Enhancing systemic lupus erythematosus treatment outcomes with an early initiation of belimumab: insights from a multicenter retrospective study within the first five years

Abstract

Background: The human monoclonal antibody belimumab (BEL) has emerged as a promising treatment for systemic lupus erythematosus (SLE), particularly for reducing the need for glucocorticoids and minimizing organ damage. The optimal timing of BEL initiation has been unclear; emerging evidence suggests that early intervention with BEL, particularly within the first 5 years of diagnosis, may yield better outcomes by modulating disease progression and reducing flare frequency. Understanding the relationship between disease duration and BEL efficacy is essential for the development of tailored strategies.

Patients and methods: We analyzed patients with SLE treated at our hospital and associated facilities who were diagnosed according to the 1997 ACR or 2012 SLICC criteria and who began BEL treatment between December 2017 and August 2021. Patients who were followed for ≥ 12 months after BEL initiation were included. We investigated the changes in the patients' Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores at 3, 6, 9, and 12 months after the introduction of BEL, comparing patients with disease durations ≤ 5 years to those with > 5 years. A mixed-effects model was adjusted for the patients' ages, prednisolone dosages, initial SELENA-SLEDAI scores, Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI), hydroxychloroquine use, and lupus nephritis. Clinical manifestations including arthritis, skin lesions, and hematological abnormalities were monitored to assess the broader impacts of BEL.

Results: One hundred eleven patients were initially registered; among them, 97 patients were included in the final analysis. The study population (mean age, 41 years; mean SELENA-SLEDAI, 7 points; 51% using hydroxychloroquine) included 19 patients with a ≤ 5-year SLE duration and 78 with SLE durations > 5 years. The baseline SELENA-SLEDAI scores were higher in the ≤ 5-year group (p = 0.047), indicating more active disease. Patients with ≤ 5 years of disease had significantly greater improvements in SELENA-SLEDAI scores at 6, 9, and 12 months (p < 0.05).

Conclusions: These results highlight the importance of early BEL initiation in SLE, demonstrating that patients with shorter disease durations achieve more substantial improvements in disease activity with early BEL treatment. Our findings also reveal the potential benefits of early BEL intervention and suggest that incorporating the disease duration into treatment decisions may optimize patient outcomes.

Keywords: B cell therapy; Belimumab; Disease duration; Early intervention; SELENA-SLEDAI; Systemic lupus erythematosus.

Fig. 1

Flow diagram of the study's patient registration and inclusion

Fig. 2

The rates of belimumab (BEL) continuation among the 97 patients with SLE (those with a disease duration ≤ 5 years or > 5 years at the time of belimumab initiation)

Fig. 3

Changes in the patients' SELENA-SLEDAI scores after the introduction of belimumab (BEL) treatment in patients with different durations of SLE. The reduction in SELENA-SLEDAI scores at 3, 6, 9, and 12 months in the two groups (disease duration ≤ 5 years and > 5 years at the time of belimumab introduction) was compared using a mixed-effects model included the following adjustment variables: age at BEL initiation, prednisone (PSL) dose, SELENA-SLEDAI score at BEL initiation, Systemic Lupus International Collaborating Clinics damage index (SDI) at BEL initiation, hydroxychloroquine (HCQ) use/non-use, and the presence of lupus nephritis (LN). Error bar: standard deviation. **p < 0.01