EARLY (3 MONTHS) IMPROVEMENT IN PHYSICIAN GLOBAL ASSESSMENT OF DISEASE ACTIVITY PREDICTS LONG-TERM RETENTION OF BELIMUMAB TREATMENT IN SLE: A MULTICENTRE OBSERVATIONAL STUDY OF 184 PATIENTS

BackgroundBelimumab has been introduced in the management of SLE for more than 10 years, however long-term efficacy and safety data are still limited and mostly derive from the extended phase of randomized clinical trials.ObjectivesTo evaluate the long-term survival of belimumab treatment, reasons for treatment cessation and associated predictors in routine care setting.MethodsMulticentre observational study of adult SLE patients who were treated with belimumab according to physician discretion and in line with the EULAR recommendations. Disease activity (Physician Global Assessment [PGA]: scale 0-3; SLE disease activity index-2000 [S2K]), flares (SELENA-SLEDAI Flare Index), organ damage (SLICC damage index [SDI]), co-administered treatments and dosage, adverse events and causes of belimumab discontinuation were monitored prospectively at 3–6-month intervals. Cox-regression analysis was performed to identify factors associated with reduced drug survival.ResultsA total 184 patients treated with belimumab for at least 3 months were included (women 95.6%; mean ± SD age 48.8 ± 13.4 years; disease duration 9.2 ± 11.3 years). Baseline S2K and PGA were 7.5 ± 3.0 and 1.64 ± 0.42, respectively, both demonstrating significant improvement at 6 months (4.5 ± 3.5 and 1.02 ± 0.69, respectively; p<0.001) and 12 months (3.5 ± 3.1 and 0.68 ± 0.55, respectively; p<0.001). Of patients receiving glucocorticoids at onset, 49.0% tapered the dose and 17.6% completely withdrew them. After a median (interquartile range) follow-up of 15.1 (16.9) months, 44.0% of patients discontinued belimumab due to suboptimal efficacy as judged by the treating physician (28.3%), adverse events (including infections) (9.8%) or other causes (e.g., pregnancy, patient decision). Accordingly, efficacy-related drug survival rates at 1 and 2 years were 70% and 61%, respectively, with corresponding safety-related survival rates of 94% and 87%, respectively. Baseline factors associated with belimumab discontinuation due to suboptimal efficacy included PGA >1.50 (hazard ratio [HR] 3.66; 95% confidence interval [95% CI] 1.14–11.73; p=0.029) and severe (RA-like) arthritis (HR 2.56; 95% CI 1.16–5.68; p=0.020) but not disease duration, use of glucocorticoids, active serology or organ damage. Notably, patients with early (3 months) improvement (i.e., any decrease in PGA) showed significantly lower risk for treatment cessation (HR 0.38; 95% CI 0.22–0.67; p=0.001) (Figure 1) and this effect was independent of the initial PGA level. Baseline use of hydroxychloroquine was associated with prolonged safety-related belimumab survival (HR 0.32; 95% CI 0.12–0.88; p=0.028).Figure 1.Efficacy-related survival of belimumab according to improvement or not of PGA at 3 months since treatment initiation.ConclusionIn real-life setting, about 28% of SLE patients discontinue belimumab due to suboptimal treatment response per physician judgement, especially those with moderate-to-high activity and severe arthritis. Improvement in PGA at 3 months predicts long-term drug maintenance, therefore suggesting its value for patient monitoring. Our data confirm the very good tolerability of belimumab and identify hydroxychloroquine co-administration as a predictor for prolonged safety-related drug survival.AcknowledgementsThe study was partly funded by the Greek Rheumatology Society and the Greek Association of Professional Rheumatologists (ERE-EPERE) and by Pfizer Global Medical GrantsDisclosure of InterestsMyrto Nikoloudaki: None declared, Dionysis Nikolopoulos: None declared, SOFIA KOUTSOVITI: None declared, Irini Flouri: None declared, Noemin Kapsala: None declared, ARGYRO REPA: None declared, PELAGIA KATSIMPRI: None declared, EVANGELOS THEOTIKOS: None declared, Sofia Pitsigavdaki: None declared, Katerina Pateromichelaki: None declared, Anastasios Eskitzis: None declared, ANTONIA ELEZOGLOU: None declared, Prodromos Sidiropoulos: None declared, Antonis Fanouriakis: None declared, Dimitrios Boumpas: None declared, George Bertsias Speakers bureau: GSK, AstraZeneca, Pfizer, SOBI, UCB, Novartis, AENORASIS, Abbvie, Grant/research support from: GSK, Pfizer