The potential role of fatigue in difficult-to-treat rheumatoid arthritis.

OBJECTIVES: A subset of patients with rheumatoid arthritis (RA) who remains symptomatic after failing to multiple drugs are deemed to have "difficult-to-treat RA" (D2T RA). Fatigue is a burdensome symptom for RA patients, hindering their improvement. Our purpose was to evaluate the role of fatigue in D2T RA. METHODS: This cross-sectional study included rheumatoid arthritis (RA) patients between 2018 and 2022, treated with biological agents or targeted synthetic disease-modifying antirheumatic drugs. D2T RA was defined attending EULAR criteria. Independent variable was fatigue (dimensions and impact) assessed by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire and Numerical Rating Scales. Covariables: sociodemographic, clinical and treatment. To identify factors independently associated to D2T RA, multivariable logistic regression was run. RESULTS: The study included 145 patients and 38 (26.21%) developed D2T RA. D2T RA group were older, with more comorbidity and disability. D2T RA patients scored higher for global fatigue (p = 0.003), and almost for all their dimensions except for cognitive fatigue (p = 0.06) and fatigue coping (p = 0.07). Females with D2T RA showed more fatigue than those with non-D2T RA. In the adjusted models, all fatigue dimensions were associated with D2T RA: global fatigue RA (OR: 1.03; p = 0.007), physical (OR: 1.09; p = 0.008), living (OR: 1.09; p = 0.016), cognitive (OR: 1.1; p = 0.046) and emotional (OR: 1.18; p = 0.012). CONCLUSIONS: Despite the absence of an explicit mention of fatigue in the definition of D2T RA, it appears to be associated to this outcome. Fatigue should be evaluated in a multidimensional perspective, and gender-specific differences should be considered.

Switching related to inefficacy in biologics and targeted synthetic therapies for psoriatic arthritis: a comparative real-life study.

Background: Switching between therapies is a recommended strategy for psoriatic arthritis (PsA) patients who experience treatment failure; however, studies including real-life data are scarce. Objectives: To assess the incidence rate (IR) of switching between biologics and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) due to inefficacy in PsA, and to compare the risk of switching due to inefficacy across different b/tsDMARDs groups. Design: A longitudinal retrospective study, spanning from 2007 to 2022, was conducted on patients with PsA treated with b/tsDMARDs at an outpatient rheumatology clinic. Methods: The primary outcome was switching between b/tsDMARDs due to inefficacy. The independent variable was the exposure to b/tsDMARDs during follow-up. As covariates, clinical, treatment-related, and sociodemographic variables were considered. Survival techniques were run to estimate the IR of switching due to inefficacy per 100 patients*year and confidence interval at 95% (95% CI). Cox multivariate regression analyses were run to assess the risk of b/tsDMARDs switching due to inefficacy, expressed as hazard ratio (HR) and 95% CI. Results: In all, 141 patients were included, with 893.09 patients*year follow-ups. 52.48% of them were females in their fifties. In total, 262 courses of treatment were recorded. During the study period, 56 patients presented 121 switches and 103 related to inefficacy (IR: 11.53 (9.51-13.98)). Tumor necrosis factor-alpha inhibitors (TNFi) showed the lowest IR. In the bivariate analysis, all b/tsDMARDs had more risk of switching compared to TNFi (HR: anti-lL-17 vs TNFi: 2.26 (1.17-4.36); others vs TNFi: 3.21 (1.59-6.45)); however, this statistical significance was no longer present in the multivariate analysis once adjustments were made for the covariates. Still, the final model achieved statistical significance in the following variables: gender, clinical symptoms, prescription year, therapy courses, glucocorticoids, and sulfasalazine. Conclusion: In this study, we did not find differences in the rate of switching due to inefficacy among different groups of b/tsDMARDs. Other concomitant treatments, sociodemographic, and clinical variables were identified as risk factors for switching due to inefficacy.

METHODS: We included patients from 2007 to 2022 in which their consultant rheumatologist had decided to commence them on biologic therapy. We studied the changes due to drug failure, we also included sociodemographic, clinical and treatments information. RESULTS: The study comprised 141 patients. 52% were women in their fifties. We found that 56 patients change drugs 121 times, with 103 of those changes due to failure drug. This means about 11 out of every 100 patients change their biologic therapy each year. There was no difference in the risk of change between the different studied biologic therapies. Women, those with inflammatory back pain, and those who had tried many different drugs were more likely to change due to drug failure. Using additional therapies like glucocorticoids and sulfasalazine also increased the probability of biologic therapy change. CONCLUSION: Our work did not find differences in the risk of change due to drug failure among different biologic therapies.

Changes due to drug failure between biologic therapies: a real-life study in psoriatic arthritis patients Introduction: We wanted to evaluate how often patients with psoriatic arthritis change between different drugs because the drugs weren't working well enough. Additionally, we evaluated which factors could influence the change due to drug failure. The studied drugs are biological therapies that are arthritis-modifying drugs designed early in the last decade to prevent or reduce inflammation caused by the disease.

From Web to RheumaLpack: Creating a Linguistic Corpus for Exploitation and Knowledge Discovery in Rheumatology.

This study introduces RheumaLinguisticpack (RheumaLpack), the first specialised linguistic web corpus designed for the field of musculoskeletal disorders. By combining web mining (i.e., web scraping) and natural language processing (NLP) techniques, as well as clinical expertise, RheumaLpack systematically captures and curates structured and unstructured data across a spectrum of web sources including clinical trials registers (i.e., ClinicalTrials.gov), bibliographic databases (i.e., PubMed), medical agencies (i.e. European Medicines Agency), social media (i.e., Reddit), and accredited health websites (i.e., MedlinePlus, Harvard Health Publishing, and Cleveland Clinic). Given the complexity of rheumatic and musculoskeletal diseases (RMDs) and their significant impact on quality of life, this resource can be proposed as a useful tool to train algorithms that could mitigate the diseases' effects. Therefore, the corpus aims to improve the training of artificial intelligence (AI) algorithms and facilitate knowledge discovery in RMDs. The development of RheumaLpack involved a systematic six-step methodology covering data identification, characterisation, selection, collection, processing, and corpus description. The result is a non-annotated, monolingual, and dynamic corpus, featuring almost 3 million records spanning from 2000 to 2023. RheumaLpack represents a pioneering contribution to rheumatology research, providing a useful resource for the development of advanced AI and NLP applications. This corpus highlights the value of web data to address the challenges posed by musculoskeletal diseases, illustrating the corpus's potential to improve research and treatment paradigms in rheumatology. Finally, the methodology shown can be replicated to obtain data from other medical specialities. The code and details on how to build RheumaLpack are also provided to facilitate the dissemination of such resource.

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.

Long-Term Benefit of Perlingual Polybacterial Vaccines in Patients with Systemic Autoimmune Diseases and Active Immunosuppression.

INTRODUCTION: We have previously shown that trained-immunity-based vaccines, namely TIbV, significantly reduce the rate of recurrent infections, both of the respiratory tract (RRTI) and urinary tract infections (RUTI) in SAD patients on disease-modifying drugs (DMARDs). OBJECTIVE: We evaluated the frequency of RRTI and RUTI from 2018 to 2021 in those SAD patients that received TIbV until 2018. Secondarily, we evaluated the incidence and clinical course of COVID-19 in this cohort. METHODS: A retrospective observational study was conducted in a cohort of SAD patients under active immunosuppression immunized with TIbV (MV130 for RRTI and MV140 for RUTI, respectively). RESULTS: Forty-one SAD patients on active immunosuppression that were given TIbV up to 2018 were studied for RRTI and RUTI during the 2018-2021 period. Approximately half of the patients had no infections during 2018-2021 (51.2% no RUTI and 43.5% no RRTI at all). When we compared the 3-year period with the 1-year pre-TIbV, RRTI (1.61 ± 2.26 vs. 2.76 ± 2.57; p = 0.002) and RUTI (1.56 ± 2.12 vs. 2.69 ± 3.07; p = 0.010) episodes were still significantly lower. Six SAD patients (four RA; one SLE; one MCTD) with RNA-based vaccines were infected with SARS-CoV-2, with mild disease. CONCLUSIONS: Even though the beneficial protective effects against infections of TIbV progressively decreased, they remained low for up to 3 years, with significantly reduced infections compared to the year prior to vaccination, further supporting a long-term benefit of TIbV in this setting. Moreover, an absence of infections was observed in almost half of patients.

Difficult-to-treat rheumatoid arthritis (D2T RA): clinical issues at early stages of disease.

OBJECTIVES: Most studies on difficult-to-treat rheumatoid arthritis (D2T RA) have focused on established RA. Here, we analyse whether disease activity in the early stages of RA could influence progression to a D2T RA under real-life conditions. Other clinical and treatment-related factors were also analysed. METHODS: A longitudinal multicentre study of patients with RA was conducted from 2009 to 2018. Patients were followed up until January 2021. D2T RA was defined based on EULAR criteria (treatment failure, signs suggestive of currently active/progressive disease and management being perceived as problematic by the rheumatologist and/or patient). The main variable was disease activity in the early stages. The covariates were sociodemographic, clinical and treatment-related factors. We ran a multivariable logistic regression analysis to investigate risk factors associated with progression to D2T RA. RESULTS: The study population comprised 631 patients and 35 (5.87%) developed D2T RA. At the time of diagnosis, the D2T RA group were younger, with a higher disability, 28-joint Disease Activity Score (DAS28) score, tender joint count and pain scores. In our final model, DAS28 was not statistically significantly associated with D2T RA. No differences were found between groups for therapy. Disability was independently associated with D2T RA (OR: 1.89; p=0.01). CONCLUSIONS: In this cohort of patients newly diagnosed with RA, our results do not allow us to prove the influence of active disease according to DAS28. However, we did find that younger patients and those with elevated initial disability scores are more likely to develop D2T RA regardless of other factors.

Impact of rheumatoid arthritis on sexuality: adaptation and validation of the Qualisex questionnaire for use in Spain.

Patients with rheumatoid arthritis (RA) have a significantly increased risk of sexual dysfunction. However, it is not properly included in commonly used questionnaires to assess health-related quality of life in RA. Qualisex is a questionnaire developed in France to assess the impact of RA on patients´ sexual function. Our aim was to adapt and validate this questionnaire for use with Spanish RA patients. Two independent translations and a backward translation were obtained. The final version was tested in a pilot study with 10 RA patients to detect any aspects that could hinder interpretation. The validity and reliability of the linguistically validated questionnaire were studied in a multicenter cross-sectional study, with a longitudinal component for reliability estimation. 125 RA patients were included. The response process, discrimination, internal consistency, internal structure, convergent validity (correlation with MGH-SFQ questionnaire, DAS-28, physician global assessment, patient global health assessment, RAID, HAQ, HADS and SF-12©) and reliability were analyzed. The inclusion of two extra items was proposed in the pilot study. The validity analysis detected responses for item 10 that were not coherent with responses for the rest of items. The Cronbach alpha coefficient was 0.971. The highest correlation (0.665) was obtained with MGH-SFQ (questionnaire measuring sexual functioning), followed by RAID (0.516). The intra-class correlation was 0.880 (95% CI 0.815; 0.923), higher than 0.85, which indicates excellent reliability. All parameters used to assess this questionnaire show highly acceptable values. Qualisex allows for a global score of RA patients' sexual functioning and can be self-administered.

Mortality rate in rheumatoid arthritis-related interstitial lung disease: the role of radiographic patterns.

BACKGROUND: To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality. METHODS: A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization. RESULTS: 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4-104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4-4.17]. Women of 60-75 years of age were the group with the highest SMR. CONCLUSIONS: RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.

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.

Efficacy, safety and cost-effectiveness of a web-based platform delivering the results of a biomarker-based predictive model of biotherapy response for rheumatoid arthritis patients: a protocol for a randomized multicenter single-blind active controlled clinical trial (PREDIRA).

BACKGROUND: Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism. First-line therapy with synthetic disease-modifying antirheumatic drugs (sDMARD) is insufficiently effective in 40% of cases and these patients are treated with biotherapies. The increased use of these drugs each year is becoming a public health issue with considerable economic burden. This cost is 20 times higher than that of sDMARD. However, among patients treated with biotherapies, clinical practice shows that about one third will not respond to the selected drug. In nonresponse cases, practitioners currently have no choice but to perform an empirical switching between different treatments, because no tool capable of predicting the response or nonresponse to these molecules is currently available. METHODS: The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial, including RA patients with a previous failure to anti-TNF therapies. The main objective is the analysis of the clinical and pharmacoeconomic impact after 6 months of treatment. Intervention arm: prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software, a prediction software based on proteomic biomarkers. Control arm: prescription of biotherapy based on current practice, without the SinnoTest® software (any biotherapy). In addition, a substudy will be carried out within this trial to generate a biobank and further analyze the proteomic profile of the patients and their modification throughout the study. DISCUSSION: This clinical trial study will be the first validation study of a biotherapy response prediction software, bringing personalized medicine into the management of RA. We expect that the findings from this study will bring several benefits for the patient and the Health Care System. TRIAL REGISTRATION: ClincalTrials.gov NCT04147026 . Registered on 31 October, 2019.

Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19. METHODS: An observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission. RESULTS: The study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3-10) days. The median length of stay was 9 (6-14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model. CONCLUSION: Our results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.