Glucocorticoids (GC) have long been one of the cornerstones of the treatment of systemic lupus erythematosus (SLE). However, it is now a well-established fact that GC are a major cause of irreversible damage.¹ Therefore, strategies to decrease GC load without compromising the adequate control of disease activity are essential in the management of SLE.

Hydroxychloroquine (HCQ) should be considered the main GC-sparing drug in lupus. Its continued use has been associated to a myriad of beneficial effects, including the prevention of damage accrual and the improvement of survival, but also to a better control of lupus activity and, thus, a reduced need for GC use. Also, immunosuppressive drugs such as cyclophosphamide, azathioprine and methotrexate, have been extensively used throughout different clinical scenarios in order to decrease GC doses.² Although clinical trials with this group of drugs are few, their use has long been validated by clinical practice. More recently, biologic agents approved for SLE such as belimumab and anifrolumab have also been shown to allow a good control of disease activity whilst reducing the dose of GCs.^{3 4}

However, it is my view that the best GC-sparing drugs are…GCs. Pulses of methyl-prednisolone (MP), 125–500 mg/d, given for short periods of time (usually 3 days) have been shown to be the most effective way of rapidly controlling lupus flares through the activation of the non-genomic pathway.^{5 6} Therefore, the use of MP in the induction of remission, not only in life-threatening scenarios, combination therapy with HCQ and immunosuppressive drugs and a rapid tapering with a slow withdrawal of prednisone is our proposal for the successful management of SLE. In cases in which this scheme fails to adequately control lupus activity, the addition of biologic drugs should be considered.

References

1. Ugarte-Gil MF, et al. Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies. Lupus Sci Med. 2021 Dec;8(1):e000590. doi: 10.1136/lupus-2021-000590.

2. Pego-Reigosa JM, et al. Efficacy and safety of nonbiologic immunosuppressants in the treatment of nonrenal systemic lupus erythematosus: a systematic review. Arthritis Care Res. (Hoboken). 2013 Nov;65(11):1775–85. doi: 10.1002/acr.22035.

3. Touma Z, et al. Belimumab use, clinical outcomes and glucocorticoid reduction in patients with systemic lupus erythematosus receiving belimumab in clinical practice settings: results from the OBSErve Canada Study. Rheumatol Int. 2017 Jun;37(6):865–873. doi: 10.1007/s00296-017-3682-9. Epub 2017 Mar 9.

4. Bruce IN, et al. Sustained glucocorticoid tapering in the phase 3 trials of anifrolumab: a post hoc analysis of the TULIP-1 and TULIP-2 trials. Rheumatology (Oxford). 2023 Apr 3;62(4):1526–1534. doi: 10.1093/rheumatology/keac491.

5. Ruiz-Irastorza G, et al. Prolonged remission in SLE is possible by using reduced doses of prednisone: an observational study from the lupus-cruces and lupus-bordeaux inception cohorts. Autoimmun Rev. 2019 Sep;18(9):102359. doi: 10.1016/j.autrev.2019.102359. Epub 2019 Jul 16.

6. Ruiz-Irastorza G, Bertsias G. Treating systemic lupus erythematosus in the 21st century: new drugs and new perspectives on old drugs. Rheumatology (Oxford). 2020 Dec 5;59(Suppl5):v69-v81. doi: 10.1093/rheumatology/keaa403.

Learning Objectives

• Describe the concept and the need for sparing GC

• Describe different drugs used to treat SLE with a GC-sparing effect

• Discuss results from recent studies on the efficacy and toxicity of therapeutic schemes using methyl-prednisolone pulses followed by lower doses of prednisone in active lupus

• Describe practical guidelines for using glucocorticoid-sparing drugs in the different settings of active lupus