Glucocorticoids (GCs) have long been one of the cornerstones of the treatment of systemic lupus erythematosus (SLE). However, for many years, recommendations for GC therapy have been more based on custom than on true evidence.

It is now a well-established fact that GCs are a major cause of irreversible damage. This association is dose dependent and has a close relationship with the progressive saturation of the genomic way with increasing doses over 7.5 mg/d of prednisone.^{1 2} On the contrary, pulses of methylprednisolone (MP), 125–500 mg/d for short periods of time (usually 3 days) have been consistently free from secondary damage in observational studies and a recent meta-analysis.²

Considering these thresholds, the use of MP in the induction phase followed by a rapid tapering of prednisone to reach maintenance doses of 2.5–5 mg/d is the safest and most effective approach to treat lupus flares, always in combination with hydroxychloroquine and, when necessary, immunosuppressive drugs.

The complete withdrawal of prednisone has been aimed as a main objective in recent recommendations. Recent studies and meta-analysis have shown that this is possible in about 80% of cases, however, the remaining patients would experience flares when GCs are completely stopped.³ A slowly gradual tapering from 5 mg/d when SLE is in longstanding remission maximises the chance of a successful withdrawal of the drug.⁴ If this is not possible, long-term maintenance doses of 2.5–5 mg/d are a reasonably safe option, much better than facing recurrent flares with the subsequent use of higher doses of GCs.

Therefore, combination therapy with hydroxychloroquine and immunosuppressive drugs, the use of MP in the induction of remission, not only in life-threatening scenarios, and a rapid tapering with a slow withdrawal of prednisone is our proposal for the successful management of SLE.^{4 5}

References

1. Buttgereit F, et al. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum 2004 Nov;50(11):3408–3417.

2. 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.

3. Ji L, Xie W, Zhang Z. Low-dose glucocorticoids should be withdrawn or continued in systemic lupus erythematosus? A systematic review and meta-analysis on risk of flare and damage accrual. Rheumatology (Oxford) 2021 Dec 1;60(12):5517–5526.

4. Ruiz-Irastorza G. Prednisone in systemic lupus erythematosus: taper quickly, withdraw slowly. Rheumatology (Oxford) 2021 Dec 1;60(12):5489–5490.

5. 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.

Learning Objectives

• Describe the role of the genomic and non-genomic ways in the therapeutic and toxic effects of GCs

• Discuss the association of different doses of GCs with side effects including damage

• Explain the results from recent studies on the efficacy and toxicity of therapeutic schemes using MP pulses followed by lower doses of prednisone in active lupus

• Discuss practical guidelines for using GCs in the different settings of active lupus