IDENTIFYING A POPULATION OF PATIENTS FOR INTENSIVE FIRST-LINE THERAPY IN SLE: A CLINICAL AND BIOMARKER MODEL TO PREDICT THE NEED FOR INTENSIVE THERAPY.

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All Authors

Intapiboon, P.
Ul Hassan S.
Arnold J.
Mahmoud K.
Vital E.M.
Yusof M.Y.M.

LTHT Author

Ul Hassan
Vital, Edward
Yusof

LTHT Department

NIHR Leeds Biomedical Research Centre

Non Medic

Publication Date

2024

Item Type

Conference Abstract

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Abstract

Objective To investigate the clinical and biomarkers factors predicting a requirement for intensive therapy or time to intensive therapy from diagnosis of Systemic Lupus Erythematosus (SLE). Methods We conducted a retrospective longitudinal study of all patients with a diagnosis of SLE from two Leeds Cohort databases (CONVAS and DEFINITION) for over 30 years follow-up. Data collection included demographics, clinical characteristics, the 2019 EULAR/ACR classification criteria score, the SLEDAI-2K score, and routine immunological tests. The primary endpoint was the time from SLE diagnosis to initiation of intensive therapy (cyclophosphamide, rituximab, belimumab, or other biologic agents). Univariable analysis (UVA) and multivariable (MVA) Cox proportional hazards regression models were used to test the potential predictors of the primary endpoint. MVA was done using forward selection and backward elimination with p<0.1 associated with the deviance used for inclusion in and exclusion from the model. Results 229 SLE patients were included, and baseline characteristics are summarised in table 1. Total follow-up 3448 patient-years; median (IQR) follow up time was 11.6 (6.7, 21.4) years. Intensive therapy was initiated in 110 (48%) patients. The median (IQR) time to intensive therapy was 2 (0.5,8) years. Rituximab was the most common intensive therapy followed by cyclophosphamide (51.8% and 40.9%, respectively). In UVA, factors associated with increased risk of intensive therapies requirement were antibodies positivity for anti-Ro, anti-Sm and anti-RNP, cumulative number of Ab positivity, low complement levels, 2019 EULAR/ACR criteria score>=20, and higher cSLEDAI-2K score. While in MVA, anti- Ro+, low complement levels, and higher cSLEDAI-2K were associated with increased risk of intensive therapies requirement. Conclusions Nearly half of SLE patients required intensive therapy and this was predicted by anti-Ro+, low complement levels, and high clinical-SLEDAI-2K score at SLE diagnosis. At present, it is unclear whether patients should receive initial antimalarials, then immunosuppressants, then biologic therapies, or whether some patients should receive a first-line biologic therapy. Our data suggest that patients with these predictive factors develop more severe SLE, fail conventional therapies, and therefore are suitable for first-line biologic therapy. If our results can be validated, then such a strategy may prevent severe SLE.

Journal

Lupus Science and Medicine