Treatment targets in SLE: remission and low disease activity state

Treat-to-target strategies have changed the approach to management of many chronic conditions, with improvements in patient outcomes. The key to success of treat to target is the availability of validated treatment endpoints, which have been difficult to derive for SLE, a condition notorious for its heterogeneity. This review will focus on the development and validation of the definitions of remission in SLE framework and the lupus low disease activity state. Lupus low disease activity state is more attainable than remission, with a stepwise concentric relationship between the target states indicating increasing stringency. Both lupus low disease activity state and definitions of remission in SLE remission have been proven to be associated with reduction in disease flares, reduced risk of accrual of irreversible end organ damage, and improvement in patient reported outcomes. These endpoints have therefore provided the key for the development of a treat-to-target approach in clinical practice in SLE and for the design of future clinical trials

New developments in systemic lupus erythematosus

In this review, the results of recent and ongoing clinical trials in patients with SLE are discussed. After many unsuccessful trials in the past decade, belimumab was the first biologic specifically designed for SLE that met its primary end point. At the same time, studies on the pathophysiology of SLE have further elucidated the pathways involved in the disease, which has led to the identification of new possible therapeutics and has encouraged the initiation of new trials. These new drugs include biologics that target B cells, T cells and type 1 interferons, and small molecules that inhibit kinases. Other therapeutics aim to restore immunological balance by restoring tolerance. Results from phase II and even phase III trials are promising and it is likely that some of the therapeutics discussed will receive approval in the following years. Hopefully, this will allow for more tailor-made medicine for SLE patients in the future

The relationship between remission and health-related quality of life in a cohort of SLE patients

OBJECTIVE: To investigate the relationship between remission and health-related quality of life (HRQoL) in patients with SLE in a longitudinal observational cohort. METHODS: HRQoL was measured at cohort visits using the physical and mental component score (PCS and MCS, respectively) of the Short Form 36 questionnaire. Definitions of Remission in SLE remission categories (no remission/remission on therapy/remission off therapy) were applied. Determinants of PCS and MCS were identified with simple linear regression analyses. Association between remission and HRQoL was assessed using generalized estimating equation models. RESULTS: Data from 154 patients with 2 years of follow-up were analysed. At baseline 60/154 (39.0%) patients were in either form of remission. Patients in remission had higher Short Form 36 scores in all subdomains compared with patients not in remission. PCS was positively associated with remission and employment, and negatively associated with SLICC damage index, ESR, medication, patient global assessment and BMI. MCS was positively associated with Caucasian ethnicity and negatively associated with patient global assessment. In generalized estimating equation analysis, a gradual and significant increase of PCS was observed from patients not in remission (mean PCS 36.0) to remission on therapy (41.8) to remission off therapy (44.8). No significant difference in MCS was found between remission states. CONCLUSION: we show a strong and persistent association between remission and PCS, but not MCS. These results support the relevance (construct validity) of the Definition of Remission in SLE remission definitions and the further development of a treat-to-target approach in SLE

Web-based eHealth Clinical Decision Support System as a tool for the treat-to-target management of patients with systemic lupus erythematosus: development and initial usability evaluation

Background Treat-to-target (T2T) is a therapeutic strategy currently being studied for its application in systemic lupus erythematosus (SLE). Patients and rheumatologists have little support in making the best treatment decision in the context of a T2T strategy, thus, the use of information technology for systematically processing data and supporting information and knowledge may improve routine decision-making practices, helping to deliver value-based care.Objective To design and develop an online Clinical Decision Support Systems (CDSS) tool “SLE-T2T”, and test its usability for the implementation of a T2T strategy in the management of patients with SLE.Methods A prototype of a CDSS was conceived as a web-based application with the task of generating appropriate treatment advice based on entered patients’ data. Once developed, a System Usability Score (SUS) questionnaire was implemented to test whether the eHealth tool was user-friendly, comprehensible, easy-to-deliver and workflow-oriented. Data from the participants’ comments were synthesised, and the elements in need for improvement were identified.Results The beta version web-based system was developed based on the interim usability and acceptance evaluation. 7 participants completed the SUS survey. The median SUS score of SLE-T2T was 79 (scale 0 to 100), categorising the application as ‘good’ and indicating the need for minor improvements to the design.Conclusions SLE-T2T is the first eHealth tool to be designed for the management of SLE patients in a T2T context. The SUS score and unstructured feedback showed high acceptance of this digital instrument for its future use in a clinical trial

Macrophages in Lupus Nephritis: Exploring a potential new therapeutic avenue

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) that occurs in about half of patients. LN is characterized by glomerular deposition of immune complexes, leading to subendothelial, mesangial and subepithelial electron dense deposits, triggering immune cell infiltration and glomerular as well as tubulointerstitial injury. Monocytes and macrophages are abundantly present in inflammatory lesions, both in glomeruli and the tubulointerstitium. Here we discuss how monocytes and macrophages are involved in this process and how monocytes and macrophages may represent specific therapeutic targets to control LN

Fc-gamma receptor polymorphisms differentially influence susceptibility to systemic lupus erythematosus and lupus nephritis

Objective. To determine relevant Fc-gamma receptor (FcgR) polymorphisms in relation to susceptibility to SLE and LN, and to determine the functional consequences of genetic associations found. Methods. Using multiplex ligation-dependent probe amplification, copy number regions (CNRs) and relevant known functional single nucleotide polymorphisms of Fc gamma RII and Fc gamma RIII were determined in a LN-enriched cohort of 266 Dutch Caucasian SLE patients and 919 healthy Caucasian controls. Expression of Fc gamma Rs on leukocytes was assessed using flow cytometry. Results. In multivariable analysis, low copy number of CNR1 (including FCGR3B; odds ratio (OR) 2.04; 95% CI: 1.29, 3.23), FCGR2A-131RR (OR 2.00; 95% CI: 1.33, 2.99), and the 2B.4 haplotype of FCGR2B (OR 1.59; 95% CI: 1.13, 2.24), but not FCGR2C open reading frame, were significantly (all P <0.01) and independently associated with susceptibility to SLE. The 2B.4 haplotype was negatively associated with LN and led to surface expression of Fc gamma RIIb on neutrophils and monocytes. Conclusion. This study is the first to investigate the most relevant and functional single nucleotide polymorphisms and copy number variations of Fc gamma RII and Fc gamma RIII polymorphisms in one study population, enabling the determination of the individual contribution of each polymorphism in multivariable analysis. Three polymorphisms were shown to be independently associated with susceptibility to SLE. The novel findings of a negative association of the 2B.4 haplotype with LN, and increased expression of Fc gamma RIIb on neutrophils and monocytes as a result of this 2B.4 haplotype warrant future research in the role of these cells and Fc gamma Rs in the pathogenesis of SLE and LN