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Background: Neuropsychiatric (NP) flares in systemic lupus erythematosus (SLE) constitute a challenging issue for the clinician on many levels as they are rather unpredictable and include severe and potentially life-threatening manifestations [1]. The identification of clinical and serological profiles predictive of NP flares would be instrumental for early detection of NP involvement, thus allowing early treatment, and hopefully resulting in improved outcomes. The B-cell depleting agent belimumab has widely shown ability to reduce rates of flare in SLE (2), but little is known on its potential benefits in the treatment of NPSLE. Objectives: To evaluate predictors of NP flares in patients with SLE under standard therapy (ST) with or without add-on belimumab, given for active disease yet not ongoing severe NP involvement. Methods: Data from five clinical trials of belimumab in SLE (BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS-NEA (NCT01345253), BLISS-SC (NCT01484496), and EMBRACE (NCT01632241)) were used (N=3638). Flares were defined using the British Isles Lupus Assessment Group (BILAG) activity index as development of any new NP BILAG score A in patients with baseline NP BILAG score B, and development of any new NP BILAG score A or B in patients with baseline NP BILAG score C–E during a 52-week follow-up. Predictors of NP flare were investigated using univariable and multivariable Cox regression analysis. A subgroup analysis was performed to determine predictors of de novo NP flare in patients with no NP history (baseline NP BILAG E). Organ damage was assessed using the SLICC/ACR Damage Index (SDI). p values <0.05 were considered statistically significant. Results: In total, 105 (2.9%) NP flares were documented. Of these, NP flare occurred in 52 (1.6%) patients with baseline NP BILAG E. In multivariable analysis adjusting for age, sex, ethnicity, and variables that were significant in univariable analysis, male sex (HR: 2.37; 95% CI: 1.31–4.28; p=0.004)

Background including aims: Identification of clinical features and serological markers that are predictive of neuropsychiatric systemic lupus erythematosus (NPSLE) would contribute to early detection of NP involvement, early initiation of treatment, and hopefully, improved outcomes. Thus, we aimed to identify determinants of NPSLE flares in patients treated for active SLE yet no ongoing severe NPSLE with non-biologic standard therapy plus belimumab or placebo. Methods: We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, EMBRACE; N=3638) after exclusion of patients with baseline NP BILAG A. Factors associated with NPSLE flare, defined as a new NP BILAG A or B, were investigated using Cox regression. In a subgroup analysis, we studied patients with baseline NP BILAG E for determinants of de novo NPSLE flare. Organ damage was assessed using the SLICC/ACR Damage Index (SDI). Results: We documented 105 (2.9%) NPSLE flares. In multivariable analysis, male sex (HR=2.37; 95% CI: 1.31–4.28; p=0.004), baseline NP BILAG B–D (HR=5.92; 95% CI: 3.86–9.06; p<0.001), and increasing SDI scores (HR=1.35; 95% CI: 1.21–1.50; p<0.001) were strongly associated with NPSLE flare. Belimumab use yielded no association at any dose or administration form. In analysis of SDI domains, NP damage was the strongest determinant of NPSLE flare (HR=3.25; 95% CI: 2.72–3.88; p<0.001), holding true for cognitive impairment (HR=14.29; 95% CI: 9.22–22.14; p<0.001), transverse myelitis (HR=21.89; 95% CI: 5.40–88.72; p<0.001), and neuropathy (HR=8.87; 95% CI: 5.59–14.09; p<0.001). Male sex was the strongest determinant of de novo NPSLE flare (HR=3.26; 95% CI: 1.51–7.04; p=0.003). Conclusion: Male sex, NPSLE history, and NP damage were strong determinants of impending NPSLE flare. No clear protection or predisposition was conferred from add-on belimumab.

Background including aims: Each lupus nephritis (LN) flare causes substantial nephron loss. Identification of reliable signals of impending flare is imperative. In light of observed cases of de novo LN during belimumab treatment, we evaluated predictors of de novo renal flare occurrence in patients with systemic lupus erythematosus (SLE) and no prior history of renal disease undergoing standard therapy with or without add-on belimumab within the frame of five phase III clinical trials. Methods: Data from five phase III clinical trials of belimumab in SLE i.e., BLISS-52 (NCT00424476; N=865); BLISS-76 (NCT00410384; N=819); BLISS-NEA (NCT01345253; N=677); BLISS-SC (NCT01484496; N=836); EMBRACE (NCT0163224; N=448) were utilised. De novo renal flares were defined as a change from renal British Isles Lupus Assessment Group (BILAG) E to A or B within a 52-week follow-up. Predictors of renal flare occurrence were investigated using Cox regression analysis. Results: Of 1844 eligible patients, 136 (7.4%) developed a de novo renal flare during a 52-week long follow-up. In multivariable analysis adjusting for potential confounders, Asian origin (HR: 1.97; 95% CI: 1.33–2.94; p=0.001), high mean prednisone dose from baseline until renal flare occurrence or throughout follow-up (HR: 1.03; 95% CI: 1.02–1.04; p<0.001), and positive levels of anti-dsDNA (HR: 1.32; 95% CI: 1.08–1.63; p=0.008) were associated with de novo renal flares. Low-dose intravenous (IV) belimumab (1 mg/kg) yielded a nearly 3-fold lower hazard of de novo renal flare occurrence (HR: 0.38; 95% CI: 0.20–0.73; p=0.004) and subcutaneous (SC) belimumab (200 mg weekly) yielded a lower, but less decreased, hazard (HR: 0.69; 95% CI: 0.54–0.88; p=0.003). However, the labelled dose of IV belimumab (10 mg/kg) did not provide protection (HR: 0.74; 95% CI: 0.50–1.09; p=0.127). Conclusions: Our findings corroborate the substantial vulnerability of Asian SLE populations to renal affliction. Add-on low-dose IV belimumab 1 mg

Background and study aims The aim of thi systematic review and consensus report is to standardize the practice of endoscopic ultrasound (EUS-guided needle-based confocal laser endomicroscopy (nCLE) for pancreatic cystic lesion (PCL) evaluation. Methods We performed an international, systematic, evidence-based review of the applications, outcomes, procedural processes, indications, training, and credentialing of EUS-nCLE in management of PCLs. Based on available clinical evidence, preliminary nCLE consensus statements (nCLE-CS) were developed by an international panel of 15 experts in pancreatic diseases. These statements were then voted and edited by using a modified Delphi approach. An a priori threshold of 80 % agreement was used to establish consensus for each statement. Results Sixteen nCLE-CS were discussed. Thirteen (81 %) nCLE-CS reached consensus addressing indications (noncommunication PCL meeting criteria for EUS-FNA or with prior non-diagnostic EUS-FNA), diagnostic outcomes (improved accuracy for mucinous PCLs and serous cystadeno mas with substantial interobserver agreement of image patterns), low incidence of adverse events (fluoresceinassociated and pancreatitis), procedural processes (nCLE duration, manipulation of needle with probe), and training (physician knowledge and competence). Conclusion Based on a high level of agreement pertaining to expert consensus statements, this report standardizes the practice of EUS-nCLE. EUS-nCLE should be systematically considered when EUS-FNA is indicated for PCL evaluation.