Serum Advanced Glycation End Products and Their Soluble Receptor as New Biomarkers in Systemic Lupus Erythematosus.

It has been postulated that advanced glycation end products (AGEs) and their soluble receptor (sRAGE) may play a relevant role as inducers in the chronic inflammatory pathway in various conditions, among them, in immune-mediated diseases such as systemic lupus erythematosus (SLE). However, previous studies show conflicting results about their association with SLE characteristics and their usefulness as disease biomarkers. We aimed to study the association of specific serum AGEs (pentosidine, Nξ-(carboxymethyl)lysine (CML), Nξ-(carboxyethyl)lysine (CEL)), sRAGE levels and AGEs (specific serum AGEs and skin AGEs) to sRAGE ratios with various disease parameters, in order to clarify their potential as new biomarkers in SLE and to study their relationship with cardiovascular disease (CVD). To this aim, serum pentosidine, CML, CEL and sRAGE were measured via ELISA, and skin AGEs levels were measured by skin autofluorescence. Correlations of pentosidine levels with demographic and clinical data, indexes of activity, accrual damage and patient-reported outcomes were analyzed through multiple linear regression models, while correlations of the rest of the AGEs, sRAGE and AGE to sRAGE ratios (non-normal) were analyzed using both an OLS regression model and a GML. All of the analyses were adjusted for confounders. A total of 119 SLE patients were recruited. Serum AGEs and sRAGEs were significantly associated with SLE activity indexes and/or demographic or disease characteristics: pentosidine with pulmonary manifestations; CML with anti-dsDNA antibodies, IL-6, disease duration and non-Caucasian ethnicities; CEL with anti-dsDNA antibodies, IL-6 and accumulated number of manifestations; and sRAGE with male gender, photosensitivity and being on specific immunosuppressants. These results suggest that the AGE-sRAGE axis may serve as a novel biomarker for managing and prognosticating this disease. Its correlation with certain antibodies, demographics and disease presentations may indicate a distinct clinical phenotype associated with varying levels of AGEs and/or sRAGE. The significance of specific AGE/sRAGE ratios, introduced in this study for the first time, warrants additional investigation in forthcoming research. Our study did not confirm the link between serum AGEs and CVD, which merits further exploration through studies designed for this specific purpose.

Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus.

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

Musculoskeletal involvement in systemic lupus erythematosus: a contrast-enhanced magnetic resonance imaging study in 107 subjects.

OBJECTIVE: Joint involvement in SLE is the most frequent manifestation and shows a wide heterogeneity. It has not a valid classification and it is often underestimated. Subclinical inflammatory musculoskeletal involvement is not well known. We aim to describe the prevalence of joint and tendon involvement in hand and wrist of SLE patients, either with clinical arthritis, arthralgia or asymptomatic and compare it with healthy subjects using contrasted MRI. METHODS: SLE patients fulfilling SLICC criteria were recruited and classified as follows: group (G) 1: hand/wrist arthritis, G2: hand/wrist arthralgia, G3: no hand/wrist symptoms. Jaccoud arthropathy, CCPa and RF positivity, hand OA or surgery were excluded. Healthy subjects (HS) were recruited as controls: G4. Contrasted MRI of non-dominant hand/wrist was performed. Images were evaluated following RAMRIS criteria extended to PIP, Tenosynovitis score for RA and peritendonitis from PsAMRIS. Groups were statistically compared. RESULTS: A total of 107 subjects were recruited (G1: 31, G2:31, G3:21, G4:24). Any lesion: SLE patients 74.7%, HS 41.67%; P 0.002. Synovitis: G1: 64.52%, G2: 51.61%, G3: 45%, G4: 20.83%; P 0.013. Erosions: G1: 29.03%; G2: 54.84%, G3: 47.62%; G4: 25%; P 0.066. Bone marrow oedema: G1: 29.03%, G2: 22.58%, G3: 19.05%, G4: 0.0%; P 0.046. Tenosynovitis: G1: 38.71%; G2: 25.81%, G3: 14.29%, G4: 0.0%; P 0.005. Peritendonitis: G1: 12.90%; G2: 3.23%, G3: 0.0%, G4: 0.0%; P 0.07. CONCLUSION: SLE patients have a high prevalence of inflammatory musculoskeletal alterations confirmed by contrasted MRI, even if asymptomatic. Not only tenosynovitis but peritendonitis is also present.

Central Sensitization and Chronic Pain Personality Profile: Is There New Evidence? A Case-Control Study.

BACKGROUND: Personality traits are relevant for pain perception in persistent pain disorders, although they have not been studied in depth in sensitized and nonsensitized patients with knee osteoarthritis (OA). OBJECTIVE: To explain and compare the personality profile of patients with OA, with and without central sensitization (CS), and fibromyalgia (FM). SETTING: Participants were selected at the Rheumatology Department in two major hospitals in Spain. PARTICIPANTS: Case-control study where the sample consists of 15 patients with OA and CS (OA-CS), 31 OA without CS (OA-noCS), 47 FM, and 22 controls. We used a rigorous and systematic process that ensured the sample strictly fulfilled all the inclusion/exclusion criteria, so the sample is very well delimited. PRIMARY OUTCOME MEASURES: Personality was assessed by the Temperament and Character Inventory of Cloninger. RESULTS: The percentile in harm-avoidance dimension for the FM group is higher compared to OA groups and controls. The most frequent temperamental profiles in patients are cautious, methodical, and explosive. Patients with FM are more likely to report larger scores in harm-avoidance, with an increase in logistic regression adjusted odds ratio (ORadj) between 4.2% and 70.2%. CONCLUSIONS: Harm-avoidance seems to be the most important dimension in personality patients with chronic pain, as previously found. We found no differences between OA groups and between sensitized groups, but there are differences between FM and OA-noCS, so harm-avoidance might be the key to describe personality in patients with CS rather than the presence of prolonged pain, as found in the literature before.

EUROVISCO Good Practice Recommendations for a First Viscosupplementation in Patients with Knee Osteoarthritis.

RATIONALE: Viscosupplementation (VS) with hyaluronic acid is widely used in the management of knee osteoarthritis. There is no clear recommendation on the decision-making to achieve VS. DESIGN: Based on extensive research of the literature and expert opinion, the members of the EUROVISCO (European Viscosupplementation Consensus Group) task force were asked to give their degree of agreement with 60 issues, using a Delphi method. RESULTS: The expert panel achieved unanimous agreement in favor of the following statements: It is recommended to assess pain on a visual or 10-point numeric scale before considering VS. VS can be considered for patients with pain scores between 3 and 8. A standard x-ray must be obtained before the decision of VS. If the x-ray is normal, osteoarthritis must be confirmed by MRI or computed tomography (CT) arthrogram before considering VS. The aims of VS are relieving pain, improving function, and reducing non-steroidal anti-inflammatory drug (NSAID) consumption. The use of VS must not be considered for treating an osteoarthritis flare. VS can be envisaged as a first-line pharmacological treatment in patients having a contra-indication to NSAIDs or analgesics. VS can be considered in patients with contra-indications to arthroplasty. In the case of severe comorbidities (diabetes, hypertension, gastrointestinal disorders, renal failure), VS can avoid the use of potentially dangerous treatments. VS can be considered in patients receiving antiplatelet agents, vitamin K antagonists, and direct factor Xa or thrombin inhibitors. Five other statements obtained a high level of consensus. CONCLUSION: These recommendations, illustrated in a decision algorithm, have been established to help practitioners in the decision-making of knee VS.

Distinctive alterations in the functional anatomy of the cerebral cortex in pain-sensitized osteoarthritis and fibromyalgia patients.

BACKGROUND: Pain-sensitized osteoarthritis and fibromyalgia patients characteristically show nociceptive system augmented responsiveness as a common feature. However, sensitization can be originally related to the peripheral injury in osteoarthritis patients, whereas pain and bodily discomfort spontaneously occur in fibromyalgia with no apparent origin. We investigated the distinct functional repercussion of pain sensitization in the cerebral cortex in both conditions. METHODS: Thirty-one pain-sensitized knee osteoarthritis patients and 38 fibromyalgia patients were compared with matched control groups. And new samples of 34 sensitized knee osteoarthritis and 63 fibromyalgia patients were used to directly compare each condition. A combined measure of local functional connectivity was estimated to map functional alterations in the cerebral cortex at rest. RESULTS: In osteoarthritis, weaker local connectivity was identified in the insula, which is a cortical area processing important aspects of the brain response to painful stimulation. In contrast, fibromyalgia patients showed weaker connectivity in the sensorimotor cortex extensively affecting the cortical representation of the body. CONCLUSIONS: In osteoarthritis, weaker insular cortex connectivity is compatible with reduced neural activity during metabolic recovery after repeated activation. In the fibromyalgia neurophysiological context, weaker connectivity may better express both reduced neural activity and increased excitability, particularly affecting the sensorimotor cortex in patients with spontaneous body pain. Such a combination is compatible with a central gain enhancement mechanism, where low sensory tolerance results from the over-amplification of central sensory reception to compensate a presumably weak sensory input. We propose that deficient proprioception could be a factor contributing to weak sensory input.

Real-world effectiveness and persistence of reference etanercept versus biosimilar etanercept GP2015 among rheumatoid arthritis patients: A cohort study.

Although several randomized clinical trials have confirmed that there is no difference in efficacy between etanercept and its biosimilar versions in the treatment of rheumatoid arthritis (RA), limited real-world evidence is available. We conducted a cohort study to compare the effectiveness and treatment persistence between the reference etanercept (ETN) and the biosimilar GP2015 in RA patients in a real-life setting. Adults with a diagnosis of RA who initiated treatment with ETN or GP2015, between January 2007 and December 2019, were included. The follow-up period was 52 weeks. The primary outcome was the mean of change in the DAS28-CRP values and the adjusted mean difference from baseline to 52 weeks between ETN and GP2015. Other effectiveness endpoints assessed were the rate of patients who achieved remission or low disease activity (LDA) at week 52, who showed a reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 and rate of good responder patients (those meeting both effectiveness measures) at week 52. Treatment effectiveness over time (baseline, 26 and 52 weeks) was compared between the ETN and GP2015 groups using mixed effects models. Treatment persistence (probability of maintaining the same treatment over time) was also evaluated and shown using Kaplan-Meier survival curves. A total of 115 RA patients were included (ETN, n = 90; GP2015, n = 25). No differences were observed in the primary outcome: DAS28-CRP score decreased from baseline to week 52 [5.1 to 2.7 (mean of change -2.37) in ETN group and 5.0 to 2.2 (mean of change -2.84) in GP2015 group, p-value = 0.372] and the adjusted mean difference was -0.37 (-1.03 to 0.29). No differences were also observed in the other effectiveness endpoints assessed among patients treated with ETN or GP2015: rate of patients who achieved remission (54.1% vs. 66.7%, p-value = 0.303) and LDA (71.6% vs. 80.9%, p-value = 0.391) at week 52, reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 (75.6% vs. 80.9%, p-value = 0.613) and rate of good responder patients (58.1% vs. 76.1%, p-value = 0.202). Drug survival was 82% and 80% for ETN and GP2015, respectively (log-rank p-value = 0.804). Etanercept and its biosimilar GP2015 show similar effectiveness and treatment persistence in RA patients in a real-life setting.

Evaluation of a single-shot of a high-density viscoelastic solution of hyaluronic acid in patients with symptomatic primary knee osteoarthritis: the no-dolor study.

BACKGROUND: Pronolis®HD mono 2.5% is a novel, one-shot, high-density sterile viscoelastic solution, recently available in Spain, which contains a high amount of intermediate molecular weight hyaluronic acid (HA), highly concentrated (120 mg in 4.8 mL solution: 2.5%). The objective of the study was to analyze the efficacy and safety of this treatment in symptomatic primary knee osteoarthritis (OA). METHODS: This observational, prospective, multicenter, single-cohort study involved 166 patients with knee OA treated with a single-shot of Pronolis®HD mono 2.5% and followed up as many as 24 weeks. RESULTS: Compared with baseline, the score of the Western Ontario and McMaster Universities Arthritis Osteoarthritis Index (WOMAC) pain subscale reduced at the 12-week visit (primary endpoint, median: 9 interquartile range [IQR]: 7-11 versus median: 4; IQR: 2-6; p < 0.001). The percentage of patients achieving > 50% improvement in the pain subscale increased progressively from 37.9% (at 2 weeks) to 66.0% (at 24 weeks). Similarly, WOMAC scores for pain on walking, stiffness subscale, and functional capacity subscale showed significant reductions at the 12-week visit which were maintained up to the 24-week visit. The EuroQol visual analog scale score increased after 12 weeks (median: 60 versus 70). The need for rescue medication (analgesics/nonsteroidal anti-inflammatory drugs) also decreased in all post-injection visits. Three patients (1.6%) reported local adverse events (joint swelling) of mild intensity. CONCLUSIONS: In conclusion, a single intra-articular injection of the high-density viscoelastic gel of HA was associated with pain reduction and relief of other symptoms in patients with knee OA. TRIAL REGISTRATION: ClinicalTrial# NCT04196764.

Relationship Between the Choice of Clinical Treatment, Gait Functionality and Kinetics in Patients With Comparable Knee Osteoarthritis.

Objective: The objective of this study was to investigate the relationship between the choice of clinical treatment, gait functionality, and kinetics in patients with comparable knee osteoarthritis. Design: This was an observational case-control study. Setting: The study was conducted in a university biomechanics laboratory. Participants: Knee osteoarthritis patients were stratified into the following groups: clinical treatment (conservative/total knee replacement (TKR) planned), sex (male/female), age (60-67/68-75), and body mass index (BMI) (<30/≥30). All patients had a Kellgren-Lawrence score of 2 or 3 (N = 87). Main Outcome Measures: All patients underwent gait analysis, and two groups of dependent variables were extracted: • Spatiotemporal gait variables: gait velocity, stride time, and double-support time, which are associated with patient functionality. • Kinetic gait variables: vertical, anterior-posterior, and mediolateral ground reaction forces, vertical free moment, joint forces, and moments at the ankle, knee, and hip. Multifactorial and multivariate analyses of variance were performed. Results: Functionality relates to treatment decisions, with patients in the conservative group walking 25% faster and spending 24% less time in the double-support phase. However, these differences vary with age and are reduced in older subjects. Patients who planned to undergo TKR did not present higher knee forces, and different joint moments between clinical treatments depended on the age and BMI of the subjects. Conclusions: Knee osteoarthritis is a multifactorial disease, with age and BMI being confounding factors. The differences in gait between the two groups were mitigated by confounding factors and risk factors, such as being a woman, elderly, and obese, reducing the variability of the gait compression loads. These factors should always be considered in gait studies of patients with knee osteoarthritis to control for confounding effects.

Corrigendum: Impact of Non-Persistence on Healthcare Resource Utilization Costs in Patients With Immune-Mediated Rheumatic Diseases Initiating Subcutaneous TNF-Alpha Inhibitors: A Before-and-After Study.

[This corrects the article DOI: 10.3389/fphar.2021.752879.].

Regulatory network-based model to simulate the biochemical regulation of chondrocytes in healthy and osteoarthritic environments.

In osteoarthritis (OA), chondrocyte metabolism dysregulation increases relative catabolic activity, which leads to cartilage degradation. To enable the semiquantitative interpretation of the intricate mechanisms of OA progression, we propose a network-based model at the chondrocyte level that incorporates the complex ways in which inflammatory factors affect structural protein and protease expression and nociceptive signals. Understanding such interactions will leverage the identification of new potential therapeutic targets that could improve current pharmacological treatments. Our computational model arises from a combination of knowledge-based and data-driven approaches that includes in-depth analyses of evidence reported in the specialized literature and targeted network enrichment. We achieved a mechanistic network of molecular interactions that represent both biosynthetic, inflammatory and degradative chondrocyte activity. The network is calibrated against experimental data through a genetic algorithm, and 81% of the responses tested have a normalized root squared error lower than 0.15. The model captures chondrocyte-reported behaviors with 95% accuracy, and it correctly predicts the main outcomes of OA treatment based on blood-derived biologics. The proposed methodology allows us to model an optimal regulatory network that controls chondrocyte metabolism based on measurable soluble molecules. Further research should target the incorporation of mechanical signals.

The neurologic pain signature responds to nonsteroidal anti-inflammatory treatment vs placebo in knee osteoarthritis.

INTRODUCTION: Many drug trials for chronic pain fail because of high placebo response rates in primary endpoints. Neurophysiological measures can help identify pain-linked pathophysiology and treatment mechanisms. They can also help guide early stop/go decisions, particularly if they respond to verum treatment but not placebo. The neurologic pain signature (NPS), an fMRI-based measure that tracks evoked pain in 40 published samples and is insensitive to placebo in healthy adults, provides a potentially useful neurophysiological measure linked to nociceptive pain. OBJECTIVES: This study aims to validate the NPS in knee osteoarthritis (OA) patients and test the effects of naproxen on this signature. METHODS: In 2 studies (50 patients, 64.6 years, 75% females), we (1) test the NPS and other control signatures related to negative emotion in knee OA pain patients; (2) test the effect of placebo treatments; and (3) test the effect of naproxen, a routinely prescribed nonsteroidal anti-inflammatory drug in OA. RESULTS: The NPS was activated during knee pain in OA (d = 1.51, P < 0.001) and did not respond to placebo (d = 0.12, P = 0.23). A single dose of naproxen reduced NPS responses (vs placebo, NPS d = 0.34, P = 0.03 and pronociceptive NPS component d = 0.38, P = 0.02). Naproxen effects were specific for the NPS and did not appear in other control signatures. CONCLUSION: This study provides preliminary evidence that fMRI-based measures, validated for nociceptive pain, respond to acute OA pain, do not appear sensitive to placebo, and are mild-to-moderately sensitive to naproxen.

Tapentadol effects on brain response to pain in sensitized patients with knee osteoarthritis.

OBJECTIVE: Pain sensitization, in the form of knee tenderness and anatomically spread hyperalgesia, is notably common in patients with knee OA and is often refractory to conventional interventions. Tapentadol, as an opioid receptor agonist and noradrenaline reuptake inhibitor, has been proposed as a potentially effective symptomatic treatment for pain-sensitized OA patients. We empirically tested whether tapentadol could attenuate brain response to painful stimulation on the tender knee using functional MRI. METHODS: Painful pressure stimulation was applied to the articular interline and the tibial surface, a commonly sensitized site surrounding the joint. Thirty patients completed the crossover trial designed to compare prolonged release tapentadol and placebo effects administered over 14 days. RESULTS: We found no effects in the direction of the prediction. Instead, patients administered with tapentadol showed stronger activation in response to pressure on the tender site in the right prefrontal cortex and somatosensory cortices. The somatosensory effect was compatible with the spread of neural activation around the knee cortical representation. Consistent with the functional MRI findings, the patients showed higher clinical ratings of pain sensitization under tapentadol and a significant positive association was identified between the number of tapentadol tablets and the evoked subjective pain. CONCLUSION: The tapentadol effect paradoxically involved both the spread of the somatosensory cortex response and a stronger activation in prefrontal areas with a recognized role in the appraisal of pain sensations. Further studies are warranted to explore how OA patients may benefit from powerful analgesic drugs without the associated risks of prolonged use. TRIAL REGISTRATION: EudraCT, https://eudract.ema.europa.eu, 2016-005082-31.

Impact of Non-Persistence on Healthcare Resource Utilization and Costs in Patients With Immune-Mediated Rheumatic Diseases Initiating Subcutaneous TNF-Alpha Inhibitors: A Before-and-After Study.

Rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are chronic progressive immune-mediated rheumatic diseases (IMRD) that can cause a progressive disability and joint deformation and thus can impact in healthcare resource utilization (HCRU) and costs. The main outcome of the study was to assess the effect of non-persistence to treatment with subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) on HCRU costs in naïve patients with IMRD who started treatment with adalimumab, etanercept, golimumab or certolizumab pegol during 12 months after initiation of treatment. The impact of persistence and non-persistence of SC-TNFis on HCRU costs was compared between 12 months before and 12 months after initiating SC-TNFis. Persistence was defined as the duration of time from initiation to discontinuation of therapy. The study was conducted in an acute care teaching hospital in Barcelona, Spain. Data for the period between 2015 and 2018 were extracted from the hospital cost management control database. HCRU costs comprised outpatient care, outpatient specialized rheumatology care, in-patient care, emergency care, laboratory testing and other non-biological therapies. The study population included 110 naïve SC-TNFis patients, divided into the cohorts of persistent (n = 85) and non-persistent (n = 25) patients. Fifty-six percent of patients were women, with a mean (standard deviation) age of 47.6 (14.8) years. Baseline clinical features and HCRU costs over the 12 months before the index prescription were similar in the two study groups. Before-and-after differences in mean (standard deviation) HCRU costs were significantly higher in the non-persistence group as compared to the persistence group for outpatient rheumatology care (€110.90 [234.56] vs. €20.80 [129.59], p = 0.023), laboratory testing (-€193.99 [195.88] vs. -€241.3 [217.88], p = 0.025), other non-biological drugs (€3849.03 [4046.14] vs. -€10.90 [157.42], p < 0.001) and total costs (€3268.90 [4821.55] vs. -€334.67 (905.44), p < 0.001). Treatment persistence with SC-TNFis may be associated with HCRU cost savings in naïve IMRD patients. Prescribing SC-TNFis with the best long-term persistence is beneficial.

Documento de expertos sobre el uso apropiado de los SYSADOA en situaciones clínicas controvertidas / Experts Document About an Adequate Utilization of SYSADOAs in Controversial Clinical Situations

Antecedentes y objetivo: Los SYSADOA (del inglés, symptomatic slow-acting drugs for osteoarthritis) orales son compuestos naturales que han demostrado ser útiles y seguros en el tratamiento de la artrosis (AO). Sin embargo, su uso en ciertas situaciones clínicas carece aún de evidencia científica y recomendaciones claras. El objetivo de este trabajo fue conocer la opinión de un grupo de expertos sobre el uso de los SYSADOA en el tratamiento de la AO en situaciones clínicas controvertidas. Materiales y métodos: Siguiendo el método del uso apropiado mediante la técnica Delphi, se valoraron 206 consultas concretas, estructuradas en 24 preguntas clínicas. Un panel de expertos, compuesto por un total de 15 especialistas, respondió a las dos rondas de consulta a través de una plataforma online. Los resultados se analizaron y debatieron en una reunión presencial con los coordinadores y el comité científico. Según el porcentaje de panelistas que coincidieron en los mismos, se clasificaron los resultados en términos de unanimidad, consenso, mayoría y discrepancia. Resultados: Se consensuaron los siguientes puntos: (1) el fenotipo del paciente condiciona el uso de los SYSADOA orales; (2) los SYSADOA orales se consideran adecuados en la AO primaria (rodilla, mano y cadera) y en algunos tipos de AO secundaria; no se consideran adecuados en AO erosiva de manos, hombro, columna y tobillo; (3) los SYSADOA orales pueden ser prescritos a pacientes con riesgo o enfermedad cardiovascular, enfermedad digestiva, hipertensión, dislipemia, enfermedad vascular periférica, diabetes tipo 2 y, a excepción de diacereína, en pacientes con reflujo esofágico. No se obtuvo acuerdo en la prescripción de los SYSADOA orales en pacientes con enfermedad hepática y renal.(AU)

Background and objective: SYSADOAs (symptomatic slow-acting drugs for osteoarthritis) are natural compounds that have been shown to be useful and safe in the treatment of osteoarthritis (OA). However, their use in certain clinical situations still lacks scientific evidence and clear recommendations. The objective of this work was to learn the opinion of a group of experts regarding the appropriate use of SYSADOA in the treatment of OA in controversial clinical situations. Materials and methods: Following the Delphi technique, 206 specific consultations, structured in 24 clinical questions, were evaluated. A panel of experts composed of a total of 15 specialists, answered the two rounds of consultation through an online platform. The results were analysed and discussed in a face-to-face meeting with the coordinators and the scientific committee. According to the percentage of panellists who agreed on their findings, the results were classified in terms of unanimity, consensus, majority and discrepancy. Results: The following points were agreed upon: (1) the patient's phenotype determines the use of SYSADOAs; (2) SYSADOAs are considered appropriate in primary OA (knee, hand and hip) and in some types of secondary OA; they are not considered appropriate in OA of the shoulder, spine, ankle and erosive OA of the hands; (3) SYSADOAs may be prescribed for patients at risk of or with cardiovascular disease, digestive disease, hypertension, dyslipaemia, peripheral vascular disease, type 2 diabetes and, excluding diacerein, for patients with oesophageal reflux. No agreement was obtained on the prescription of SYSADOAs for patients with hepatic and renal disease. Conclusions: There is limited literature on the use of SYSADOAs for the treatment of OA in controversial situations. Through this work it has been possible to establish the position of a group of experts regarding clinical situations for which there is no scientific evidence concerning their use.(AU)