Radmila Petrovic

The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide

Objective: To update the follow-up of the Euro-Lupus Nephritis Trial (ELNT), a randomised prospective trial comparing low-dose (LD) and high-dose (HD) intravenous (IV) cyclophosphamide (CY) followed by azathioprine (AZA) as treatment for proliferative lupus nephritis. Patients and methods: Data for survival and kidney function were prospectively collected during a 10-year period for the 90 patients randomised in the ELNT, except in 6 lost to follow-up. Results: Death, sustained doubling of serum creatinine and end-stage renal disease rates did not differ between the LD and HD group (5/44 (11%) vs 2/46 (4%), 6/44 (14%) vs 5/46 (11%) and 2/44 (5%) vs 4/46 (9%), respectively) nor did mean serum creatinine, 24 h proteinuria and damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. After 10 years of follow-up, the positive predictive value for a good outcome of an early drop in proteinuria in response to initial immunosuppressive therapy was confirmed. Conclusion: The data confirm that a LD IVCY regimen followed by AZA—the “Euro-Lupus regimen”—achieves good clinical results in the very long term.

Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial

Background Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment. Methods A total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months. Results The baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out. Conclusions Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.

Diagnostic Value of Salivary Gland Ultrasonographic Scoring System in Primary Sjögren’s Syndrome: A Comparison with Scintigraphy and Biopsy

Objective. To compare an ultrasonographic (US) scoring system of salivary glands with scintigraphy and salivary gland biopsy, in order to evaluate its diagnostic value in primary Sjögren’s syndrome (SS). Methods. In 135 patients with suspected SS, the grades of 5 US measures of both parotid and submandibular salivary glands were scored (0–48 scale). Diagnosis of primary SS was established following the American-European Consensus Group criteria of 2002. The patients’ total scintigraphic score (0–12 scale) was determined and the histopathological changes of minor salivary glands graded. Area under the receiver-operating characteristic (ROC) curve was employed to evaluate the diagnostic value of the US scoring system. Results. Primary SS was diagnosed in 107 (79.2%) patients and the remaining 28 subjects (20.8%) constituted the control group. US changes of salivary glands were established in 98/107 patients with SS and in 14/28 controls. Mean US score was 26 in SS patients and 6 in controls. Through ROC curves, US arose as the best performer (0.95 ± 0.01), followed by scintigraphy (0.86 ± 0.31). Setting the cutoff score for US at 19 resulted in the best ratio of specificity (90.8%) to sensitivity (87.1%), while setting the cutoff scintigraphic score at 6 resulted in specificity of 86.1% and sensitivity of 67.1%. Among 70 patients with US score ≥ 19, a scintigraphic score > 6 was recorded in 54/70 (77.1%) and positive biopsy findings in 62/70 (88.5%) patients. Conclusion. We show high diagnostic accuracy of a novel US scoring system of salivary glands (0–48) in patients with primary SS comparable to invasive methods, i.e., scintigraphy and salivary gland biopsy.

Ultrasonography of major salivary glands could be an alternative tool to sialoscintigraphy in the American–European classification criteria for primary Sjögren's syndrome

OBJECTIVE To test the diagnostic accuracy of modified American-European classification criteria (AEC) for primary SS (pSS) by replacing sialoscintigraphy (sSC) with ultrasonography of the major salivary glands. METHODS One hundred and ninety subjects were evaluated for the diagnosis of pSS, including US of the salivary glands. We tested the diagnostic accuracy of the three different sets of five diagnostic criteria for pSS. Each set combined these four criteria (ocular symptoms, oral symptoms, Schirmer-I test and auto-SS-A antibody) and one of the following: US (US set), sSC (sSC set) or biopsy (Biopsy set). The area under the receiver operating characteristics curve (AUC-ROC) was used to evaluate the diagnostic accuracy of each set of criteria. RESULTS Out of 190 subjects examined, 140 subjects fulfilled the AEC for the diagnosis of pSS, whereas 50 subjects were classified as non-pSS subjects. US score was positive in 129 (92%), sSC in 123 (88%) and biopsy in 93 (66%) of 140 pSS patients. Among 140 patients with pSS, 88 (63%) patients fulfilled the criteria of the US set, 85 (61%) patients of the sSC set and 71 (51%) patients of the Biopsy set. None of the subjects from the non-pSS group fulfilled any of the sets of criteria. Diagnostic accuracy of each of the three sets of criteria was high and similar [AUC-ROC (s.e.) for the US set was 0.99 (0.00), followed by the sSC set at 0.98 (0.00) and the Biopsy set at 0.97 (0.00)]. CONCLUSION US finding of major salivary gland involvement could replace sSC in AEC for the diagnosis of pSS.