Recommendations for physical activity and exercise in persons living with Systemic Lupus Erythematosus (SLE): consensus by an international task force.

OBJECTIVE: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE. METHODS: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus. RESULTS: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers. The 15 specific recommendations state that physical activity is generally recommended for all people with SLE, but in some instances, a medical evaluation may be needed to rule out contraindications. Pertaining to outdoor activity, photoprotection is necessary. Both aerobic and resistance training programmes are recommended, with a gradual increase in frequency and intensity, which should be adapted for each individual, and ideally supervised by qualified professionals. CONCLUSION: In summary, the consensus reached by the international task force provides a valuable framework for the integration of physical activity and exercise into the management of SLE, offering a tailored evidence-based and eminence-based approach to enhance the well-being of individuals living with this challenging autoimmune condition.

Title: Sarcopenia assessed by DXA and hand-grip dynamometer: a potential marker of damage, disability and myokines imbalance in inflammatory myopathies.

OBJECTIVES: To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM). METHODS: . Forty adult IM patients with a disease duration ≥12 months, low or no disease activity for ≥6 months, were prospectively enrolled. Thirty healthy age and sex-matched volunteers were enrolled as controls. Whole-body DXA and hand-grip dynamometer were used to measure muscle mass, grip strength and diagnose sarcopenia (EWGSOP2 criteria). Relationships between the results of strength in 12 muscles, functional tests, patient-reported disability, IMACS damage score, and history of the disease were assessed. The serum levels of potential molecular actors of the damage were measured. RESULTS: DXA and grip strength measurements took ≤20 min. Both muscle mass and grip strength were decreased in IM patients vs volunteers (-10% and -30% respectively) with a dispersion that varied widely (IQR -24.3% to + 7.8% and -51.3% to -18.9% respectively). Muscle mass and grip strength were non-redundantly correlated (r up to 0.6, p= 0.0001) with strength in 14 muscles (manual muscle test and hand-held dynamometer), functions (of limbs, respiratory and deglutition muscles), patient-reported disability, damage (extension and severity in muscular and extra-muscular domains), and blood-levels of several myokines. Seven IM patients (17.5%) were sarcopenic. They had the worst damage, functions impairment, disability and history of severe myopathy. Decreased irisin and osteonectin levels were associated with sarcopenia (AUC 0.71 and 0.80, respectively). CONCLUSION: DXA and hand-grip dynamometer are useful tools to assess damage in IM. Irisin and osteonectin may play a role in IM damage pathogenesis.

Assessment and personalised advice for fatigue in systemic lupus erythematosus using an innovative digital tool: the Lupus Expert system for the Assessment of Fatigue (LEAF) study.

BACKGROUND: Fatigue is reported as the most prevalent symptom by patients with systemic lupus erythematosus (SLE). Fatigue management is complex due to its multifactorial nature. The aim of the study was to assess the usefulness of an innovative digital tool to manage fatigue in SLE, in a completely automated manner. METHODS: The «Lupus Expert System for Assessment of Fatigue¼ (LEAF) is free digital tool which measures the intensity and characteristics of fatigue and assesses disease activity, pain, insomnia, anxiety, depression, stress, fibromyalgia and physical activity using validated patient-reported instruments. Then, LEAF automatically provides personalised feedback and recommendations to cope with fatigue. RESULTS: Between May and November 2022, 1250 participants with SLE were included (95.2% women, median age 43yo (IQR: 34-51)). Significant fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue <34) was reported by 78.9% of patients. In univariate analysis, SLE participants with fatigue were more likely to be women (p=0.01), perceived their disease as more active (p<0.0001), had higher levels of pain (p<0.0001), anxiety (p<0.0001), depression (p<0.0001), insomnia (p<0.0001), stress (p<0.0001) and were more likely to screen for fibromyalgia (p<0.0001), compared with patients without significant fatigue. In multivariable analysis, parameters independently associated with fatigue were insomnia (p=0.0003), pain (p=0.002), fibromyalgia (p=0.008), self-reported active SLE (p=0.02) and stress (p=0.045). 93.2% of the participants found LEAF helpful and 92.3% would recommend it to another patient with SLE. CONCLUSION: Fatigue is commonly severe in SLE, and associated with insomnia, pain, fibromyalgia and active disease according to patients' perspective. Our study shows the usefulness of an automated digital tool to manage fatigue in SLE.

Benefits & risks of physical activity in patients with Systemic Lupus Erythematosus: a systematic review of the literature.

INTRODUCTION: Most patients with Systemic Lupus Erythematosus (SLE) have limited levels of physical activity (PA). The aim of this systematic review was to examine the evidence regarding the benefits and potential risks of PA in SLE. METHODS: We searched the medical literature on MEDLINE (via PubMed) from inception to March 2022 using the Medical Subject Headings (MeSH) terms "Exercise" and "Lupus Erythematosus, Systemic" as well as free text combinations such as "physical activity". We also searched the reference lists of retrieved studies. Two authors independently assessed all studies identified by the search for inclusion in the review and independently extracted data. RESULTS: A total of 40 articles (2291 SLE patients) published between 1989 and 2022 were included in this systematic review. Compared to the general population, SLE patients had low levels of PA, with 11% to 29.8% objectively meeting World Health Organization (WHO) recommendations. SLE patients also had impaired aerobic capacities (VO2max ranging from 18.8 to 25.78 ml/kg/min). Aerobic programs had significant benefits on global aerobic capacity and estimated cardiovascular risk while resistance training programs improved strength and function in SLE. Fatigue, depression and Health-Related Quality of life improved significantly following PA training. No severe adverse event was reported across included studies. CONCLUSION: Aerobic and resistance training programs had clear benefits and were well tolerated in SLE patients with stable disease. There is currently no universal recommendations about PA in SLE. Dedicated recommendations informed by this systematic review are needed to promote physical activity and its benefits in SLE patients.

Immunosuppressive agents for rheumatoid arthritis: a systematic review of clinical trials and their current development stage.

AIMS: With the arrival of conventional synthetic (csDMARDs), biological (bDMARDS) and then targeted synthetic (tsDMARDs) disease-modifying anti-rheumatic drugs, the therapeutic arsenal against rheumatoid arthritis (RA) has recently expanded. However, there are still some unmet needs for patients who do not achieve remission and continue to worsen despite treatments. Of note, most randomized controlled trials show that, for methotrexate-inadequate responders, only 20% of patients are ACR70 responders. With our better understanding of RA pathogenesis, finding new treatments is a necessary challenge. The objective of our study was to analyse the whole pipeline of immunosuppressive and immunomodulating drugs evaluated in RA and describe their mechanisms of action and stage of clinical development. METHODS: We conducted a systematic review of all drugs in clinical development in RA, in 17 online registries of clinical trials. RESULTS: The search yielded 4652 trials, from which we identified 243 molecules. Those molecules belong to csDMARDs (n = 22), bDMARDs (n = 118), tsDMARDs (n = 103). Twenty-four molecules are already marketed in RA in at least one country: eight csDMARDs, 10 bDMARDs and six tsDMARDs. Molecules under current development are mainly bDMARDs (n = 34) and tsDMARDs (n = 33). Seven of those have reached phase III. A large number of molecules (150/243, 61.7%) have been withdrawn. CONCLUSION: Despite the availability of 24 marketed molecules, the development of new targeted molecules is ongoing with a total of 243 molecules in RA. With seven molecules currently reaching phase III, we can expect an increase in the armamentarium in the years to come.

Shared development of targeted therapies among autoimmune and inflammatory diseases: a systematic repurposing analysis.

BACKGROUND: Pathogenic inflammatory pathways are largely shared between different autoimmune and inflammatory diseases (AIDs). This offers the potential to develop a given targeted therapy in several AIDs. METHODS: We analyzed two clinical trials registries (ClinicalTrials.gov and EU Clinical Trials Register) to identify the targeted therapies whose development is shared between at least two of the most common AIDs [rheumatoid arthritis (RA), spondyloarthritis (SpA), cutaneous psoriasis (cPso), inflammatory bowel diseases (IBD), systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), giant cell arteritis (GCA), and multiple sclerosis (MS)] using an in-depth repurposing analysis. RESULTS: We identified 142 shared targeted therapies. The four diseases in which shared targeted therapies were the most numerous were RA (n = 92), cPso (n = 67), IBD (n = 58), and SLE (n = 56). The two clusters of diseases between which the overlap of targeted therapies was the most important were RA and SLE as well as RA, SpA, cPso, and IBD. The targeted therapies which were shared by five diseases or more were abatacept, ustekinumab, rituximab, anakinra, etanercept, infliximab, secukinumab, tofacitinib, alemtuzumab, tocilizumab, adalimumab, apremilast, baricitinib, belimumab, brodalumab, filgotinib, and upadacitinib. The most frequently targeted molecules and pathways were (by descending frequency): JAK-STAT pathways, Th17 axis, TNF-α, IL-6, costimulation molecules, BAFF, CD20, BTK, chemokines and integrins, IL-1, and type I interferon. CONCLUSION: Many targeted therapies are developed in several AIDs, reflecting the overlap of pathogenic pathways and potential of drug repurposing. This suggests that a revision of the current, clinically based classification of AIDs towards a more mechanistic-based taxonomy might be relevant.