van Schaik Mieke, Arends Eline J, Wetzels Marjolein J A L, Kraaij Tineke, Verbruggen Stéphanie H, van der Kooij Sandra W, Kamerling Sylvia W A, Huizinga Tom, Goekoop Robbert J, van Kooten Cees, Rabelink Ton, Teng Y K Onno
Center of Expertise for Lupus, Vasculitis and Complement-mediated Systemic disease (LuVaCs), Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Lupus Sci Med. 2025 Feb 12;12(1):e001424. doi: 10.1136/lupus-2024-001424.
Combination therapy with rituximab and belimumab is a novel treatment strategy for severe SLE and lupus nephritis. Phase II studies have shown promising results, although long-term data are currently lacking. To address this, we analysed outcomes of patients with severe treatment-refractory SLE who previously participated in the phase II Synbiose Study, with a particular focus on immunological parameters.
Eight patients continued belimumab treatment beyond the 2-year duration of the original trial. We conducted a descriptive study to evaluate the course of treatment and immunological parameters over an extended follow-up. Our analyses include blood cell counts, immunoglobulins, autoantibodies, complement markers and clinical disease activity parameters. Additionally, we examined long-term effects on the B cell compartment employing high-sensitivity flow cytometry.
Over a median follow-up period of 6.8 years, six out of eight previously treatment-refractory patients maintained long-term clinical remission, while two experienced a major flare. Among those in remission, two patients achieved immunosuppression-free remission, and four continued belimumab. Long-term effects on humoral (auto-)immunity were a persistent decrease in IgM levels, while IgG normalised. Most patients maintained low autoantibody titres, and complement markers remained normal. On the cellular level, belimumab treatment after rituximab prevented B cell repopulation. Notably, patients exhibited a stable reduction of double-negative (DN) B cells, irrespective of continuing or stopping belimumab.
Long-lasting remission was observed in patients with SLE following combination treatment with rituximab and belimumab. We observed no significant hypogammaglobulinaemia and, notably, persistent reduction of DN B cells.
利妥昔单抗与贝利尤单抗联合治疗是重度系统性红斑狼疮（SLE）和狼疮性肾炎的一种新型治疗策略。II期研究已显示出有前景的结果，尽管目前缺乏长期数据。为解决这一问题，我们分析了先前参与II期Synbiose研究的重度难治性SLE患者的结局，特别关注免疫参数。
8名患者在原试验的2年疗程后继续接受贝利尤单抗治疗。我们进行了一项描述性研究，以评估延长随访期内的治疗过程和免疫参数。我们的分析包括血细胞计数、免疫球蛋白、自身抗体、补体标志物和临床疾病活动参数。此外，我们采用高灵敏度流式细胞术检查了对B细胞区室的长期影响。
在中位随访期6.8年期间，8名先前难治性患者中有6名维持长期临床缓解，而2名经历了严重病情复发。在缓解的患者中，2名患者实现了无免疫抑制缓解，4名继续使用贝利尤单抗。对体液（自身）免疫长期影响是IgM水平持续下降，而IgG恢复正常。大多数患者维持低自身抗体滴度，补体标志物保持正常。在细胞水平上，利妥昔单抗治疗后使用贝利尤单抗可防止B细胞再增殖。值得注意的是，无论继续或停止使用贝利尤单抗，患者的双阴性（DN）B细胞均持续稳定减少。
利妥昔单抗与贝利尤单抗联合治疗的SLE患者观察到持久缓解。我们未观察到明显的低丙种球蛋白血症，值得注意的是，DN B细胞持续减少。
