Team: Steroid dose in SLE

Base article: Figueroa-Parra G, Cuéllar-Gutiérrez MC, González-Treviño M, Sanchez-Rodriguez A, Flores-Gouyonnet J, Meade-Aguilar JA, Prokop LJ, Murad MH, Dall’Era M, Rovin BH, Houssiau F, Tamirou F, Fervenza FC, Crowson CS, Putman MS, Duarte-García A. Impact of Glucocorticoid Dose on Complete Response, Serious Infections, and Mortality During the Initial Therapy of Lupus Nephritis: A Systematic Review and Meta-Analysis of the Control Arms of Randomized Controlled Trials. Arthritis Rheumatol. 2024 Sep;76(9):1408-1418. doi: 10.1002/art.42920. Epub 2024 Jun 28. PMID: 38766897.

Authors: Washington University in St. Louis Fellowship Program

1. Sambhawana Bhandari, MD, 2^nd year rheumatology fellow, Washington University in St. Louis School of Medicine
2. Ariella Coler- Reilly, MD PhD candidate, Washington University in St. Louis School of Medicine
3. Alfred Kim, MD PhD, Associate Professor, Division of Rheumatology, Washington University in St. Louis School of Medicine
4. Lacey Feigl-Lenzen, Rheumatology fellowship program coordinator, Washington University in St. Louis School of Medicine
5. Sarah Goodman, MD, 2^nd year rheumatology fellow, Washington University in St. Louis

Team Overview: 

Glucocorticoids, our savior and the bane of our existence! Since their dramatic debut in 1948, transforming the life of a patient with rheumatoid arthritis and earning Hench, Kendall, and Reichstein the Nobel Prize, they have remained a cornerstone of rheumatic disease management (1). However, overutilization leads to infections and damage accrual, even at lower doses (2,3). Closing the evidence gap on optimal prescribing is crucial, and glucocorticoid-free induction therapies are emerging as safer alternatives (4). This meta-analysis included 50 RCT arms with data from 3,231 lupus nephritis (LN) patients to assess how different glucocorticoid doses influence complete response (CR), serious infections, and mortality.

Key Results:

• Rates of CR: 19.5% (95% CI 7.3–31.5) at 25 mg/day vs 34.6% (95% CI 16.9–52.3) at 60 mg/day
• Rates of serious infections: 3.2% (95% CI 2.4–4.0) at 25 mg/day vs 12.1% (95% CI 9.3–14.9) at 60 mg/day
• Rate of death: 0.2% (95% CI 0.0–0.4) at 25 mg/day vs 2.7% (95% CI 0.0–5.3) at 60 mg/day

This study is foundational as LN poses high mortality risks, and current glucocorticoid practices lead to severe side effects. By analyzing protocolized practices across many trials, this study highlights the impact of steroid dosing on kidney outcomes and safety emphasizing the need for personalized tapering strategies to prevent complications like infections and death. Limitations include variability in trial designs, participant populations, and tapering regimens, which may affect generalizability, as well as a lack of data on infection risk factors.

Related content on theMednet.org:

What steroid regimen do you typically use for induction therapy in patients with lupus nephritis?

References

1. Conn et al, The Story Behind the Use of Glucocorticoids in the Treatment of Rheumatoid Arthritis, Seminars in Arthritis and Rheumatism, Volume 51, Issue 1, 2021, https://doi.org/10.1016/j.semarthrit.2020.09.016
2. Abe K, Ishikawa Y, Kita Y, Yajima N, Inoue E, Sada KE, Miyawaki Y, Yoshimi R, Shimojima Y, Ohno S, Kajiyama H, Ichinose K, Sato S, Fujiwara M. Association of low-dose glucocorticoid use and infection occurrence in systemic lupus erythematosus patients: a prospective cohort study. Arthritis Res Ther. 2022 Jul 28;24(1):179. doi: 10.1186/s13075-022-02869-9. PMID: 35902976; PMCID: PMC9330647.
3. Ugarte-Gil MF, Mak A, Leong J, Dharmadhikari B, Kow NY, Reátegui-Sokolova C, Elera-Fitzcarrald C, Aranow C, Arnaud L, Askanase AD, Bae SC, Bernatsky S, Bruce IN, Buyon J, Costedoat-Chalumeau N, Dooley MA, Fortin PR, Ginzler EM, Gladman DD, Hanly J, Inanc M, Isenberg D, Jacobsen S, James JA, Jönsen A, Kalunian K, Kamen DL, Lim SS, Morand E, Mosca M, Peschken C, Pons-Estel BA, Rahman A, Ramsey-Goldman R, Reynolds J, Romero-Diaz J, Ruiz-Irastorza G, Sánchez-Guerrero J, Svenungsson E, Urowitz M, Vinet E, van Vollenhoven RF, Voskuyl A, Wallace DJ, Petri MA, Manzi S, Clarke AE, Cheung M, Farewell V, Alarcon GS. 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. PMID: 34930819; PMCID: PMC8689160.
4. Condon MB, Ashby D, Pepper RJ, Cook HT. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis. 2013 Aug;72(8):1280-6. doi: 10.1136/annrheumdis-2012-202844. Epub 2013 Jun 5. PMID: 23740227.

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