EULAR 2022 (VIRTUAL)—Since its discovery in the 1950s, prednisone has revolutionized our ability to care for patients with rheumatic disease. However, prednisone has two faces—good and evil. And despite a growing array of old and novel therapeutics, prednisone remains a prominent part of care for many patients with systemic lupus erythematosus (SLE).
At the 2022 Congress of the European Alliance of Associations for Rheumatology (EULAR), Guillermo Ruiz-Irastorza, MD, PhD, professor of medicine, BioCruces Bizkaia Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Bizkaia, Spain, shared data from his institution regarding its approach to glucocorticoid usage in SLE.
A Patient with Severe SLE
A 52-year-old woman with severe SLE was admitted with acute onset of fever, hemoptysis, bilateral lung infiltrates and hypoxia. One month earlier, she was diagnosed with lupus nephritis class IV and treated with 200 mg of hydroxychloroquine daily, 10 mg of prednisone daily (maximum dose 20 mg) and 500 mg of intravenous cyclophosphamide every 14 days as per the Euro-Lupus protocol, adding 125 mg of methylprednisolone with each cyclophosphamide dose.1 Bronchoalveolar lavage confirmed diffuse alveolar hemorrhage. Blood cultures grew Streptococcus pneumoniae, which was treated with antibiotics.
For treatment of severe SLE, she received 250 mg of intravenous methylprednisolone daily for three days, and rituximab was added to her prior regimen. Her prednisone taper was resumed as per center protocol, with no increase from her pre-flare dose of 10 mg daily. Her oxygenation status improved, and she ultimately achieved a complete renal response.
2 Faces, 2 Mechanisms of Action
Glucocorticoids operate via two separate mechanisms of action: genomic and nongenomic.2 The genomic effects of glucocorticoids occur when binding to the cytosolic glucocorticoid receptor to induce or inhibit the synthesis of regulator proteins. The genomic mechanism of action is fully active from both an anti-inflammatory and toxic perspective at a 30–40 mg dose of prednisone daily.
On the other hand, the nongenomic effects of glucocorticoids, which don’t induce regulator proteins, occur only at high doses (e.g., 125 mg of prednisone daily, with peak effect at 250–500 mg daily).2 Nongenomic effects are anti-inflammatory, but nontoxic.
“We could say in a simplistic view that the genomic way is the ‘crappy’ way since patients suffer toxic effects,” Dr. RuizIrastorza explained. “The nongenomic way is the ‘cool’ way in which we have big anti-inflammatory and immunomodulatory effects without the toxicity.”