Clinical response trajectories and drug persistence in systemic lupus erythematosus patients on belimumab treatment: A real-life, multicentre observational study

Abstract

ObjectiveTo obtain real-world data on outcomes of belimumab treatment and respective prognostic factors in patients with systemic lupus erythematosus (SLE).MethodsObservational study of 188 active SLE patients (median disease duration 6.2 years, two previous immunosuppressive/biological agents) treated with belimumab, who were monitored for SLEDAI-2K, Physician Global Assessment (PGA), LLDAS (lupus low disease activity state), remission (DORIS/Padua definitions), SELENA-SLEDAI Flare Index, SLICC/ACR damage index and treatment discontinuations. Group-based disease activity trajectories were modelled followed by multinomial regression for predictive variables. Drug survival was analysed by Cox-regression.ResultsAt 6, 12 and 24 months, LLDAS was attained by 36.2%, 36.7% and 33.5%, DORIS-remission by 12.3%, 11.6% and 17.8%, and Padua-remission by 21.3%, 17.9% and 29.0%, respectively (attrition-corrected). Trajectory analysis of activity indices classified patients into complete (25.5%), partial (42.0%) and non-responder (32.4%) groups, which were predicted by baseline PGA, inflammatory rash, leukopenia and prior use of mycophenolate. During median follow-up of 15 months, efficacy-related discontinuations occurred in 31.4% of the cohort, especially in patients with higher baseline PGA (hazard ratio [HR] 2.78 per 1-unit; 95% CI 1.32-5.85). Conversely, PGA improvement at 3 months predicted longer drug retention (HR 0.57; 95% CI 0.33-0.97). Use of hydroxychloroquine was associated with lower risk for safety-related drug discontinuation (HR 0.33; 95% CI 0.13-0.85). Although severe flares were reduced, flares were not uncommon (58.0%) and contributed to treatment stops (odds ratio [OR] 1.73 per major flare; 95% CI 1.09-2.75) and damage accrual (OR 1.83 per mild/moderate flare; 95% CI 1.15-2.93).ConclusionsIn a real-life setting with predominant long-standing SLE, belimumab was effective in the majority of patients, facilitating the achievement of therapeutic targets. Monitoring PGA helps to identify patients who will likely benefit and stay on the treatment. Vigilance is required for the prevention and management of flares while on belimumab.

Evaluating the real-world effectiveness of belimumab in patients with SLE using SLE-related laboratory values and rheumatoid arthritis-derived disease activity measures: RAPID3, swollen joint count and tender joint count

“… 26 In another observational analysis of patients with long-standing disease, most patients treated with belimumab demonstrated a gradual decrease in SLEDAI-2K score over 6–12 months while a minority experienced a rapid decrease over 3–6 months. 28 In the present study, the proportion of patients who achieved improvements in RAD disease activity measures increased the most within the first 6 months. However, the proportion continued to increase for the remainder of the on-treatment follow-up period, and trajectory analyses suggest that the full treatment benefit of belimumab continues to be evident after the first 6 months, according to RAD disease activity measures.…”

Glucocorticoid-free remission in patients with SLE in the era of biologics: Immune complex disease is likely to benefit from current medications

“…27 Two cohort studies in Japan showed 1 year treatment with belimumab significantly reduced average dose of PSL from 4.4 ± 2.9 mg to 2.2 ± 2.7 mg 28 and median dose from 8.9 mg (interquartile range 6.0-15.0) to 5.0 mg (2.0-7.0). 29 Large cohort studies on belimumab showed a glucocorticoid discontinuation rate of 7.5-10.2% in half year, [30][31][32] 10.9-15.4% in 1 year, 32,33 and 25.6% in 2 years. 32 Although there have been fewer real-world observations for anifrolumab, a long-term extension study of phase III trials showed that the rates of glucocorticoid discontinuation in the anifrolumab group were 25.9% at 1 year and 36.6% at 4 years compared to 20.5% and 26.8%, respectively, in the placebo group.…”

EULAR recommendations for the management of systemic lupus erythematosus: 2023 update

“…Since 2019, anifrolumab was approved for the treatment of extrarenal SLE in 2021. On the other hand, there is now more than 10 years real-life experience with belimumab, with results confirming good control of disease activity, reduction of flares and halting of damage accrual 111 112. The two drugs have a different mechanism of action and have not been directly compared.…”