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Review
. 2024 May 22;11(1):e001124.
doi: 10.1136/lupus-2023-001124.

Disease-modifying therapies in systemic lupus erythematosus for extrarenal manifestations

Anca D Askanase  1 , Richard A Furie  2 , Maria Dall'Era  3 , Andrew S Bomback  1 , Andreas Schwarting  4   5 , Ming-Hui Zhao  6 , Ian N Bruce  7 , Munther Khamashta  8 , Bernie Rubin  9 , Angela Carroll  9 , Mark Daniels  10 , Roger Abramino Levy  11 , Ronald van Vollenhoven  12 , Murray B Urowitz  13
Affiliations
Review

Disease-modifying therapies in systemic lupus erythematosus for extrarenal manifestations

Anca D Askanase et al. Lupus Sci Med. .

Abstract

Our 2022 published working definition of disease modification in systemic lupus erythematosus (SLE) was 'minimising disease activity with the fewest treatment-associated toxicities and slowing or preventing organ damage progression'. The objective of this review was to classify current SLE treatments according to the proposed non-renal disease modification criteria excluding toxicities. Based on a review of select clinical trial (n=32) and observational study (n=54) publications for 14 SLE medications across different therapeutic classes, and the authors' clinical experience, we evaluated disease modification potential as per the proposed framework at three time points. Specific criteria used to determine disease modification potential included a drug's capacity to reduce: (1) non-renal disease activity, (2) severe flares, (3) use of steroids/immunosuppressants and (4) organ damage accrual. Criteria 1-3 were assessed at 1 year and 2-5 years and, when positive, were considered evidence for disease modification potential; criterion 4 was used to confirm disease modification at >5 years. Each treatment received one of four mutually exclusive designations at each time point: (a) criterion met, (b) indications of criterion met despite insufficient evidence in the literature, (c) inconclusive and (d) no available supportive data. This review excludes an assessment of potential toxicities. Eight of the 14 SLE treatments met ≥1 disease modification criteria up to year 5. Hydroxychloroquine improved overall survival at >5 years, suggesting long-term disease modification, but no data on specific organ systems were reported. Belimumab was the only treatment to meet all criteria. Belimumab and hydroxychloroquine met disease modification definitions across three time points. Evidence for other SLE therapies was incomplete, particularly at >5 years. Future studies are warranted for other treatments to meet the disease modification criteria. We discuss challenges to classification and possible updates to our published criteria.

Keywords: Biological Products; Glucocorticoids; Lupus Nephritis; Systemic Lupus Erythematosus.

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Conflict of interest statement

Competing interests: ADA has received consulting fees from AbbVie, Amgen, Aurinia, AstraZeneca, BMS and GSK; and has been an investigator for GSK, Janssen, Pfizer, UCB, Vielo, AstraZeneca and Eli Lilly. RAF has received research support from GSK and is an advisory board member for GSK. MD has received consulting fees from Aurinia, AstraZeneca, Biogen, Gilead, Pfizer and GSK. ASB has received consulting fees from Alexion, Principio, Calliditas, Aurinia, Catalyst, Travere, GSK, Visterra, Silence, Novo Nordisk, Otsuka, ChemoCentrx and Novartis. AS has received research grant support from GSK, Novartis and Pfizer; and has been an advisory board and speaker bureau member for GSK. M-HZ has been a consultant or advisory board member for GSK, AstraZeneca, Roche, Novartis, Bayer and BeiGene. INB is a National Institute for Health Research (NIHR) Senior Investigator and is funded by the NIHR Manchester Biomedical Research Centre (NIHR 203308). His institution has received research grants from GSK and Genzyme/Sanofi and consultancy fees from GSK, UCB, Eli Lilly, BMS, Merck Serono, Aurinia and IL-TOO. He has received speaker fees from GSK, AstraZeneca and UCB. RvV has received consulting fees from AbbVie, AstraZeneca, Biogen, Biotest, BMS, Galapagos, Gilead, Janssen, Pfizer, Sanofi, Servier, UCB and Vielabio; speaker honoraria from AbbVie, Galapagos, GSK, Janssen, Pfizer and UCB; and support for educational programmes and institutional grants from Pfizer and Roche. MBU has received research grant support from GSK and has been an advisory board and speaker bureau member for GSK, and an advisory board member for AstraZeneca, Eli Lilly and UCB. MD was an employee of GSK at the initial time of writing, and held a stock and shares in the company. MK, BR, AC and RAL are employees of GSK and hold stocks and shares in the company.

References

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