Measuring Disease Damage and Its Severity in Childhood-Onset Systemic Lupus Erythematosus

Objective: To describe the frequency and types of disease damage occurring with childhood-onset systemic lupus erythematosus (SLE) as measured by the 41-item Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and to assess the SDI's ability to reflect damage severity. Methods: Information for the SDI was prospectively collected from 1,048 childhood-onset SLE patients. For a subset of 559 patients, physician-rated damage severity measured by visual analog scale (MD VAS damage) was also available. Frequency of SDI items and the association between SDI summary scores and MD VAS damage were estimated. Finally, an international consensus conference, using nominal group technique, considered the SDI's capture of childhood-onset SLE\u2013associated damage and its severity. Results: After a mean disease duration of 3.8 years, 44.2% of patients (463 of 1,048) already had an SDI summary score >0 (maximum 14). The most common SDI items scored were proteinuria, scarring alopecia, and cognitive impairment. Although there was a moderately strong association between SDI summary scores and MD VAS damage (Spearman's r = 0.49, P < 0.0001) in patients with damage (SDI summary score >0), mixed-effects analysis showed that only 4 SDI items, each occurring in <2% of patients overall, were significantly associated with MD VAS damage. There was consensus among childhood-onset SLE experts that the SDI in its current form is inadequate for estimating the severity of childhood-onset SLE\u2013associated damage. Conclusion: Disease damage as measured by the SDI is common in childhood-onset SLE, even with relatively short disease durations. Given the shortcomings of the SDI, there is a need to develop new tools to estimate the impact of childhood-onset SLE\u2013associated damage

Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein

OBJECTIVE: Participants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy. METHODS: Subgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score ≥4 as post-pubertal or <4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or <110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or <1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models. RESULTS: Significant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures. CONCLUSIONS: Pubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy. CLINICALTRIALS.GOV IDENTIFIER: NCT00065806