53.8% were iatrogenic preterm deliveries. There was an incidence of pre-eclampsia of 11.9% and 10... more 53.8% were iatrogenic preterm deliveries. There was an incidence of pre-eclampsia of 11.9% and 10.7% of the pregnancies were complicated by fetal growth restriction. The percentage of caesarean delivery was 40.5%. 10.7% of neonates had criteria of neonatal lupus, and there was one case of congenital complete heart block, which required a neonatal cardiac pacemaker. There were no cases of neonatal deaths or asphyxia. Conclusions In SLE pregnant patients, to ensure the best maternal and fetal outcomes, it is crucial that the pregnancy occurs in a period of immunological stability as well as an adequate surveillance by a multidisciplinary team prepared to control all the complications that may arise.
fueled by a post-hoc analysis of the BLISS-52 and BLISS-76 datasets that suggested improvement of... more fueled by a post-hoc analysis of the BLISS-52 and BLISS-76 datasets that suggested improvement of kidney parameters in those patients who entered the Phase 3 programme with kidney abnormalities and who were randomized to belimumab. 1 BLISS-LN was the largest LN study ever performed and introduced several unique design features. The primary and key secondary endpoints were all successfully achieved. 2 3 The successful use of calcineurin inhibitors in LN justified studying voclosporin for this disease. Voclosporin had unsettling beginnings with a Phase 2 study where the mortality rate in the lower of the two dose groups was extraordinarily high. 4 Despite the observed efficacy, the safety signals created some degree of anxiety in moving forward. However, there was no uniform pattern to the deaths and furthermore, excessive mortality was not seen in the higher dose group. The Phase 3 study, known as AURORA, attained its primary endpoint as well as all key secondary endpoints. 5 In December 2020 the US FDA approved belimumab for the treatment of LN. This was a historical event in that belimumab was the very first drug approved for LN. One month later in January 2021, voclosporin received FDA approval. Not only will the availability of these two drugs improve LN response rates, their successful development programmes will provide inspiration to others that the challenges of drug development in LN can be overcome. Learning Objectives. Explain the optimal properties for disease activity instruments and treatment targets in SLE
Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophos... more Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV ¼ 3, class V ¼ 2, class III ¼ 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2-3 g and CsA was dosed up to 2.6-3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMFþCsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMFþCsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated. Lupus (2018) 0, 1-5.
ObjectivesThere is an unmet need for accurate and user-friendly definitions of systemic lupus ery... more ObjectivesThere 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.MethodsDerivation 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 sus...
Epub ahead of print. 2 Jesus D, Matos A, Henriques C, et al. Derivation and validation of the SLE... more Epub ahead of print. 2 Jesus D, Matos A, Henriques C, et al. Derivation and validation of the SLE disease activity score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity.
Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose g... more Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.
The authors describe the case of a 49 year-old male patient with a 3-year history of antiphosphol... more The authors describe the case of a 49 year-old male patient with a 3-year history of antiphospholipid syndrome, admitted after presenting in the emergency room with erythematous nodular skin lesions, affecting the face and neck, with a week's duration. Local biopsies were suggestive of interstitial granulomatous dermatitis. The patient described lesions compatible with bilateral auricular chondritis, two weeks prior to the appearance of the nodules, which resolved spontaneously after 3 days. There was a previous episode of nasal chondritis, two years previously, and another episode starting at the 7th day of hospitalization. These findings, taken together with a diagnosis of seronegative polyarthritis established 5 years before the current events, lead to a diagnosis of relapsing polychondritis.
Diffuse infiltrative lymphocytic syndrome is a clinical identity that can be part of the spectrum... more Diffuse infiltrative lymphocytic syndrome is a clinical identity that can be part of the spectrum of Human Immunodeficiency Virus infection. It is characterized by sicca symptoms, parotid and lachrymal enlargement and extra-articular manifestations. We report the case of a 60 years old woman with clinical sicca syndrome in association with leukopenia, positive anti-nuclear antibody (ANA) and polyclonal hypergammaglobulinemia. In the follow up the patient developed a mucosa-associated lymphoid tissue pulmonary neoplasm. Furthermore, the clinical surveys revealed human immunodeficiency virus (HIV) positive markers. In this particular case report, we must underline the clinical presentation of a sicca syndrome as a manifestation of the HIV infection, bearing in mind that, frequently, the differential diagnosis from other diseases, namely the Sjögren's syndrome, is a real challenge.
The authors report a clinical case of a woman who had a 3 years diagnosis of hipersensitivity pne... more The authors report a clinical case of a woman who had a 3 years diagnosis of hipersensitivity pneumonitis based on intersticial lung disease without other manifestations. The diagnosis of antisynthetase syndrome was made three years after the initial symptoms upon the onset of systemic manifestations with articular involvement, myositis and determination of anti-PL 7 antibodies. In this syndrome, the isolated pulmonary involvement is rare.
Drug development in lupus has improved over the past 10 years but still lags behind that of other... more Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes. Given these factors, the Addressing Lupus Pillars for Health Advancement Global Advisory Committee members who serve on the drug development team identified an opportunity to convene a meeting to facilitate information sharing on completed and existing outcome measure development efforts. This meeting report highlights information presented during the meeting as well as a discussion on how the lupus community may work together with regulatory agencies to simplify and standardise outcome...
Objectives. To apply the lupus low disease activity state (LLDAS) definition within a large cohor... more 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 j 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.
Objective: To compare damage and mortality, from inception up to 10-year follow-up, between SLE p... more Objective: To compare damage and mortality, from inception up to 10-year follow-up, between SLE patients meeting at baseline the 1997 ACR criteria or only the 2012 SLICC classification criteria. Methods: Patients fulfilling the ACR and/or the SLICC classification criteria for SLE were enrolled at inception and followed-up to 10 years at an academic lupus clinic. Damage was defined as SLICC Damage Index (SDI) score 1. We assessed with multivariate Cox models the damage and mortality outcomes, according to SLE classification status at inception, adjusting for potential baseline confounders. Results: We recruited 192 patients (69.8% fulfilling at inception the ACR criteria and 30.2% only the SLICC criteria). During follow-up, 24.0% of patients accrued organ damage and 4.2% died. Patients meeting ACR criteria compared to those with SLICC criteria alone presented during follow-up with more cases of lupus nephritis (35.1% versus 13.8%, p < 0.01), but less thrombotic antiphospholipid syndrome (4.5% versus 17.2%, p < 0.01). The Cox models showed no significant differences in risk for damage [hazard ratio (HR) (95% CI) 0.991 (0.453-2.167)] or death [hazard ratio (HR) (95% CI) 0.694 (0.107-4.506)] between groups. Conclusion: The SLE classification status at inception identified different patterns of clinical phenotype, but did not influence damage accrual or mortality up to 10-year follow-up. Lupus (2017) 0, 1-8.
The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Di... more The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) in detecting clinically meaningful changes in SLE disease activity. Methods: A longitudinal cohort study was conducted of 334 SLE patients during a 36-month follow-up. At each outpatient visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI-2K. Correlations between PGA and SLEDAI-2K were assessed. A clinically meaningful change in SLE disease activity was defined as a ÁPGA ! 0.3 points from baseline. Performance of SLEDAI-2K in detecting a clinically meaningful worsening or improvement was tested using receiver operating characteristic (ROC) analysis. Results: Adjusted mean PGA and SLEDAI-2K scores presented a high correlation (rho ¼ 0.824, p < 0.0005). In ROC analysis, a SLEDAI-2K variation presented an area under the curve (AUC) of 0.697 (95% confidence interval (CI) (0.628-0.766), p < 0.0005) to detect a clinically meaningful improvement, with a sensitivity of 28.8% for a SLEDAI-2K ! 4 reduction. The AUC to detect a clinically meaningful worsening was 0.877 (95% CI (0.822-0.932), p < 0.0005), with a sensitivity of 35.3%. Conclusions: SLEDAI-2K has a limited ability to detect clinically meaningful changes in SLE disease activity, failing to identify almost two-thirds of cases judged as having a clinically meaningful improvement or worsening. There is a need for more sensitive SLE disease activity measures in clinical practice and research. Lupus (2019) 0, 1-6.
from tramadol for worst pain, average pain, and the pain interference index, with exception of th... more from tramadol for worst pain, average pain, and the pain interference index, with exception of the pain interference index for tanezumab 10mg (p=0.01). Mean dose of tramadol was 203mg/day at week 16. Tanezumab 10mg significantly (p<0.05) improved individual domains of the pain interference index (general activity, walking ability, sleep, and normal work) vs placebo and vs tramadol. Tanezumab 5mg significantly (p<0.05) improved pain interference with general activity and normal work vs placebo, and sleep vs placebo and vs tramadol. No statistical differences in any domain was observed for tramadol vs placebo. Conclusion: Tanezumab 5mg and 10mg significantly improved worst pain, average pain, and overall pain interference index scores vs placebo in patients with CLBP. Tanezumab 10mg also significantly improved the overall pain interference index vs tramadol. Tanezumab 5mg significantly improved most individual domains of the pain interference index vs placebo, while tanezumab 10mg significantly improved all domains assessed vs placebo and vs tramadol.
Conclusion: The SLE-DAS is an accurate and easy to use tool for defining clinical remission state... more Conclusion: The SLE-DAS is an accurate and easy to use tool for defining clinical remission state and SLE disease activity categories, validated with both the expert assessment and BILAG. REFERENCES: [1] Jesus D, et al. Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity.
Infections are a major cause of morbidity and death in systemic lupus erythematosus (SLE). Perfec... more 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. 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. 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. 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. 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.
53.8% were iatrogenic preterm deliveries. There was an incidence of pre-eclampsia of 11.9% and 10... more 53.8% were iatrogenic preterm deliveries. There was an incidence of pre-eclampsia of 11.9% and 10.7% of the pregnancies were complicated by fetal growth restriction. The percentage of caesarean delivery was 40.5%. 10.7% of neonates had criteria of neonatal lupus, and there was one case of congenital complete heart block, which required a neonatal cardiac pacemaker. There were no cases of neonatal deaths or asphyxia. Conclusions In SLE pregnant patients, to ensure the best maternal and fetal outcomes, it is crucial that the pregnancy occurs in a period of immunological stability as well as an adequate surveillance by a multidisciplinary team prepared to control all the complications that may arise.
fueled by a post-hoc analysis of the BLISS-52 and BLISS-76 datasets that suggested improvement of... more fueled by a post-hoc analysis of the BLISS-52 and BLISS-76 datasets that suggested improvement of kidney parameters in those patients who entered the Phase 3 programme with kidney abnormalities and who were randomized to belimumab. 1 BLISS-LN was the largest LN study ever performed and introduced several unique design features. The primary and key secondary endpoints were all successfully achieved. 2 3 The successful use of calcineurin inhibitors in LN justified studying voclosporin for this disease. Voclosporin had unsettling beginnings with a Phase 2 study where the mortality rate in the lower of the two dose groups was extraordinarily high. 4 Despite the observed efficacy, the safety signals created some degree of anxiety in moving forward. However, there was no uniform pattern to the deaths and furthermore, excessive mortality was not seen in the higher dose group. The Phase 3 study, known as AURORA, attained its primary endpoint as well as all key secondary endpoints. 5 In December 2020 the US FDA approved belimumab for the treatment of LN. This was a historical event in that belimumab was the very first drug approved for LN. One month later in January 2021, voclosporin received FDA approval. Not only will the availability of these two drugs improve LN response rates, their successful development programmes will provide inspiration to others that the challenges of drug development in LN can be overcome. Learning Objectives. Explain the optimal properties for disease activity instruments and treatment targets in SLE
Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophos... more Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue induction regimens is scarce. We analyzed efficacy and tolerability of multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all six refractory LN patients (class IV ¼ 3, class V ¼ 2, class III ¼ 1) from our 400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients had previously received pulse CYC. All six received MMF as first or second induction therapy and CsA was added once failure to reach remission was established. Daily dose of MMF was 2-3 g and CsA was dosed up to 2.6-3.7 mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the MMFþCsA regimen to 544 mg/day after six months. The mean prednisolone dose was reduced from 17.5 to 6 mg/day after six months of MMFþCsA. Four patients achieved a complete renal response, one patient had a partial renal response and one failed to respond. None of the patients presented with adverse events. These data suggest that adding CsA to MMF can induce complete remission of refractory LN and is well tolerated. Lupus (2018) 0, 1-5.
ObjectivesThere is an unmet need for accurate and user-friendly definitions of systemic lupus ery... more ObjectivesThere 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.MethodsDerivation 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 sus...
Epub ahead of print. 2 Jesus D, Matos A, Henriques C, et al. Derivation and validation of the SLE... more Epub ahead of print. 2 Jesus D, Matos A, Henriques C, et al. Derivation and validation of the SLE disease activity score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity.
Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose g... more Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.
The authors describe the case of a 49 year-old male patient with a 3-year history of antiphosphol... more The authors describe the case of a 49 year-old male patient with a 3-year history of antiphospholipid syndrome, admitted after presenting in the emergency room with erythematous nodular skin lesions, affecting the face and neck, with a week's duration. Local biopsies were suggestive of interstitial granulomatous dermatitis. The patient described lesions compatible with bilateral auricular chondritis, two weeks prior to the appearance of the nodules, which resolved spontaneously after 3 days. There was a previous episode of nasal chondritis, two years previously, and another episode starting at the 7th day of hospitalization. These findings, taken together with a diagnosis of seronegative polyarthritis established 5 years before the current events, lead to a diagnosis of relapsing polychondritis.
Diffuse infiltrative lymphocytic syndrome is a clinical identity that can be part of the spectrum... more Diffuse infiltrative lymphocytic syndrome is a clinical identity that can be part of the spectrum of Human Immunodeficiency Virus infection. It is characterized by sicca symptoms, parotid and lachrymal enlargement and extra-articular manifestations. We report the case of a 60 years old woman with clinical sicca syndrome in association with leukopenia, positive anti-nuclear antibody (ANA) and polyclonal hypergammaglobulinemia. In the follow up the patient developed a mucosa-associated lymphoid tissue pulmonary neoplasm. Furthermore, the clinical surveys revealed human immunodeficiency virus (HIV) positive markers. In this particular case report, we must underline the clinical presentation of a sicca syndrome as a manifestation of the HIV infection, bearing in mind that, frequently, the differential diagnosis from other diseases, namely the Sjögren's syndrome, is a real challenge.
The authors report a clinical case of a woman who had a 3 years diagnosis of hipersensitivity pne... more The authors report a clinical case of a woman who had a 3 years diagnosis of hipersensitivity pneumonitis based on intersticial lung disease without other manifestations. The diagnosis of antisynthetase syndrome was made three years after the initial symptoms upon the onset of systemic manifestations with articular involvement, myositis and determination of anti-PL 7 antibodies. In this syndrome, the isolated pulmonary involvement is rare.
Drug development in lupus has improved over the past 10 years but still lags behind that of other... more Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes. Given these factors, the Addressing Lupus Pillars for Health Advancement Global Advisory Committee members who serve on the drug development team identified an opportunity to convene a meeting to facilitate information sharing on completed and existing outcome measure development efforts. This meeting report highlights information presented during the meeting as well as a discussion on how the lupus community may work together with regulatory agencies to simplify and standardise outcome...
Objectives. To apply the lupus low disease activity state (LLDAS) definition within a large cohor... more 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 j 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.
Objective: To compare damage and mortality, from inception up to 10-year follow-up, between SLE p... more Objective: To compare damage and mortality, from inception up to 10-year follow-up, between SLE patients meeting at baseline the 1997 ACR criteria or only the 2012 SLICC classification criteria. Methods: Patients fulfilling the ACR and/or the SLICC classification criteria for SLE were enrolled at inception and followed-up to 10 years at an academic lupus clinic. Damage was defined as SLICC Damage Index (SDI) score 1. We assessed with multivariate Cox models the damage and mortality outcomes, according to SLE classification status at inception, adjusting for potential baseline confounders. Results: We recruited 192 patients (69.8% fulfilling at inception the ACR criteria and 30.2% only the SLICC criteria). During follow-up, 24.0% of patients accrued organ damage and 4.2% died. Patients meeting ACR criteria compared to those with SLICC criteria alone presented during follow-up with more cases of lupus nephritis (35.1% versus 13.8%, p < 0.01), but less thrombotic antiphospholipid syndrome (4.5% versus 17.2%, p < 0.01). The Cox models showed no significant differences in risk for damage [hazard ratio (HR) (95% CI) 0.991 (0.453-2.167)] or death [hazard ratio (HR) (95% CI) 0.694 (0.107-4.506)] between groups. Conclusion: The SLE classification status at inception identified different patterns of clinical phenotype, but did not influence damage accrual or mortality up to 10-year follow-up. Lupus (2017) 0, 1-8.
The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Di... more The objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) in detecting clinically meaningful changes in SLE disease activity. Methods: A longitudinal cohort study was conducted of 334 SLE patients during a 36-month follow-up. At each outpatient visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI-2K. Correlations between PGA and SLEDAI-2K were assessed. A clinically meaningful change in SLE disease activity was defined as a ÁPGA ! 0.3 points from baseline. Performance of SLEDAI-2K in detecting a clinically meaningful worsening or improvement was tested using receiver operating characteristic (ROC) analysis. Results: Adjusted mean PGA and SLEDAI-2K scores presented a high correlation (rho ¼ 0.824, p < 0.0005). In ROC analysis, a SLEDAI-2K variation presented an area under the curve (AUC) of 0.697 (95% confidence interval (CI) (0.628-0.766), p < 0.0005) to detect a clinically meaningful improvement, with a sensitivity of 28.8% for a SLEDAI-2K ! 4 reduction. The AUC to detect a clinically meaningful worsening was 0.877 (95% CI (0.822-0.932), p < 0.0005), with a sensitivity of 35.3%. Conclusions: SLEDAI-2K has a limited ability to detect clinically meaningful changes in SLE disease activity, failing to identify almost two-thirds of cases judged as having a clinically meaningful improvement or worsening. There is a need for more sensitive SLE disease activity measures in clinical practice and research. Lupus (2019) 0, 1-6.
from tramadol for worst pain, average pain, and the pain interference index, with exception of th... more from tramadol for worst pain, average pain, and the pain interference index, with exception of the pain interference index for tanezumab 10mg (p=0.01). Mean dose of tramadol was 203mg/day at week 16. Tanezumab 10mg significantly (p<0.05) improved individual domains of the pain interference index (general activity, walking ability, sleep, and normal work) vs placebo and vs tramadol. Tanezumab 5mg significantly (p<0.05) improved pain interference with general activity and normal work vs placebo, and sleep vs placebo and vs tramadol. No statistical differences in any domain was observed for tramadol vs placebo. Conclusion: Tanezumab 5mg and 10mg significantly improved worst pain, average pain, and overall pain interference index scores vs placebo in patients with CLBP. Tanezumab 10mg also significantly improved the overall pain interference index vs tramadol. Tanezumab 5mg significantly improved most individual domains of the pain interference index vs placebo, while tanezumab 10mg significantly improved all domains assessed vs placebo and vs tramadol.
Conclusion: The SLE-DAS is an accurate and easy to use tool for defining clinical remission state... more Conclusion: The SLE-DAS is an accurate and easy to use tool for defining clinical remission state and SLE disease activity categories, validated with both the expert assessment and BILAG. REFERENCES: [1] Jesus D, et al. Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity.
Infections are a major cause of morbidity and death in systemic lupus erythematosus (SLE). Perfec... more 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. 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. 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. 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. 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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