G Bertsias

EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics

Objective: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE. Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Key questions for the management of SLE were compiled using the Delphi technique. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries’ strategies for questions related to the diagnosis, prognosis, monitoring and treatment of SLE. For neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence, and agreement on the statements was measured across the 19 specialists. Results: Twelve questions were generated regarding the prognosis, diagnosis, monitoring and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus nephritis. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements. The average agreement among experts was 8.8 out of 10. Conclusion: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.

EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs

Objectives To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations. Methods The authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design. Results Systemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD. Conclusions Neuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.

Metabolic syndrome is common among middle-to-older aged Mediterranean patients with rheumatoid arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study

Objectives: Patients with rheumatoid arthritis have an increased risk for cardiovascular disease (CVD). The prevalence of metabolic syndrome (MetS)—a major contributor to CVD—in a cohort of patients with rheumatoid arthritis and its relationship with rheumatoid arthritis related factors is investigated here. Methods: 200 outpatients with rheumatoid arthritis (147 women and 53 men), with a mean (standard deviation (SD)) age of 63 (11) years, and 400 age and sex-matched controls were studied. MetS was assessed according to the adult treatment panel III criteria and rheumatoid arthritis disease activity by the disease activity score of 28 joints (DAS28). A standard clinical evaluation was carried out, and a health and lifestyle questionnaire was completed. Results: The overall prevalence of MetS was 44% in patients with rheumatoid arthritis and 41% in controls (p = 0.5). Patients with rheumatoid arthritis were more likely to have low high-density lipoprotein cholesterol compared with controls (p = 0.02), whereas controls were more likely to have increased waist circumference or raised blood pressure (p = 0.001 and 0.003, respectively). In multivariate logistic regression analysis adjusting for demographics and rheumatoid arthritis treatment modalities, the risk of having moderate-to-high disease activity (DAS28>3.2) was significantly higher in patients with MetS compared with those with no MetS components (OR 9.24, 95% CI 1.49 to 57.2, p = 0.016). Conclusion: A high, albeit comparable to the control population, prevalence of MetS was found in middle-to-older aged patients with rheumatoid arthritis. The correlation of rheumatoid arthritis disease activity with MetS suggests that the increased prevalence of coronary heart disease in patients with rheumatoid arthritis may, at least in part, be attributed to the inflammatory burden of the disease.

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.

Objectives Develop recommendations for womens health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). Methods Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. Results Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. Conclusions Recommendations for womens health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus

Objective: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions. Designing a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE. Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE. Results: The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications. Conclusions: Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints

OBJECTIVE To assess available evidence on the use of end-points (outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE. METHODS The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists. RESULTS Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken. CONCLUSION This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.

Quality of life before and after laparoscopic sleeve gastrectomy. A prospective cohort study

BACKGROUND There is a lack of adequate prospective data on quality-of-life (QOL) and its predictors in patients undergoing laparoscopic sleeve gastrectomy (LSG). The aim of this study was to assess longitudinal changes in QOL after LSG with the use of the obesity-specific Moorehead-Ardelt II questionnaire (MAII) and to identify clinical parameters associated with QOL outcome. METHODS Morbidly obese patients consecutively admitted for LSG, over a 30-month period, were prospectively studied. QOL was assessed using the validated Greek version of the MAII questionnaire and a visual analogueue scale (VAS), preoperatively and at 6, 12, and 24 months postoperatively. Anthropometric data and obesity-related co-morbidities were recorded. RESULTS A total of 111 patients with a mean age 36.8±9.2 years were included. Mean preoperative body mass index (BMI) was 49.1±7.5 kg/m2. Percentage excess BMI loss (%EBL) was 51.1±14.9, 64.2±17.9 and 66.4±18.0 at 6, 12, and 24 months, respectively. Postoperatively, all obesity-related co-morbidities were significantly improved. MAII score increased from -.40±1.30 preoperatively to 1.75±.83, 2.18±.80, and 1.95±.71 at 6, 12, and 24 months postoperatively (trend P<.001). Preoperative median (interquartile range) VAS was 3 (1) increasing to 9 (2), 10 (1), and 9 (1) at 6, 12, and 24 months postoperatively (P<.001). %EBL and reduction in obesity-related co-morbidities, especially resolution of diabetes and sleep apnea, correlated significantly with higher QOL during the course of the study. CONCLUSION LSG, a safe and effective bariatric operation, results in sustained weight loss and significant improvements in QOL. Both weight loss and amelioration of co-morbidities contribute to higher level of postsurgical QOL.

OP0092 Remission in Sle: Consensus Findings from a Large International Panel on Definitions of Remission in SLE (DORIS)

Background Treat-to-target recommendations identified “remission” as a target in SLE but recognize that there is no generally accepted definition for remission in this disease. Objectives To achieve consensus, in a large multi-party international panel, on potential definitions for remission in SLE. Methods An international expert panel of sixty rheumatologists, nephrologists, dermatologists, clinical immunologists, and patient representatives participated in preparatory exercises, a full-day face-to-face meeting, and follow-up exercises and electronic voting rounds. Results Eight key statements regarding remission in SLE achieved >90% agreement (table). There were different viewpoints on the required duration of remission. In addition, the panel expressed strong support (>90%) for the following principles which will guide the further development of remission definitions: I. A definition of remission in SLE will be worded as follows: Remission in SLE is a durable state characterized by [a definition of: absence of symptoms, signs, abnormal labs, (serology)] Ia. Remission-off-therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials. Ib. Remission-on-therapy allows patients to be treated with maintenance antimalarials, stable, low-dose steroids (prednisone ≤5 mg/d), maintenance immunosuppressives and/or stable (maintenance) biologics. II. Assessment of clinical symptoms and signs should be based on a validated index, e.g., clinical-SLEDAI =0, BILAG D/E only, clinical ECLAM =0; supplemented with PhysGA <0.5 (0-3), and with labs included. III. For testing the construct validity of each potential remission definition the most appropriate outcomes (dependent variables) are: Death, Damage, Flares, and HR-QOL measures. Conclusions The work of this international consensus panel provides a framework for testing individual definitions of remission against longer-term outcomes. Disclosure of Interest R. van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, C. Aranow: None declared, G. Bertsias: None declared, E. Bonfá: None declared, R. Cervera: None declared, N. Costedoat-Chalumeau: None declared, T. Dörner: None declared, F. Houssiau: None declared, K. Lerstrom: None declared, E. Morand: None declared, M. Mosca: None declared, S. Navarra: None declared, M. Petri: None declared, M. Urowitz: None declared, A. Voskuijl: None declared, A. Voss: None declared, M. Ward: None declared, V. Werth: None declared, M. Schneider: None declared

Validation of the Greek Translation of the Obesity-Specific Moorehead–Ardelt Quality-of-Life Questionnaire II

Morbid obesity adversely affects quality of life. The assessment of health-related quality of life (HRQoL) needs specific measuring instruments. The Moorehead–Ardelt Quality-of-Life Questionnaire II (MA II) is an obesity-specific instrument widely used in bariatric surgery. The objective of this study was to translate and validate the MA II in Greek language. The study included the translation of the MA II followed by cross-validation with the Greek version of 36-item Short Form Health Survey (SF-36) and a Visual Analogue Scale (VAS) in subjects visiting an obesity clinic. Internal consistency was indicated by Cronbach’s alpha coefficient and test–retest reliability by intraclass correlation coefficient (ICC). Construct validity was studied using Pearson’s correlations between the MA II, the SF-36 and the VAS. A total of 175 patients were enrolled in the study. Test–retest analysis was applied to 40 patients with a 15-day interval. A very good internal consistency with Cronbach’s alpha coefficient of 0.85 was shown. Excellent test–retest reliability was observed with an overall ICC of 0.981. Significant correlations between the Greek MA II and the other instruments as well as of each item of the MA II with the scores of SF-36 and the VAS indicated high construct and convergent validity. A negative correlation between the translated MA II total score and BMI confirmed high clinical validity. The Greek version of the MA II questionnaire has been generated and shown to be valid and reliable in measuring HRQoL in morbidly obese patients before and after bariatric surgery.

JOINT EULAR/ERA-EDTA RECOMMENDATIONS FOR THE MANAGEMENT OF ADULT AND PEDIATRIC LUPUS NEPHRITIS

Background There is increasing evidence from clinical trials on which to base a rational approach to the care of lupus nephritis (LN). Objectives To develop recommendations for the management of LN. Methods Questions were compiled using a modified Delphi technique. A systematic PubMed search was performed, and evidence-based and expert-opinion approach was followed to prepare recommendations. Results No clinical, serologic or laboratory tests can accurately predict renal biopsy findings in SLE; any sign of renal involvement, especially proteinuria >0.5 g/24-hr, should be an indication for biopsy. Assessment should include glomerular changes, activity and chronicity indices, tubulointerstitial lesions, and vascular lesions. Because of more favourable efficacy/toxicity ratio, for most patients with ISN/RPS2003 Class IIIA or A/C and Class IVA or A/C (±V) LN, mycophenolate mofetil (MMF) or low-dose intravenous cyclophosphamide (CY) in combination with glucocorticoids is recommended. Induction regimens should be combined initially with three daily pulses of IV methylprednisolone, followed by oral prednisolone 0.5 mg/kg/day. In patients with adverse clinical or histological features, CY can also be prescribed monthly at higher doses (0.75-1g/m2) for 6 months or orally for 3 months. For pure class V disease with nephrotic-range proteinuria, MMF in combination with oral prednisolone may be used initially. In patients responding to initial therapy (≥50% reduction in proteinuria and stable/improved GFR) within 6-12 months, maintenance immunosuppression is recommended with MMF or azathioprine for at least 3 years. For MMF or CY failures, we recommend switching to the other or rituximab. Pregnancy should be planned in stable patients with inactive lupus and serum creatinine <2 mg/dL. The intensity of treatment should not be reduced in anticipation of pregnancy. Nephritis is more frequent at presentation in children with SLE and its diagnosis, management, and monitoring is similar to that in adults. Conclusions Recommendations for LN were developed using an evidence-based approach followed by expert consensus. Disclosure of Interest None Declared