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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

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 (rs = 0.42), parent's global assessment of pain and well-being (rs = 0.55 and 0.53, respectively), and the physical summary score of the Child Health Questionnaire (rs = −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 α = 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.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Systemic lupus erythematosus (SLE) is a chronic, inflammatory, and multisystem disease associated with severe morbidity. The chronic process of illness, fatigue, general malaise, psychological problems, and an unpredictable course affects different aspects of patients' lives, determining an impairment of quality of life and physical function.

In a combined meeting held in 1997, the World Health Organization and the International League Against Rheumatism (1) reached a consensus on the following definitions: quality of life is an individual's perception of his or her own position in life in the context of the culture and value systems of the countries in which the individual lives and in relation to the individual's goals, expectations, standards, and concerns; health-related quality of life (HRQOL) is the physical, emotional, and social aspects of quality of life influenced by an individual's disease and/or its treatment; and disability is the limitation in an individual's ability to act in a usual, customary, and personally desired way caused by 1 or more health conditions affecting physical or mental functioning.

Previous studies have demonstrated that women with active SLE were more disabled than those with inactive disease (2–5). The Health Assessment Questionnaire (HAQ) (6), the most widely used instrument to evaluate disability, was initially designed to identify patient-perceived changes in daily living activities caused by rheumatic diseases, focusing mainly on arthritis. Because this questionnaire is completed by patients and is based on their subjective perceptions, it is also sensitive to other physical symptoms (not only arthritis) or factors such as fatigue, pain, and psychological and social disturbances, which are unspecific symptoms in patients with SLE. This means that the HAQ reflects the patient's disability to perform day-to-day activities not only in arthritis but also in other rheumatic diseases. The Childhood Health Assessment Questionnaire (C-HAQ) has been demonstrated to be a valid tool for the assessment of disability in both juvenile idiopathic arthritis (JIA) (7) and juvenile dermatomyositis (DM) (8). Conversely, little is known about the evaluation of disability in children with SLE. The aim of the present study was to validate the C-HAQ as a measure of disability in patients with active juvenile SLE.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Study design.

Between June 2001 and March 2004, 557 consecutive patients from 118 centers in 39 countries were enrolled in a prospective study, the objective of which was to validate a core set of criteria and a definition of improvement for the evaluation of response to therapy (9–11). In brief, patients were included according to the following criteria: 1) diagnosis of SLE (1997 revised American College of Rheumatology [ACR] classification criteria) (12, 13), 2) age at onset <18 years, and 3) active phase of disease defined as either the need to start corticosteroid therapy and/or a new immunosuppressive medication or the need to undergo a major increase in the dose of ongoing corticosteroid therapy and/or immunosuppressive drugs.

For the purpose of the present study, 504 juvenile SLE patients who had a C-HAQ assessment available at baseline and then after 6 months were selected from the Paediatric Rheumatology International Trials Organisation (PRINTO) database. At each center, written or verbal informed consent was obtained from a parent or legal guardian, according to the requirements of the local ethics committees.

Assessment of measures.

At baseline and 6 months later, the following assessments were performed. The C-HAQ was administered, which consists of a 30-item parent or self-report questionnaire that examines the child's ability to perform functions included in 8 areas (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities). The scores of these 8 areas are averaged to calculate the C-HAQ disability index (DI), which ranges from 0 (no or minimal physical dysfunction) to 3 (very severe physical dysfunction). A “not applicable” option is also available for patients who are not developmentally able to perform an activity. Each area is scored as the highest item in that area. If aids or assistance are required for an activity, the minimum score is 2 for the corresponding area. The C-HAQ includes a parent's global assessment of the patient's overall well-being in the previous week rated on a 0–10-cm visual analog scale (VAS; 0 = very well, 10 = very poor) and a parent's global assessment of the child's pain in the previous week rated on a 0–10-cm VAS (0 = no pain, 10 = very severe pain). The parent's version of the C-HAQ has been cross-culturally adapted and validated in all of the languages of the participating countries (14, 15).

A physician's global assessment of the patient's overall disease activity was performed using a 0–10-cm VAS (0 = no activity, 10 = maximum activity).

Global disease activity was assessed using the European Consensus Lupus Activity Measure (ECLAM) (16, 17), the Systemic Lupus Activity Measure (SLAM) (18), and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (19).

Laboratory parameters for the evaluation of organ involvement were assessed, including 24-hour proteinuria (gm per 24 hours), serum creatinine (normal value 0.6–1.2 mg/dl), complete blood cell count, serum complement fractions C3 (normal value 0.7–1.6 gm/liter) and C4 (normal value 0.2–0.4 gm/liter), and Westergren erythrocyte sedimentation rate (ESR; normal value 0–30 mm/hour). The laboratory test results were standardized based on the normal values provided by each local laboratory as previously described (10).

HRQOL was assessed using the Child Health Questionnaire (CHQ) parent version (15, 20). Briefly, the CHQ is a generic instrument designed to capture the physical, emotional, and social components of the health status of children at least 5 years of age. The CHQ includes 15 subscales and 2 summary measures: the physical score (PhS) and the psychosocial score (PsS), which are standardized to have a mean of 50 and a standard deviation of 10. Higher scores on the scales indicate better HRQOL. The parent's version of the CHQ has been cross-culturally translated and validated in all of the languages of the participating countries (15).

Evaluation of response to therapy.

As a standard for the evaluation of response to therapy at 6 months, we used the PRINTO/ACR juvenile SLE definition of improvement, which classifies as responders all patients who show an improvement of at least 50% versus baseline in any 2 of the 5 PRINTO core set variables, with no more than 1 of the remaining variables worsening by more than 30% (11, 15). The variables included in the PRINTO juvenile SLE core set measures are the physician's global assessment of the patient's overall disease activity, the parent's global assessment of the patient's overall well-being, 24-hour proteinuria, the ECLAM, and HRQOL as measured with the CHQ PhS (10). For the purposes of this report, we also applied a modified version of the PRINTO/ACR definition by substituting the CHQ PhS with the C-HAQ.

Validation procedures.

The validation procedures of the C-HAQ were conducted according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) filter for outcome measures in rheumatology (21, 22).

Responsiveness.

Responsiveness assesses the ability of each variable to detect clinically important change with respect to a therapeutic intervention between baseline and 6 months, and was measured using the standardized response mean (SRM). The SRM was calculated as the absolute mean change in score divided by the SD of individuals' change in score; 95% confidence intervals (95% CIs) were provided (23, 24). Absolute values between 0.2 and ≤0.5 are considered small, values >0.5 and <0.8 are moderate, and those ≥0.8 represent large effects (10, 25). The SRM was calculated for patients who improved or did not improve according to the PRINTO/ACR juvenile SLE definition of improvement as external indicators of change.

Feasibility or practicality.

Feasibility was determined by addressing the percentage of missing values. We also computed the endorsement rates by calculating the number and percentage of patients with a score >0 for each item and domain. When calculating the item endorsement rates, patients were excluded if the item in question was not developmentally applicable.

Internal consistency.

Internal consistency for the C-HAQ was calculated by Cronbach's alpha (26) for baseline data; cutoffs were defined as follows: <0.6 = poor, 0.6–0.64 = slight, 0.65–0.69 = fair, 0.7–0.79 = moderate, 0.8–0.89 = substantial, and >0.9 = excellent. We also calculated item-total and domain-total correlations (for baseline data) using Spearman's correlation coefficient (rs).

Convergent construct validity.

To assess construct validity, we tested the correlations between absolute change in the C-HAQ DI (after 6 months of a major therapeutic intervention) and the change in the variables used to assess disease activity. We hypothesized that the C-HAQ DI would have a moderate correlation with the parent's evaluation of the child's overall well-being and pain and with physical well-being as measured by the CHQ, and a poor correlation with the disease activity variables such as the physician's global evaluation of disease activity, the ECLAM, the SLAM, and the SLEDAI. Spearman's correlation coefficients were used because the data were not normally distributed. Spearman's rank correlation >0.7 was considered high, 0.4–0.7 moderate, and <0.4 low.

Collinearity (or redundancy).

Collinearity was investigated by means of Spearman's correlation coefficient, with coefficients ≥0.7 considered as evidence of collinearity.

Discriminative ability.

Discriminative ability was assessed by comparing the ability of the C-HAQ DI, the parent's evaluation of the child's overall well-being and pain, and other disease activity variables (Table 1 and Figure 1) to discriminate patients who improved from those who did not (after 6 months of treatment compared with baseline), based on the PRINTO/ACR juvenile SLE definition of improvement (11). Patients who improved were compared with those who did not improve by the Mann-Whitney U test.

Table 1. Descriptive characteristics of the variables collected*
VariablesSample at t0-t6Month 0, mean ± SDMonth 6, mean ± SDSRM (95% CI)
  • *

    P values for change <0.0001 for all variables except serum creatinine (P = 0.52). SRM = standardized response mean; 95% CI = 95% confidence interval; [UPWARDS ARROW] = higher score denotes worse activity; CHQ = Child Health Questionnaire; PhS = physical summary score; [DOWNWARDS ARROW] = lower score denotes worse values; PsS = psychosocial summary score; ECLAM = European Consensus Lupus Activity Measure; SLEDAI = Systemic Lupus Erythematosus Disease Activity Index; SLAM = Systemic Lupus Activity Measure; ESR = erythrocyte sedimentation rate.

  • The sample for each variable refers to the number of patients for whom both baseline and 6-month evaluations were available.

  • SRMs were calculated for patients who responded to treatment according to the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology definition of improvement (see Patients and Methods) (11).

Physician's global assessment of the patient's overall disease activity (range 0–10 cm)[UPWARDS ARROW]4995.77 ± 2.661.78 ± 2.091.74 (1.61–1.87)
CHQ PhS (range 40–60)[DOWNWARDS ARROW]42938.64 ± 12.3248.38 ± 8.771.06 (0.95–1.17)
CHQ PsS (range 40–60)[DOWNWARDS ARROW]42943.76 ± 10.2048.20 ± 9.420.50 (0.40–0.61)
ECLAM (range 0–10)[UPWARDS ARROW]5036.03 ± 2.462.23 ± 2.001.81 (1.67–1.95)
SLEDAI (range 0–105)[UPWARDS ARROW]50118.12 ± 10.146.21 ± 6.461.45 (1.31–1.58)
SLAM (range 0–90)[UPWARDS ARROW]50415.70 ± 7.474.97 ± 4.711.72 (1.59–1.85)
24-hour proteinuria (gm per 24 hours)[UPWARDS ARROW]3761.18 ± 2.020.56 ± 1.290.53 (0.45–0.59)
Serum creatinine (range 0.6–1.2 mg/dl)[UPWARDS ARROW]4840.78 ± 0.440.74 ± 0.360.17 (0.09–0.24)
ESR (range 0–30 mm/hour)[UPWARDS ARROW]45960.84 ± 37.1726.55 ± 21.211.15 (1.04–1.26)
C3 (range 0.7–1.6 gm/liter)[DOWNWARDS ARROW]4580.55 ± 0.440.86 ± 0.430.66 (0.50–0.82)
C4 (range 0.2–0.4 gm/liter)[DOWNWARDS ARROW]4490.18 ± 0.070.22 ± 0.080.45 (0.33–055)
Hemoglobin (gm/liter)[DOWNWARDS ARROW]49010.71 ± 2.0312.43 ± 1.570.97 (0.85–1.08)
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Figure 1. Ability of absolute change in mean Childhood Health Assessment Questionnaire (C-HAQ) score, pain visual analog scale (VAS) assessment, parent's global assessment, Child Health Questionnaire (CHQ) score, physician's global assessment, and European Consensus Lupus Activity Measure (ECLAM) to discriminate between patients who improved versus patients who did not improve according to the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology definition (11). The circles inside the boxes represent mean values and the lines outside the boxes represent 95% confidence intervals. P values were determined according to the Mann-Whitney U test.

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Agreement of the definitions of improvement.

Agreement between the PRINTO/ACR juvenile SLE definition of improvement and a modified version of the same definition, using the C-HAQ instead of the CHQ PhS, was evaluated by means of Cohen's kappa (27). This coefficient was considered small if ≤0.20, sufficient if >0.20 and ≤0.40, moderate if >0.40 and ≤0.60, substantial if >0.60 and ≤0.80, and almost perfect if >0.80, according to the Landis and Koch definition (28).

Further statistical analysis.

Data are reported as the mean ± SD or median and interquartile range (IQR). Quantitative data were compared using the Mann-Whitney U test for 2-group comparison and Wilcoxon's matched pairs test for paired data.

Collected data were entered into an Access XP database (Microsoft, Redmond, WA). Descriptive and bivariate analyses were performed using the software Statistica, release 6.0 (StatSoft, Tulsa, OK), and the analysis for internal consistency was performed using XLStat, release 6.1.9 (Addinsoft, Paris, France).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Demographic and clinical characteristics.

Of the 504 patients who had both baseline and 6-month C-HAQ assessment data, 415 (82.3%) were female and 89 (17.6%) were male; the median age at onset was 12.3 years (IQR 10.2–14.1 years), and the median disease duration was 0.5 years (IQR 0.2–2.4 years). The median number of ACR classification criteria met at diagnosis was 6 (IQR 5–7). There were no statistically significant differences in demographic and clinical or laboratory characteristics when patients included in the present study were compared with the 53 (9.5%) patients excluded due to lack of C-HAQ assessment data.

The descriptive characteristics for each clinical and laboratory variable are shown in Table 1. At baseline, patients showed a high level of disease activity as demonstrated by the ECLAM, SLEDAI, and SLAM and by the physician's assessment of disease activity. Proteinuria >0.5 gm/day was detectable at baseline in 170 (45.2%) patients. Serum creatinine >1.2 mg/dl was observed in 29 (6.0%) children. A statistically significant improvement from baseline to 6 months was observed for all clinical and laboratory measures shown in Table 1 (all P < 0.0001), with the exception of serum creatinine (P = 0.52).

The mean and median scores for each area of the C-HAQ are shown in detail in Table 2. The mean values of the C-HAQ domains ranged from 0.63 to 1.14. Parents reported that their children had greater difficulty with activities that involve gross motor movements, such as riding a bike or doing household chores, and less difficulty with fine motor movement, such as eating. The C-HAQ DI and the pain and overall well-being VAS also indicated that patients experienced some discomfort attributable to their disease. All areas of the C-HAQ demonstrated statistically significant improvement after 6 months of treatment (all P < 0.0001).

Table 2. Descriptive characteristics for all areas of the C-HAQ*
VariablesSample at t0-t6Month 0, mean ± SDMonth 6, mean ± SDSRM (95% CI)
  • *

    P values for change <0.0001 for all variables. C-HAQ = Childhood Health Assessment Questionnaire; DI = disability index; see Table 1 for additional definitions.

  • The sample for each variable refers to the number of patients for whom both baseline and 6-month evaluations were available.

  • SRMs were calculated for patients who responded to treatment according to the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology definition of improvement (see Patients and Methods) (11).

Dressing and personal care4930.89 ± 1.100.23 ± 0.600.66 (0.56–0.76)
Arising4920.74 ± 0.980.17 ± 0.520.63 (0.54–0.72)
Eating4910.65 ± 0.990.12 ± 0.430.59 (0.52–0.67)
Walking4900.72 ± 1.000.17 ± 0.510.64 (0.54–0.73)
Hygiene5000.78 ± 1.050.17 ± 0.530.59 (0.50–0.68)
Reach4990.89 ± 1.080.25 ± 0.620.60 (0.51–0.70)
Grip5000.78 ± 1.060.16 ± 0.500.60 (0.51–0.69)
Activities4961.14 ± 1.140.29 ± 0.630.78 (0.68–0.88)
C-HAQ DI (total)5040.83 ± 0.940.19 ± 0.430.74 (0.66–0.82)
Parent's global assessment of patient's overall well-being (range 0–10 cm)4844.41 ± 3.081.27 ± 1.841.18 (1.03–1.33)
Parent's global assessment of patient's pain (0–10 cm)4853.67 ± 3.310.90 ± 1.700.95 (0.83–1.06)

Responsiveness.

According to the PRINTO/ACR definition of improvement, 353 (76%) of 465 patients were identified as responders. Using this definition as an external indicator of change, most of the variables reported in Table 1 showed a moderate or good responsiveness to clinical change; the responsiveness was particularly good (≥0.80) for the physician's global assessment of overall disease, the CHQ PhS, the 3 composite disease activity tools (ECLAM, SLAM, and SLEDAI), ESR, and hemoglobin concentration. A moderate responsiveness (SRM >0.5 and <0.8) was demonstrated by 2 laboratory variables (C3 and 24-hour proteinuria). Poor responsiveness (SRM ≤0.5) was observed for the CHQ PsS, C4, and serum creatinine.

The SRM for the C-HAQ, as shown in Table 2, was good for the parent's global assessment of the patient's overall well-being VAS and the assessment of pain VAS. The SRM was in the moderate range for all areas (from 0.78 for activities to 0.59 for eating and hygiene) and for the C-HAQ DI (0.74). A decrease in responsiveness, for all variables in Tables 1 and 2, was observed when the SRM was calculated in the subgroup of patients who did not respond to treatment (data not shown).

C-HAQ feasibility.

The frequency of missing data on single items of the C-HAQ at baseline and at 6 months was uniformly less than 5% (mean 1.2%, range 0.2–3.0%), demonstrating that all items had an excellent feasibility and were easy to understand and complete.

The percentage of patients who had an individual item score >0 at baseline ranged from 16.2% (“Lift up a cup or glass to mouth”) to 50.4% (“Run and play”), with a mean percentage of 28.4%. The percentage of patients who had a domain score >0 at baseline ranged from 33.8% (“Eating”) to 57.3% (“Activities”), with a mean percentage of 43%. After 6 months of treatment, the percentage of patients with scores >0 was lower for both the single items (mean 8.0%, range 2.8–22.1%) and the individual domains (mean 16.9%, range 11.0–28.0%).

Internal consistency.

Cronbach's alpha measured for the 8 functional domains (with baseline data) was 0.96, meaning that the domains had excellent internal consistency (Table 3). Each time we removed 1 domain, the Cronbach's alpha values did not change (range 0.951–0.956), demonstrating that each single domain is equally important for the internal consistency of the C-HAQ. Similar results were obtained when we removed 1 item at each time (data not shown).

Table 3. Internal consistency evaluated by Cronbach's alpha coefficient (baseline values)*
C-HAQ domainWithout the domainWith all the domains
  • *

    C-HAQ = Childhood Health Assessment Questionnaire; DI = disability index.

  • The value if that particular domain is removed.

  • Indicates the internal consistency of the C-HAQ DI measured on all 8 domains.

Dressing and personal care0.954 
Getting up0.953 
Eating0.956 
Walking0.955 
Hygiene0.951 
Reach0.952 
Grip0.955 
Activities0.956 
Total C-HAQ DI 0.960

Correlations between individual items of the C-HAQ and the total score were satisfactory (mean rs = 0.70); the item “run and play” had the highest correlation (rs = 0.82) and the item “turn neck to look back over shoulder” had the lowest correlation (rs = 0.54). Each domain of the C-HAQ correlated well with the total C-HAQ score (mean rs = 0.84), ranging from a minimum rs of 0.77 for the domain “eating” to a maximum rs of 0.89 for “activities.”

Construct validity and redundancy.

Spearman's correlation coefficient matrix of the final C-HAQ DI and the variables studied for the absolute change from baseline to 6 months after a therapeutic intervention is presented in Table 4. We observed a moderate correlation between the C-HAQ and the CHQ PhS, the parent's global assessment of pain, the parent's global assessment of overall well-being, and the SLAM (range rs = −0.61–0.42). The C-HAQ correlated poorly with the other variables reported in Table 4. No evidence of redundancy was observed between C-HAQ score and all other variables, including the CHQ PhS.

Table 4. Construct validity by Spearman's correlation matrix between absolute change in C-HAQ score and the variables included in the Paediatric Rheumatology International Trials Organisation juvenile systemic lupus erythematosus activity core set (value at month 6 minus value at month 0) and other variables analyzed*
VariablesC-HAQ scoreParent's global VASPhysician's global VASCHQ PhSECLAM24-hour proteinuriaPain VASSLAMSLEDAI
  • *

    C-HAQ = Childhood Health Assessment Questionnaire; VAS = visual analog scale; see Table 1 for additional definitions.

Parent's global VAS0.53        
Physician's global VAS0.300.43       
CHQ PhS−0.61−0.57−0.37      
ECLAM0.300.340.47−0.38     
24-hour proteinuria0.100.180.32−0.230.33    
Patient's pain VAS0.550.630.35−0.560.340.07   
SLAM0.420.440.53−0.510.610.260.39  
SLEDAI0.230.270.42−0.290.610.390.190.54 
CHQ PsS−0.20−0.26−0.130.02−0.120.04−0.18−0.16−0.09

Discriminant validity.

Figure 1 shows box plots of the absolute change (means) of the C-HAQ DI, the parent's assessment of the child's pain and overall well-being, the CHQ PhS, the physician's global assessment, and ECLAM as disease activity parameters, all of which demonstrated significant ability to discriminate between patients who were improved and those who were not improved at 6 months based on the PRINTO/ACR juvenile SLE definition of improvement. The discriminative validity of all other variables reported in Table 1 was also statistically significant (all P < 0.0001 except for C4: P = 0.004); the only 2 variables showing no discriminative ability were serum creatinine (P = 0.10) and CHQ PsS (P = 0.06).

Agreement.

When we substituted the CHQ PhS with the C-HAQ DI in the PRINTO juvenile SLE core set and recalculated the PRINTO/ACR juvenile SLE definition of improvement, we observed an almost perfect agreement (κ= 0.88, 95% CI 0.79–0.97) between the 2 definitions.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

We have demonstrated that the C-HAQ is a valid measure of disability in patients with active juvenile SLE. Our results indicate that, according to the validation procedures in the OMERACT filter for outcome measures in rheumatology, the C-HAQ exhibits moderate responsiveness to clinical change, construct validity, good feasibility, internal consistency, and discriminative ability.

The studied population was well distributed in terms of age, sex, and geographic origin and had a high level of baseline disease activity and renal involvement with significant proteinuria, present in almost half of the patients. After 6 months of treatment, according to the treating physician's decision, response to steroids and/or immunosuppressive therapy was significant for all clinical and laboratory variables except for creatinine, probably due to the low number of patients whose laboratory test results were above the normal range at baseline and followup.

Multidimensional health status instruments such as the C-HAQ have been developed to evaluate disability in patients in whom musculoskeletal components are predominant, such as arthritis and pain in JIA, or muscle weakness in juvenile DM. In a heterogeneous disease such as juvenile SLE, disability seems to be influenced not only by musculoskeletal symptoms but also by other factors such as fatigue. Indeed, in juvenile SLE, overall disability is moderate at baseline (mean C-HAQ DI 0.83), while analysis of the individual areas of the C-HAQ demonstrates a higher degree of difficulty to perform activities of daily living associated with fatigue (such as household chores or riding a bike) than activities that involve fine motor movements such as the use of hands for eating.

The C-HAQ DI was moderately responsive to clinically important change after 6 months of treatment. Notably, the responsiveness of the parent's assessment of pain and overall well-being, measured with a 10-cm VAS, was higher than that of the C-HAQ categorical scores.

The Cronbach's alpha observed (0.960) in juvenile SLE was remarkably similar to the values seen in patients with JIA (7). In addition, an excellent level of internal consistency was observed, because all 8 areas that comprise the C-HAQ were significantly correlated with the overall C-HAQ DI score.

The construct validity of the C-HAQ was demonstrated by the moderate correlation with the parent's global assessment of well-being and pain, and the CHQ physical well-being. Correlation with the physician's assessment of disease activity parameters was moderate for the SLAM (0.42) and poor for all other variables, including the SLEDAI and the ECLAM. This is in line with similar findings by Fortin et al (5), who reported a positive correlation between disability and the SLAM but not with the SLEDAI.

The C-HAQ DI and pain and overall well-being VAS scales demonstrated good discriminative properties when the PRINTO/ACR definition of improvement was applied. There was an almost perfect level of agreement between the PRINTO/ACR definition of improvement and its modified version in which physical well-being measured by the CHQ PhS was replaced with disability measured by the C-HAQ DI. This finding suggests that physical well-being and disability are partially overlapping concepts and both might be considered when evaluating improvement.

Although the C-HAQ demonstrated good performance characteristics, it cannot be used to obtain an overall multidimensional assessment of the health status of patients with juvenile SLE due to the heterogeneity of the disease with multiorgan involvement and a fluctuating course. Therefore, use of the C-HAQ to properly assess the health status of a patient with juvenile SLE requires the concomitant assessment of other parameters for the evaluation of disease activity, physical function, and quality of life as measured by the domains included in the PRINTO core set for the evaluation of response to therapy.

It is well known that the C-HAQ used in a convenience sample of children with JIA or juvenile DM in a different phase of the disease has a marked floor effect (7, 8, 14, 15). However, the floor effect is also known to be lower when patients with active disease are considered (29–31). We acknowledge that the results of this study are valid only for patients with active juvenile SLE, and it is not clear if the C-HAQ would perform as well in a different population (such as the general juvenile SLE population). Another possible limitation is the lack of data concerning the intra- and interrater reliability, which has been extensively addressed for JIA (7, 14, 15).

In conclusion, this study provides evidence that the C-HAQ is a suitable tool to measure disability in patients with active juvenile SLE and can be used in both clinical trials and in individual patient followup by the clinician.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Dr. Ruperto had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study design. Ruperto.

Acquisition of data. Meiorin, Filocamo, Trail, Oliveira, Cuttica, Espada, Alessio, Mihaylova, Cortis, Ruperto.

Analysis and interpretation of data. Meiorin, Pistorio, Ravelli, Filocamo, Trail, Martini, Ruperto.

Manuscript preparation. Meiorin, Pistorio, Ravelli, Iusan, Cortis, Martini, Ruperto.

Statistical analysis. Pistorio, Ruperto.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

We thank all members of PRINTO who participated as investigators in the study trial and whose enthusiastic effort made this work possible.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES
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