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OBJECTIVE: Skin involvement is common in systemic lupus erythematosus (SLE), but may be resistant to conventional treatment. We sought to evaluate the efficacy of anifrolumab (ANI) in refractory cutaneous manifestations of SLE. METHODS: Case series of patients with refractory cutaneous SLE from three Rheumatology Departments in Greece. Outcome measures were improvement in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), physician global assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Clinically relevant improvement in skin was defined as decrease ≥50% (CLASI50) from baseline values. RESULTS: Eighteen patients received ANI; all had active skin involvement at baseline. Mean (SD) SLEDAI and PGA at ANI initiation were 7.4 (2.7) and 1.4 (0.5), respectively, with a mean prednisone dose 4.9 (4.5) mg/day. Mean CLASI (Activity/Damage) at baseline was 13.9 (9.7)/2.9 (4.6). Patients were refractory to a mean 6.3 (1.5) immunomodulatory agents (including hydroxychloroquine and glucocorticoids) before the initiation of ANI. After a mean 8.5 (4.6) months, 89% (n = 16/18) of patients demonstrated significant improvement in general lupus and cutaneous disease activity, and glucocorticoid tapering. Mean SLEDAI and mean CLASI at last visit were 3.4 (1.9) and 2.1 (2.4)/1.4 (2.2), respectively, and mean daily prednisone dose decreased to 2.4 (2.2). Of note, in this group of highly refractory patients CLASI50 was achieved in 16/18 (89%) patients. One patient discontinued ANI after 4 infusions due to a varicella-zoster virus infection and one patient, who initially responded to treatment with ANI, experienced a skin flare due to temporary discontinuation due to Covid 19 infection. DORIS remission and LLDAS were attained in two (11.1%) and eleven (61.1%) patients, respectively. CONCLUSION: Anifrolumab is highly effective in various skin manifestations of SLE, even after prior failure to multiple treatments.
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OBJECTIVES: Treatment targets in systemic lupus erythematosus (SLE) have been validated in unselected-in terms of severity-cohorts, which limits their generalisability. We assessed remission (Definition of Remission in SLE (DORIS)) and Lupus Low Disease Activity State (LLDAS) in a historical cohort of 348 patients with active moderate-to-severe disease and median follow-up of 5 years. METHODS: Active SLE was defined as Physician Global Assessment ≥1.5 and/or SLE Disease Activity Index 2000 ≥6, requiring therapy intensification. DORIS/LLDAS, organ damage, flares and adverse events were monitored. Shared frailty survival, generalised linear models and K-means clustering were applied. RESULTS: Sustained DORIS and LLDAS for ≥6 months occurred in 41.1% and 80.4%, respectively, and resulted in reduced damage accrual (HR: 0.58; 95% CI 0.36 to 0.93 and 0.61; 0.43 to 0.86) and severe flares (HR: 0.14; 0.08 to 0.27 and 0.19; 0.13 to 0.27). LLDAS without DORIS was also protective (HR: 0.65; 0.43 to 0.98 for damage, 0.49; 0.36 to 0.67 for flares). Models fitting increasing duration of targets showed that DORIS ≥50% and LLDAS ≥60% of time, or alternatively, ≥24 and ≥36 months, achieved optimal balance between feasibility (20.2-41.7%) and specificity (73.3-86.1%) for damage-free outcome. These targets were linked to reduced serious adverse events (risk ratio (RR): 0.56-0.71), hospitalisation (RR: 0.70) and mortality (RR: 0.06-0.13). Patients with predominant arthritis and mucocutaneous disease experienced reduced DORIS/LLDAS, compared with counterparts with major organ involvement. Conventional drugs were more frequently used in the former group, whereas potent immunosuppressive/biological agents in the latter. CONCLUSIONS: In moderate-to-severe SLE, sustained DORIS/LLDAS for at least 6 months is sufficient, while attainment for at least 24 months ensures higher specificity for damage-free progression, thus facilitating treat-to-target strategies and clinical trials. Arthritis and skin disease represent unmet therapeutic needs that could benefit from novel biologics.
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Artritis , Lupus Eritematoso Sistémico , Enfermedades de la Piel , Humanos , Artritis/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Inducción de Remisión , Índice de Severidad de la Enfermedad , Enfermedades de la Piel/tratamiento farmacológico , Ensayos Clínicos como AsuntoRESUMEN
BACKGROUND: Characterisation of the long-term outcome of patients with 'difficult to treat' (D2T) rheumatoid arthritis and factors contributing to its evolution are unknown. Herein, we explored the heterogeneity and contributing factors of D2T long-term outcome. METHODS: Patients included from a prospective single centre cohort study. The EULAR definition of D2T was applied. Longitudinal clustering of functional status (modified Health Assessment Questionnaire (mHAQ)) and disease activity (Disease Activity Score-28 (DAS28)) were assessed using latent-class trajectory analysis. Multiple linear mixed models were used to examine the impact of comorbidities and their clusters on the long-term outcome. RESULTS: 251 out of 1264 patients (19.9%) were identified as D2T. Younger age, fibromyalgia, osteoarthritis, DAS28-erythrocyte sedimentation rate (ESR) at first biological or targeted synthetic disease-modifying antirheumatic drug (b/ts-DMARD) initiation and failure to reduce DAS28-ESR scores within the first 6 months of b/ts-DMARD therapy were significant predictors of patients becoming D2T. Long-term follow-up (total of 5872 person-years) revealed four groups of functional status evolution: 18.2% had stable, mildly compromised mHAQ (mean 0.41), 39.9% had gradual improvement (1.21-0.87) and two groups had either slow deterioration or stable significant functional impairment (HAQ>1). Similarly, four distinct groups of disease activity evolution were identified. Among the different clusters of comorbidities assessed, presence of 'mental-health and pain-related illnesses' or 'metabolic diseases' had significant contribution to mHAQ worsening (p<0.0001 for both) and DAS28 evolution (p<0.0001 and p=0.018, respectively). CONCLUSION: D2T patients represent a heterogeneous group in terms of long-term disease course. Mental-health/pain-related illnesses as well as metabolic diseases contribute to long-term adverse outcomes and should be targeted in order to optimise the prognosis of this subset of rheumatoid arthritis.
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Antirreumáticos , Artritis Reumatoide , Mitoxantrona/análogos & derivados , Humanos , Preescolar , Estudios de Cohortes , Estudios Prospectivos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Antirreumáticos/uso terapéutico , Dolor/tratamiento farmacológicoRESUMEN
To characterize disease activity trajectories and compare long-term drug retention between rheumatoid (RA) and spondylarthritis (SpA) patients initiating tumor necrosis factor inhibitor (TNFi) treatment (etanercept). Prospective observational study of RA, axial (AxSpA) and peripheral SpA (PerSpA) patients initiating etanercept during 2004-2020. Kaplan-Meier plots were used for drug retention comparisons and multivariable Cox regression models for predictors of discontinuation. Long-term disease activity trajectories were identified by latent class growth models using DAS28-ESR or ASDAS-CRP as outcome for RA and AxSpA respectively. We assessed 711 patients (450 RA, 178 AxSpA and 83 PerSpA) with a median (IQR) follow-up of 12 (5-32) months. At 5 years, 22%, 30% and 21% of RA, AxSpA and PerSpA patients, respectively, remained on therapy. Etanercept discontinuation was independent of the diagnosis and was predicted by gender and obesity in both RA and SpA groups. Four disease activity (DA) trajectories were identified from 6th month of treatment in both RA and AxSpA. RA patients in remission-low DA groups (33.7%) were younger, had shorter disease duration, fewer comorbidities and lower baseline disease activity compared to moderate (40.6%) & high DA (25.7%) groups. In AxSpA 74% were in inactive-low DA and they were more often males, non-obese and had lower number of comorbidities compared to higher ASDAS-CRP trajectories. In RA and AxSpA patients, disease activity trajectories revealed heterogeneity of TNFi treatment responses and prognosis. Male gender, lower baseline disease activity and fewer comorbidities, characterize a favourable outcome in terms of disease burden accrual and TNFi survival.
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Antirreumáticos , Artritis Reumatoide , Espondiloartritis Axial , Espondiloartritis , Humanos , Masculino , Etanercept/uso terapéutico , Antirreumáticos/uso terapéutico , Estudios Prospectivos , Espondiloartritis/diagnóstico , Espondiloartritis/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Resultado del Tratamiento , Factor de Necrosis Tumoral alfaRESUMEN
Abatacept (CTLA4-Ig)-a monoclonal antibody which restricts T cell activation-is an effective treatment for rheumatoid arthritis (RA). Nevertheless, only 50% of RA patients attain clinical responses, while predictors of response are rather limited. Herein, we aimed to investigate for early biomarkers of response to abatacept, based on a detailed immunological profiling of peripheral blood (PB) cells and serum proteins. We applied flow cytometry and proteomics analysis on PB immune cells and serum respectively, of RA patients starting abatacept as the first biologic agent. After 6 months of treatment, 34.5% of patients attained response. At baseline, Th1 and FoxP3+ T cell populations were positively correlated with tender joint counts (p-value = 0.047 and p-value = 0.022, respectively). Upon treatment, CTLA4-Ig effectively reduced the percentages of Th1 and Th17 only in responders (p-value = 0.0277 and p-value = 0.0042, respectively). Notably, baseline levels of Th1 and myeloid cell populations were significantly increased in PB of responders compared to non-responders (p-value = 0.009 and p-value = 0.03, respectively). Proteomics analysis revealed that several inflammatory mediators were present in serum of responders before therapy initiation and strikingly 10 amongst 303 serum proteins were associated with clinical responses. Finally, a composite index based on selected baseline cellular and proteomics' analysis could predict response to abatacept with a high sensitivity (90%) and specificity (88.24%).
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Antirreumáticos , Artritis Reumatoide , Humanos , Abatacept/farmacología , Abatacept/uso terapéutico , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Mediadores de Inflamación , Células MieloidesRESUMEN
Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by reactivation of the polyomavirus JC (JCV) typically in immunocompromised individuals. The risk of PML among rheumatic diseases may be higher for systemic lupus erythematosus (SLE), without, however, a clear association with the type and intensity of background therapy. We present the development and outcome of PML in a 32-year-old female lupus patient under mild immunosuppressive treatment, yet with marked B-cell lymphopenia in the peripheral blood and bone marrow (<1% of total lymphocytes). Despite treatment with the immune checkpoint inhibitor pembrolizumab, the patient showed progressive neurological and brain imaging deterioration and eventually died 15 months after PML diagnosis. To unveil possible underlying genetic liabilities, whole exome sequencing was performed which identified deleterious variants in GATA2 and CDH7 genes, which both have been linked to defective T- and/or B-lymphocyte production. These findings reiterate the possible role of disease-/patient-intrinsic factors, rather than that of drug-induced immunosuppression, in driving immune dysregulation and susceptibility to PML in certain patients with SLE.
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New biologic and small molecule targeted agents have expanded the armamentarium of Spondyloarthritides (SpA), allowing more therapeutic options for patients who do not respond to therapy. The implementation of the treat-to-target (T2T) strategy with close monitoring and frequent treatment adaptations targeting disease remission has been proposed as the means to prevent radiographic progression and long-term adverse outcomes. In this project we will employ the "University of Crete Rheumatology Clinic Registry" to prospectively study in real-world practice musculoskeletal and extraarticular disease activity, patient function, comorbidities, sociodemographics, imaging, compliance to therapy and other lifestyle factors in axial and peripheral SpA patients. The predictive value of these variables in long-term (2years) outcomes will be evaluated. We will also assess the implementation of the T2T approach as well as its impact on long-term patients' outcomes (quality of life, productivity, adverse events). The successful completion of this study could pave the way for improved and personalized therapy in patients with SpA.
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Mental disorders such as anxiety and depression are prevalent in systemic lupus erythematosus (SLE) patients, yet their association with the underlying disease activity remains uncertain and has been mostly evaluated at a cross-sectional level. To examine longitudinal trends in anxiety, depression, and lupus activity, a prospective observational study was performed on 40 adult SLE outpatients with active disease (SLE Disease Activity Index [SLEDAI]-2K ≥ 3 [excluding serology]) who received standard-of-care. Anxiety and depression were determined at baseline and 6 months by the Hospital Anxiety and Depression Scale. Treatment adherence was assessed with the Morisky Medication Adherence Scale-4. Increased anxiety (median [interquartile range] HADS-A: 11.0 [7.8]) and depression (HADS-D: 8.0 [4.8]) were found at inclusion, which remained stable and non-improving during follow-up (difference: 0.0 [4.8] and −0.5 [4.0], respectively) despite reduced SLEDAI-2K by 2.0 (4.0) (p < 0.001). Among possible baseline predictors, paid employmentbut not disease activitycorrelated with reduced HADS-A and HADS-D with corresponding standardized beta-coefficients of −0.35 (p = 0.017) and −0.27 (p = 0.093). Higher anxiety and depression correlated with lower treatment adherence (p = 0.041 and p = 0.088, respectively). These results indicate a high-mental disease burden in active SLE that persists despite disease control and emphasize the need to consider socioeconomic factors as part of comprehensive patient assessment.
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BACKGROUND: Rituximab is used for the treatment of active rheumatoid arthritis. In the present study, we examined the long-term flare risk and safety of reduced doses of rituximab. PATIENTS-METHODS: This was a prospective, observational, single-center study of patients starting rituximab on standard dose (SD). Patients were switched to low dose (LD) (1 g every 6 months), based on the treating rheumatologist's decision after having achieved sustained clinical responses, while the rest of the patients continued on standard dose (SD). During a 60-month period, we assessed (Kaplan-Meier survival analysis) the relapse rate (increase ≥ 1.2 in DAS28-ESR for ≥ 6 months) and discontinuations due to treatment failure in the low dose group, and we compared the incidence of serious adverse events (SAEs) between LD and SD groups. RESULTS: Out of 361 patients [females 83.4%, mean age 61.9 (10.6) years, seropositive 50.3%, median total comorbidities count 4], 81 patients (22.4%) entered LD in a median time of 24 months (95% CI 18-30 months). Seropositivity (OR 1.823), more than 2 previous bDMARDs failures (OR 0.428), and DAS28 < 4.88 at 6 months (OR 2.329) predicted the odds of entering LD (p < 0.05 for all). During 60 months of follow-up, only 7.5% of patients on LD relapsed. Patients on LD had significantly less SAEs and all-cause hospitalizations as compared to the SD group (p < 0.05 for all). Linear regression analysis showed that previous hospitalization while on bDMARDs (p < 0.0001), use of prednisolone > 5 mg/day while on rituximab (p < 0.0001), and a history of ≥ 2 previous csDMARDs (p = 0.041) predicted the risk of SAEs. CONCLUSION: In a cohort of patients with established RA and significant comorbidities who taper rituximab after substantial initial disease activity improvement, a low rate of relapses and lower risk of SAEs compared to SD were recorded. Seropositivity, a lower number of previous bDMARDs use, and lower DAS28 at 6 months predicted the probability of entering the LD regimen.
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Artritis Reumatoide , Artritis Reumatoide/tratamiento farmacológico , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Prednisolona , Estudios Prospectivos , Rituximab/efectos adversosRESUMEN
This study aimed at assessing the impact of golimumab on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) in real-world settings. GO-Q was an observational, prospective, 12-month study, which recruited patients with moderate-to-severely active RA initiating golimumab treatment per label in rheumatology clinics and private practices. Primary endpoint was the change in PROs [EuroQol-5 Dimensions-3 Levels (EQ-5D-3L) questionnaire, Health Assessment Questionnaire Disease Index (HAQ-DI), and Work Productivity and Activity Index for RA (WPAI:RA)] after 12 months of treatment. Other endpoints included Disease Activity Score for 28 joints with erythrocyte sedimentation rate (DAS28-ESR), healthcare resource utilization, and golimumab adherence. Changes in continuous variables from baseline were evaluated with the paired t test. One hundred forty-five patients were recruited. The mean [standard deviation (SD)] EQ-5D-3L index increased significantly at 12 months versus baseline [from 0.427 (0.206) to 0.801 (0.229); p < 0.0001], with changes as early as 3 and 6 months (both p < 0.0001). Accordingly, there were statistically significant changes in all WPAI:RA domains from baseline to 3, 6, and 12 months (p < 0.0001). Patients' function improved gradually from the third month until the end of follow-up (p < 0.0001 for all time-points). Thirty (27.3%) and 60 (54.6%) patients achieved remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR ≤ 3.2), respectively, at 12 months. Adherence rate to golimumab was high (mean [SD] 90.3% (7.5) at 12 months). In patients with moderate-to-severely active RA, golimumab significantly improved HRQoL, physical function, and work productivity and activity, with improvements in disease activity over 12 months in real-world settings.
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Antirreumáticos , Artritis Reumatoide , Anticuerpos Monoclonales , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Grecia , Humanos , Atención Dirigida al Paciente , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Introduction: Patients with rheumatoid arthritis (RA) are at increased risk for serious infections. Pneumococcal vaccination is among the most important preventive measures, however, vaccine uptake is suboptimal. We explored the rate and factors associated with pneumococcal vaccination in a contemporary RA cohort. Materials and methods: Multi-center, prospective, RA cohort study in Greece. Patient and disease characteristics and influenza and pneumococcal vaccinations were documented at baseline and 3 years later. Results: One thousand six hundred and ninety-seven patients were included and 34.5% had already received at least one pneumococcal vaccine at baseline. Among 1,111 non-vaccinated patients, 40.1% received pneumococcal vaccination during follow-up, increasing the vaccine coverage to 60.8%. By multivariate analysis, positive predictors for pneumococcal vaccination included prescription of influenza vaccine (OR = 33.35, 95% CI: 18.58-59.85), history of cancer (OR = 2.35, 95% CI: 1.09-5.06), bDMARD use (OR = 1.85, 95% CI: 1.29-2.65), seropositivity (OR = 1.47, 95% CI: 1.05-2.05), and high disease activity (DAS28-ESR, OR = 1.33, 95% CI: 1.17-1.51). Male sex (OR = 0.65, 95% CI: 0.43-0.99) was a negative predictor for pneumococcal vaccination during follow-up. Discussion: Despite increasing rates of pneumococcal vaccine coverage, 40% of RA patients remain unvaccinated. Severe disease, bDMARD use, comorbidities, and more importantly flu vaccination were the most significant factors associated with pneumococcal vaccination, emphasizing the currently unmet need for cultivating a "vaccination culture" in RA patients.
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Objective: To obtain real-world data on outcomes of belimumab treatment and respective prognostic factors in patients with systemic lupus erythematosus (SLE). Methods: Observational study of 188 active SLE patients (median disease duration 6.2 years, two previous immunosuppressive/biological agents) treated with belimumab, who were monitored for SLEDAI-2K, Physician Global Assessment (PGA), LLDAS (lupus low disease activity state), remission (DORIS/Padua definitions), SELENA-SLEDAI Flare Index, SLICC/ACR damage index and treatment discontinuations. Group-based disease activity trajectories were modelled followed by multinomial regression for predictive variables. Drug survival was analysed by Cox-regression. Results: At 6, 12 and 24 months, LLDAS was attained by 36.2%, 36.7% and 33.5%, DORIS-remission by 12.3%, 11.6% and 17.8%, and Padua-remission by 21.3%, 17.9% and 29.0%, respectively (attrition-corrected). Trajectory analysis of activity indices classified patients into complete (25.5%), partial (42.0%) and non-responder (32.4%) groups, which were predicted by baseline PGA, inflammatory rash, leukopenia and prior use of mycophenolate. During median follow-up of 15 months, efficacy-related discontinuations occurred in 31.4% of the cohort, especially in patients with higher baseline PGA (hazard ratio [HR] 2.78 per 1-unit; 95% CI 1.32-5.85). Conversely, PGA improvement at 3 months predicted longer drug retention (HR 0.57; 95% CI 0.33-0.97). Use of hydroxychloroquine was associated with lower risk for safety-related drug discontinuation (HR 0.33; 95% CI 0.13-0.85). Although severe flares were reduced, flares were not uncommon (58.0%) and contributed to treatment stops (odds ratio [OR] 1.73 per major flare; 95% CI 1.09-2.75) and damage accrual (OR 1.83 per mild/moderate flare; 95% CI 1.15-2.93). Conclusions: In a real-life setting with predominant long-standing SLE, belimumab was effective in the majority of patients, facilitating the achievement of therapeutic targets. Monitoring PGA helps to identify patients who will likely benefit and stay on the treatment. Vigilance is required for the prevention and management of flares while on belimumab.
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Lupus Eritematoso Sistémico , Humanos , Resultado del Tratamiento , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Inmunosupresores/uso terapéuticoRESUMEN
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BACKGROUND: Cognitive impairment (CI) is one of the most frequent neuropsychiatric manifestations of systemic lupus erythematosus (SLE). Given that extensive neuropsychological testing is not always feasible in routine clinical practice, brief cognitive screening tools are desirable. The aim of this study was to evaluate the Montreal Cognitive Assessment (MoCA) as a screening tool for CI in SLE. METHODS: Consecutive SLE patients followed at a single centre were evaluated using MoCA and an extensive neuropsychological test battery (NPT), including the Digits Forward and Digits Backwards, Rey Auditory Verbal Learning Memory Test, Trail Making Test, Stroop Colour-Word Test, Semantic and Phonetic Verbal Fluency tests and a 25-problem version of the General Adult Mental Ability test. The criterion validity of MoCA was assessed through receiver operating characteristic (ROC) analyses using three different case definitions: i) against normative population data, ii) and iii) against average performance of a comparison group of rheumatoid arthritis (RA) patients, to adjust for possible confounding effects of chronic illness and inflammatory processes on cognitive performance. The effect of patient-related (age, years of education, anxiety, depression, fatigue and pain) and disease-related (activity, damage, age at diagnosis, disease duration, use of glucocorticoid, psychotropic and pain medication) parameters on the MoCA was examined. RESULTS: A total of 71 SLE patients were evaluated. MoCA significantly correlated with all NPT scores and was affected by education level (p < 0.001), but not by other demographic or clinical variables. The optimal cutoff for detecting CI, as defined on the basis of normative population data, was 23/30 points, demonstrating 73% sensitivity and 75% specificity. A cutoff of 22/30 points, using neuropsychological profiles of the RA group as inflammatory disease controls, exhibited higher sensitivity (100%, based on both definitions) and specificity (87% and 90%, depending on the definition). The standard cutoff of 26/30 points displayed excellent sensitivity (91-100%) with significant expenses in specificity (43-45%). CONCLUSION: The MoCA is an easily applied tool, which appears to be reliable for identifying CI in SLE patients. The standard cutoff score (26/30) ensures excellent sensitivity while lower cutoff scores (22-23/30) may, also, provide higher specificity.
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Artritis Reumatoide , Disfunción Cognitiva , Lupus Eritematoso Sistémico , Adulto , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Grecia , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Pruebas de Estado Mental y Demencia , Pruebas Neuropsicológicas , DolorRESUMEN
OBJECTIVES: Diagnostic reasoning in systemic lupus erythematosus (SLE) is a complex process reflecting the probability of disease at a given timepoint against competing diagnoses. We applied machine learning in well-characterised patient data sets to develop an algorithm that can aid SLE diagnosis. METHODS: From a discovery cohort of randomly selected 802 adults with SLE or control rheumatologic diseases, clinically selected panels of deconvoluted classification criteria and non-criteria features were analysed. Feature selection and model construction were done with Random Forests and Least Absolute Shrinkage and Selection Operator-logistic regression (LASSO-LR). The best model in 10-fold cross-validation was tested in a validation cohort (512 SLE, 143 disease controls). RESULTS: A novel LASSO-LR model had the best performance and included 14 variably weighed features with thrombocytopenia/haemolytic anaemia, malar/maculopapular rash, proteinuria, low C3 and C4, antinuclear antibodies (ANA) and immunologic disorder being the strongest SLE predictors. Our model produced SLE risk probabilities (depending on the combination of features) correlating positively with disease severity and organ damage, and allowing the unbiased classification of a validation cohort into diagnostic certainty levels (unlikely, possible, likely, definitive SLE) based on the likelihood of SLE against other diagnoses. Operating the model as binary (lupus/not-lupus), we noted excellent accuracy (94.8%) for identifying SLE, and high sensitivity for early disease (93.8%), nephritis (97.9%), neuropsychiatric (91.8%) and severe lupus requiring immunosuppressives/biologics (96.4%). This was converted into a scoring system, whereby a score >7 has 94.2% accuracy. CONCLUSIONS: We have developed and validated an accurate, clinician-friendly algorithm based on classical disease features for early SLE diagnosis and treatment to improve patient outcomes.
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Lupus Eritematoso Sistémico , Nefritis , Adulto , Anticuerpos Antinucleares , Humanos , Aprendizaje Automático , ProbabilidadRESUMEN
OBJECTIVES: Predicting serious infections (SI) in patients with rheumatoid arthritis (RA) is crucial for the implementation of appropriate preventive measures. Here we aimed to identify risk factors for SI and to validate the RA Observation of Biologic Therapy (RABBIT) risk score in real-life settings. METHODS: A multi-centre, prospective, RA cohort study in Greece. Demographics, disease characteristics, treatments and comorbidities were documented at first evaluation and one year later. The incidence of SI was recorded and compared with the expected SI rate using the RABBIT risk score. RESULTS: A total of 1557 RA patients were included. During follow-up, 38 SI were recorded [incidence rate ratio (IRR): 2.3/100 patient-years]. Patients who developed SI had longer disease duration, higher HAQ at first evaluation and were more likely to have a history of previous SI, chronic lung disease, cardiovascular disease and chronic kidney disease. By multivariate analysis, longer disease duration (IRR: 1.05; 95% CI: 1.005, 1.1), history of previous SI (IRR: 4.15; 95% CI: 1.7, 10.1), diabetes (IRR: 2.55; 95% CI: 1.06, 6.14), chronic lung disease (IRR: 3.14; 95% CI: 1.35, 7.27) and daily prednisolone dose ≥10 mg (IRR: 4.77; 95% CI: 1.47, 15.5) were independent risk factors for SI. Using the RABBIT risk score in 1359 patients, the expected SI incidence rate was 1.71/100 patient-years, not different from the observed (1.91/100 patient-years; P = 0.97). CONCLUSION: In this large real-life, prospective study of RA patients, the incidence of SI was 2.3/100 patient-years. Longer disease duration, history of previous SI, comorbidities and high glucocorticoid dose were independently associated with SI. The RABBIT score accurately predicted SI in our cohort.
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Artritis Reumatoide/epidemiología , Infecciones/epidemiología , Infecciones Oportunistas/epidemiología , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Comorbilidad , Femenino , Glucocorticoides/uso terapéutico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The therapeutic armamentarium in Systemic Lupus Erythematosus (SLE) is expanding with the introduction of novel biologic and small-molecule agents. Complementary to randomized controlled trials, registry-based studies are advantageous due to the inclusion of a wider range of patients from daily practice and the potential for long-term monitoring of the efficacy and safety of therapies. Moreover, data from registries can be used to identify disease phenotypes that best respond to biologic agents, and to correlate clinical response with parameters such as co-administered therapies and comorbidities. In this project, we will use the configuration of the Hellenic Registry of Biologic Therapies for inflammatory arthritides in order to design a dedicated SLE module with variables pertaining to global and organ-specific disease activity, severity, flares, organ damage/outcome, comorbidities and adverse events. The second stage will involve the pilot implementation of this platform for the multicentric registration of SLE patients who are treated with belimumab. The significance lies in the development of a structured registry that enables the assessment of the disease burden and the long-term efficacy and safety of existing and future biological agents in SLE. Piloting the registry can serve as a basis for establishing nationwide collaborative efforts.
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This prospective study aimed to examine whether illness-related negative emotions mediate the relationship of cognitive reappraisal and expressive suppression to the well-being of 99 patients with rheumatoid arthritis or multiple sclerosis. After adjusting for disease and patient-related parameters, only cognitive reappraisal was associated with physical and psychological well-being through emotions. Expressive suppression was associated with psychological well-being only for patients reporting less use of cognitive reappraisal. These results underscore the need for prospective studies that will investigate the long-term impact of emotion regulation on adaptation to chronic illness and the conditions under which this impact takes place.
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Enfermedades Autoinmunes , Regulación Emocional , Enfermedades Autoinmunes/psicología , Enfermedad Crónica , Cognición , Emociones , Humanos , Estudios ProspectivosRESUMEN
OBJECTIVES: Systemic lupus erythematosus (SLE) diagnosis and treatment remain empirical and the molecular basis for its heterogeneity elusive. We explored the genomic basis for disease susceptibility and severity. METHODS: mRNA sequencing and genotyping in blood from 142 patients with SLE and 58 healthy volunteers. Abundances of cell types were assessed by CIBERSORT and cell-specific effects by interaction terms in linear models. Differentially expressed genes (DEGs) were used to train classifiers (linear discriminant analysis) of SLE versus healthy individuals in 80% of the dataset and were validated in the remaining 20% running 1000 iterations. Transcriptome/genotypes were integrated by expression-quantitative trail loci (eQTL) analysis; tissue-specific genetic causality was assessed by regulatory trait concordance (RTC). RESULTS: SLE has a 'susceptibility signature' present in patients in clinical remission, an 'activity signature' linked to genes that regulate immune cell metabolism, protein synthesis and proliferation, and a 'severity signature' best illustrated in active nephritis, enriched in druggable granulocyte and plasmablast/plasma-cell pathways. Patients with SLE have also perturbed mRNA splicing enriched in immune system and interferon signalling genes. A novel transcriptome index distinguished active versus inactive disease-but not low disease activity-and correlated with disease severity. DEGs discriminate SLE versus healthy individuals with median sensitivity 86% and specificity 92% suggesting a potential use in diagnostics. Combined eQTL analysis from the Genotype Tissue Expression (GTEx) project and SLE-associated genetic polymorphisms demonstrates that susceptibility variants may regulate gene expression in the blood but also in other tissues. CONCLUSION: Specific gene networks confer susceptibility to SLE, activity and severity, and may facilitate personalised care.
Asunto(s)
Perfilación de la Expresión Génica/métodos , Predisposición Genética a la Enfermedad/epidemiología , Interferón Tipo I/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Adulto , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , ARN Mensajero/genética , Valores de Referencia , Transcriptoma/genética , Adulto JovenRESUMEN
BACKGROUND: Systemic Sclerosis (SSc) is a rare, multisystemic connective tissue disease associated with significant morbidity. Early recognition of patients at risk for adverse prognosis may help towards optimized monitoring and treatment, thus improving disease outcome. OBJECTIVE: To correlate nailfold videocapillaroscopy (NVC) findings ('early', 'active', 'late' scleroderma patterns and non-specific capillary abnormalities) with major organ involvement and prognosis in patients with systemic sclerosis (SSc). METHODS: Patients from the Scleroderma cohort followed at the Rheumatology clinic of the University Hospital of Heraklion will be included. The study will include a prospective and a retrospective part. Prospective part: All newly diagnosed patients will undergo NVC at baseline and subsequently every six months. We will review demographics, clinical features and autoantibodies status. Major organ involvement will be monitored (Pulmonary Function Test, DLCO, heart echocardiogram, chest XR, modified Rodnan skin score) at baseline and then every 6-12 months. Retrospective part: Existing SSc patients with available NVC data at diagnosis will be included. We will correlate the NVC findings at the time of diagnosis with disease outcomes such as major organ involvement, end stage organ failure, need for hospitalization, and death. We will also correlate longitudinal changes of the NVC patterns with treatment responses and outcomes.