Scope and Purpose of the Guideline
SLE (or lupus for short) is a multisystem, autoimmune disease, involving complex pathogenetic mechanisms that can present at any age. It most commonly presents in women in the reproductive age group, although lupus is increasingly recognized after the age of 40 years, particularly in Europeans.[1–3] Lupus affected nearly 1 in 1000 of the population in the UK in 2012 and was most frequently observed in people of African-Caribbean and South Asian descent.[4–6] The age-standardized incidence in the UK according to the Clinical Practice Research Datalink is 8.3/100 000/year for females and 1.4/100 000/year for males, and the highest incidence rates are seen in those of African-Caribbean descent: 31.4/100 000/year, compared with 6.7/100 000/year for those of white European descent. The mean age at diagnosis is 48.9 years, but it is lower in those of African ancestry in the UK[4–6] and North America.[2,7]
The disease is prone to relapses and remissions, resulting in considerable morbidity due to flares of disease activity and accumulated damage, and an increased risk of premature death, mostly due to infection or cardiovascular disease.[2,8–14] Death from active lupus is rare in the UK;[15,16] however, a 10% mortality over 20 years and a mean age of death of 53.7 years was recently reported. About one-third of SLE patients in the UK develop LN.[16–18] Patients of African ancestry tend to present young with LN in the UK, as in the USA and elsewhere,[2,17,19] and are at considerable risk of developing end-stage renal disease (ESRD) and of dying prematurely. In another UK cohort, ESRD occurred in 20% of LN patients within 10 years of diagnosis, and the mean age at death in LN patients was 40.3 years, with an average of 7.5 years between development of LN and death.
The mainstay of therapy for active lupus until recently has been NSAIDs, CSs, antimalarials such as HCQ, and immunosuppressants such as AZA and CYC, although only prednisolone and HCQ are licensed for lupus.[8,20] With the exception of LN, there were relatively few trials until the last 15 years, and in 2011, belimumab became the first drug to be licensed for the treatment of active lupus for over 50 years. New therapies that will reduce the need for CSs to control lupus activity and to reduce the development of damage and infection are needed to improve outcome.[10–12,16,21] In the meantime it is important to manage patients optimally with the treatment strategies that are available.
Need for the Guideline
Despite some improvement in survival data over the last 40 years,[2,13] lupus patients still die on average 25 years earlier than the mean for women and men in the UK. The disease can present with slowly or rapidly progressive active disease at any age and can be associated with the rapid accumulation of damage if not promptly diagnosed, appropriately treated and regularly monitored.[2,8,14,19,20] An up-to-date comprehensive guideline to optimize these aspects of management that is consistent with current evidence and National Health Service (NHS) practice is warranted to improve the outcome of this variable and potentially life-threatening disease that causes considerable morbidity. There have been no previous UK-based guidelines for lupus. The European (EULAR) recommendations for the management of lupus in general were not very detailed and were published in 2008, although more specific recommendations were published for neuropsychiatric lupus in 2010, and joint EULAR and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for LN were published in 2012, as well as ACR guidelines for the management of LN in 2012.
Objectives of the Guideline
The aim of this guideline was to produce recommendations for the management of adult lupus patients in the UK that cover the diagnosis, assessment and monitoring of lupus and the treatment of mild, moderate and severe active lupus disease, but which do not imply a legal obligation. The resulting recommendations are based on an extensive review of the literature up to June 2015 to produce evidence-based guidelines, particularly for the treatment of non-renal lupus, supplemented as necessary by expert opinion and consensus agreement (Table 1 and Table 2). The guideline development group recommended that patients with LN are managed according to the EULAR/ERA-EDTA recommendations for LN and provide their strengths of agreement (SOAs) with a summary of the most important items in those recommendations (Table 3).
Target Population, Target Audience and Stakeholder Involvement
The guidelines address the management of adult patients only and have been developed by a multidisciplinary guideline development group set up by the British Society for Rheumatology (BSR) and led by C.G., consisting of academic (C.G., I.N.B., D.D.C., M.K., D.I.) and NHS consultants in rheumatology (M.A., B.G.) and nephrology (D.J., L.L.), rheumatology trainees (M.G., K.S.), a GP (B.E.), a clinical nurse specialist (S.B.), a patient representative (Y.N.) and a lay member (P.N.). All participants declared any conflicts of interest and these are listed at the end of this article. The target audience includes rheumatologists and other clinicians such as nephrologists, immunologists and dermatologists, trainees in these specialties and emergency medicine, GPs, clinical nurse specialists and other allied health professionals involved in the care of adult lupus patients. Opinions of other key stakeholders such as other consultant members of the BSR, additional trainees, podiatrists, nurse specialists and representatives of Lupus UK were sought during the preparation of these guidelines.
Areas That the Guideline Does not Cover
This guideline does not cover the evidence for topical or systemic therapy for isolated cutaneous lupus, nor does it discuss paediatric lupus, as there is relatively little literature on paediatric lupus. As the disease tends to come on after puberty, most of the recommendations are likely to be appropriate for children/adolescents, with suitable dose modifications. We provide only summary advice about the use of drugs in the management of pregnant lupus patients, and refer to the extensive review of drugs used in pregnancy and breast-feeding that have been recently published.[239,240] The management of complications of lupus, including chronic fatigue, cardiovascular risk, osteoporosis, infection and cancer risk are not discussed in detail, as these issues should be managed as for other patients with similar risk factors according to national and international guidelines. Management of thrombosis will depend on whether or not the criteria for APS are met.
Rheumatology. 2018;57(1):e1-e45. © 2018 Oxford University Press