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BACKGROUND: Since the development of the OMERACT Systemic Lupus Erythematosus (SLE) Core Outcome Set (COS) in 1998, many new SLE domains have been identified and measures developed, creating a need to update the SLE COS. To revisit the 1998 SLE COS and research agenda domains, and generate new candidate domains, we conducted this study of patients with SLE and collaborators. OBJECTIVE: (1) To evaluate existing candidate SLE domains for inclusion in the SLE COS. (2) To generate additional candidate SLE domains for COS consideration. (3) To engage SLE collaborators, including patients, in developing the updated SLE COS. METHODS: The OMERACT SLE Working Group's steering committee developed a survey to assess the importance of candidate SLE domains and generate additional domains for consideration towards the SLE COS. Patients with SLE followed at the University of Toronto Lupus Clinic (patient group) and members of the OMERACT SLE Working Group (collaborator group) were invited to complete the survey between August 2022 and February 2023. RESULTS: A total of 175 patients were invited and 100 completed the survey. Of 178 collaborators invited, 145 completed the survey. Patients tended to prioritize life-impact domains while collaborators prioritized clinical domains. Both patients and collaborators recommended additional domains to those included in the 1998 SLE COS and research agenda. CONCLUSION: The domain inclusion and importance results demonstrate that patients and collaborators prioritize different domains, so capturing the perspectives of both groups is essential to ensure a holistic assessment of SLE. The results of the study identify domains that already have a high level of agreement for potential inclusion in the SLE COS, domains that require further explanation, and novel domains that warrant consideration.
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OBJECTIVES: To compare proliferative (PLN) and membranous (MLN) lupus nephritis (LN) regarding clinical and laboratory presentation and long-term outcomes; To investigate predictors of progression to chronic kidney disease (CKD). METHODS: Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Rheumatic Diseases Portuguese Registry-Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Cox regression survival analysis was used to investigate predictors of CKD. RESULTS: 260 patients were included. Median follow-up was 8 years (IQR 11; minimum 1, maximum 35 years). MLN patients presented with significantly lower serum creatinine (0.70 (IQR 0.20; minimum 0.50, maximum 1.30) mg/dl vs 0.80 (IQR 0.31; minimum 0.26, maximum 2.60) in PLN, p= 0.003). Proteinuria levels did not differ between groups (p= 0.641). Levels of complement were reduced in PLN but nearly normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (p< 0.001). One year after the beginning of treatment, 62% of the patients achieved EULAR/ERA-EDTA complete response, with further 5% achieving partial response. Patients with lower proteinuria at diagnosis were more likely to achieve a complete renal response at one year, however, proteinuria at diagnosis or at one year did not predict long term CKD. Estimated glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 at one year was the strongest predictor of progression to CKD (HR 23 [95% CI 8-62], p< 0.001). Other possible predictors included the use of azathioprine for induction of remission, older age at diagnosis and male sex. CONCLUSION: Proteinuria levels did not predict LN histologic class in our cohort. eGFR cutoff of 75 mL/min/1.73 m2 after one year of treatment was strongly predictive of progression to CKD.
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OBJECTIVES: Anti-SSA autoantibodies can be differentiated according to their antigenic target proteins as anti-Ro60 (60 kDa) or anti-Ro52 (52 kDa). Anti-SSA(Ro60) antibodies are clearly associated with connective tissue diseases (CTD), but the clinical significance of anti-SSA(Ro52) antibodies remains unclear. The aim of the present study was to analyse the disease phenotype of patients with anti-Ro52 and/or anti-Ro60 antibodies. METHODS: A multicentre, cross-sectional study was carried out of positive anti-Ro52 and/or Ro60 antibodies patients followed at 10 Rheumatology centres from January 2018 until December 2021. Patients were categorised into 3 groups: group 1 (Ro52+/Ro60-); group 2 (Ro52-/Ro60+); group 3 (Ro52+/Ro60+). Antinuclear antibodies were evaluated by indirect immunofluorescence assay and further screened for anti-extractable nuclear antigen (ENA) antibodies. Demographicsand clinical data were compared between the 3 groups, by patients' medical chart review. Univariate analysis was performed and subsequently logistic regression was used to identify intergroup differences and calculate the odds ratio with a 95% confidence interval (95% CI). RESULTS: We included 776 patients [female: 83.1%; median age: 59 (46-71) years]. Groups 1, 2, and 3 comprised 31.1%, 32.6%, and 36.3% of the patients, respectively. Anti-Ro52 antibody alone was more frequently associated with non-rheumatic diseases, older age, and men (p<0.05). Among patients with CTD, the diagnosis of systemic lupus erythematosus is 3 and 2 times more prevalent in groups 2 and 3, respectively, than in group 1 [OR 2.8 (95% CI 1.60, 4.97), p<0.001; OR 2.2 (95% CI 1.28, 3.86), p<0.01]. In group 2, the diagnosis of undifferentiated CTD is more frequent than in the other groups. Group 1 was more frequently associated with inflammatory myositis than group 2 [OR 0.09 (95% CI 0.01, 0.33), p<0.001] or group 3 [OR 0.08 (95% CI 0.01, 0.29), p<0.001]. Group 1 was also more frequently associated with arthritis (p<0.01), interstitial lung disease (p<0.01), and myositis (p<0.01). CONCLUSIONS: Anti-Ro52+ antibody alone is frequently found in patients with non-rheumatic diseases. In addition, anti-Ro52+ antibody is also prevalent in patients with CTD and associated with clinical phenotypes that are different from anti-Ro60+ antibody.
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Anticuerpos Antinucleares , Fenotipo , Ribonucleoproteínas , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Ribonucleoproteínas/inmunología , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Anciano , Autoanticuerpos/sangre , Adulto , Enfermedades del Tejido Conjuntivo/inmunología , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades del Tejido Conjuntivo/sangre , Biomarcadores/sangre , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/sangre , ARN Citoplasmático Pequeño/inmunología , AutoantígenosAsunto(s)
Anticuerpos Monoclonales Humanizados , Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Enfermedades Musculares , Humanos , Rituximab/efectos adversos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , PulmónRESUMEN
OBJECTIVE: Our objective was to evaluate the ability of Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) remission and low disease activity (LDA) to discriminate active drug from placebo and to discriminate outcomes in the patients' perspective (health-related quality of life [HR-QoL]) in SLE trials. METHODS: This was a post hoc analysis of the pooled Belimumab in Subjects With SLE (BLISS)-52 (NCT00424476) and BLISS-76 (NCT00410384) trials data. SLE-DAS remission and LDA attainment and discrimination between belimumab and placebo at 52 weeks were compared using chi-square tests. At week 52, 36-item Short Form Health Survey (SF-36) and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores were compared between patients attaining SLE-DAS remission versus nonremission and SLE-DAS LDA versus non-LDA using the t-test and Mann-Whitney test. Mean changes from week 0 to 52 in SF-36 and FACIT-F scores were compared between groups using multivariate regression analysis adjusted for baseline scores. RESULTS: At week 52, significantly more patients attained SLE-DAS LDA taking belimumab 1 mg/kg (17.9% vs 13.0%; P = 0.023; odds ratio [OR] 1.459; relative risk [RR] 1.377; number needed to treat [NNT] 20.4) and 10 mg/kg (21.7% vs 13.0%; P < 0.001; OR 1.853; RR 1.668; NNT 11.5) compared with placebo. Likewise, more patients attained SLE-DAS remission taking belimumab 10 mg/kg compared to placebo (14.7% vs 10.1%; P = 0.019; OR 1.532; RR 1.454; NNT 21.7). At week 52, patients attaining SLE-DAS remission and LDA presented higher SF-36 domain and summary scores (all P < 0.001) and FACIT-F scores (both P < 0.001). Mean improvements from baseline in SF-36 and FACIT-F scores were significantly higher in patients achieving SLE-DAS remission and LDA. CONCLUSION: SLE-DAS remission and LDA showed discriminant ability for identifying patients receiving active drug in SLE clinical trials. Attainment of these SLE-DAS targets are associated with better HR-QoL.
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Anticuerpos Monoclonales Humanizados , Lupus Eritematoso Sistémico , Calidad de Vida , Inducción de Remisión , Índice de Severidad de la Enfermedad , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/diagnóstico , Femenino , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Inmunosupresores/uso terapéutico , Método Doble CiegoRESUMEN
OBJECTIVES: To assess agreement between the 2021 Definition Of Remission In SLE (DORIS) and physician-judged lupus activity. METHODS: A cross-sectional analysis was conducted of data from a Spanish prospective multicentre study of SLE patients. We applied the 2021 DORIS criteria and assessed whether remission status based on this definition agreed with remission as per physician clinical judgement and reasons for disagreement between them. RESULTS: Out of 508 patients [92% women; mean age (s.d.): 50.4 years (13.7)] studied, 267 (54.4%) met the criteria for 2021 DORIS remission. Based on physicians' judgement, 277 (55.9%) patients were classified as in remission or serologically active clinically quiescent (SACQ). The overall rate of agreement between these assessments was 81.2% (95% CI: 79.9, 82.9%) with a Cohen's kappa of 0.62 (0.55-0.69). Overall, 46 (9.1%) patients were classified as in remission/SACQ by rheumatologists but did not meet the 2021 DORIS criteria for remission. The main reasons for discrepancies were a clinical SLE Disease Activity Index (cSLEDAI) score >0 in 39 patients, a Physician Global Assessment score >0.5 in five patients, and prednisone >5 mg/day in another five patients. CONCLUSIONS: The 2021 DORIS remission is an achievable target in clinical practice. There is substantial agreement between the DORIS definition and physician-judged remission. The discordance was mainly due to physicians classifying some patients with ongoing mild disease activity as in remission. Thus, the standardized DORIS definition should be used to define the target in a treat-to-target strategy for the management of SLE.
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Juicio , Lupus Eritematoso Sistémico , Humanos , Femenino , Masculino , Estudios Prospectivos , Estudios Transversales , Reumatólogos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Inducción de RemisiónRESUMEN
OBJECTIVE: To assess the criterion validity of the SLE disease activity score (SLE-DAS) flare tool and compare its performance in identifying flares against other instruments. METHODS: Patients with SLE fulfilling SLE-DAS low disease activity at baseline were included from two academic lupus clinics. During follow-up, flares were identified by the senior attending clinician, applying the expert-consensus-based definition as gold-standard. The first clinical flare from flaring patients, and the first visit after baseline in patients without flares were analysed. In each no flare/flare visits, we assessed flares by SLE-DAS (score increase ≥1.72), classic-SELENA Flare Index (c-SELENA FI), revised-SELENA FI (r-SELENA FI), and SLEDAI-2K (score increase ≥4). We estimated the sensitivity, specificity, and Cohen's Kappa agreement of each flare tool against the gold-standard. RESULTS: A total of 442 patients were included and followed-up for 22.9 (14.2) months. Incidence of flares was 8.19/100 patient-years, with 69 patients experiencing flares. The SLE-DAS identified 96.6% of the expert-defined flares implying a treatment change and classified 28.0% of those as moderate/severe. Sensitivity and specificity for the gold-standard flare definition were: SLE-DAS 97.1% and 97.3%, c-SELENA FI 88.4% and 98.1%, r-SELENA FI 88.4% and 96.8%, SLEDAI-2K 56.5% and 99.2%, respectively. Kappa coefficients of these instruments were 0.902 (95% CI: 0.847, 0.957), 0.870 (95% CI: 0.805, 0.935), 0.832 (95% CI: 0.761, 0.903), and 0.663 (95% CI: 0.557, 0.769), respectively. The number of flare misclassifications was lowest with the SLE-DAS, and highest with the SLEDAI-2K. CONCLUSION: The SLE-DAS accurately identifies and categorizes flares as mild or moderate/severe. It is feasible and, thus, may help the physicians' treatment decisions in the clinical practice setting.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Índice de Severidad de la Enfermedad , Sensibilidad y EspecificidadRESUMEN
Systemic lupus erythematosus (SLE) is a heterogeneous condition making assessment of disease activity challenging. However, thorough assessment is essential to evaluate patients longitudinally, to guide therapeutic decisions, and for clinical trials. Currently, the most popular disease activity index in clinical practice and trials is SLEDAI-2K. Its main advantage is ease of use, but significant weaknesses of SLEDAI-2K are omission of several serious manifestations, inability to capture change within an organ system, and fixed severity weightings that are often inappropriate. Recently several groups have developing improved tools. We report here the debate held at CORA meeting on this issue. SLE-DAS includes 17 weighted clinical and laboratory parameters including continuous measures in 4 items with an online calculator. A higher sensitivity to change compared to SLEDAI-2K has been demonstrated in its validation studies. Easy BILAG is an improved format of the BILAG-2004 that retains its content but greatly simplified. Its scoring using a single-page form that incorporates concise definitions for key terms next to clinical items. Easy-BILAG demonstrates higher accuracy and less variability and increased and better user feedback compared to the standard BILAG-2004 format. Both the indices discussed at CORA showed an advantage in measuring disease activity compared to SLEDAI.
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Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Índice de Severidad de la Enfermedad , LaboratoriosRESUMEN
OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
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Azatioprina , Lupus Eritematoso Sistémico , Humanos , Azatioprina/uso terapéutico , Tacrolimus/uso terapéutico , Rituximab/uso terapéutico , Metotrexato/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Inmunosupresores/uso terapéutico , Ciclofosfamida/uso terapéutico , Hidroxicloroquina/uso terapéutico , Glucocorticoides/uso terapéutico , Inhibidores Enzimáticos/uso terapéuticoRESUMEN
OBJECTIVES: The treatment target in SLE should be maintained stable by preventing flares. The objectives were to identify predictors of flare in patients attaining lupus low disease activity state (LLDAS), and to assess whether remission with no glucocorticoids is associated with lower risk of flares. METHODS: This was a cohort study of SLE patients followed in a referral centre over 3 years. Baseline was the first visit where each patient attained LLDAS. Flares up to 36 months' follow-up were identified by three instruments: revised Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) Flare Index (r-SFI), SLEDAI-2000 (SLEDAI-2K) and SLE Disease Activity Score (SLE-DAS). Demographic, clinical and laboratory parameters at baseline were evaluated as predictors of flare, with distinct models for each flare instrument, using survival analysis with univariate followed by multivariate Cox regression. Hazard ratios (HR) were determined with 95% CI. RESULTS: A total of 292 patients fulfilling LLDAS were included. Over follow-up, 28.4%, 24.7% and 13.4% of the patients developed one or more flare, according to r-SFI, SLE-DAS and SLEDAI-2K definitions, respectively. After multivariate analysis, the predictors of SLE-DAS flares were presence of anti-U1-ribonucleoprotein (anti-U1RNP) (HR = 2.16, 95% CI 1.30, 3.59), SLE-DAS score at baseline (HR = 1.27, 95% CI 1.04, 1.54) and immunosuppressants (HR = 2.43, 95% CI 1.43, 4.09). These predictors were equally significant for r-SFI and SLEDAI-2K flares. Remitted patients with no glucocorticoids presented a lower risk of SLE-DAS flares (HR = 0.60, 95% CI 0.37, 0.98). CONCLUSION: In patients with LLDAS, anti-U1RNP, disease activity scored by SLE-DAS and SLE requiring maintenance immunosuppressants predict higher risk of flare. Remission with no glucocorticoids is associated with lower risk of flares.
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Lupus Eritematoso Sistémico , Humanos , Estudios de Cohortes , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Estudios de Seguimiento , Inmunosupresores/uso terapéutico , Glucocorticoides/uso terapéutico , Índice de Severidad de la EnfermedadAsunto(s)
Enfermedades Autoinmunes , Humanos , Estudios Transversales , Antígenos Nucleares , AutoanticuerposRESUMEN
(1) Background: Patients with systemic lupus erythematous (SLE) experience profound effects on health-related quality of life (HRQoL) that cannot be explained by objective indicators of mortality and morbidity. This study aimed to adapt the SLE Quality of Life (SLEQoL) questionnaire to the European Portuguese population and to assess its reliability and validity for patients with SLE. (2) Methods: Two independent translators translated the original version of the SLEQoL questionnaire into Portuguese. A back-translated version was produced. The Portuguese version of the questionnaire was reviewed and tested for validity and reliability. Cronbach's alpha and the internal validity index were calculated to verify the internal reliability and validity of the content. Rheumatologists filled out the SLE Disease Activity Score (SLE-DAS) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index SLICC/ACR-DI questionnaires. (3) Results: This study involved 180 patients, of which 93.8% were females. The results indicated very high internal consistency reliability (α = 0.949), low correlations between the SLEQoL and the SLE-DAS, a correlation between all SLEQoL dimensions and all SF-36 dimensions (except for "response to treatment" and "self-image"), and good correlation scores with both the EQ-5D-5L index and VAS. (4) Conclusion: The Portuguese version of the SLEQoL questionnaire is valid and reliable for the measurement of HRQoL in SLE patients.
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Lupus Eritematoso Sistémico , Calidad de Vida , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Portugal , Encuestas y Cuestionarios , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: To apply the lupus low disease activity state (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician's subjective evaluation of lupus activity. METHODS: We conducted a cross-sectional analysis of a prospective multicentre study of SLE patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physician's opinion. RESULTS: A total of 508 patients [92% women; mean age 50.4 years (s.d. 3.7)] were recruited and 304 (62.7%) patients were in the LLDAS. According to physician assessment, 430 (86.1%) patients were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1, 70.5) with a Cohen's κ of 0.3 [interquartile range (IQR) 0.22-0.37]. Most cases (96.1%) in the LLDAS were classified as remission or low activity by the expert. Of the patients who did not fulfil the LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2K score >4, mainly based on serological activity. CONCLUSIONS: Almost two-thirds of SLE patients were in the LLDAS. There was a fair correlation between the LLDAS and the physician's evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of the LLDAS with better outcomes and the fact that the LLDAS is more stringent than the physician's opinion imply that we should use the LLDAS as a treat-to-target goal.
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Testimonio de Experto , Lupus Eritematoso Sistémico , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Transversales , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION/OBJECTIVES: Recognising systemic lupus erythematosus (SLE) patients at higher risk for hospitalization, aiming at developing tailored management strategies, may help minimize admissions and improve long-term health outcomes. Our study aimed to identify predictors for hospitalization in patients with SLE. METHOD: Cohort study of SLE patients followed in a referral centre. All hospitalizations from study baseline up to 120 months were identified, and the primary indication for admission was categorized as follows: (1) SLE disease activity; (2); infection; and (3) other conditions. Demographic, clinical, and laboratory parameters at baseline were sought as predictors of hospitalization for (i) any cause, (ii) disease activity, and (iii) infection using survival analysis with Kaplan-Meier curves and log-rank tests. Potential predictors were further tested using multivariate Cox proportional hazards regression models. RESULTS: We included 398 patients (median follow-up: 120 months). The incidence rate of hospitalization was 17.7 per 100 patient-years. The most frequent indications for hospitalization were SLE disease activity (29.4%) and infection (23.4%). In multivariate analysis, male gender, age > 50 years, antiphospholipid antibodies positivity (aPL), SLEDAI-2 K > 5, organ damage, and prednisone daily dose (PDN) predicted hospitalization for any cause. SLEDAI-2 K > 5, aPL, PDN, and IS medication predicted hospitalization for active SLE. Male gender, prior biopsy-proven lupus nephritis, aPL, organ damage, and ongoing treatment with high-risk IS predicted hospitalization for infection. Treatment with antimalarials was associated with a lower risk of hospitalization for any cause and for infection. CONCLUSIONS: Positive aPL identifies SLE patients presenting a higher risk of hospitalization, while medication with antimalarials was associated with a lower risk. Key Points ⢠Positive aPL is predictive of hospitalization for any medical condition, disease activity, and infection ⢠Organ damage is predictive of hospitalization for any condition and infection ⢠Antimalarials are predictive of a lower risk of hospitalization for any condition and infection.
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Antimaláricos , Lupus Eritematoso Sistémico , Anticuerpos Antifosfolípidos , Antimaláricos/uso terapéutico , Estudios de Cohortes , Hospitalización , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). METHODS: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. RESULTS: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. CONCLUSION: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.
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Antirreumáticos , Artritis Reumatoide , Reumatología , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Consenso , Humanos , Portugal/epidemiologíaRESUMEN
INTRODUCTION/OBJECTIVES: Infections are a major cause of morbidity and death in systemic lupus erythematosus (SLE). Perfecting the understanding of contributors to infection burden in SLE is pivotal to improve management and outcomes. This study aims to identify clinical predictors of infection in SLE. METHOD: We conducted a prospective cohort study at a referral SLE clinic. Infections were identified at each visit and categorized as (a) any type, (b) serious, (c) non-serious, and (d) bacterial. Survival analysis followed by multivariate Cox regression with an estimation of hazard ratios (HR) with 95% confidence intervals (95%CI) was performed. RESULTS: We included 259 patients during a mean follow-up of 23.3 ± 5.7 months. The incidence rate of infection of any type was 59.3 cases per 100 patient-years. Multivariate Cox models showed that (a) prednisolone ≥ 7.5 mg/day (HR = 1.95, 95%CI 1.26-3.03) and female gender (HR = 2.08, 95%CI 1.12-3.86) were associated with higher risk of infection of any type; (b) prednisolone ≥ 10 mg/day was associated with higher (HR = 4.32, 95%CI 1.39-13.40), and antimalarials with lower risk (HR = 0.18, 95%CI 0.06-0.51) of serious infection; (c) female gender (HR = 1.92, 95%CI 1.04-3.57) and prednisolone ≥ 7.5 mg/day (HR = 1.89, 95%CI 1.21-2.96) were associated with higher risk of non-serious infection; (d) antimalarials were associated with lower (HR = 0.49, 95%CI 0.26-0.93) and female gender (HR = 5.12; 95%CI 1.62-16.18) with higher risk of bacterial infection. CONCLUSIONS: The risk of infection was higher in females in this young, well-controlled, low-comorbidity SLE cohort. Antimalarials were associated with lower and prednisolone ≥ 7.5 mg with higher risk of infection. Key Points ⢠Lupus patients treated with prednisolone ≥ 7.5 mg/day were 89% more likely to present infections. ⢠Lupus patients receiving prednisolone ≥ 10 mg/day were four times more likely to present serious infections. ⢠Lupus patients receiving antimalarials were 82% less likely to present serious infections.
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Antimaláricos , Lupus Eritematoso Sistémico , Antimaláricos/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Prednisolona/uso terapéutico , Estudios Prospectivos , Factores de RiesgoRESUMEN
OBJECTIVES: To derive and validate a definition of low disease activity (LDA) for SLE based on the SLE Disease Activity Score (SLE-DAS), in a real-life multicentre cohort of SLE patients. METHODS: Derivation was conducted using data from a monocentric cohort of SLE (Portugal), and validation was performed in a multicentre cohort (Italy, France and Spain). The Lupus Low Disease Activity State (LLDAS) was used as comparator. We applied receiver operating characteristics curve analysis against the LLDAS to determine the cut-off of SLE-DAS for LDA using bootstrap methodology. In a second step, we tested a definition of SLE-DAS LDA that included: (i) the statistically derived SLE-DAS upper threshold for LDA and (ii) prednisone dose ≤7.5 mg/day. In the multicentre validation cohort, we assessed the classification performance of this SLE-DAS LDA definition. RESULTS: We included 774 patients, 300 in the derivation and 474 in the validation cohort. In the derivation cohort, the optimal cut-off to identify patients in LLDAS was SLE-DAS ≤2.48, presenting an area under the curve of 0.965 (95% CI 0.935, 0.994). When applied to the multicentre validation cohort, the SLE-DAS LDA definition showed a sensitivity of 97.1% and a specificity of 97.7% for LLDAS and an almost perfect agreement (Cohen's Kappa = 0.933; P < 0.001). McNemar's test found no significant differences between the two definitions (P = 0.092). CONCLUSION: The SLE-DAS LDA is a validated, accurate and easy-to-use definition for classifying SLE patients in LDA state.
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Lupus Eritematoso Sistémico , Estudios de Cohortes , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Prednisona , Índice de Severidad de la Enfermedad , EspañaRESUMEN
OBJECTIVES: There is an unmet need for accurate and user-friendly definitions of systemic lupus erythematosus (SLE) disease activity and remission. We aimed to derive and validate the SLE Disease Activity Score (SLE-DAS) definitions for disease activity categories and clinical remission state. METHODS: Derivation was conducted at Padova Lupus Clinic (Italy). Validation was prospectively performed at Cochin Lupus Clinic (France) and by post hoc analysis of BLISS-76 trial. At each clinic, an expert classified patients in three categories: remission, mild or moderate/severe activity. The SLE-DAS cut-offs were derived using the receiver operating characteristic curve analysis in Padova cohort; its performance was assessed against expert classification in Cochin cohort and British Isles Lupus Assessment Group (BILAG) index in BLISS-76. Gold standard for clinical remission state was the fulfilment of Definition Of Remission In SLE. A Boolean and an index-based definitions of remission were sustained by chi-square automatic interaction detection algorithm. An SLE-DAS online calculator was developed and tested. RESULTS: We included 1190 patients with SLE: 221 in the derivation cohort and 969 in the validation cohorts (150 from Cochin; 819 from BLISS-76). Derived cut-offs were: remission, SLE-DAS ≤2.08; mild activity, 2.08
Asunto(s)
Lupus Eritematoso Sistémico/fisiopatología , Adulto , Antirreumáticos/uso terapéutico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Prednisona/uso terapéutico , Inducción de Remisión , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
Introduction: Systemic Lupus Erythematosus (SLE) mainly occurs during childbearing age. Remission or low disease activity state (LDAS) before conception are recommended by experts to achieve a favourable lupus pregnancy outcome but little is known on the best way to evaluate remission or activity status during pregnancy. Objectives: We tested SLE-disease activity score (SLE-DAS) in the first trimester as predictor of maternal flares and obstetrical complications in 2nd and 3rd trimester in a cohort of SLE pregnant women. Patients and Methods: Inclusion criteria were: 1) women ≥ 18 years; 2) affected with SLE (SLICC 2012); 3) enrolled in two referral centers (Italy and France) 4) with an ongoing singleton pregnancy at 12 weeks (only one pregnancy per patient). Disease activity was assessed at first trimester of pregnancy, using SLE-pregnancy disease activity index (SLEPDAI) and retrospectively applying SLE-DAS. Maternal lupus flares at 2nd and 3rd trimester were defined by the SELENA-SLEDAI Flare Index (SFI). Adverse pregnancy outcome (APO) included: fetal and neonatal death, placental insufficiency with premature delivery <37 weeks, and small for gestational age (SGA) (≤3rd percentile). Results: We included 158 pregnant patients affected with SLE. At first trimester the median SLEPDAI (IQR) was 2 (0-4) and the median SLE-DAS (IQR) 1.32 (0.37-2.08). At least one flare occurred in 25 (15.8%) women during the 2nd and 3rd trimester. APO occurred in 19 (12.0%) patients. A significant correlation between SLE-DAS and SLEPDAI was found in this cohort (Spearman's ρ = 0.97, Figure 1). At multivariate analysis, both SLE-DAS and SLEPDAI predicted maternal flares (adjOR = 1.2; 95% CI = 1.0-1.3, p = 0.02; adjOR 1.3, 95% CI = 1.1-1.6 per unit increase, p = 0.01, respectively). SLE-DAS and SLEPDAI were associated with APO at univariate analysis (p = 0.02). Conclusions: SLE-DAS was highly correlated with SLEPDAI and its use in the first trimester predicted maternal flares in the 2nd and 3rd trimester, making SLE-DAS a reliable instrument to measure SLE activity during pregnancy.
RESUMEN
Despite promising candidates for new therapeutic options in the treatment of systemic lupus erythematosus (SLE), many clinical trials have failed in the past few years. The disappointing results have been at least partly be attributed to trial designs. With the aim of stimulating new developments in SLE trial design, an international open space meeting was held on occasion of the European Lupus Meeting 2018 in Duesseldorf, Germany about 'What are the topics you care about for making trials in lupus more effective?'. The Open Space is a participant-driven technology, where the discussion topics and schedule are selected during the meeting by all participants and discussion rounds are led by the people attending encouraging active contributions. Eleven topics were selected for further discussion, of which 6 were voted to be more intensively discussed in two consecutive rounds. Major topics were the optimal handling of glucocorticoids in clinical trials, the improvement of outcome measures, reducing or controlling the placebo response and the identification of biomarkers and stratification parameters. Further, the importance of local and international networks was emphasised. By networking, collaborations are facilitated, patient recruitment is more efficient and treatment can be harmonised thus lead to more successful SLE trials. Further discussions are needed to substantiate the results and develop new trial designs.