Management

The main aim of lupus treatment is to manage acute periods of potentially life threatening ill health, minimize the risk of flares during periods of relative stability and controlling the less life-threatening, but often incapacitating day to day symptoms (1).

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The choice of treatment is largely dependent on the severity of the disease and the site of organ involvement (2).

Treatment should target complete remission (the absence of clinical activity with no use of corticosteroids), but this is rarely achieved (3)

• treatment of non organ specific symptoms such as fatigue and chronic pain can be challenging since the causes are multifactorial and no specific therapies exist.
  • good overall control of lupus may improve these symptoms to a certain extent
  • exercise programmes have been shown to be useful in fatigue without causing disease flares
• other general measures include:
  • mild disease may respond to rest, NSAID's (see notes below),
  • life style changes e.g. - avoid sitting in direct sunlight and to use physical protection from the sun (e.g. long sleeves, hats and sun-protective clothing), avoidance of oestrogens e.g. in contraceptive pill
  • vitamin D supplements reduce disease activity; increase serum levels; and improve levels of inflammatory markers, fatigue, and endothelial function (4)
  • a diet rich in polyunsaturated fatty acids should be recommended (5)
  • topical agents e.g. - simple measures such as the use of sunscreens
  • management of co-morbidities e.g - prompt or prophylactic treatment of infection
• management of patients without major organ involvement
  • mild - moderate disease is managed by
    • oral corticosteroids at low-moderate doses
      • for mild disease, low doses (e.g. 5-10 mg daily) are often sufficient
      • for moderate disease the dose can be increased to 0.5 mg/kg
    • antimalarial therapy
      • hydroxychloroquine (HCQ) (up to 6.5 mg/kg daily) - is useful in the treatment of mucocutaneous disease, serositis and fatigue
  • symptoms not controlled by above mentioned methods require:
    • higher-dose of steroids
      • the therapeutic aim should be to maximise benefit while minimising steroid-related side effects
    • steroid-sparing agents
      • azathioprine (AZA) (1–3 mg/kg) - commonly used,
      • methotrexate - beneficial in patients with inflammatory arthritis
      • sulfasalazine - is usually avoided (due to its association with drug induced lupus)
• management of lupus with major organ involvement
  • the main aim in this group is rapid suppression of inflammation to prevent irreversible damage.
  • available therapeutic options include
    • high-dose intravenous (IV) methylprednisolone
    • immunosuppressant therapies - cyclophosphamide (CYC), mycophenolate mofetil (MMF)
    • biological therapies - rituximab, belimumab (6)
• at all times, careful monitoring is required for treatment induced side effects. Associated joint and skin disease may require the addition of antimalarials e.g. chloroquine derivatives. Dialysis may be used if there is renal failure. Anticoagulants are used if the lupus anticoagulant is present
• monitoring of levels of anti-dsDNA and treatment with steroids as soon as there is a significant rise in this marker prevents relapse in most cases, without increasing the cumulative dose of steroid given

Notes:

• new approaches that target both immune cells and cytokine pathways important in SLE show promise as treatment targets (7):
  • B-cell depletion with rituximab treatment can improve clinical manifestations of SLE, indicating that B cells are crucial not only for the development of SLE but also for continued activity of established disease
  • anti-TNF therapy experience with infliximab (and etanercept) suggests significant benefit for rapidly reducing inflammation and possible long-term effects on proteinuria, despite the transient occurrence of autoantibodies
  • NICE have suggested that belimumab is recommended as an option as add-on treatment for active autoantibody-positive systemic lupus erythematosus in people with high disease activity despite standard treatment, only if:
    • high disease activity is defined as at least 1 serological biomarker (positive anti-double-stranded DNA or low complement) and a Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score of greater than or equal to 10
    • treatment is continued beyond 24 weeks only if the SELENA-SLEDAI score has improved by 4 points or more
  • a systematic review concluded (8):
    • at the FDA-approved dose of 10 mg/kg, based on moderate to high-certainty data, belimumab was probably associated with a clinically meaningful efficacy benefit compared to placebo in participants with SLE at 52 weeks. Evidence related to harms is inconclusive and mostly of moderate to low-certainty evidence. More data are needed for the longer-term efficacy of belimumab
      
• NSAID use in SLE (2):
  • all NSAIDs and selective COX-2 inhibitors can adversely affect renal function, promote fluid retention and exacerbate hypertension
  • newer selective COX-2 inhibitors have been associated with an excess of cardiovascular events which has led to the withdrawal of rofecoxib and significant changes to the labelling and use of celecoxib and etoricoxib
  • the use of non-selective (ns) NSAIDs/selective COX-2 inhibitors should be considered carefully in patients with SLE
    • continued requirement for NSAID/selective COX-2 inhibitor therapy in some patients may indicate that further adjustment to their disease-modifying anti-rheumatic drug (DMARD) therapy is indicated to control inflammation better
  • the NSAID/selective COX-2 inhibitor dose should be reviewed and the lowest effective dose should be used for the shortest period of time
  • the majority of patients on aspirin plus a NSAID will also require some form of gastroprotection
    
    
• lupus nephritis
  • mycophenolate or low-dose intravenous cyclophosphamide are recommended as initial induction treatment for lupus nephritis as they have the best efficacy/toxicity ratio. (9).

References:

1. van Vollenhoven R, Voskuyl A, Bertsias G, et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis. 2017 Mar;76(3):554-61.
2. Gordon C, Amissah-Arthur MB, Gayed M, et al. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology (Oxford). 2017 Oct 6.
3. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019 Jun;78(6):736-45.
4. Sousa JR, Cunha Rosa EP, Costa Nunes IF, et al. Effect of vitamin D supplementation on patients with systemic lupus erythematosus: a systematic review. Rev Bras Reumatol Engl Ed. Sep-Oct 2017;57(5):466-71.
5. Rodríguez Huerta MD, Trujillo-Martín MM, Rúa-Figueroa Í, et al. Healthy lifestyle habits for patients with systemic lupus erythematosus: a systemic review. Semin Arthritis Rheum. 2016 Feb;45(4):463-70.
6. NICE (December 2021).Belimumab for treating active autoantibody-positive auto systemic lupus erythematosus
7. Iwata S, Saito K, Hirata S, et al. Efficacy and safety of anti-CD20 antibody rituximab for patients with refractory systemic lupus erythematosus. Lupus. 2018 Apr;27(5):802-11.
8. Singh JA et al Belimumab for systemic lupus erythematosus. Cochrane Database of Systematic Reviews 2021, Issue 2. Art. No.: CD010668.
   DOI: 10.1002/14651858.CD010668.pub2.
9. Tunnicliffe DJ, Palmer SC, Henderson L, et al. Immunosuppressive treatment for proliferative lupus nephritis. Cochrane Database Syst Rev. 2018 Jun 29;(6):CD002922.