Recommendations for the management of patients with systemic lupus erythematosus
| Overarching principles |
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| Recommendation/Statement | Level of agreement, mean (SD) |
| 1. Goals of treatment | |
| 1.1 Treatment in SLE should aim at remission or low disease activity (2b/B) and prevention of flares (2b/B) in all organs, maintained with the lowest possible dose of glucocorticoids. | 10.0 (0) |
| 1.2 Flares of SLE can be treated according to the severity of organ(s) involvement by adjusting ongoing therapies (glucocorticoids, immunomodulating agents) to higher doses, switching or adding new therapies (2b/C). | 9.95 (0.22) |
| 2. Treatment of SLE | |
| 2.1 HCQ | |
| 2.1.1 HCQ is recommended for all patients with SLE (1b/A), unless contraindicated, at a dose not exceeding 5 mg/kg/real BW (3b/C). | 9.65 (1.11) |
| 2.1.2 In the absence of risk factors for retinal toxicity, ophthalmological screening (by visual fields examination and/or spectral domain-optical coherence tomography) should be performed at baseline, after 5 years, and yearly thereafter (2b/B). | 9.75 (0.70) |
| 2.2 GC | |
| 2.2.1 GC can be used at doses and route of administration that depend on the type and severity of organ involvement (2b/C). | 9.95 (0.22) |
| 2.2.2 Pulses of intravenous methylprednisolone (usually 250–1000 mg per day, for 1–3 days) provide immediate therapeutic effect and enable the use of lower starting dose of oral GC (3b/C). | 9.85 (0.36) |
| 2.2.3 For chronic maintenance treatment, GC should be minimised to less than 7.5 mg/day (prednisone equivalent) (1b/B) and, when possible, withdrawn. | 9.65 (0.65) |
| 2.2.4 Prompt initiation of immunomodulatory agents can expedite the tapering/discontinuation of GC (2b/B). | 9.90 (0.30) |
| 2.3 Immunosuppressive therapies | |
| 2.3.1 In patients not responding to HCQ (alone or in combination with GC) or patients unable to reduce GC below doses acceptable for chronic use, addition of immunomodulating/immunosuppressive agents such as methotrexate, (1b/B) azathioprine (2b/C) or mycophenolate (2a/B) should be considered. | 9.85 (0.48) |
| 2.3.2 Immunomodulating/immunosuppressive agents can be included in the initial therapy in cases of organ-threatening disease (2b/C). | 9.85 (0.48) |
| 2.3.3 Cyclophosphamide can be used for severe organ-threatening or life-threatening SLE as well as ‘rescue’ therapy in patients not responding to other immunosuppressive agents (2b/C). | 9.90 (0.30) |
| 2.4 Biologics | |
| 2.4.1 In patients with inadequate response to standard-of-care (combinations of HCQ and GC with or without immunosuppressive agents), defined as residual disease activity not allowing tapering of glucocorticoids and/or frequent relapses, add-on treatment with belimumab should be considered (1a/A). | 9.20 (0.81) |
| 2.4.2 In organ-threatening disease refractory or with intolerance/contraindications to standard immunosuppressive agents, rituximab can be considered (2b/C). | 9.85 (0.48) |
| 3 Specific manifestations | |
| 3.1 Skin disease | |
| 3.1.1 First-line treatment of skin disease in SLE includes topical agents (GC, calcineurin inhibitors) (2b/B), antimalarials (HCQ, quinacrine) (1a/A) and/or systemic GC (4/C). | 10.0 (0) |
| 3.1.2 In non-responsive cases or cases requiring high-dose GC, methotrexate (3a/B), retinoids (4/C), dapsone (4/C) or mycophenolate (4/C) can be added. | 9.85 (0.48) |
| 3.2 Neuropsychiatric disease | |
| 3.2.1 Attribution to SLE—as opposed to non-SLE—related neuropsychiatric manifestations, is essential and can be facilitated by neuroimaging, investigation of cerebrospinal fluid, consideration of risk factors (type and timing of the manifestation in relation to the onset of lupus, patient age, non-neurological lupus activity, presence of aPL) and exclusion of confounding factors (2b/C). | 9.65 (0.85) |
| 3.2.2 Treatment of SLE-related neuropsychiatric disease includes glucocorticoids/immunosuppressive agents for manifestations considered to reflect an inflammatory process (1b/A), and antiplatelet/anticoagulants for atherothrombotic/aPL-related manifestations (2b/C). | 9.85 (0.48) |
| 3.3 Haematological disease | |
| 3.3.1 Acute treatment of lupus thrombocytopenia includes high-dose GC (including pulses of intravenous methylprednisolone) (4/C) and/or intravenous immunoglobulin G (4/C). | 9.95 (0.22) |
| 3.3.2 For maintenance of response, immunosuppressive/GC-sparing agents such as mycophenolate (2b/C), azathioprine (2b/C) or cyclosporine (4/C) can be used. | 9.75 (0.62) |
| 3.3.3 Refractory cases can be treated with rituximab (3a/C) or cyclophosphamide (4/C). | 9.65 (0.73) |
| 3.4 Renal disease | |
| 3.4.1 Early recognition of signs of renal involvement and—when present—performance of a diagnostic renal biopsy are essential to ensure optimal outcomes (2b/B). | 9.95 (0.22) |
| 3.4.2 Mycophenolate (1a/A) or low-dose intravenous cyclophosphamide (2a/B) are recommended as initial (induction) treatment, as they have the best efficacy/toxicity ratio. | 9.85 (0.36) |
| 3.4.3 In patients at high risk for renal failure (reduced glomerular filtration rate, histological presence of fibrous crescents or fibrinoid necrosis, or tubular atrophy/interstitial fibrosis], similar regimens may be considered but high-dose intravenous cyclophosphamide can also be used (1b/A). | 9.45 (0.80) |
| 3.4.4 For maintenance therapy, mycophenolate (1a/A) or azathioprine (1a/A) should be used. | 9.75 (0.62) |
| 3.4.5 In cases with stable/improved renal function but incomplete renal response (persistent proteinuria >0.8–1 g/24 hours after at least 1 year of immunosuppressive treatment), repeat biopsy can distinguish chronic from active kidney lesions (4/C). | 9.85 (0.48) |
| 3.4.6 Mycophenolate may be combined with low dose of a calcineurin inhibitor in severe nephrotic syndrome (2b/C) or incomplete renal response (4/C), in the absence of uncontrolled hypertension, high chronicity index at kidney biopsy and/or reduced GFR. | 9.50 (0.81) |
| 4 Comorbidities | |
| 4.1 Antiphospholipid syndrome | |
| 4.1.1 All patients with SLE should be screened at diagnosis for aPL (1a/A). | 10.0 (0) |
| 4.1.2 Patients with SLE with high-risk aPL profile (persistently positive medium/high titres or multiple positivity) may receive primary prophylaxis with antiplatelet agents (2a/C), especially if other atherosclerotic/thrombophilic factors are present, after balancing the bleeding hazard. | 9.45 (0.80) |
| 4.1.3 For secondary prevention (thrombosis, pregnancy complication/loss), the therapeutic approach should be the same as for primary antiphospholipid syndrome (1b/B). | 10.0 (0) |
| 4.2 Infectious diseases | |
| 4.2.1 Patients with SLE should be assessed for general and disease-related risk factors for infections, such as advanced age/frailty (–/D), diabetes mellitus (–/D), renal involvement (2b/B), immunosuppressive/biological therapy (1b-2b/B-C) and use of GC (1a/A). | 9.85 (0.65) |
| 4.2.2 General preventative measures (including immunisations) and early recognition and treatment of infection/sepsis are recommended (–/D). | 9.90 (0.44) |
| 4.3 Cardiovascular disease | |
| 4.3.1 Patients with SLE should undergo regular assessment for traditional (1b/B-C) and disease-related risk factors for cardiovascular disease, including persistently active disease (1b/B), increased disease duration (1b/A), medium/high titres of aPL (1b/A), renal involvement (1b/B) (especially, persistent proteinuria and/or GFR <60 mL/min) and chronic use of GC (1b/B). | 9.85 (0.65) |
| 4.3.2 Based on their individual cardiovascular risk profile, patients with SLE may be candidates for preventative strategies as in the general population, including low-dose aspirin (2b/D) and/or lipid-lowering agents (2b/D). | 9.85 (0.48) |
aPL, antiphospholipid antibodies; GC, glucocorticoids; GFR, glomerular filtration rate; HCQ, hydroxychloroquine; SLE, systemic lupus erythematosus.