You are here
In the UK, NICE has accredited the British Society of Rheumatology (BSR) to develop a guidance document on the management of systemic lupus erythematosus in adults. The last published guidelines for lupus were published in 2008 by EULAR and in 2012 by the ACR.
The guidelines address the management of adult patients only and have been developed by a multidisciplinary guideline development group set up by the BSR. The guideline does not cover topical or systemic therapy for cutaneous lupus, nor does it discuss pediatric lupus management. There is an overview of the drugs used in the management of pregnant lupus patients and does not address the complications associated with SLE. Guidelines are expressed according to strength of agreement (SOA), level of evidence (LOE) and grade of recommendation (GOR).
Recommendations for a clinical and serological diagnosis of SLE
- SLE is a multisystem autoimmune disorder. The diagnosis requires a combination of clinical features and the presence of at least one relevant immunological abnormality. If there is a clinical suspicion of lupus, blood tests (including serological marker tests) should be checked (LOE 2 ++, GOR B, SOA 98%).
- ANAs are present in ∼95% of SLE patients. If the test is negative, there is a low clinical probability of the patient having SLE. A positive ANA test occurs in ∼5% of the adult population, and alone it has poor diagnostic value in the absence of clinical features of autoimmune rheumatic disease (2 ++/B, SOA 96%).
- The presence of anti-dsDNA antibodies (2 ++/B), low complement levels (2+/C) or anti-Smith (Sm) antibodies (2+/C) are highly predictive of a diagnosis of SLE in patients with relevant clinical features. Anti-Ro/La and anti-RNP antibodies are less-specific markers of SLE (2+/C) as they are found in other autoimmune rheumatic disorders as well as SLE (2+/C) (SOA 95%).
- aPLs should be tested in all lupus patients at baseline, especially in those with an adverse pregnancy history or arterial/venous thrombotic events (2 ++/B). Confirmatory tests for APS are positive LA, aCL (IgG, IgM) and/or anti-beta-2 glycoprotein-1 (IgG, IgM) on two occasions at least 12 weeks apart (2 ++/B) (SOA 97%).
Recommendations for the assessment of SLE patients
- Clinical manifestations in SLE patients may be due to disease activity, damage, drug toxicity or the presence of co-morbidity. In the case of disease activity, it is important to ascertain whether this is due to active inflammation or thrombosis, as this will define treatment strategies (LOE 2 ++, GOR B, SOA 97%).
- Clinical assessment of a lupus patient should include a thorough history and review of systems, full clinical examination and monitoring of vital signs, urinalysis, laboratory tests, assessment of health status and quality of life, and measurement of disease activity and damage using standardized SLE assessment tools (2 ++/B). Imaging (4/D), renal (2 ++/B) and other biopsies (4/D) should be performed where indicated (SOA 100%).
- Disease activity is categorized into mild, moderate and severe, with the occurrence of flares (2+/C). Mild disease activity is clinically stable lupus with no life-threatening organ involvement, mainly manifesting as arthritis, mucocutaneous lesions and mild pleuritis. Patients with moderate disease activity have more serious manifestations, and severe disease is defined as organ- or life-threatening (4/D) (SOA 93%).
Recommendations for monitoring of SLE
- Patients with lupus should be monitored on a regular basis for disease manifestations, drug toxicity and co-morbidities (LOE 2 ++, GOR B, SOA 99%).
- Those with active disease should be reviewed at least every 1–3 months (2+, C/D), with blood pressure (1+/A), urinalysis (1+/A), renal function (1+/A), anti-dsDNA antibodies (2 ++/B), complement levels (2+/C), CRP (2+/C), full blood count (3/C), and liver function tests (4/D) forming part of the assessment, and further tests as necessary (4/D). Patients with stable low disease activity or in remission can be reviewed less frequently, for example, 6–12 monthly (4/D) (SOA 99%).
- The presence of aPLs is associated with thrombotic events, damage, and adverse outcomes in pregnancy (2 ++/B). If previously negative, they should be re-evaluated prior to pregnancy or surgery, or in the presence of a new severe manifestation or vascular event (4/D) (SOA 96%).
- Anti-Ro and anti-La antibodies are associated with neonatal lupus (including CHB) and should be checked prior to pregnancy (1+/A) (SOA 100%).
- Patients with lupus are at increased risk of co-morbidities, such as atherosclerotic disease, osteoporosis, avascular necrosis, malignancy and infection (2+/C). Management of modifiable risk factors, including hypertension, dyslipidaemia, diabetes, high BMI and smoking, should be reviewed at baseline and at least annually (4/D) (SOA 98%).
- Immunosuppressive therapy may lead to toxicities. Close monitoring of drugs by regular laboratory tests and clinical assessment should be performed in accordance with drug monitoring guidelines (4/D) (SOA 98%).
Recommendations for the management of mild SLE
- Treatments to be considered for the management of mild non–organ-threatening disease include the disease-modifying drugs HCQ (1 ++/A) and MTX (1+/A), and short courses of NSAIDs (3/D) for symptomatic control. These drugs allow for the avoidance of or dose reduction of CSs (SOA 94%).
- Prednisolone treatment at a low dose of ⩽7.5 mg/day may be required for maintenance therapy (2+/C). Topical preparations may be used for cutaneous manifestations, and IA injections for arthritis (4/D) (SOA 93%).
- High–Sun Protection Factor (SPF) UV-A and UV-B sunscreen are important in the management and prevention of UV radiation–induced skin lesions (2 ++/B). Patients must also be advised about sun avoidance and the use of protective clothing (4/D) (SOA 97%).
Recommendations for the management of moderate SLE
- The management of moderate SLE involves higher doses of prednisolone (up to 0.5 mg/kg/day) (2+/C), or the use of i.m. (4/D) or i.v. doses of methylprednisolone (MP) (2+/C). Immunosuppressive agents are often required to control active disease and are steroid-sparing agents (2+/C). They can also reduce the risk of long-term damage accrual (4/D) (SOA 98%).
- MTX (1+/A), AZA (2+/C), MMF (2 ++/B), ciclosporin (2+/C) and other calcineurin inhibitors (3/D) should be considered in cases of arthritis, cutaneous disease, serositis, vasculitis or cytopaenias if HCQ is insufficient (SOA 97%).
- For refractory cases, belimumab (1+/B) or rituximab (2+/C) may be considered (SOA 98%).
Algorithm for the Use of rituximab or belimumab in SLE
Recommendations for the management of severe SLE
- Patients who present with severe SLE, including renal and NP manifestations, need thorough investigation to exclude other aetiologies, including infection (4/D). Treatment is dependent on the underlying aetiology (inflammatory and/or thrombotic), and patients should be treated accordingly with immunosuppression and/or anticoagulation, respectively (4/D) (SOA 98%).
- Immunosuppressive regimens for severe active SLE involve i.v. MP (2+/C) or high-dose oral prednisolone (up to 1 mg/kg/day) (4/D) to induce remission, either on their own or more often as part of a treatment protocol with another immunosuppressive drug (4/D) (SOA 98%).
- MMF or CYC are used for most cases of LN and for refractory, severe non-renal disease (2 ++/B) (SOA 98%).
- Biologic therapies belimumab (1+/B) or rituximab (2+/C) may be considered, on a case-by-case basis, where patients have failed to respond to other immunosuppressive drugs, due to inefficacy or intolerance (SOA 98%).
- IVIG (2−/D) and plasmapheresis (3/D) may be considered in patients with refractory cytopaenias, thrombotic thrombocytopaenic purpura (TTP) (1+/B), rapidly deteriorating acute confusional state and the catastrophic variant of APS (SOA 93%).
Future Research priorities to improve the management of lupus patients
- Analysis of the BILAG Biologics Register data is needed to assess the efficacy and safety of using rituximab for treating refractory lupus disease, administered according to the NHS England Interim Clinical Commissioning Policy Statement.
- Analysis of the BILAG Biologics Register should also provide some data on the use of MMF in non-renal lupus patients; this is needed to support data from previous renal trials.
- More research into stratified and personalised medicine and the cost-effectiveness of immunosuppressive drugs in lupus patients is warranted to help identify which drug will be most suitable for an individual.
- Trials of immunosuppressive regimens and biologic therapies that will significantly reduce the need for CSs are needed in renal and non-renal lupus patients.
- The cost-effectiveness and value of monitoring drug levels in order to improve adherence/compliance with drug therapy and improve the outcome in terms of reduced disease activity, damage and steroid usage should be investigated (e.g. for HCQ, MMF).
- The role of IVIG and plasma exchange in the management of lupus patients requires further evaluation.
- More data are required on the long-term outcome for children born to mothers with lupus who were exposed to drugs used pre-conception, while pregnant and/or while breast-feeding.