FRI0175 PREDICTORS OF LOW DISEASE ACTIVITY AND CLINICAL REMISSION FOLLOWING BELIMUMAB TREATMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Ioannis Parodis, Petter Johansson, Alvaro Gomez, Sofia Soukka, Sharzad Emamikia, Katerina Chatzidionysiou
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Post-hoc analyses of the pivotal phase III clinical trials of belimumab BLISS-52 and BLISS-76 have revealed superiority of belimumab over placebo in systemic lupus erythematsus (SLE) patients with high baseline disease activity, positive anti-double stranded (ds)DNA titres and low complement levels, as well as in patients receiving corticosteroids (1). Later, real-life observations demonstrated that established organ damage prior to treatment initiation predicted reduced belimumab efficacy based on the SLE Responder Index 4 (SRI-4) (2), which was recently corroborated in a post-hoc analysis of data from the BLISS trials (3). From a clinical point of view, clinical remission and low disease activity are more meaningful targets than reduced SLE activity (SRI-4). <h3>Objectives:</h3> To identify predictors of low disease activity and clinical remission following belimumab treatment in patients with SLE. <h3>Methods:</h3> SLE patients who received belimumab 10 mg/kg (N=563) in the BLISS-52 and BLISS-76 clinical trials were surveyed. Access to data was granted by GlaxoSmithKline. The performance of baseline factors in predicting attainment of low disease activity defined as Lupus Low Disease Activity State (LLDAS) (4) or clinical remission defined as clinical (c)SLEDAI-2K=0 at week 52 from treatment initiation was evaluated using logistic regression. Organ damage was assessed using the SLICC/ACR Damage Index (SDI). <h3>Results:</h3> We demonstrated a negative impact of established organ damage on attainment of LLDAS (SDI&gt;0; OR: 0.44; 95% CI: 0.22–0.90; P=0.024) and the primary LLDAS condition, i.e. SLEDAI-2K≤4 with no renal activity, pleurisy, pericarditis or fever (SDI&gt;1; OR: 0.46; 95% CI: 0.27–0.77; P=0.004); cognitive impairment/psychosis was found to mainly account for the latter association. Baseline SDI scores&gt;1 predicted failure to attain cSLEDAI-2K=0 (OR: 0.53; 95% CI: 0.30–0.94; P=0.030), with cutaneous damage mainly driving this association. Anti-dsDNA positivity increased (OR: 1.82; 95% CI: 1.08–3.06; P=0.025) and cardiovascular damage reduced (OR: 0.13; 95% CI: 0.02–0.97; P=0.047) the probability to attain cSLEDAI-2K=0 with the daily prednisone equivalent intake restricted to ≤7.5 mg. <h3>Conclusion:</h3> Belimumab might be expected to be more efficacious in inducing low disease activity and clinical remission in SLE patients with limited or no organ damage accrued prior to treatment initiation. Patients with positive anti-dsDNA titers might be more likely to achieve clinical remission along with limited or no corticosteroid use. The findings contribute to a better selection of SLE patients expected to benefit from belimumab, and provide useful information towards refinement of SLE treatment recommendations. <h3>References:</h3> [1] van Vollenhoven RF, Petri MA, Cervera R, et al. Ann Rheum Dis 2012. [2] Parodis I, Sjowall C, Jonsen A, et al. Autoimmun Rev 2017. [3] Parodis I, Gomez A, Emamikia S, et al. Ann Rheum Dis 2019. [4] Franklyn K, Lau CS, Navarra SV, et al. Ann Rheum Dis 2016. <h3>Acknowledgement:</h3> The authors would like to thank GlaxoSmithKline (Uxbridge, UK) for granting access to the data from the BLISS-52 and BLISS-76 trials (ClinicalTrials.gov identifiers NCT00424476 and NCT00410384, respectively) through the Clinical Study Data Request (CSDR) consortium. <h3>Disclosure of Interests:</h3> None declared