Principles

1. SLE requires multidisciplinary, individualized management with patient education and shared decision-making, taking into consideration the costs to patients and the society.

2. SLE disease activity should be assessed at each clinic visit (the frequency depending on physician’s discretion), with evaluation of organ damage (at least annually), using validated instruments.

3. Non-pharmacologic interventions, including sun protection, smoking cessation, healthy, balanced diet, regular exercises, and measures to promote bone health are important to improve long-term outcomes.

4. Pharmacological interventions are directed by patient characteristics, type and severity of organ involvement, treatment-related harms, comorbidities, the risk of progressive organ damage and patient preferences.

5. Early SLE diagnosis (including serological assessment), regular screening for organ involvement (especially nephritis), prompt initiation of treatment aiming at remission (or low disease activity if this is not possible), and strict adherence to treatment are essential to prevent flares and organ damage, improve prognosis and enhance quality of life.

Recommendations

LoA, mean (SD)

1. HCQ is recommended for all patients (1b/A), unless contraindicated, at a target dose of 5mg/kg real body weight/day (2b/B) but individualized based on the risk for flares (2b/B) and retinal toxicity.

9.21 (1.35)

2. GCs, if needed, are dosed based upon the type and severity of organ involvement (2b/C) and should be reduced to maintenance dose of ≤5mg/day (prednisone equivalent) (2a/B) and, when possible, withdrawn; in patients with moderate-to-severe disease, pulses of IV methylprednisolone (125-1,000mg/day, for 1-3 days) (3b/C) can be considered.

9.57 (0.77)

3. 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 [for example methotrexate (1b/B), azathioprine (2b/C) or mycophenolate (2a/B)] and/or biologic agents [for example belimumab (1a/A) or anifrolumab (1a/A)] should be considered.

9.32 (0.91)

4. In patients with organ- or life-threatening disease, IV cyclophosphamide (2b/C) should be considered; in refractory cases rituximab (2b/C) may be considered.

9.38 (0.99)

5. Treatment of active skin disease should include topical agents (GC, CNI) (2b/B), antimalarials (HCQ, CQ) (1a/A), and/or systemic GCs (4/C) as needed, with methotrexate (1b/B), mycophenolate (4/C), anifrolumab (1a/A) or belimumab (1a/B), considered as the second-line therapy.

9.35 (1.06)

6. In active neuropsychiatric disease attributed to SLE, GCs and immunosuppressive agents for inflammatory manifestations (1b/A) and antiplatelet agents/anticoagulants for atherothrombotic/aPL-related manifestations (2b/C) should be considered.

9.68 (0.81)

7. For acute treatment of severe autoimmune thrombocytopenia, high-dose GC [including pulses of IV methylprednisolone (4/C), with or without IV immunoglobulin G (4/C), and/or rituximab (2b/B), and/or high-dose intravenous cyclophosphamide (4/C) followed by maintenance therapy with rituximab (2b/B), azathioprine (2b/C), mycophenolate (2b/C), or cyclosporine (4/C)] should be considered.

9.48 (0.86)

8. Patients with active proliferative lupus nephritis should receive low-dose (EuroLupus) IV cyclophosphamide (1a/A) or mycophenolate (1a/A) and GCs (pulses of IV methylprednisolone followed by lower-dose oral GCs). Combination therapy with belimumab [either with cyclophosphamide or mycophenolate (1b/A)] or CNI (especially voclosporin or tacrolimus, combined with mycophenolate, 1b/A) should be considered.

9.36 (1.06)

9. Following renal response, treatment of lupus nephritis should continue for at least 3 years (2b/B); patients initially treated with mycophenolate alone or in combination with belimumab or a CNI should remain on these drugs (1a/A), whereas mycophenolate or azathioprine should replace cyclophosphamide for those initially treated with cyclophosphamide alone (1a/A) or in combination with belimumab.

9.56 (0.81)

10. In patients at high-risk for renal failure (defined as reduced GFR, histological presence of cellular crescents or fibrinoid necrosis, or severe interstitial inflammation), high-dose (NIH regimen) IV cyclophosphamide (1a/A) in combination with pulse IV methylprednisolone can be considered.

9.57 (0.86)

11. In SLE patients achieving sustained remission, gradual tapering of treatment should be considered with withdrawal of GC first (2a/B).

9.89 (0.38)

12. SLE associated with thrombotic APS should be managed with long-term vitamin K antagonists after the first arterial or unprovoked venous thrombotic event (1b/B); low-dose aspirin (75-100mg/day) should be considered as primary prevention in SLE/non-APS patients with high-risk aPL profile (2a/B).

9.57 (0.83)

13. Immunizations for the prevention of infections (HZV, HPV, influenza, COVID-19, and pneumococcus), the management of bone health, renoprotection and CV risk, and the screening for malignancies should be performed (-/D).

9.85 (0.36)