, @v_ritschl

    • Contributors IP wrote the first draft of the manuscript with help and guidance from CG-G, TAS and CB. All authors participated in the work of the task force, including the formulation of the overarching principles and recommendation statements, as well as read and approved the final manuscript. The convenor (CB) is responsible for the overall content as guarantor, controlled the decision to publish, and accepts full responsibility for the finished work and conduct of the project.

    • Funding This project was funded by the European Alliance of Associations for Rheumatology (EULAR) [ref.: HPR046].

    • Competing interests IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia, Elli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Otsuka, and Roche. LA has received research funding and/or consultancies from Alexion, Alpine, Amgen, AstraZeneca, Abbvie, Biogen, BMS, Boehringer-Ingelheim, GlaxoSmithKline, Janssen-Cilag, Kezar, Elli Lilly and Company, Medac, Novartis, Pfizer, Roche-Chugaï, Sêmeia, and Union Chimique Belge (UCB). OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for 4P-Pharma, Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Redxpharma, Roivant, Sanofi, and Topadur. AK has/had consultancy relationship with and/or has received research funding from Boehringer Ingelheim, Pfizer, Swiss Nursing Science Foundation, Swiss League Against Rheumatism, and University of Basel. MN reports research grants from BMS, Vifor Pharma and Sanofi paid to his institution, speaking fees from CCIS The Conference Company and Eli Lilly, all outside the submitted work. JEV reports speaker fees from Eli Lilly, and Galapagos. RW has received honoraria from Galapagos, Celltrion, Gilead Sciences, and Union Chimique Belge (UCB). The other authors declare that they have no conflicts of interest.

    • Provenance and peer review Not commissioned; externally peer reviewed.