Belimumab efficacy on different subsets of musculoskeletal features in patients with systemic lupus erythematosus treated in real world setting. Results from a multicentric, nationwide cohort (BeRLiSS-Joint)

Background. Belimumab is a monoclonal antibody that has long been used for the treatment of systemic lupus erythematosus (SLE) and has shown efficacy in managing the joint manifestations of the disease. Despite many studies on belimumab, none have so far analyzed in detail its efficacy in real-life on musculoskeletal manifestations in SLE. Aims. To evaluate the efficacy of belimumab on different joint manifestations of the disease in a nationwide prospective multicenter cohort (BeRLISS-Joint) of patients with systemic lupus erythematosus (SLE). Methods. In this retrospective observational study, we stratified adult SLE patients treated with belimumab (10 mg/kg/month IV or 200 mg/week SC) based on the joint phenotype (non-deforming non-erosive arthritis - NDNE, JA, and rhupus) at belimumab initiation. We analyzed the variation of DAS28 scores at baseline, 6, 12, 18, 24, 30 and 36 months of follow-up. The average daily dosage of glucocorticoids (prednisone equivalent) was analyzed at baseline and at 6, 12, 18, 24, 30, and 36 months of follow-up. Additionally, the glucocorticoid consumption stratified by daily dosage was analyzed at baseline and at 6, 12, 18, 24, 30, and 36 months of follow-up, but this analysis was limited to the cohort from Padua in this case. Parametric and nonparametric tests were used according to the data distribution. Results. A total of 443 patients from 14 Italian centers were enrolled (F=394; 88.9%); the mean age at diagnosis was 29.9±13.2 years, and the mean treatment duration was 52.2±38.0 months. At the initiation of belimumab treatment, 272 patients had joint manifestations (61.4%), of which: 221 had non-deforming non-erosive arthritis (NDNE) (81.3%), 30 had Jaccoud's arthropathy (JA) (11%), and 21 had rhupus (7.7%). The median DAS28 value significantly decreased from baseline to 6 months (p<0.001) and from 6 to 12 months (p=0.046) for NDNE, while it significantly decreased from baseline to 6 months for JA (p=0.005) and rhupus (p=0.011). For all three phenotypes, the decrease was also significant from baseline to 36 months (NDNE p<0.001, JA p<0.001, rhupus p=0.047). Regarding remission rates based on DAS28 < 2.6, the difference between phenotypes was significant at 6 months (p=0.002) and at 36 months (p=0.043). While the percentage of NDNE patients in remission increased over time, the percentage of JA and rhupus patients in remission showed irregular and less substantial improvement. Considering all phenotypes the mean glucocorticoid daily dosage decreased, reaching mean values of ≤ 5 mg/day as recommended by 2023 EULAR recommendations. Regarding glucocorticoid consumption stratified by daily dosage and joint involvement subtype in the cohort of patients from Padua, at baseline 32,5% of NDNE patients, 25% of JA patients, and 20% of rhupus patients were on 0,1-5 mg/day of glucocorticoids, whereas 5% of NDNE patients, 8.33% of JA patients and 0% of rhupus patients did not use glucocorticoids. At 36 months, more than 90% of patients of all three joint phenotypes had a dosage of ≤ 5 mg/day or did not use glucocorticoids. Specifically, 60,71% of NDNE patients, 40% of JA patients and 100% of rhupus patients were on 0,1-5 mg/day of glucocorticoids, whereas 32.14% of NDNE patients and 60% of JA patients did not use glucocorticoids. No rhupus patients completely discontinued the glucocorticoids. Conclusions. Belimumab was effective in reducing GC use and joint involvement activity at 6, 12, 18, 24, 30 and 36 months, with a significant decrease in DAS28 observable as early as 6 months from treatment initiation across all joint phenotypes.