PMS41 The Challenges Of Comparing Therapeutic Responses Of Systemic Lupus Erythematosus (SLE) Treatments: A Network Meta-Analysis (NMA) On Two Composite Endpoint

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multisystemic involvement. There are no established guidelines to evaluate treatment responses, which makes evaluation of potential SLE interventional treatments challenging. Composite endpoints (CEPs) have been developed to detect therapeutic effects across different disease manifestations. The most commonly used CEPs are SLE Responder Index (SRI-4) and the British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA); the comparability of response levels measured by these two CEPs is not demonstrated. A systematic literature review identified five randomized-controlled trials which investigated 11 active treatments by assessing both SRI-4 and BICLA after 48/52 weeks. A random-effects meta-analysis using a binomial likelihood model was conducted for both CEPs. Treatments were ranked using the surface under the cumulative ranking (SUCRA) curve. SUCRA values range between 0 and 1, with a higher value indicating a higher likelihood of a treatment to be the most effective option. The range of SUCRA values was wider using BICLA (35%–60%) than for SRI-4 (42%–55%), indicating a difference in sensitivity between both endpoints when capturing treatment responses. Treatment rankings varied between both CEPs with the treatment ranked most effective using BICLA (SUCRA=59.7%), only ranked fifth when compared using SRI-4 (SUCRA=47.5%). The second-best treatment in the BICLA comparison (SUCRA=51.7%) was ranked the second-worst in the SRI-4 comparison (SUCRA=41.7%). The treatment ranked first in the SRI-4 comparison (SUCRA=54.6%) occupied the third rank in the BICLA comparison (SUCRA=49.0%). Treatment rankings differed between the two analysed CEPs. This highlights the need for future research to increase the understanding of the unique attributes of the CEPs when considering potential treatments. The difference in sensitivity between CEPs to evaluate and compare therapeutic responses should be considered if indirect treatment comparisons are conducted to appropriately inform formal value assessments and reimbursement decision-making for future interventions in SLE.