Long-term improvement of lipid profile in patients with refractory systemic lupus erythematosus treated with B-cell depletion therapy: a retrospective observational study.

OBJECTIVE: Lipid abnormalities contribute to the increased risk of premature atherosclerosis in patients with SLE. This study was undertaken to investigate changes in lipid profile after B-cell depletion therapy (BCDT) in patients with active SLE who had failed standard immunosuppressive therapy. METHODS: Twelve patients with refractory SLE treated with BCDT based on rituximab (two biweekly infusions of 1 g) were examined. Lipid profile and lupus activity were measured before the infusions and 1 year later. The control group consisted of 26 age- and sex-matched lupus patients not treated with BCDT. RESULTS: In the study group, the mean levels of total, high-density lipoprotein (HDL) and low-density lipoprotein cholesterols were 4.6, 1.4 and 2.4 mmol/l at baseline and changed to 4.1, 1.6 and 2.0 mmol/l (P = NS, P = 0.04 and P = NS) at 1 year, respectively. The atherogenic index was 3.8 at baseline and decreased to 2.7 (P = 0.02). The triglyceride (TG) level was 2.1 mmol/l at baseline and decreased to 1.3 mmol/l (P = 0.04). BCDT was followed by a significant decrease in global BILAG scores and a drop in the mean dose of prednisolone at 1 year (P = 0.01). Reduction in disease activity was significantly associated with a reduction in total cholesterol and TG levels and an increase in HDL cholesterol levels. In the control group, there were no differences in any of the lipid determinations over a 1-year period. CONCLUSION. This provisional observational study suggests a favourable long-term effect of BCDT on the lipid profile of patients with refractory SLE, which correlated with decreasing activity of the disease.

Urinary neutrophil gelatinase-associated lipocalin as a novel biomarker for disease activity in lupus nephritis.

OBJECTIVES: Clinical and laboratory markers in current use have limited specificity and sensitivity for predicting the development of renal disease in lupus patients. In this longitudinal study, we investigated whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts active nephritis and renal flares in lupus patients with and without a history of biopsy-proven lupus nephritis. METHODS: Renal disease activity and flare status was determined by SLEDAI and BILAG scores. Random effects models were used to determine whether uNGAL was a significant predictor for renal disease activity in SLE patients, and for renal flares in patients with established nephritis. To assess the predictive performance of uNGAL, receiver operating characteristic (ROC) curves were constructed using the previous visit's uNGAL level. These curves were then compared with curves constructed with currently used biomarkers. Cut-offs determined by ROC curves were tested in an independent validation cohort. RESULTS: uNGAL was found to be a significant predictor of renal disease activity in all SLE patients, and a significant predictor for flare in patients with a history of biopsy-proven nephritis, in multivariate models adjusting for age, race, sex and anti-double-stranded (ds)DNA antibody titres. As a predictor of renal flare in patients with biopsy-proven nephritis, uNGAL outperformed anti-dsDNA antibody titres. These results were confirmed in an independent validation cohort. CONCLUSIONS: uNGAL predicts renal flare in patients with a history of biopsy-proven nephritis with high sensitivity and specificity. Furthermore, uNGAL is a more sensitive and specific forecaster of renal flare in patients with a history of lupus nephritis than anti-dsDNA antibody titres.

Inflammatory muscle disease assessment.

In recent years, idiopathic inflammatory muscle disease assessment has advanced significantly with the development of an international consensus on outcome measurement indices. The International Myositis Assessment and Clinical Studies Group continues to evaluate the validity and reliability of various disease activity and disease damage tools, which will facilitate adequately controlled randomized trials of recently developed therapeutic agents.

A retrospective seven-year analysis of the use of B cell depletion therapy in systemic lupus erythematosus at University College London Hospital: the first fifty patients.

OBJECTIVE: To describe the 6-month clinical outcome and the long-term safety profile of B cell depletion therapy (BCDT) in 50 patients with active systemic lupus erythematosus (SLE), who were nonresponsive or poorly responsive to conventional immunosuppression. METHODS: All except 4 of 50 patients with active SLE received 1 gm of rituximab, 750 mg of cyclophosphamide, and 100-250 mg of methylprednisolone, administered on 2 occasions 2 weeks apart, to achieve B cell depletion. Clinical outcome was assessed using the British Isles Lupus Assessment Group (BILAG) activity index and serial serologic measurements of disease activity. Remission was defined as a change from a BILAG A or B score to a C or D score in every organ system. Partial remission was a change from a BILAG A or B score to a C or D score in at least 1 system, but with the persistence of 1 score of A or B in another system. No improvement was defined as a BILAG A or B score that remained unchanged after treatment. RESULTS: Of the 45 patients available for followup at 6 months, 19 patients (42%) achieved remission, and 21 patients (47%) reached partial remission after 1 cycle of BCDT (mean followup 39.6 months). BCDT resulted in a decrease in median global BILAG scores from 12 to 5 (P < 0.0001) and median anti-double-stranded DNA antibody titers from 106 to 42 IU/ml (P < 0.0001), and an increase in the median C3 level from 0.81 to 0.95 mg/liter (P < 0.02) at 6 months. Five serious adverse events were observed. CONCLUSION: BCDT is an effective treatment for patients with active SLE whose disease has failed to respond to standard immunosuppressive therapy. Although the safety profile of BCDT is favorable, ongoing monitoring is required.

Breast cancer and systemic sclerosis: a clinical description of 21 patients in a population-based cohort study.

Previous studies have demonstrated an increased risk of breast cancer among patients with systemic sclerosis (scleroderma). To describe the clinical characteristics of 21 patients with both systemic sclerosis and breast cancer, and compare their risk factors to female scleroderma patients without breast cancer, in a population-based cohort study of South Australia. Subjects with scleroderma and breast cancer were identified from the South Australian Scleroderma Register with cross-linking to the South Australian Cancer Registry, last updated to the end of December 2005. Clinical information was obtained from standardised self-administered questionnaires and case note reviews. Odds ratios for the risk factors for breast cancer in scleroderma were determined, and clinical variables were analysed using chi square, Fisher's exact, Mann-Whitney and t tests. At the end of December 2005 there were a total of 389 female patients with scleroderma. Of these, 21 (5.4%) had been diagnosed with breast cancer. The mean age of onset of scleroderma was 43.5 years, and the mean age of breast cancer was 60.5 years in those with scleroderma and breast cancer. The majority (71.4%) had limited scleroderma, with anti-centromere antibody being the most prevalent serological abnormality. In 16 (76%) patients the diagnosis of breast cancer occurred on an average of 22.3 years after the onset of their first scleroderma symptom. When compared to 48 controls, scleroderma patients with breast cancer were found to have a higher incidence of a positive family history of breast cancer (Fisher's exact test, p = 0.04) and a lower incidence of hormone-replacement therapy use (Fisher's exact test, p = 0.0026). This population-based cohort study provides evidence that the majority of patients with scleroderma and breast cancer have limited scleroderma and anti-centromere antibody. Given the increased incidence of solid tumours in systemic sclerosis, we suggest regular screening of female patients for breast cancer, especially in those with a family history.