Comparison of the validity and sensitivity to change of 5 activity indices in systemic lupus erythematosus

OBJECTIVE: To compare the construct validity and sensitivity to change of the Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Lupus Activity Index (LAI), British Isles Lupus Assessment Group index (BILAG), and the European Consensus Lupus Activity Measure (ECLAM). METHODS: Twenty-three patients with systemic lupus erythematosus (SLE) were examined prospectively every 2 weeks for up to 40 weeks. Nineteen patients completed all 20 assessments. At each assessment, each of the 5 activity indices was scored, along with physicians' and patients' global assessments of SLE activity. Construct validity was determined by the strength of correlations between changes over time in each activity index and changes in physician and patient global assessments. Sensitivity to change was determined by the magnitude of change in each index over the 2 week interval of greatest change in the physician or patient global assessments, and calculated as standardized response means (SRM; mean change/standard deviation of change). Thirteen patients were also examined monthly by a second physician who was blinded to previous scores on the activity indices and to the patient global assessments. RESULTS: Patients had substantial changes in SLE activity during the study. Changes in each activity index were correlated with changes in the physician global assessment (SLAM r = 0.54; SLEDAI r = 0.52; LAI r = 0.75; BILAG r = 0.61; ECLAM r = 0.65; all p < 0.0001). Correlations were somewhat lower with the blinded physician assessment (SLAM r = 0.42; SLEDAI r = 0.12; LAI r = 0.30; BILAG r = 0.28; ECLAM r = 0.32). The SLAM was the only index that was positively correlated with changes in the patient global assessment (r = 0.22; p < 0.0001). Sensitivity to change was greatest for the LAI (SRM = 0.74) and the ECLAM (SRM = 0.75) and smallest for the SLEDAI (SRM = 0.48) when the physician global assessment was used as the standard. Sensitivity to change was greatest for the SLAM (SRM = 0.61) and the BILAG (SRM = 0.57) and smallest for the SLEDAI (SRM = -0.01) when the patient global assessment was used as the standard. CONCLUSION: Each index is a valid measure of SLE activity. The SLAM captures patients' assessments better than the other indices, perhaps because it assesses the patients' subjective complaints to a greater extent. Estimates of sensitivity to change varied with the standard used, but the SLEDAI was least sensitive to change. Larger studies are indicated to further compare the sensitivity to change of these indices.     

Psychological distress and changes in the activity of systemic lupus erythematosus

OBJECTIVE: To determine if changes in depressive symptoms or anxiety lead to changes in the activity of systemic lupus erythematosus (SLE). METHODS: Twenty-three patients with SLE were examined prospectively every 2 weeks for up to 40 weeks. At each assessment, patients completed the Centers for Epidemiologic Studies--Depression scale (CES-D), the State subscale of the State-Trait Anxiety Inventory and a global assessment of the activity of their SLE by visual analogue scale. SLE activity was also assessed at each visit by physician global assessment, the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measure (ECLAM). RESULTS: Changes in depression and anxiety were positively correlated with simultaneous changes in the patient global assessment of SLE activity and in the SLAM, but not with changes in the physician global assessment, SLEDAI or ECLAM. Depression and anxiety scores were also correlated with patient global assessments and SLAM scores 2 weeks later, but lagged scores were not significantly associated with the patient global assessment or SLAM after controlling for current depression and anxiety scores. The associations between depression and anxiety scores and the SLAM were not present when SLAM scores were modified to exclude ratings of depression and fatigue. No measure of SLE activity increased in the 2 weeks immediately after a large increase in CES-D or State Anxiety scores. CONCLUSIONS: Depression and anxiety scores parallel changes in patients' assessments of the activity of their SLE. We found no evidence to support the hypothesis that psychological distress causes increased SLE activity.     

Assessment of patients with systemic lupus erythematosus and the use of lupus disease activity indices

The assessment of disease activity in systemic lupus erythematosus (SLE) is a task faced by clinicians in every day care, but it is also required for clinical research and in randomised controlled trials. It is crucial to distinguish disease activity from infection, chronic damage and co-morbid disease. Over the past 20 years, many indices have been developed to objectively measure lupus disease activity and several of these have been validated. The most widely used indices are the British Isles Lupus Assessment Group (BILAG) index, the European Consensus Lupus Activity Measurement (ECLAM), the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Lupus Activity Index (LAI). All these indices have been validated and have excellent reliability, validity and responsiveness to change. In addition to the assessment of disease activity, the evaluation of damage using the validated SLICC/ACR damage index and health-related quality of life is advised for clinical research.     

Prospective validation of the provisional criteria for the evaluation of response to therapy in childhood‐onset systemic lupus erythematosus

Objective

To prospectively validate the provisional criteria for the evaluation of response to therapy in children with systemic lupus erythematosus (SLE).

Methods

In this multicenter study, childhood‐onset SLE patients (n = 98; 81 girls, 17 boys, 50% white, 88% non‐Hispanic) were followed every 3 months for up to 7 visits (total number of visits 623). The 5 childhood‐onset SLE core response variables were obtained at the time of each visit: 1) physician assessment of overall disease activity, 2) parent assessment of patient well‐being, 3) Child Health Questionnaire, 4) proteinuria, and 5) global disease activity measure score, as measured by the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or the Systemic Lupus Activity Measure (SLAM). Physician‐rated relevant changes in the disease course (clinically relevant improvement, no change in disease, or worsening) between visits served as the criterion standard. Mixed models were used to assess the diagnostic accuracy of the 4 highest‐ranked provisional definitions of response to therapy.

Results

There were 89 episodes of clinically relevant improvement between 2 consecutive visits, and 448 episodes without improvement. Irrespective of the choice of the global disease activity measure (ECLAM, SLAM, SLEDAI), sensitivities of all 4 highest‐ranked definitions were low (all ≤31%), whereas their specificities were excellent (all >88%). Using logistic models, alternative definitions can be developed with both 80% sensitivity and specificity.

Conclusion

The provisional criteria of response to therapy in childhood‐onset SLE may have considerably lower sensitivity than previously reported. Additional validation in clinical trials is necessary to further evaluate the measurement properties of the provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology criteria for response to therapy in children with SLE.     

Evaluation of systemic lupus erythematosus activity during pregnancy

Pregnancy in patients with systemic lupus erythematosus (SLE) is considered a high-risk pregnancy. It is complicated by preeclampsia, premature labour and miscarriage more frequently than in the general population. Improved prognosis depends on low disease activity during conception and on appropriate medical care (SLE activity monitoring, selection of therapy safe for the mother and the developing foetus, advances in neonatology). Because symptoms of physiological pregnancy and SLE exacerbation are similar, their correct interpretation is essential for skin lesions, arthralgias, arterial hypertension or results of laboratory tests: proteinuria, thrombocytopenia or leucopenia observed in the patient. In order to standardise the assessment of SLE activity during pregnancy, scores of this activity are used. In the past, scores validated on non-pregnant populations (including male patients) were used: Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Systemic Lupus Activity Measure (SLAM), European Consensus Lupus Activity Measurment (ECLAM). Only recently have SLE activity scores been introduced that are specific for pregnant women: Lupus Activity Index In Pregnancy (LAI-P), Systemic Lupus Erythematosus Pregnancy Disease Activity Index (SLEPDAI), modified--Systemic Lupus Activity Measure (m-SLAM) and a visual three-grade score modified--Physician Global Assessment (m-PGA). So far, only scores LAI-P and m-PGA have been validated. According to the LAI-P score, clinical data are divided into 4 groups. Group 1 includes mild clinical symptoms, group 2--symptoms of involvement of internal organs, group 3 pertains to modifications of treatment and group 4 to laboratory parameters. Point values are ascribed to individual parameters depending on their intensity.     

五种系统性红斑狼疮活动指数的比较

目的 国外大约有60多种系统性红斑狼疮（SLE）活动指数系统,国内尚我公认的SLE病情活动的判断指标。本文将五种国外应用较多的活动指数进行了可行性、敏感性、特异性及可靠性的比较。以了解其实用性。方法 根据美国风湿病学会1982年SLE标准确诊的324例SLE患者,年龄15-58岁,病程2个月-26年,女：男=10.96:1。以专家会诊评定是否活动作为金标准,其中218例活动,80例不活动,26例可疑活动,上述患者分别根据五种目前国际上常用的活动指数标准进行计分。这五种标准分别是：BILAG（The British Isles Lupus AssessmentGroup Scale),SLE-DAI(The University of Toronto SLE Disease Activity Index),SLAM(Systemic Lupus Activity Measure),LACC(The Lupus Activity Criteria Count),NYHSS(The New York Hospital for Special Surgery Sdystem)。计分结果通过SAS统计软件分析数据。结果 五种指数的表面可行性、标准可行构成可行性、敏感性及特异性均较好,但NYHSS及SLAM的可重复性较其他三种为差。结论 本研究推荐LACC和SLE-DAI两种活动指数作为临床使用较为可靠和简便。     

Quantitative clinical assessment of disease activity in systemic lupus erythematosus: progress report and research agenda

Summary No single test allows an adequate measure of disease activity in multisystem diseases such as systemic lupus erythematosus (SLE). In order to evaluate the spectrum of manifestations of disease activity in SLE, investigators have developed numerous ad hoc scales which have not been tested for their validity or reliability. Three instruments have been extensively studied: the British Isles Lupus Activity Group instrument (BILAG), the SLE Disease Activity Index (SLEDAI), and the Systemic Lupus Activity Measure (SLAM). All three have been demonstrated to have convergent and construct validity when compared to the clinician's judgement. The summation of the number of criteria of the American Rheumatism Association (ARA) SLE criteria has been shown to be an inadequate measure of disease activity. Standardized measures of disease activity for SLE should enhance our ability to compare results from different centers in finer distinctions than dead or alive.     

The relationship between health related quality of life and disease activity and damage in systemic lupus erythematosus

OBJECTIVE: To evaluate the relationship between self-reported quality of life and disease activity, damage, impairment, disability, and handicap in systemic lupus erythematosus (SLE). METHODS: In this cross sectional study disease activity was measured with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus Activity Measure (SLAM), and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). Quality of life was assessed by the Medical Outcome Survey Short Form 36 (SF-36) and the EuroQol (EQ-5D). Multiple linear regression was used to identify significant associations of patients' health status, and logistic regression was used to evaluate the relationship of each of the 5 dimensions of the EQ-5D in terms of impairment, disability, and handicap. RESULTS: Damage was associated with the Physical Function (PF) and Social Function subscales of the SF-36. Disease activity was associated with the General Health (GH) subscale. Ability to carry out usual activities was strongly related to PF and GH as well as to global rating of the thermometer rating scale of the EQ-5D. Role Physical (RP) and Bodily Pain (BP) of the SF-36 were also associated with the EQ-5D rating scale. In addition, patients' ratings of anxiety and depression were strongly related to the Mental Health (MH) summary scale of the SF-36. CONCLUSION: Perceived health status of patients with lupus was associated with disease activity, damage, role physical, bodily pain, capacity for usual activity, and mobility. EQ-5D is a valid instrument for the measure of health related quality of life in SLE.     

Reliability and validity of systemic lupus activity measure-revised (SLAM-R) for measuring clinical disease activity in systemic lupus erythematosus.

New clinical scales for semiquantitating disease activity in systemic lupus erythematosus (SLE) are widely used in research. They are reliable and valid measures. One of the original scales, the Systemic Lupus Activity Measure (SLAM), has been modified based on experience with it in multi-observer studies and training of individuals in its use. We tested the psychometric properties of the revised SLAM (SLAM-R). SLAM-R was tested on 30 SLE patients, who fulfilled 1997 revised ACR criteria and were selected to represent a range of disease activity. The patients were evaluated independently by two physicians, who studied the instruction booklet and who had never used SLAM-R, on two occasions 2-4 weeks apart. At the first visit, the physician's global assessment of activity using visual analog scale, anti-dsDNA Ab, C3 and C4 were checked for construct validity. The psychometric properties were analyzed with nested analysis of variance and Pearson's correlation coefficient using SAS. All patients were female, the median age was 31 (15-52) y, and the mean score of SLAM-R was 10.5 +/- 5.3 (3-26). Estimates of reliability were 0.78 of inter-rater, 0.61 of inter-visit, 0.76 of physician 1 between visits, and 0.56 of physician 2 between visits. Among subcategories except 'Eye,' the 'Gastrointestinal' category had the highest (0.96) and the 'Neuromotor' category had the lowest inter-rater reliability (0.50). With respect to construct validity, the correlation of SLAM-R scores with the disease activity variables except C4 was high and statistically significant. In conclusion, the SLAM-R is reliable and valid for measuring clinical disease activity in SLE.     

Systemic lupus erythematosus in three ethnic groups. XI. Sources of discrepancy in perception of disease activity: a comparison of physician and patient visual analog scale scores

OBJECTIVE: To compare patient's and physician's assessment of disease activity in a multiethnic (Hispanic, African American, and Caucasian) cohort of systemic lupus erythematosus (SLE) patients. METHODS: Three hundred patients with SLE from the LUMINA (Lupus in Minority populations: Nature versus nurture) cohort were included. Disease activity was assessed with the Systemic Lupus Activity Measure (SLAM); patients and physicians assessed disease activity using a 10-cm anchored visual analog scale (VAS). The difference between VAS scores was termed discrepancy (>1 cm was considered a priori clinically relevant). Selected sociodemographic, clinical, behavioral, and psychological variables were examined in relation to discrepancy in univariable and multivariable models adjusting for the physician global VAS score in order to eliminate ceiling and floor effects. RESULTS: A discrepancy was exhibited by 58% of the patients. Abnormal laboratory findings were negatively associated with discrepancy, and poor self-perceived functioning and joint involvement were positively associated with discrepancy. Ethnicity did not account for discrepant perception of disease activity. CONCLUSION: Patients and physicians rate disease activity in SLE differently. Physicians appear to place more emphasis on laboratory features while patients place more emphasis on function.     

Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus

Six systems for defining and evaluating disease activity in patients with systemic lupus erythematosus (SLE) (the Ropes system, the National Institutes of Health [NIH] system, the New York Hospital for Special Surgery system, the British Isles Lupus Assessment Group [BILAG] scale, the University of Toronto SLE Disease Activity Index [SLE-DAI], and the Systemic Lupus Activity Measure [SLAM]) were tested on 25 SLE patients who were selected to represent a range of disease activity. The patients were evaluated independently by 2 physicians on 2 occasions approximately 1 month apart. Differences between patients demonstrated the largest source of variation in scores, accounting for 56-84% of the total variance, depending on the instrument. Differences between physicians (i.e., error) showed the next largest variation, 11-28% of the total variance, and differences between visits made up 5-16% of the total. The BILAG, SLE-DAI, and SLAM had the best inter-visit and inter-rater reliability. Convergent validity was shown by the strong correlations of scores among the different instruments (r = 0.81-0.97). All instruments correlated highly with the physicians' clinical impression of disease but less well with their evaluation of disease severity. The number of American Rheumatism Association criteria for SLE that were met by the patients correlated poorly with the physicians' global evaluation and with the scores of the instruments. The patients' self-reported disease activity scores correlated highly with the physicians' assessments of disease activity (r = 0.85-0.91), and the mean values from self-reports and from physicians' assessments were nearly equal. In contrast, severity scores correlated less well between self-reports and physician assessments (r = 0.49-0.69), and mean self-reported severity values were lower than the means from physicians. The BILAG, SLE-DAI, and SLAM systems appear to have better psychometric properties than the others for clinical research.     

Organ manifestations influence differently the responsiveness of 2 lupus disease activity measures,according to patients' or physicians' evaluations of recent lupus activity

OBJECTIVE: To determine (1) which organ system manifestations contribute to the overall responsiveness of the Systemic Lupus Activity Measure (SLAM, revised 1991 with minor modifications as SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and (2) whether responsive items differ for physicians and patients. METHODS: Blinded data were obtained from repeated visits of 76 patients in the Study of Methotrexate in Lupus Erythematosus. At each visit, physicians and patients reported improvement, no change, or deterioration, and physicians then completed SLAM-R and SLEDAI. Items in SLAM-R and SLEDAI were grouped by organ system. The generalized estimating equations approach was used to measure associations between change in organ system activity and physician or patient perception of change in overall disease activity. The outcomes assessed, in separate analyses, were improvement and deterioration from the previous visit. RESULTS: Seventy-six patients contributed a total of 471 observations. The strongest correlates of physician-reported improvement were decreased constitutional, gastrointestinal (GI), and musculoskeletal involvement (components of SLAM-R), and decreased musculoskeletal (MSK) and central nervous system involvement (SLEDAI). Improvement reported by patients was most strongly associated with decreases in erythrocyte sedimentation rate and MSK and reticuloendothelial activity (SLAM-R), and in MSK activity (SLEDAI). Increased integument and MSK subscores (SLAM-R) and serosal and MSK subscores (SLEDAI) were associated with overall deterioration reported by physicians. Patient-reported deterioration was associated with increased GI subscores (SLAM-R) and with no changes in organ system involvement in SLEDAI. CONCLUSION: Organ systems associated with reported change in overall SLE activity differed between SLAM-R and SLEDAI, between patients and physicians, and between each direction of change.     

The Systemic Lupus Activity Measure-revised, the Mexican Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and a modified SLEDAI-2K are adequate instruments to measure disease activity in systemic lupus erythematosus

OBJECTIVE: To assess the validity, reliability, and feasibility of the Systemic Lupus Activity Measure-Revised (SLAM-R), the Mexican version of the Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI), and a Modified SLEDAI-2000 (SLEDAI-2K) compared with the SLEDAI-2K in a multiethnic population of patients with SLE. METHODS: We studied 92 SLE patients from 3 US geographic areas (Alabama, Texas, and Puerto Rico). Assessment occurred during regular outpatient, inpatient, or study encounters. A trained physician scored the 4 instruments and also assessed disease activity globally [physician global assessment (PGA)]. Convergent (with SLEDAI-2K) and construct validity (with PGA) were determined by Spearman rank (rs) correlation test. Level of agreement between the instruments was assessed using Bland-Altman plots. Discriminant validity (distinguishing clearly active vs mildly/nonactive disease) was assessed considering the SLEDAI-2K (and the PGA) as the gold standard. Feasibility was explored by cost analyses. RESULTS: The SLAM-R, the MEX-SLEDAI, and the Modified SLEDAI-2K were highly correlated with the SLEDAI-2K (rs = 0.566, 0.755, 0.924, respectively) and with the PGA (rs = 0.650, 0.540, 0.634, respectively). The 3 instruments showed good agreement with the SLEDAI-2K (Bland-Altman plots). The Modified SLEDAI-2K had better discriminant validity than the SLAM-R and the MEX-SLEDAI. The Modified SLEDAI-2K was the least expensive instrument. CONCLUSION: The SLAM-R, the MEX-SLEDAI, and the Modified SLEDAI-2K are adequate options for assessment of SLE disease activity; they are also less costly than the SLEDAI-2K.     

Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized,double-blind,placebo-controlled trial

OBJECTIVE: To evaluate the efficacy and tolerability of dehydroepiandrosterone (DHEA) at a dosage of 200 mg/day in adult women with active systemic lupus erythematosus (SLE). METHODS: In a multicenter randomized, double-blind, placebo-controlled trial, 120 adult women with active SLE received oral DHEA (200 mg/day; n = 61) or placebo (n = 59) for 24 weeks. The primary end point was the mean change from baseline in the Systemic Lupus Activity Measure (SLAM) score at 24 weeks of therapy. Secondary end points included time to first flare, change in SLE Disease Activity Index (SLEDAI) score, and physician's and patient's global assessment scores at week 24. RESULTS: The two groups were well balanced for baseline characteristics. Mean reductions in SLAM scores from baseline were similar and were not statistically significantly different between treatment groups (DHEA -2.6 +/- 3.4 versus placebo -2.0 +/- 3.8, mean +/- SD). The number of patients with flares was decreased by 16% in the DHEA group (18.3% of DHEA-treated patients versus 33.9% of placebo-treated patients; P = 0.044, based on time to first flare). The mean change in the patient's global assessment was statistically significant between the two groups (DHEA -5.5 versus placebo 5.4; P = 0.005). The number of patients with serious adverse events, most of which were related to SLE flare, was significantly lower in DHEA-treated patients compared with placebo-treated patients (P = 0.010). Expected hormonal effects, including increased testosterone levels and increased incidence of acne, were observed. No life-threatening reactions or serious safety issues were identified during this study. CONCLUSION: The overall results confirm that DHEA treatment was well-tolerated, significantly reduced the number of SLE flares, and improved patient's global assessment of disease activity.     

Learning from discordance in patient and physician global assessments of systemic lupus erythematosus disease activity

OBJECTIVE: Differences have been described between patient and physician assessments of well being in several chronic illnesses, and these differences may affect outcome. Disagreement may lead to dissatisfaction and to behaviors with dangerous consequences. We describe and identify predictors of patient-physician differences on ratings of disease activity in systemic lupus erythematosus (SLE). METHODS: Data collected on 154 patients included age, education, disease duration, and patient and physician global assessments of lupus activity on a 10 cm visual analog scale (VAS), the Health Assessment Questionnaire (HAQ), the Medical Outcome Study Short-Form 36 (SF-36), the Systemic Lupus Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM-R), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Multiple linear regression models were performed using patient VAS scores, physician VAS scores, and patient minus physician VAS scores as the dependent variables, and age, disease duration, selected SF-36 and SLAM-R subscales, and SDI as independent variables. RESULTS: Patients were 90% female and 80% Caucasian, with a mean education of 13 +/- 2.8 years and a mean age of 43.1 +/- 13.6 years. The overall mean disease duration was 10.5 +/- 7.8 years. Physicians overscored patients by 2.5 cm in 6% of the cases and patients overscored physicians in 16% of the cases. The best multivariate model to predict overall differences included SF-36 mental health and SLAM-R kidney scores. CONCLUSION: Patient-physician differences may result from a divergence in focus. Patients score lupus activity based on their psychological status, while physicians rely more heavily on the physical effect of the disease.     

European Consensus Lupus Activity Measurement is sensitive to change in disease activity in childhood-onset systemic lupus erythematosus

OBJECTIVES: To evaluate the European Consensus Lupus Activity Measurement (ECLAM) for responsiveness to change in disease activity when used in childhood-onset systemic lupus erythematosus (cSLE). To confirm the construct validity and to characterize the measurement properties of the ECLAM by assessing its ability to predict damage and steroid requirements.METHODS: The disease courses of 66 newly diagnosed cSLE patients were reviewed. The ECLAM and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were scored for all clinic visits and hospitalizations. Damage was assessed at the end of the followup period using the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index. Disease activity at the time of diagnosis, 6 months after diagnosis, at the time of first flare, and 6 months after first flare was used to estimate responsiveness of the measures. Responsiveness was measured by the effect size, the effect size index, the standardized response mean, and the relative efficiency index (REI). The measurement properties of the ECLAM and SLEDAI over time were examined by comparing the ability of both measures to predict damage and oral steroid requirement. RESULTS: The ECLAM and SLEDAI are both responsive to change in disease activity irrespective of the statistic used. The ECLAM is more sensitive than the SLEDAI using the REI (all >1.9). Cumulative disease activity as measured by the SLEDAI or the ECLAM are important predictors of damage. There are no statistically important differences between the 2 measures with regard to their ability to predict steroid requirements. CONCLUSIONS: The ECLAM has construct validity in cSLE and, like the SLEDAI, is highly sensitive to clinically important change in disease activity. The ECLAM may be more responsive. The quantitative properties of the 2 measures are very similar. The SLEDAI likely remains the preferable disease activity measure for cSLE given its overall measurement properties and ease of use.     

Sensitivity analyses of four systemic lupus erythematosus disease activity indices in predicting the treatment changes in consecutive visits: a longitudinal study

This study was conducted to assess the ability of the British Isles Lupus Assessment Group-2004 (BILAG-2004), the SLE Disease Activity Index-2K (SLEDAI-2K), the European Consensus Lupus Activity Measurement (ECLAM), and the Revised Systemic Lupus Activity Measure (SLAM-R) to detect the need to treatment change in daily clinical practice. One hundred and two patients with SLE were enrolled and followed up for 2 to 8 months and visited at least 3 times. Physician Global Assessment, BILAG-2004, SLEDAI-2K, SLAM-R, and ECLAM, were calculated in every visit. Treatment change, dependent variable, was categorized as decrease/no change vs. increase. The aforementioned indices, independent variables, were compared to learn their ability in predicting the treatment change. The probability of treatment change was measured by generalized linear-mixed effect model (GLMM) and generalized estimating equations (GEE). Adjusted odds ratios were calculated. Predictive power of indices was compared by area under the curve (AUC) in plots of sensitivity vs. 1-specificity and application of receiver operating characteristic curves (ROC). BILAG-2004 and SLEDAI-2K had substantial correlation with treatment change. Among different GLMM models, BILAG-2004 followed by SLEDAI-2K showed the highest associations with treatment change. Among various GEE models, similar findings were observed. Also, these 2 indices had the highest sensitivity (the largest AUC) towards treatment change; BILAG-2004 (AUC?=?0.779, 95% CI?=?0.710–0.848, p?=?0.001) and SLEDAI-2K (AUC?=?0.771, 95% CI?=?0.698–0.843, p?=?0.001). BILAG-2004 followed by SLEDAI-2K had the highest predictability of treatment change.     

Validation of the Childhood Health Assessment Questionnaire in active juvenile systemic lupus erythematosus

OBJECTIVE: To validate the Childhood Health Assessment Questionnaire (C-HAQ) as a measure of disability in patients with active juvenile systemic lupus erythematosus (SLE). METHODS: Of 557 patients with juvenile SLE included in the Paediatric Rheumatology International Trials Organisation (PRINTO) database, 504 (90.5%) were included in the present study and underwent C-HAQ assessment at the time of a major therapeutic intervention and then after 6 months. Validation procedures, according to the Outcome Measures in Rheumatology Clinical Trials filter for outcome measures in rheumatology, included assessment of responsiveness, feasibility, internal consistency, construct validity, collinearity, and discriminative ability. Response to therapy was evaluated with the PRINTO/American College of Rheumatology (ACR) juvenile SLE definition of improvement. RESULTS: At baseline, patients showed a high level of disease activity (mean physician global 5.8) and moderate disability (mean C-HAQ 0.83); both disease activity and disability improved after 6 months of treatment. The change in C-HAQ score correlated moderately with the Systemic Lupus Activity Measure (r(s) = 0.42), parent's global assessment of pain and well-being (r(s) = 0.55 and 0.53, respectively), and the physical summary score of the Child Health Questionnaire (r(s) = -0.61), and poorly with other clinical and laboratory parameters. The absolute change in C-HAQ demonstrated a significant ability to discriminate between patients who improved and those who did not improve based on the PRINTO/ACR definition of improvement. Responsiveness of the C-HAQ was moderate (standardized response mean 0.74). Internal consistency was excellent (Cronbach's alpha = 0.96). CONCLUSION: The C-HAQ showed moderate responsiveness to clinical change, construct validity, good feasibility, internal consistency, and discriminative ability. These findings demonstrate that the C-HAQ represents a good measure to capture disability in patients with active juvenile SLE.     

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE.

A European Consensus Group study, involving 29 centres from 14 countries, was performed in order to reach agreement on the definition of disease activity in systemic lupus erythematosus (SLE) and to construct a new disease index. Data on 704 lupus patients were collected and analysed, using univariate and multivariate statistical procedures, to select those clinical and laboratory features of the disorder which best correlate with the global assessment of disease activity assigned to the patients by the physician of each participating centre. A combination of 15 clinical and laboratory variables was shown to be the best predictor of disease activity in SLE. A European Consensus Lupus Activity Measurement (ECLAM) was then formulated. This index included the 15 selected variables, weighted (with some adjustments) according to their respective regression coefficients in the multivariate model. ECLAM appears to be an effective instrument for scoring patients with different degrees of disease activity. This is the first SLE disease activity index based on data from a very large number of lupus patients followed at a large number of lupus centres in different countries. It might therefore very well serve as a standardised measure for future European clinical studies. Final assessment of the validity, reliability and sensitivity of this index is now underway.     

Validation of a Systemic Lupus Activity Questionnaire (SLAQ) for population studies

The goal of this work was to develop an economical way of tracking disease activity for large groups of systemic lupus erythematosus (SLE) patients in clinical studies. A Systemic Lupus Activity Questionnaire (SLAQ) was developed to screen for possible disease activity using items from the Systemic Lupus Activity Measure (SLAM) and tested for its measurement properties. The SLAQ was completed by 93 SLE patients just prior to a scheduled visit. At the visit, a rheumatologist, blinded to SLAQ results, examined the subject and completed a SLAM. Associations among SLAQ, and SLAM (omitting laboratory items) and between individual items from each instrument were assessed with Pearson correlations. Correlations between pairs of instruments were compared using Student's t-tests. The mean score across all 24 SLAQ items was 11.5 (range 0-33); mean SLAM without labs was 3.0 (range 0-13). The SLAQ had a moderately high correlation with SLAM-nolab (r = 0.62, P < 0.0001). Correlations between patient-clinician matched pairs of items ranged from r = 0.06 to 0.71. Positive predictive values for the SLAQ ranged from 56 to 89% for detecting clinically significant disease activity. In studies of SLE, symptoms suggesting disease can be screened by self-report using the SLAQ and then verified by further evaluation.