Objective: Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low‐dose IV CYC prescribed as a remission‐inducing treatment, followed by azathioprine (AZA) as a remission‐maintaining treatment.Methods: In this multicenter, prospective clinical trial (the Euro‐Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high‐dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low‐dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent‐to‐treat analyses were performed.Results: Followup continued for a median of 41.3 months in the low‐dose group and 41 months in the high‐dose group. Sixteen percent of those in the low‐dose group and 20% of those in the high‐dose group experienced treatment failure (not statistically significant by Kaplan‐Meier analysis). Levels of serum creatinine, albumin, C3, 24‐hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low‐dose group and 54% of the high‐dose group (not statistically significant). Renal flares were noted in 27% of the low‐dose group and 29% of the high‐dose group. Although episodes of severe infection were more than twice as frequent in the high‐dose group, the difference was not statistically significant.Conclusion: The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission‐inducing regimen of low‐dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high‐dose regimen.

Objective: In the Euro‐Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high‐dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low‐dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors.Methods: Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan‐Meier method.Results: After a median followup of 73 months, there was no significant difference in the cumulative probability of end‐stage renal disease or doubling of the serum creatinine level in patients who received the low‐dose IV CYC regimen versus those who received the high‐dose regimen. At long‐term followup, 18 patients (8 receiving low‐dose and 10 receiving high‐dose treatment) had developed permanent renal impairment and were classified as having poor long‐term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 gm/24 hours) was the best predictor of good long‐term renal outcome.Conclusion: Long‐term followup of patients from the ELNT confirms that, in lupus nephritis, a remission‐inducing regimen of low‐dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high‐dose regimen. Early response to therapy is predictive of good long‐term renal outcome.

Aims The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data. Methods Cross-sectional analysis of IIM cases from 11 countries was performed. Associations between clinical subtypes, extramuscular involvement, environmental exposures and medications were investigated. Results Of 3067 IIM cases, 69% were female. The most common IIM subtype was dermatomyositis (DM) (31%). Smoking was more frequent in connective tissue disease overlap cases (45%, OR 1.44, 95% CI 1.09 to 1.90, p=0.012). Smoking was associated with interstitial lung disease (ILD) (OR 1.32, 95% CI 1.06 to 1.65, p=0.013), dysphagia (OR 1.43, 95% CI 1.16 to 1.77, p=0.001), malignancy ever (OR 1.78, 95% CI 1.36 to 2.33, p<0.001) and cardiac involvement (OR 2.40, 95% CI 1.60 to 3.60, p<0.001). Dysphagia occurred in 39% and cardiac involvement in 9%; either occurrence was associated with higher Health Assessment Questionnaire (HAQ) scores (adjusted OR 1.79, 95% CI 1.43 to 2.23, p<0.001). HAQ scores were also higher in inclusion body myositis cases (adjusted OR 3.85, 95% CI 2.52 to 5.90, p<0.001). Malignancy (ever) occurred in 13%, most commonly in DM (20%, OR 2.06, 95% CI 1.65 to 2.57, p<0.001). ILD occurred in 30%, most frequently in antisynthetase syndrome (71%, OR 10.7, 95% CI 8.6 to 13.4, p<0.001). Rash characteristics differed between adult-onset and juvenile-onset DM cases (‘V’ sign: 56% DM vs 16% juvenile-DM, OR 0.16, 95% CI 0.07 to 0.36, p<0.001). Glucocorticoids were used in 98% of cases, methotrexate in 71% and azathioprine in 51%. Conclusion This large multicentre cohort demonstrates the importance of extramuscular involvement in patients with IIM, its association with smoking and its influence on disease severity. Our findings emphasise that IIM is a multisystem inflammatory disease and will help inform prognosis and clinical management of patients.

Autoimmune diseases are a group of disorders resulting from an alteration of immune tolerance, characterized by the formation of autoantibodies and the consequent development of heterogeneous clinical manifestations. Diagnosing autoimmune diseases is often complicated, and the available prognostic tools are limited. Machine learning allows us to analyze large amounts of data and carry out complex calculations quickly and with minimal effort. In this work, we examine the literature focusing on the use of machine learning in the field of the main systemic (systemic lupus erythematosus and rheumatoid arthritis) and organ-specific autoimmune diseases (type 1 diabetes mellitus, autoimmune thyroid, gastrointestinal, and skin diseases). From our analysis, interesting applications of machine learning emerged for developing algorithms useful in the early diagnosis of disease or prognostic models (risk of complications, therapeutic response). Subsequent studies and the creation of increasingly rich databases to be supplied to the algorithms will eventually guide the clinician in the diagnosis, allowing intervention when the pathology is still in an early stage and immediately directing towards a correct therapeutic approach.

Objective: To describe the treatment of polymyositis (PM) and dermatomyositis (DM) with prednisone (PRED) and cyclosporin A (CSA) alone or associated with intravenous immunoglobulin (IVIg) and plasmapheresis (PEX). Methods: Between 1992 and 1999 CSA and PRED were used to treat 20 patients with idiopathic myositis (12 with DM, eight with PM), diagnosed according to the Bohan and Peter criteria. In patients with refractory or relapsed disease, IVIg was added alone (seven cases) or synchronised with PEX (six cases). A standardised protocol was used to evaluate the patients, and assess disease activity and treatment response. Results: Despite a transient response to PRED and CSA in 16/20 cases, this combination did not induce full remission in 13/20 cases, which led to the IVIg trial with or without PEX. Patients receiving PRED and CSA plus IVIg had a significantly higher probability of maintaining complete remission at the end of the four year follow up period than those treated with PRED and CSA alone (p<0.001). No further benefit was added by the PEX. The presence of arthritis significantly correlated with a poorer response to treatment (p<0.05). Adverse effects were gingival hyperplasia (one patient) and transient renal dysfunction (one). Conclusions: This open study suggests that combined treatment with PRED, CSA, and IVIg is useful in patients with myositis, even those with refractory or relapsed disease; no increase in the number or type of side effects is seen.