Dysregulation of Glypicans and Notum in Osteoarthritis: Plasma Levels, Bone Marrow Mesenchymal Stromal Cells and Osteoblasts.

In this study of the alterations of Glypicans 1 to 6 (GPCs) and Notum in plasma, bone marrow mesenchymal stromal cells (BM-MSCs) and osteoblasts in Osteoarthritis (OA), the levels of GPCs and Notum in the plasma of 25 patients and 24 healthy subjects were measured. In addition, BM-MSCs from eight OA patients and eight healthy donors were cultured over a period of 21 days using both a culture medium and an osteogenic medium. Protein and gene expression levels of GPCs and Notum were determined using ELISA and qPCR at 0, 7, 14 and 21 days. GPC5 and Notum levels decreased in the plasma of OA patients, while the BM-MSCs of OA patients showed downexpression of GPC6 and upregulation of Notum. A decrease in GPC5 and Notum proteins and an increase in GPC3 were found. During osteogenic differentiation, elevated GPCs 2, 4, 5, 6 and Notum mRNA levels and decreased GPC3 were observed in patients with OA. Furthermore, the protein levels of GPC2, GPC5 and Notum decreased, while the levels of GPC3 increased. Glypicans and Notum were altered in BM-MSCs and during osteogenic differentiation from patients with OA. The alterations found point to GPC5 and Notum as new candidate biomarkers of OA pathology.

Harnessing ChatGPT and GPT-4 for evaluating the rheumatology questions of the Spanish access exam to specialized medical training.

The emergence of large language models (LLM) with remarkable performance such as ChatGPT and GPT-4, has led to an unprecedented uptake in the population. One of their most promising and studied applications concerns education due to their ability to understand and generate human-like text, creating a multitude of opportunities for enhancing educational practices and outcomes. The objective of this study is twofold: to assess the accuracy of ChatGPT/GPT-4 in answering rheumatology questions from the access exam to specialized medical training in Spain (MIR), and to evaluate the medical reasoning followed by these LLM to answer those questions. A dataset, RheumaMIR, of 145 rheumatology-related questions, extracted from the exams held between 2010 and 2023, was created for that purpose, used as a prompt for the LLM, and was publicly distributed. Six rheumatologists with clinical and teaching experience evaluated the clinical reasoning of the chatbots using a 5-point Likert scale and their degree of agreement was analyzed. The association between variables that could influence the models' accuracy (i.e., year of the exam question, disease addressed, type of question and genre) was studied. ChatGPT demonstrated a high level of performance in both accuracy, 66.43%, and clinical reasoning, median (Q1-Q3), 4.5 (2.33-4.67). However, GPT-4 showed better performance with an accuracy score of 93.71% and a median clinical reasoning value of 4.67 (4.5-4.83). These findings suggest that LLM may serve as valuable tools in rheumatology education, aiding in exam preparation and supplementing traditional teaching methods.

The complex HLA-E-nonapeptide in Behçet disease.

Introduction: The knowledge of the aetiology of Behçet disease (BD), an immune-mediated vasculitis, is limited. HLA-B, mainly HLA-B51, and HLA-A molecules are associated with disease, but the ultimate cause of this association remains obscure. There is evidence that NK cells participate in the etiopathology of BD. NK cells have activator and inhibitor surface receptors, like the KIR and the NKG2 families. Classical HLA-class I molecules (A, B and C) are keys in the activity control of the NK because they are KIR ligands. Most NKG2 receptors bind HLA-E, which presents only nonapeptides derived from the signal peptide of other class-I molecules. Objective: This study investigates the contribution of the pair HLA-E and ligand, nonapeptide derived from the 3-11 sequence of the signal peptides of class I classical molecules, to the susceptibility to BD. Methods: We analyzed the frequency of the HLA-derivated nonapeptide forms in 466 BD patients and 444 controls and an HLA-E functional dimorphism in a subgroup of patients and controls. Results: In B51 negative patients, the frequency of VMAPRTLLL was lower (70.4% versus 80.0% in controls; P=0.006, Pc=0.04, OR=0.60, 95%CI 0.41-0.86), and the frequency of VMAPRTLVL was higher (81.6% versus 71.4% in controls; P=0.004, Pc=0.03, OR=1.78, 95%CI 1.20-2.63). In homozygosity, VMAPRTLLL is protective, and VMAPRTLVL confers risk. The heterozygous condition is neutral. There were no significant differences in the distribution of the HLA-E dimorphism. Discussion: Our results explain the association of BD with diverse HLA-A molecules, reinforce the hypothesis of the involvement of the NK cells in the disease and do not suggest a significant contribution of the HLA-E polymorphism to disease susceptibility.

Understanding the role and adoption of artificial intelligence techniques in rheumatology research: An in-depth review of the literature.

The major and upward trend in the number of published research related to rheumatic and musculoskeletal diseases, in which artificial intelligence plays a key role, has exhibited the interest of rheumatology researchers in using these techniques to answer their research questions. In this review, we analyse the original research articles that combine both worlds in a five- year period (2017-2021). In contrast to other published papers on the same topic, we first studied the review and recommendation articles that were published during that period, including up to October 2022, as well as the publication trends. Secondly, we review the published research articles and classify them into one of the following categories: disease identification and prediction, disease classification, patient stratification and disease subtype identification, disease progression and activity, treatment response, and predictors of outcomes. Thirdly, we provide a table with illustrative studies in which artificial intelligence techniques have played a central role in more than twenty rheumatic and musculoskeletal diseases. Finally, the findings of the research articles, in terms of disease and/or data science techniques employed, are highlighted in a discussion. Therefore, the present review aims to characterise how researchers are applying data science techniques in the rheumatology medical field. The most immediate conclusions that can be drawn from this work are: multiple and novel data science techniques have been used in a wide range of rheumatic and musculoskeletal diseases including rare diseases; the sample size and the data type used are heterogeneous, and new technical approaches are expected to arrive in the short-middle term.

Perspectives of Therapeutic Drug Monitoring of Biological Agents in Non-Infectious Uveitis Treatment: A Review.

Biological drugs, especially those targeting anti-tumour necrosis factor α (TNFα) molecule, have revolutionized the treatment of patients with non-infectious uveitis (NIU), a sight-threatening condition characterized by ocular inflammation that can lead to severe vision threatening and blindness. Adalimumab (ADA) and infliximab (IFX), the most widely used anti-TNFα drugs, have led to greater clinical benefits, but a significant fraction of patients with NIU do not respond to these drugs. The therapeutic outcome is closely related to systemic drug levels, which are influenced by several factors such as immunogenicity, concomitant treatment with immunomodulators, and genetic factors. Therapeutic drug monitoring (TDM) of drug and anti-drug antibody (ADAbs) levels is emerging as a resource to optimise biologic therapy by personalising treatment to bring and maintain drug concentration within the therapeutic range, especially in those patients where a clinical response is less than expected. Furthermore, some studies have described different genetic polymorphisms that may act as predictors of response to treatment with anti-TNFα agents in immune-mediated diseases and could be useful in personalising biologic treatment selection. This review is a compilation of the published evidence in NIU and in other immune-mediated diseases that support the usefulness of TDM and pharmacogenetics as a tool to guide clinicians' treatment decisions leading to better clinical outcomes. In addition, findings from preclinical and clinical studies, assessing the safety and efficacy of intravitreal administration of anti-TNFα agents in NIU are discussed.

Therapeutic Response After Immunosuppressive Drug Prescription in Non-infectious Uveitis: A Survival Analysis.

INTRODUCTION: To identify factors affecting the response rate to immunosuppressive drugs (ISDs) in patients with non-infectious uveitis (NIU). METHODS: This longitudinal retrospective cohort study included patients from the Hospital Clinico San Carlos Uveitis Clinic diagnosed with NIU from 1992 to 2016. Subjects were followed up from ISD prescription until the achievement of good therapeutic response (GTR), ISD treatment change, or up to 12 months. GTR was defined as the complete resolution of the eye inflammatory manifestations with a corticosteroid dose ≤ 10 or ≤ 5 mg per day of prednisone or equivalent (GTR10 and GTR5, respectively) maintained for at least 28 days. Kaplan-Meier curves were estimated for GTR. Demographic, clinical, and treatment-related factors were analyzed using Cox robust regression. RESULTS: A total of 73 patients (100 episodes of ISD prescription) were analyzed. In 44 and 41 episodes, GTR10 and GTR5 were achieved, respectively. A lower hazard for both GTRs was associated with uveitic macular edema at prescription and with a higher "highest oral corticosteroid dose prescribed in the year before ISD prescription". GTR10 was higher if cyclosporine was prescribed (compared to other ISDs), and if a higher number of ISDs had been previously prescribed. GTR5 hazard was lower for patients with posterior uveitis or if the ISDs were prescribed before 2008, and higher if periocular corticosteroids had been administered before ISD prescription, or if the duration of the posterior segment activity was shorter. CONCLUSIONS: Factors associated with GTR to ISDs may help to identify patients with NIUs who could benefit from a thorough follow-up.

Corneal Biomechanics in Non-infectious Uveitis Measured by Corvis ST: A Pilot Study.

PURPOSE: To assess differences between corneal biomechanical properties in patients with non-infectious uveitis and healthy subjects using CorVis. METHODS: 77 patients with non-infectious uveitis and 47 control subjects were recruited. Biomechanical parameters were measured: deformation amplitude (DA), A-1 length and A-2 length (L1, L2), A-1 velocity and A-2 velocity (V1, V2), peak distance (PD) and HC radius (highest concavity radius). AUC ROC and correlation between clinical variables and biomechanical properties were determined. RESULTS: Lower HC Radius and IOPb and higher DA and V1 was found in uveitis group. Statistical differences between cases using systemic medications and those with topical treatment were found in L1. Differences were showed between those cases with active and inactive uveitis in PD, DA, V2 and L2. The biomechanical parameter with the best discriminatory capacity of uveitis disease was HC Radius. CONCLUSION: Differences in corneal biomechanical properties between non-infectious uveitis and healthy eyes were found.

Efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis: a protocol for a multicentre, randomised, parallel three arms, active-controlled, phase III open label with blinded outcome assessment study.

INTRODUCTION: Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet. METHODS AND ANALYSIS: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects' subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers. ETHICS AND DISSEMINATION: The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation. TRIAL REGISTRATION NUMBER: 2020-000130-18; NCT04798755.

Persistent post-discharge symptoms after COVID-19 in rheumatic and musculoskeletal diseases.

OBJECTIVES: We aimed to describe persistent symptoms and sequelae in patients with rheumatic and musculoskeletal diseases (RMD) after admission owing to coronavirus disease 2019 (COVID-19), assessing the role of autoimmune rheumatic diseases (ARDs) compared with non-autoimmune rheumatic and musculoskeletal diseases (NARDs) on persistent symptoms and sequelae. METHODS: We performed an observational study including RMD patients who attended a rheumatology clinic in Madrid and required admission owing to COVID-19 (between March and May 2020) and survived. The study began at discharge and ran until October 2020. Main outcomes were persistence of symptoms and sequelae related to COVID-19. The independent variable was the RMD group (ARD and NARD). Covariates included sociodemographics, clinical and treatment data. We ran a multivariate logistic regression model to assess the risk of the main outcomes by RMD group. RESULTS: We included 105 patients, of whom 51.5% had ARD and 68.57% reported at least one persistent symptom. The most frequent symptoms were dyspnoea, fatigue and chest pain. Sequelae were recorded in 31 patients. These included lung damage in 10.4% of patients, lymphopenia in 10%, a central retinal vein occlusion and an optic neuritis. Two patients died. Eleven patients required re-admission owing to COVID-19 problems (16.7% ARD vs 3.9% NARD; P = 0.053). No statistically significant differences were found between RMD groups in the final models. CONCLUSION: Many RMD patients have persistent symptoms, as in other populations. Lung damage is the most frequent sequela. Compared with NARD, ARD does not seem to differ in terms of persistent symptoms or consequences, although ARD might have more re-admissions owing to COVID-19.

There and back again: analyzing the effect of outpatient readmission on the quality of life of patients attending a rheumatology clinic.

AIMS: The aim of this study was to assess the effect of "outpatient readmissions" on the health-related quality of life (HR-QoL) of outpatients from a rheumatology clinic, meaning the effect of the patient's return to the outpatient clinic after having received care and been discharged. METHODS: We conducted an observational longitudinal retrospective study, with patients selected from the Hospital Clínico San Carlos Musculoskeletal cohort, based on having received at least one discharge from the outpatient clinic and having returned (readmission) at least once after the discharge. The main outcomes were the patients' baseline HR-QoL (measured on the first visit of each episode) and the ΔHR-QoL (difference between the HR-QoL in the last and the first visit of each episode). Successive episodes of admission and readmission were chronologically ordered, paired and analyzed using nested linear mixed models, nested by patients and by admission-readmission tandem. We carried out bivariable and multivariable analyses to assess the effect of demographic, clinical, treatment and comorbidity-related variables in both main outcomes. RESULTS: For the first main outcome, 5887 patients (13,772 episodes) were analyzed. Based on the multivariable level, readmission showed no significant marginal effect on the baseline HR-QoL (p-value = 0.17). Conversely, when analyzing the ΔHR-QoL, we did observe a negative and significant marginal effect (p-value = 0.028), meaning that readmission was associated with a lower gain in the HR-QoL during the follow-up, compared with the previous episode. CONCLUSION: In the outpatient setting, readmission exerts a deleterious effect in patients undergoing this process. Identification of outpatients more likely to be readmitted could increase the value of the care provided.

Predictors of health-related quality of life in musculoskeletal disease patients: a longitudinal analysis.

INTRODUCTION: Rheumatic and musculoskeletal diseases (RMDs) have a significant impact on patients' health-related quality of life (HRQoL) exacerbating disability, reducing independence and work capacity, among others. Predictors' identification affecting HRQoL could help to place efforts that minimize the deleterious impact of these conditions on patients' wellbeing. This study evaluates the influence of demographic and clinical predictors on the HRQoL of a cohort of RMD patients, measured using the Rosser classification index (RCI). METHODS: We included patients attending the Hospital Clínico San Carlos (HCSC) rheumatology outpatient clinic from 1 April 2007 to 30 November 2017. The primary outcome was the HRQoL assessed in each of the patient's visits using the RCI. Demographic and clinical variables extracted from a departmental electronic health record (EHR) were used as predictors: RMD diagnoses, treatments, comorbidities, and averaged HRQoL values from previous periods (for this last variable, values were imputed if no information was available). Association between predictors and HRQoL was analyzed using penalized generalized estimating equations (PGEEs). To account for imputation bias, the PGEE model was repeated excluding averaged HRQoL predictors, and common predictors were considered. DISCUSSION: A total of 18,187 outpatients with 95,960 visits were included. From 410 initial predictors, 19 were independently associated with patients' HRQoL in both PGEE models. Chronic kidney disease (CKD), an episode of prescription of third level analgesics, monoarthritis, and fibromyalgia diagnoses were associated with worse HRQoL. Conversely, the prescription in the previous visit of acid-lowering medication, colchicine, and third level analgesics was associated with better HRQoL. CONCLUSION: We have identified several diagnoses, treatments, and comorbidities independently associated with HRQoL in a cohort of outpatients attending a rheumatology clinic.

Factors Associated with Health-Related Quality of Life in Psoriatic Arthritis Patients: A Longitudinal Analysis.

INTRODUCTION: Psoriatic arthritis (PsA) is considered a multifaceted disease, with patients reporting low health-related quality of life (HRQoL). Data on disease burden are substantial and there exists a need for properly designed studies to learn more about the evolution of HRQoL in this condition. This study aims to identify factors associated to HRQoL evolution in PsA patients followed-up in a real-world setting in Spain. METHODS: We conducted a retrospective longitudinal observational study including incident patients from the rheumatology outpatient clinic of Hospital Clínico San Carlos (Madrid, Spain), diagnosed for the first time of PsA, defined as having received any ICD9/ICD10 diagnosis code of PsA, from 2007 to 2016, and followed-up until loss of follow-up, death, or November 2017. The influence of demographic and clinical variables in baseline HRQoL [assessed with the Rosser Classification Index (RCI)] was analyzed using bivariable and multivariable generalized linear models. The influence of those variables and of treatment-related factors in repeated measures of HRQoL was analyzed using bivariable and multivariable generalized estimating equations (GEE) models nested by patient. RESULTS: Two hundred and thirty patients were included in the analysis, with 3384 registered visits. At baseline, older age, a previous diagnosis of obesity, and the presence of enthesitis were significantly associated with worse HRQoL. During follow-up, using an exchangeable working correlation structure, the presence of enthesitis was also associated with worse HRQoL, coefficient (95% CI) - 0.006 (- 0.01 to - 0.002), p = 1.00E-03; conversely, treatment with methotrexate or antimalarials was associated with better HRQoL with 0.007 (0.001-0.014), p = 0.020 and 0.003 (0.001-0.005), p = 3.00E-03, respectively. CONCLUSIONS: Musculoskeletal manifestations and comorbidities exert a deleterious effect in HRQoL of PsA patients. Therefore, the optimal management of this condition needs to also address these manifestations in order to try to restore the QoL of these patients.

Disease Activity Indices in Rheumatoid Arthritis: Comparative Performance to Detect Changes in Function, IL-6 Levels, and Radiographic Progression.

Objective: To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA). Methods: Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The "Hospital Universitario La Princesa Index" (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on the R 2 parameter and the quasi-likelihood under the independence model criterion. Results: Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R 2 = 0.351) and SDAI ones (R 2 = 0.329). For serum IL-6 levels, the SDAI (R 2 = 0.208) followed by the HUPI model (R 2 = 0.205). For radiographic progression in ACT-RAY, the HUPI (R 2 = 0.034) and the DAS28 models (R 2 = 0.026) performed best whereas the DAS28 (R 2 = 0.030) and HUPI models (R 2 = 0.023) did so in PEARL. Conclusions: HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels.

Influence of colchicine prescription in COVID-19-related hospital admissions: a survival analysis.

AIMS: To analyze the association between colchicine prescription and COVID-19-related hospital admissions in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: Patients attending a rheumatology outpatient clinic from a tertiary care center in Madrid, Spain, from 1 September 2019 to 29 February 2020 were included. Patients were assigned as exposed or unexposed based on whether they were prescribed with colchicine in their last visit to the clinic during the 6 months before the start of the observation period. Treatment changes during the observation period were also considered. The primary outcome was COVID-19-related hospital admissions between 1 March and 20 May 2020. Secondary outcome included COVID-19-related mortality. Several weighting techniques for data balancing, based and non-based on the propensity score, followed by Cox regressions were performed to estimate the association of colchicine prescription on both outcomes. DISCUSSION: The number of patients entered in the study was 9379, with 406 and 9002 exposed and unexposed follow-up periods, respectively. Generalized Boosted Models (GBMs) and Empirical Balancing Calibration Weighting (EBCW) methods showed the best balance for COVID-19-related hospital admissions. Colchicine prescription did not show a statistically significant association after covariable balancing (p-value = 0.195 and 0.059 for GBM and EBCW, respectively). Regarding mortality, the low number of events prevented a success variable balancing and analysis. CONCLUSION: Colchicine prescription does not play a significant protective or risk role in RMD patients regarding COVID-19-related hospital admissions. Our observations could support the maintenance of colchicine prescription in those patients already being treated, as it is not associated with a worse prognosis. PLAIN LANGUAGE TITLE: Colchicine influence in COVID-19-related hospital admissions.

Influence of Mesenchymal Stem Cell Sources on Their Regenerative Capacities on Different Surfaces.

Current gold-standard strategies for bone regeneration do not achieve the optimal recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells-such as mesenchymal stem cells (MSCs)-and bioactive ceramic scaffolds-such as calcium phosphate-based (CaPs) bioceramics-seem promising. The biological properties of MSCs are influenced by the tissue source. This study aims to define the optimal MSC source and construct (i.e., the MSC-CaP combination) for clinical application in bone regeneration. A previous iTRAQ analysis generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow, and dental pulp, then cultured both on a plastic surface and on CaPs (hydroxyapatite and ß-tricalcium phosphate), to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) presented the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs demonstrated the greatest capacity to colonise the bioceramics. Furthermore, the results demonstrated a trend that DPSCs had the most robust increase in ALP activity. Regarding CaPs, ß-tricalcium phosphate obtained the best viability results, while hydroxyapatite had the highest ALP activity values. Therefore, we propose DPSCs as suitable MSCs for cell-based bone regeneration strategies.

Hospital admissions in inflammatory rheumatic diseases during the peak of COVID-19 pandemic: incidence and role of disease-modifying agents.

AIMS: In this pandemic, it is essential for rheumatologists and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRDs). We wanted to assess the role of targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD. METHODS: An observational longitudinal study was conducted during the epidemic peak in Madrid (1 March to 15 April 2020). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19 was expressed per 1000 patient-months. Cox multiple regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR of hospital admission related to COVID-19. RESULTS: A total of 3951 IRD patients were included (5896 patient-months). Methotrexate was the csDMARD most used. Eight hundred and two patients were on ts/bDMARDs, mainly anti-TNF agents, and Rtx. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 (95% confidence interval: 7-11.9). In the multivariate analysis, older, male, comorbidities, and specific systemic autoimmune conditions (Sjögren, polychondritis, Raynaud, and mixed connective tissue disease) had more risk of hospital admissions. Exposition to ts/bDMARDs did not achieve statistical significance. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model. CONCLUSION: This study provides additional evidence in IRD patients regarding susceptibility to moderate-severe infection related to COVID-19.

Inflammatory Relapses after Immunosuppressive Drug Discontinuation in Uveitis Patients: A Survival Analysis.

Purpose: To estimate the incidence rate (IR) and identify risk factors associated to inflammatory relapse after immunosuppressive drug (ISD) discontinuation in noninfectious uveitis patients.Methods: Multicenter longitudinal retrospective study, including patients from four uveitis clinics followed-up until December 2018. Hazard ratios for different variables were estimated using multivariable Cox models.Results: 32 patients (34 episodes of ISD discontinuation) were analyzed (median and maximum follow-up time: 2.4 and 19.2 years, respectively). Fourteen patients presented at least one relapse: anterior (8 patients), intermediate (5) and posterior (8). IR (95% confidence interval) of the first relapse was 14.3 (8.6-23.8) episodes per 100 patient-years (median survival time: 4.8 years). Early use of ISDs, panuveitis, and higher oral corticosteroid dosage at discontinuation were associated with higher hazards of relapse in multivariable analysis.Conclusions: Relapse is a frequent and early event after ISD discontinuation. Identifying relapse risk factors could support the physician's decision regarding ISD discontinuation.