Contributors to Organ Damage in Childhood Lupus: Corticosteroid Use and Disease Activity

Maria Hanif; Chandni Sarker; Eslam Al-Abadi; Kate Armon; Kathryn Bailey; Marek Bohm; Mary Brennan; Coziana Ciurtin; Janet Gardner-Medwin; Daniel P Hawley; Alison Kinder; Alice Leahy; Gulshan Malik; Zoe McLaren; Elena Moraitis; Ellen Mosley; Athimalaipet V Ramanan; Satyapal Rangaraj; Annie Ratcliffe; Philip Riley; Heather Rostron; Ethan Sen; Michael W Beresford; Eve M D Smith

doi:10.1093/rheumatology/keae592

Contributors to Organ Damage in Childhood Lupus: Corticosteroid Use and Disease Activity

Rheumatology (Oxford). 2024 Oct 22:keae592. doi: 10.1093/rheumatology/keae592. Online ahead of print.

Authors

Maria Hanif¹, Chandni Sarker^{1

2}, Eslam Al-Abadi³, Kate Armon⁴, Kathryn Bailey⁵, Marek Bohm⁶, Mary Brennan⁷, Coziana Ciurtin⁸, Janet Gardner-Medwin⁹, Daniel P Hawley¹⁰, Alison Kinder¹¹, Alice Leahy¹², Gulshan Malik¹³, Zoe McLaren¹⁴, Elena Moraitis¹⁵, Ellen Mosley¹⁶, Athimalaipet V Ramanan¹⁷, Satyapal Rangaraj¹⁸, Annie Ratcliffe¹⁹, Philip Riley²⁰, Heather Rostron⁶, Ethan Sen²¹, Michael W Beresford^{1

22}, Eve M D Smith^{1

22}

Affiliations

¹ Department of Women's & Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
² Department of Health Data Science, Institute of Population Health, University of Liverpool, Liverpool, UK.
³ Department of Rheumatology, Birmingham Children's Hospital, Birmingham, UK.
⁴ Department of Paediatric Rheumatology, Cambridge University Hospitals, Cambridge, UK.
⁵ Department of Paediatric Rheumatology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
⁶ Department of Paediatric Rheumatology, Leeds Children Hospital, Leeds, UK.
⁷ Department of Paediatric Rheumatology, Royal Hospital for Sick Children, Edinburgh, UK.
⁸ Centre for Adolescent Rheumatology, University College London, London, UK.
⁹ Department of Child Health, University of Glasgow, Glasgow, UK.
¹⁰ Department of Paediatric Rheumatology, Sheffield Children's Hospital, Sheffield, UK.
¹¹ Leicester Children's Hospital, University Hospitals of Leicester NHS trust, Leicester, UK.
¹² Department of Paediatric Rheumatology, Southampton General Hospital, Southampton, UK.
¹³ Paediatric Rheumatology, Royal Aberdeen Children's Hospital, Aberdeen, UK.
¹⁴ Rheumatology Department, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.
¹⁵ Department of Paediatric Rheumatology, Great Ormond Street Hospital, London, UK.
¹⁶ Department of Paediatrics, Bradford Royal Infirmary, Bradford, UK.
¹⁷ University Hospitals Bristol NHS Foundation Trust & Bristol Medical School, University of Bristol, Bristol, UK.
¹⁸ Department of Paediatric Rheumatology, Nottingham University Hospitals, Nottingham, UK.
¹⁹ Department of Paediatrics, Musgrove Park Hospital, Taunton, UK.
²⁰ Department of Paediatric Rheumatology, Royal Manchester Children's Hospital, Manchester, UK.
²¹ Paediatric Rheumatology, Great North Children's Hospital & Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
²² Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK.

PMID: 39460632
DOI: 10.1093/rheumatology/keae592

Abstract

Background: Awareness of paediatric-specific predictors of damage in Childhood-lupus is needed to inform mitigation measures.

Objectives: To ascertain how clinical and demographic variables correlate with damage accrual and identify predictors of damage.

Methods: Analysis included UK JSLE Cohort Study participants. Univariable and multivariable Prentice-Williams-Peterson models investigated how demographic and clinical factors influenced hazards of new damage. Analyses were performed across the entire cohort, in patients with minimal disease activity marked by a time-adjusted average SLEDAI-2K score (AMS)≤2, low activity (AMS ≤ 4), moderate-high activity (AMS > 4) and those with no corticosteroids.

Results: Within the entire cohort (n = 430), factors associated with damage included: any methylprednisolone (Hazard Ratio, HR 2.20, [CI 1.33-3.62]), time-adjusted mean Physicians Global Assessment (PGA) (HR 2.87, [CI 1.48-5.56]) and AMS score (HR 1.13, [CI 1.03-1.24], all p< 0.05). Within the low activity subgroup, any methylprednisolone (HR 2.61, [CI 1.04-6.53]) and time-adjusted mean PGA (HR 3.41, [CI 1.52-7.76]) were associated with damage (both p< 0.05). Within the moderate-high activity subgroup, any methylprednisolone (HR 2.29, [CI 1.31-4.00]), time-adjusted mean PGA (HR 2.66, [CI 1.20-5.87]) and AMS score (HR 1.15, [CI 1.03-1.29]), were predictive of damage (all p< 0.05). Baseline organ damage was predictive of subsequent damage accrual in the minimal activity (HR 1.33, CI [1.78-8.08]) and no corticosteroids subgroups (HR 3.64, CI [1.83-7.24], both p< 0.005).

Conclusion: Disease activity levels (AMS/PGA) and proxy indicators (methylprednisolone exposure, baseline damage) were found to be key predictors of damage accrual. This highlights the importance of practical strategies, to reduce disease activity and long-term treatment toxicity, such as treat-to-target.

Keywords: Childhood-SLE; corticosteroids; damage; low disease activity; treat-to-target.