Remission in SLE: closing in on the target.

Over the past decades, the concept of ‘remission’ has emerged as a moniker for the disease state one would ideally like to achieve when a ‘cure’—the ultimate goal of medical intervention—cannot realistically be hoped for. Originally used in oncology to describe the absence of detectable tumour, remission has become an important concept among medical specialties treating autoimmune inflammatory diseases. In some of these disease areas, three distinct processes have taken place: ▸ The term remission was introduced into the parlance of the specialty area, so that physicians, researchers and patients would use the term to describe the state they wished to achieve. ▸ Remission was specifically defined for each disease; for example, in rheumatoid arthritis (RA) a preliminary American College of Rheumatology (ACR) definition was published in 1981, followed by a definition based on the disease activity score or other disease activity indices, and finally by a joint ACR and European League Against Rheumatism (EULAR) definition; similar developments took place in other chronic inflammatory disease areas, such as inflammatory bowel disease. ▸ Remission was codified as the explicit target of therapeutic interventions, again most notably in RA where ACR and EULAR guidance as well as the ‘treat-to-target’ work force have expressed remission as the goal of therapy for most patients. Needless to say, these three developments have strongly influenced each other. Thus, the existence of specific and quantitative definitions of remission made it possible to articulate it as a therapeutic target, and has made the term remission a topic of discussion in many scientific publications and in patient–physician encounters. In systemic lupus erythematosus (SLE), the concept of remission has also been discussed extensively. Remission in SLE is widely understood as a desirable disease state that should be associated with optimal health-related quality of life and a good prognosis. It is remarkable that while remission has been used to describe a favourable clinical state for patients with SLE since at least the 1970s, there has not yet been an agreed-upon definition of remission in SLE. As reviewed in a recent publication, there are a number of different ad hoc definitions of remission that have been used in clinical trials and observational studies (table 1). Accurately defining remission in SLE would serve multiple purposes. It would facilitate many types of clinical research, including epidemiological studies, health economic investigations and clinical trials, leading to standardised cohort descriptions, valid interstudy comparisons and perhaps better trial outcomes. A validated definition of remission could also facilitate communication between healthcare provider and patient, and would be useful in education. Additionally, SLE is an extraordinarily heterogeneous disease with multiple clinical manifestations, and this heterogeneity has greatly hindered agreement on methods for quantification of disease activity; patients in remission or with low disease activity are clinically (and perhaps mechanistically) more homogeneous than those with active disease, potentially permitting simpler definitions of these clinical states (illustrated in figure 1). These patients may have achieved an immunological state of tolerance, and therefore, studies of patients with SLE in remission are likely to result in better understanding of the disease. Recently, the treat-to-target for SLE (T2T/SLE) initiative established international consensus on an approach to the therapy of lupus based on (1) identifying an appropriate target for each patient, (2) directing therapy towards achieving this target and (3) reassessing the target, and if needed changing the treatment. The T2T/SLE recommendations identified ‘remission of systemic symptoms and organ manifestations’ as one of the main therapy targets in SLE. However, the panel recognised that no generally accepted definition of remission in SLE exists today, and therefore, the T2T/SLE task force identified the definition of remission as a research priority for this disease. In response, an initiative to achieve consensus on a definition of remission in SLE was undertaken by a large multiparty international task force (DORIS—Definition Of Remission In SLE); the work of this task force has been presented at the 2015 EULAR congress and is being prepared for publication. The task force agreed that remission in SLE can conceptually be described as a desirable disease state for patients with, at the very least, the absence of major symptoms and signs of SLE. It is conceived of as distinct from a cure and also meaningfully different from a low disease activity state, including the lupus low disease activity state (LLDAS) that has recently been proposed by the Asia-Pacific Lupus Collaboration. Importantly, for future work in this area, it is recognised that LLDAS and remission are states associated with reduced morbidity and mortality. Further discussions involving SLE experts and patients identified four critical domains with regard to which definitions of remission are divergent and no clear consensus exists: clinical disease activity, serological activity, duration and treatment (figure 2). Thus, a definition of remission could require complete absence of clinical disease activity without any signs or symptoms indicative of SLE activity—or alternatively, a certain minimal amount of symptomatology might be accepted. For comparison, the proposed definition of remission in paediatric SLE allows certain symptoms, such as mild fatigue, mild myalgia, mild alopecia; the aforementioned remission in RA allows one swollen and one tender joint. As a practical approach, a validated index can be used to define the clinical activity aspect of remission, and this approach has dominated the literature over the past several years. Some different proposals are: systemic lupus disease activity index (SLEDAI)<2, ‘clinical SLEDAI’ (ie, disregarding serology)=0, clinical ECLAM=0 or having BILAG categories D and E only. Department of Medicine, The Karolinska Institute, Stockholm, Sweden; Department of Rheumatology, Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, The Netherlands; School of Clinical Sciences, Monash University, Clayton, Victoria, Australia; Center for Autoimmune and Musculoskeletal, The Feinstein Institute for Medical Research, Manhasset, New York, USA