Efficacy of belimumab in SLE with hematological manifestations: retrospective analysis from the BeRLiSS-JS cohort

Background and aim Belimumab is a monoclonal antibody directed against Blys, approved for the treatment of SLE. It has been proved effective particularly for serological, cutaneous, articular and renal manifestations. Treatment of hematological manifestations often lacks specific therapies, particularly during maintenance. We aimed to investigate the potential efficacy of belimumab in the treatment of anemia, thrombocytopenia and lymphopenia in SLE. Methods We performed a retrospective analysis on BeRLiSS-NeJS cohort, considering only patients who, at baseline, presented with anemia, thrombocytopenia and lymphopenia (BILAG grade C definition). Study period spans from June 2013 to May 2024. Clinical and laboratory variables were collected at baseline and every six months. They included SLEDAI- 2K, fatigue (VAS 0-10), daily GC intake (PDN equivalents), CBC, anti-dsDNA antibodies, C3, C4, and concomitant medications. Anemia, thrombocytopenia and lymphopenia responders were defined as patients achieving Hb>10.9 g/dl, Plts>150×10^9/L, Lym>1×10^9/L, respectively. For evaluating predictors of anemia, thrombocytopenia and lymphopenia resolution we used multivariate regression models. Results Baseline characteristics of patients included in the study are reported in Table 1. According to inclusion criteria, 76, 44 and 104 patients with anemia, thrombocytopenia and lymphopenia, respectively, were included; follow-up up to month 48 was available in, respectively, 33, 20 and 86 patients. Hb, Plt and Lym values significantly increased, among patients with low Hb, Plt and Lym count from baseline to month 48 (p< 0.001, p=0.004, p< 0.001), independently of IS use (p= 0.98, p=0.12, p=0.86 respectively). Hb value, Plt Lym count normalization was achieved at 48 months respectively by 63.6%, 55%, and 64.6% of patients respectively. Lymphopenic (but not anemic or thrombocytopenic patients, regarding Hb and Plt values), patients treated with AM displayed on average higher Lym values (p=0.042), but AM use did not influence significantly Hb, Plt and Lym values trends during follow up (p= 0.68, p=0.53 and p=0.64). Mean GC dose among patients with low Hb, Plt and Lym counts, significantly declined during follow up (p=0.003, p=0.004, p <0.001 respectively). GC users, among patients with low Hb, Plt and Lym count, tended to decrease, during follow up, respectively from 73, (96.1%) to 17 (60.7%); from 42 (93.1%) to 16 (80%); from 103 (96.3%) to 26 (70.3%). Anemia resolution at 12 months was associated with: shorter disease duration (OR 0.93, 95%CI 0.87-0.99, p=0.022) and use of IS (OR 20.7, CI 1.45–287.26, p=0.024); lymphopenia resolution at 12 months was associated with anti-Sm (OR 0.132, C.I. 0.035– 0.491, p 0.003), anti-SSA seropositivity (OR 0.23, C.I. 0.075 – 0.702, p 0.01), C4 values (OR 1.162, C.I. 1.037 – 1.301, p 0.009). Adverse events (AE) and infectious-AE (i-AE) occurred more frequently among patients with lymphopenia at baseline (p <0.001 for both). I-AE occurred significantly earlier among patients with lymphopenia at baseline (p=0.0058). Discontinuations due to AE were similar between the two groups (p=0.11). Conclusion Belimumab demonstrated significant efficacy in improving anemia, thrombocytopenia and lymphopenia in a real-world cohort of SLE patients, independently of concurrent IS or AM use. These findings suggest a potential role in addressing these hematologic manifestations of SLE. The observed improvement in Hb, Plt and Lym values is likely attributable to better disease control, reduction of systemic inflammation and to a decrease of circulating autoantibodies. A decreased need for corticosteroids was also observed and mean GC daily doses at 48 months (end of follow up period) were below 5 mg/d across the three groups. Larger, prospective studies are warranted to confirm these observations and further elucidate the mechanisms underlying BEL impact on anemia, thrombocytopenia and lymphopenia.