EULAR recommendations for the involvement of patient research partners in rheumatology research: 2023 update.

BACKGROUND: Since the publication of the 2011 European Alliance of Associations for Rheumatology (EULAR) recommendations for patient research partner (PRP) involvement in rheumatology research, the role of PRPs has evolved considerably. Therefore, an update of the 2011 recommendations was deemed necessary. METHODS: In accordance with the EULAR Standardised Operational Procedures, a task force comprising 13 researchers, 2 health professionals and 10 PRPs was convened. The process included an online task force meeting, a systematic literature review and an in-person second task force meeting to formulate overarching principles (OAPs) and recommendations. The level of agreement of task force members was assessed anonymously (0-10 scale). RESULTS: The task force developed five new OAPs, updated seven existing recommendations and formulated three new recommendations. The OAPs address the definition of a PRP, the contribution of PRPs, the role of informal caregivers, the added value of PRPs and the importance of trust and communication in collaborative research efforts. The recommendations address the research type and phases of PRP involvement, the recommended number of PRPs per project, the support necessary for PRPs, training of PRPs and acknowledgement of PRP contributions. New recommendations concern the benefits of support and guidance for researchers, the need for regular evaluation of the patient-researcher collaboration and the role of a designated coordinator to facilitate collaboration. Agreements within the task force were high and ranged between 9.16 and 9.96. CONCLUSION: The updated EULAR recommendations for PRP involvement are more substantially based on evidence. Together with added OAPs, they should serve as a guide for researchers and PRPs and will ultimately strengthen the involvement of PRPs in rheumatology research.

Patient research partner involvement in rheumatology research: a systematic literature review informing the 2023 updated EULAR recommendations for the involvement of patient research partners.

BACKGROUND: Patient research partners (PRPs) are people with a disease who collaborate in a research team as partners. The aim of this systematic literature review (SLR) was to assess barriers and facilitators to PRP involvement in rheumatology research. METHODS: The SLR was conducted in PubMed/Medline for articles on PRP involvement in rheumatology research, published between 2017 and 2023; websites were also searched in rheumatology and other specialties. Data were extracted regarding the definition of PRPs, their role and added value, as well as barriers and facilitators to PRP involvement. The quality of the articles was assessed. Quantitative data were analysed descriptively, and principles of thematic content analysis was applied to qualitative data. RESULTS: Of 1016 publications, 53 articles were included; the majority of these studies were qualitative studies (26%), opinion articles (21%), meeting reports (17%) and mixed-methods studies (11%). Roles of PRPs ranged from research partners to patient advocates, advisors and patient reviewers. PRPs were reported/advised to be involved early in the project (32% of articles) and in all research phases (30%), from the conception stage to the implementation of research findings. The main barriers were challenges in communication and support for both PRPs and researchers. Facilitators of PRP involvement included more than one PRP per project, training of PRPs and researchers, a supportive environment for PRPs (including adequate communication, acknowledgement and compensation of PRPs) and the presence of a PRP coordinator. CONCLUSION: This SLR identified barriers and facilitators to PRP involvement, and was key to updating the European Alliance of Associations for Rheumatology recommendations for PRP-researcher collaboration based on scientific evidence.

Is the patient-perceived impact of psoriatic arthritis a global concept? An international study in 13 Arab countries (TACTIC study).

The Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire, a recommended measure of patient-reported impact for psoriatic arthritis (PsA), was initially developed in Europe and may lack universal validity. Recognizing the need for a culturally appropriate tool for Arab patients, this study aimed to TranslAte, CulTurally adapt, and validate the PsAID in ArabIC (TACTIC). The PsAID-12 was translated into Arabic using a rigorous process of double translation, back-translation, and cognitive debriefing. The Arabic version was then validated through a study conducted in 13 Arab countries in 2022. Participants were consecutive literate adult patients diagnosed with PsA and fulfilling the CASPAR criteria. Collected data included PsAID-12, disease activity, and legacy patient-reported outcomes. Psychometric properties, such as internal consistency, construct validity, and test-retest reliability, were examined. Factors associated with high PsAID-12 total scores (> 4) were explored using multivariable binary logistic regression. A culturally adapted Arabic PsAID-12 questionnaire was achieved with minor rephrasing. The validation study included 554 patients from 13 countries (mean age 45 years, 59% females), with a mean PsAID score of 3.86 (SD 2.33). The Arabic PsAID-12 demonstrated excellent internal consistency (Cronbach's α = 0.95), and correlations with other measures ranged from 0.63 to 0.78. Test-retest reliability (N = 138 patients) was substantial (intraclass correlation coefficient, ICC 0.90 [0.86-0.93]; Cohen's kappa 0.80). Factors associated with a high PsAID score were disability (odds ratio, OR 3.15 [2.03-4.89]), depression (OR 1.56 [1.35-1.81]), widespread pain (OR 1.31 [1.12-1.53]), and disease activity (OR 1.29 [1.13-1.47]). Pain and fatigue were identified as the most impactful PsAID-12 domains for PsA patients. The Arabic PsAID is a valid and reliable measure that reflects the priorities of patients with PsA. PsAID scores correlated with disease activity and legacy outcome measures, as expected, indicating PsAID is a consistent measure of PsA impact across cultures. These findings highlight the potential of the Arabic PsAID in improving the care provided to Arabic-speaking patients worldwide.

Drug persistence in patients with rheumatic and musculoskeletal diseases during a major economic crisis: results from a nationwide cross-sectional online survey.

To evaluate the drug persistence in patients with rheumatic and musculoskeletal diseases (RMDs) during the current economic crisis in Lebanon and to estimate predictors of persistence. A nationwide multicentric cross-sectional study using an online questionnaire was conducted in Lebanon with patients with chronic inflammatory rheumatic diseases (CIRDs) and non-inflammatory RMDs controls between July and October 2022. Disease-modifying antirheumatic drugs (DMARDs) were categorized as conventional synthetic (cs), biological (b), subcutaneous (SC) or intravenous (IV), and targeted synthetic (ts). Persistence was defined as "number of tablets or injections taken during the past month versus prescribed". The percentage of patients who discontinued or changed treatment due to cost or non-availability was reported. Factors associated with persistence were identified using multivariable linear regression. The study included 317 patients with RMDs (286 CIRDs); mean age 49.5 years, 68% females, 58% reporting currently low economic level. Persistence at one month was low for tsDMARDs (36%) and bDMARDs (SC55%, IV63%), and acceptable for csDMARDs (88%). A persistence ≥80% was found in 23.3% of patients on tsDMARDs, 42.9% on SC bDMARDs, 45.0% on IV bDMARDs, and 74.7% on csDMARDs. During the past 6 months, 55.8% of CIRD patients discontinued or changed treatment due to non-availability (45.3%) or cost (21.2%). Persistence was positively associated with finding alternative sources such as buying abroad (36%), depending on friends or families abroad (20%), charities (10%), and negatively associated with unemployment and low financial status. Persistence was significantly compromised for essential antirheumatic drugs and was mostly driven by treatment unavailability and cost.

Involving patients as research partners in research in rheumatology: a literature review in 2023.

OBJECTIVE: The inclusion of patient research partners (PRPs) in research projects is increasingly recognised and recommended in rheumatology. The level of involvement of PRPs in translational research in rheumatology remains unknown, while in randomised clinical trials (RCTs), it has been reported to be 2% in 2020. Therefore, we aimed to assess the involvement of PRPs in recent translational studies and RCTs in rheumatology. METHODS: We conducted a scoping literature review of the 80 most recent articles (40 translational studies and 40 RCTs) from four target diseases: rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus and lower extremity osteoarthritis. We selected 20 papers from each disease, published up until 1 March 2023, in rheumatology and general scientific journals. In each paper, the extent of PRP involvement was assessed. Analyses were descriptive. RESULTS: Of 40 translational studies, none reported PRP involvement. Of 40 RCTs, eight studies (20%) reported PRP involvement. These trials were mainly from Europe (75%) and North America (25%). Most of them (75%) were non-industry funded. The type of PRP involvement was reported in six of eight studies: six studies reported PRP participation in the study design or design of the intervention and two of them in the interpretation of the results. All the trials reporting the number of PRPs (75%), involved at least two PRPs. CONCLUSION: Despite a worldwide movement advocating for increased patient involvement in research, PRPs in translational research and RCTs in rheumatology are significantly under-represented. This limited involvement of PRPs in research highlights a persistent gap between the existing recommendations and actual practice.

Influence of Sex on Early Axial Spondyloarthritis: A Six-Year Longitudinal Analysis From a Large National Cohort.

OBJECTIVE: The objective was to determine sex differences in disease outcomes in recent axial spondyloarthritis (SpA) over time. METHODS: We analyzed the first 6 years of follow-up of the prospective French multicenter DESIR cohort. Patients analyzed had <3 years of disease, were naive to disease-modifying antirheumatic drugs, and fulfilled the Assessment of SpondyloArthritis international Society classification criteria for axial SpA. Disease activity (Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level), patient global assessment (PtGA), CRP level, and radiographic sacroiliitis were compared between men and women (self-reported sex) by linear and logistic mixed-effects models. Models were created for trajectories of disease activity over 6 years in men and women, using k-means. RESULTS: Of 494 patients analyzed (mean ± SD age 31.9 ± 7.5 years, symptoms duration 20.7 ± 11.7 months), 50.4% were men. Over 6 years of follow-up, both men and women showed clear improvements in ASDAS-CRP, PtGA, and CRP level. Women had higher ASDAS-CRP and PtGA over time compared to men (both P < 0.0001) with overall similar CRP levels (P = 0.089), whereas structural damage increased more in men (P < 0.0001). One-third of both men (33%) and women (34%) belonged to persistent high/very high disease activity trajectories, but ASDAS-CRP was globally higher in women in these trajectories. CONCLUSION: In early axial SpA, clinical outcomes (disease activity and symptoms) were worse in women than men over 6 years of follow-up, whereas CRP was similar and structural damage was more frequent in men. Although similarly distributed, disease activity scores were higher in women in high/very high disease activity trajectories. Sex appears to be an important contextual factor in axial SpA.

Treat-to-Target in Axial Spondyloarthritis: Are we there yet?

The Treat-to-target (T2T) strategy in axial spondyloarthritis (axSpA) stipulates that treatment should reach a predefined target and if not reached, intensification of therapy is implemented aiming at best future outcomes. Clinical remission was recommended by the 2017 international task force as the treatment target using Ankylosing spondylitis disease activity score (ASDAS) inactive disease, or alternatively, ASDAS low disease activity. The results of a recent T2T trial in axSpA were negative for the chosen primary outcome. Therefore, some concerns are still emerging regarding the optimal treatment target and the weak direct evidence proving the efficacy of such strategy. These challenges among others would preclude the application of T2T strategy in daily clinical practice. This review aims to highlight the updates of the T2T strategy in axSpA, giving an overview of the existing treatment targets, their potential benefits, and challenges to apply this strategy.

Defining and managing flares in axial spondyloarthritis.

PURPOSE OF REVIEW: Flares correspond to fluctuations in disease activity or symptoms. They should be avoided in chronic inflammatory diseases. In axial spondyloarthritis (axSpA), work is ongoing to better conceptualise and treat flares. This review highlights recent data on the definition and management of flares in axSpA. RECENT FINDINGS: Many definitions of flares have been used in clinical trials, limiting the interpretation and comparison of studies. The expert group Assessment of SpondyloArthritis International Society (ASAS) developed a data-driven definition of flares/disease worsening: an increase in Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) of at least 0.9 points, for use in axSpA clinical trials. Flares are more challenging to define in clinical practice because of their multifaceted nature. Qualitative studies have shown that flares from the patient's perspective are related not only to disease activity, but also to fatigue, mood, sleep and general well-being. The management of axSpA relies on a treat-to-target (T2T) strategy and aims at reaching clinical remission while monitoring closely disease activity to prevent and shorten flares. SUMMARY: The concept of flares has been clarified, and definitions have been developed for use in trials. The T2T approach aims at minimising flares in axSpA. The early recognition of flares and their severity may lead to better management.

Prevalence and consequences of psoriasis in recent axial spondyloarthritis: an analysis of the DESIR cohort over 6 years.

OBJECTIVES: The consequences of psoriasis associated to axial spondyloarthritis (axSpA) are unclear. The objectives were to determine the prevalence and the consequences of psoriasis in recent axSpA over 6 years of follow-up. METHODS: The multicentric prospective cohort DESIR (NCT01648907) of adult patients with recent inflammatory back pain suggestive of axSpA was analysed over 6 years. Psoriasis was recorded at each visit and cumulative prevalence and incidence were calculated. Patients with vs without psoriasis at any time point were compared. Outcomes included disease activity (Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP), joint and enthesitis count, CRP), patient-reported outcomes for function (Health Assessment Questionnaire for axSpA, HAQ-AS) and quality of life, and treatment use over 6 years. Outcomes were compared through univariable and multivariable analyses, as well as linear mixed effect models. RESULTS: In 589 patients, mean age 40.5±8.7 years, 45.8% men and baseline mean symptom duration 1.5±0.9 years, the cumulative prevalence of psoriasis increased from 16.8% (99/589) at baseline to 26.8% (158/589) at 6 years, leading to an incidence of 2.1/100 patient-years. Over 6 years of follow-up, patients with psoriasis developed more synovitis (p=0.008), and received more methotrexate (cumulative use, 25.5% vs 11.8%, p<0.001) and biological disease-modifying drugs (55.7% vs 38.5%, p<0.001). There were no significant consequences of psoriasis on other outcomes, including disease activity (ASDAS-CRP), functional capacity (HAQ-AS) and quality of life. CONCLUSION: Psoriasis is frequent in early axSpA. AxSpA patients with psoriasis had more swollen joints over time and received more biologics; they did not have worse outcomes related to axSpA in terms of activity and severity. TRIAL REGISTRATION NUMBER: NCT01648907.

Exploring remission concept in axial spondyloarthritis through the perception of rheumatologists using vignettes and priority ratings.

OBJECTIVES: The optimal treatment target in axial spondyloarthritis (axSpA) is remission; however, a consensual definition of remission is lacking. Our objective was to explore rheumatologists' perception of remission using vignette cases and a priority exercise. METHODS: A cross-sectional survey of rheumatologists' perceptions of remission in axSpA was performed in 2020 using (i) 36 vignette cases, with a single clinical picture and three varying parameters [axial pain (ranging from 2 to 5 on a 0-10 scale)], fatigue (2-8), and morning stiffness (<15 min, 30 min or 1 h), assessed as remission yes/no; and (ii) prioritization of elements to consider for remission from a list of 12 items: BASDAI, ASDAS, elements of BASDAI and ASDAS including CRP, NSAID use, extra-articular manifestations (EAMs), and other explanations of symptoms, e.g. fibromyalgia. Analyses were descriptive. RESULTS: Overall, 200 French rheumatologists participated in 2400 vignette evaluations. Of these, 463 (19%) were classified as remission. The six vignette cases representing 56% of all remission cases had <15 min duration of morning stiffness and axial pain ≤3/10, regardless of fatigue levels. Prioritized items for remission were: morning stiffness (75%), EAMs (75%), NSAID use (71%), axial pain (68%) and CRP (66%). CONCLUSIONS: When conceptualizing remission in axSpA, rheumatologists took into account morning stiffness and axial pain as expected; the link between remission and fatigue was much weaker. Furthermore, rheumatologists also included EAMs and NSAID use in the concept of remission. Consensus is needed for definition of remission in axSpA.

Outcome measures used in psoriatic arthritis registries and cohorts: A systematic literature review of 27 registries or 16,183 patients.

INTRODUCTION: Psoriatic arthritis (PsA) is a multidimensional inflammatory disease for which multiple outcome measures can be used to assess disease activity. In 2006, the OMERACT has proposed the first core domain set in PsA. Since 2006, much work has been performed on outcome measures in PsA. OBJECTIVES: The purpose of this study was to assess outcome measures collected in recent PsA registries or longitudinal cohorts. METHODS: A systematic literature review was performed in Pubmed Medline (PROSPERO CRD42020175745) to identify all articles reporting on either registries or longitudinal cohorts in PsA, published between 2010 and March 2020. Registries centered on drugs or not PsA-specific, trials and long-term extension studies were excluded. The data collection comprised patient characteristics and the clinical outcome measures reported, including composite scores and patient reported outcomes (PROs). Statistics were descriptive. RESULTS: Of 673 articles, 73 were analysed, reporting on 27 registries/cohorts. Overall, 16,183 patients were included, with a mean of 599 per study; 51% were men, weighted mean age was 49.7 ± 9.3 years and weighted mean disease duration was 6.8 ± 0.2 years. Overall, 58 different outcome measures were collected. Disease activity composite scores were used in 20/27 (74%) registries through 8 different scores (most frequently Minimal Disease Activity: 41%, DAS28: 33% and DAPSA: 30%). Among the domains of PsA, joint involvement was reported in 26/27 (96%) registries (through the 66/68 joint count: 85%) and skin psoriasis in 93% (through PASI: 72%), whereas enthesitis, dactylitis and axial involvement were less often reported (respectively, 77%, 74% and 52%). Furthermore, 22/27 (82%) studies reported HAQ; the other frequently reported PROs were patient global assessment (70%) and pain (63%). CONCLUSIONS: Data collection in PsA is very heterogeneous, reflecting the need for international consensus on outcome measures.

Cut-off value to identify a flare using the Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire: analysis of the TOSCA study.

OBJECTIVE: The Flare Assessment in RA (FLARE-RA) self-administered questionnaire aims to identify patients who had flare in the interval between two consultations. This study aimed to establish a threshold for FLARE-RA score to identify RA flare. METHODS: The Tocilizumab SubCutAneous study evaluated the efficacy and safety of s.c. tocilizumab (TCZ) to patients with active RA. Disease activity was assessed with the DAS28ESR at baseline and at week 2 (W2), W4, W12 and W24. The FLARE-RA questionnaire was administered at W12 and W24. Patient satisfaction, assessed at baseline and W24 with the Patient Acceptable Symptom State (PASS), was used as a surrogate marker of no flare. A correlation was sought between the FLARE-RA score at W12 and W24 and the area under the receiver operating characteristic (ROC) curve (AUC) for monthly DAS28ESR. The optimal FLARE-RA cut-off below which patient satisfaction reached the PASS was explored with an ROC curve. RESULTS: A total of 139 patients were included (mean age 57.3 ± 13.8 years, 74.1% women, mean RA duration 10.8 ± 9.2 years, mean DAS28ESR 5.8 ± 1.1). The correlation between the FLARE-RA score and DAS28ESR AUC was moderate at all times: ρ = 0.41 at W12 (P < 0.0001) and 0.51 at W24 (P < 0.0001). The optimal cut-off for the FLARE-RA score to identify absence of flare (i.e. an acceptable situation based on the PASS) was 2.3 with an AUC of 0.81. CONCLUSION: FLARE-RA and DAS28ESR assessment differ; we propose a FLARE-RA cut-off of 2.3, below which the situation (i.e. without flare) is acceptable for patients.

Update of imaging in the diagnosis and management of axial spondyloarthritis.

Imaging of the spine and sacroiliac joints has acquired a central role in the diagnosis and classification of axial spondyloarthritis (axSpA) in the earliest phases of the disease. New definitions of specific imaging lesions, particularly in magnetic resonance imaging (MRI), have been recently updated and revised by the ASAS MRI working group to reach a standardized understanding and diagnosis of axSpA among rheumatologists. Recognizing the misleading pitfalls of MRI lesions and differential diagnosis also represents an essential issue in clinical practice to avoid false-positive findings and establish the diagnosis of axSpA with careful regard to the clinical context, clinical signs, and biological tests. This review summarizes the current evidence on the different imaging modalities of the sacroiliac joints and the spine with their application in the clinical setting of SpA and their main pitfalls; it also highlights the newest emerging imaging techniques.

Can Imaging Be a Proxy for Remission in Axial Spondyloarthritis?

Targeting clinical remission is currently the focus of the treat-to-target strategy. Defining clinical outcomes as the main achievable treatment goal questions whether imaging remission should also be considered in the treat-to-target concept. Imaging has gained a pivotal role in diagnosing and classifying axial spondyloarthritis at the earliest phase of the disease. Its importance has been expanded to monitoring and prognosticating spondyloarthritis. This article summarizes current evidence on the use of imaging for monitoring disease activity and predicting treatment response in axial spondyloarthritis, and discusses the concept of imaging-driven treat-to-target strategy with a highlight on the newest imaging modalities in spondyloarthritis.

Imaging in the preclinical phases of rheumatoid arthritis.

There is growing evidence that the development of rheumatoid arthritis (RA) is a multistep process. The European League Against Rheumatism (EULAR) identified different phases before the onset of RA, from the presence of genetic and environmental risk factors for RA, towards clinically suspected arthralgia and undifferentiated arthritis. Currently, a new definition of "window of opportunity" is emerging; this states that the window could even lie in preclinical phase of RA, preceding diagnosis or fulfillment of classification criteria for RA. In this scenario, the detection of subclinical inflammation by imaging tools could be useful together with autoantibodies and joint symptoms to better stratify people at high risk for developing RA and to plan prevention trials in high-risk cohorts. This review will give an overview on the use of computed tomography, magnetic resonance imaging and ultrasonography in the preclinical phases of RA.

Structural progression in axial spondyloarthritis.

Functional disability in axial spondyloarthritis is related to the structural progression caused by the disease, thus largely contributing to its global burden and still representing a major challenge in management. Diagnosis at an early inflammatory stage of the disease is the hallmark for a better disease control and management. The natural history of axial spondyloarthritis is now better understood with imaging studies and long-term follow-up data, with some predictive factors for structural progression being identified. Non-steroidal anti-inflammatory drugs are still considered as the first line treatment for axial spondyloarthritis, however, their impact on structural progression is conflicting. Recent data on biologic disease-modifying anti-rheumatic drugs, such as tumor necrosis factor inhibitors have shown significant retardation of radiographic damage after several years of treatment, while first data with interleukin-17 inhibitors were also positive. Novel emerging drugs are being evaluated with promising results on halting disease progression. This review summarizes the predictors of radiographic progression in patients with axial spondyloarthritis as well as the current evidence on the effect of available treatments on structural progression.

Chronic Mercury Intoxication Masquerading as Systemic Disease: A Case Report and Review of the Literature.

BACKGROUND: Mercury is a highly toxic environmental metal that exists in three different forms: elemental, inorganic and organic. Intoxication occurs in either occupational or non-occupational settings, mainly after the inhalation of vapour and fumes in work places, laboratories or homes. Chronic mercury toxicity ranges from mild and insignificant to severe and life-threatening. We describe the case of a young male patient who presented with multiple organ dysfunction after chronic mercury exposure. CASE PRESENTATION: We report the case of 28-year-old male artisanal gold miner who was admitted to hospital for severe neurological impairment associated with inflammatory bowel disease-like symptoms and a skin rash after mercury exposure. Symptomatic treatment and corticosteroid administration assured rapid clinical improvement. Chronic mercury poisoning can masquerade as an autoimmune or systemic inflammatory disease. CONCLUSION: Physicians should be aware that low exposure to mercury, even from artisanal gold mining, may be harmful to health. Management can be simple without the need for aggressive or invasive therapeutic measures. Larger case series are required in order to establish a clear management plan. LEARNING POINTS: Mercury intoxication has a wide the variety of clinical manifestations that may involve the neurological, gastrointestinal and dermatological systems.Therefore, it can mimic degenerative neurological conditions, autoimmune diseases, as well as metabolic and mitochondrial disorders.Once diagnosed, mercury intoxication is easily treated.