PREEXISTING ANTIBODIES AGAINST VACCINE ANTIGENS ARE PRESERVED IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND SJÖGREN’S DISEASE UPON IANALUMAB TREATMENT WHILE AUTOANTIBODIES DECLINE

O062 / #591 Topic: AS24 - SLE-Treatment ABSTRACT CONCURRENT SESSION 10: INTEGRATING PROTEOMIC & TRANSCRIPTOMICS IN SLE 24-05-2025 10:40 AM - 11:40 AM Background/Purpose Ianalumab, an afucosylated monoclonal antibody, depletes B cells through enhanced antibody-dependent cellular cytotoxicity with concurrent blockade of B-cell-activating factor (BAFF):BAFF-receptor (BAFF-R) mediated signals.[1] It is currently being investigated for the treatment of immune-mediated diseases. Given its novel mechanism of action, it is crucial to assess the effects of ianalumab on preexisting antibodies against vaccine antigens. Herein, we evaluated the impact of ianalumab treatment vs placebo on preexisting antibody levels against 7 pathogens in patients with systemic lupus erythematosus (SLE) and Sjögren’s disease (SjD). Methods A retrospective analysis was conducted on serum samples from 2 randomized, double-blind, placebo-controlled phase 2 studies in patients with SjD ( NCT02962895 ) or SLE ( NCT03656562 ). Patients received either placebo or ianalumab 300 mg subcutaneous monthly for 24 weeks (79 patients with SjD) or for 28 weeks (40 patients with SLE). In the SjD study, patients on 300 mg ianalumab at Week 24 (W24) were re-randomized to receive double-blinded monthly ianalumab 300 mg or placebo until W52. Patients on placebo at W24 were switched to a lower ianalumab dose and were not subject to further testing in this analysis. In the SLE study, all patients switched from double-blind to open-label ianalumab up to W52. Antibodies (IgG isotypes) to vaccine antigens and autoantibodies were measured at baseline, W24 (SjD) or W28 (SLE) and W52. Changes in antibody levels from baseline and proportions of patients maintaining protective levels at W52 were assessed. A total of 3 patients (2 SjD and 1 SLE) received booster doses against diphtheria and tetanus toxoid (TTd) under ianalumab treatment. Results The proportion of patients with SjD and SLE maintaining protective levels of antibodies against TTd, measles, mumps, varicella, rubella, diphtheria and influenza remained stable after ianalumab treatment up to 52 weeks. In patients with SjD, the changes from baseline to W24 were <6% for all antigens in both ianalumab- and placebo-treated patients. In patients with SLE, the changes from baseline to W28 were <10% in both ianalumab- and placebo-treated patients for all antigens besides diphtheria (Figure 1). For diphtheria, up to 18% changes were observed under ianalumab treatment, likely due to the low level of preexisting protection (<50% of patients had protective levels at baseline). In contrast, several autoantibodies showed a significant reduction in ianalumab-treated patients (eg, up to 60% reduction of anti-ribosomal P antibodies at W28) compared to placebo (Figure 1). These results are in line with the ability of ianalumab to deplete memory and antibody-producing cells,[2] while likely not affecting the long-lived bone marrow plasma cells that do not express BAFF-R.[3] Among the 3 patients who received booster dose(s) against diphtheria and TTd during ianalumab treatment, 2 showed a subsequent increase in corresponding titers, whereas the other patient received the booster only 10 days before W52 sampling, likely explaining the lack of increased titers. Figure 1. Titers from vaccine antigens and auto-antibody titers following treatment with ianalumab or placebo over time in patients with SLE. Ratio to baseline of antibodies to vaccine antigens and autoantibodies were measured over time in patients with SLE treated with placebo vs ianalumab. All antibodies measured were IgG. Conclusions Treatment with ianalumab up to 52 weeks did not result in a reduction of the antibody titers to previous immunizations against tetanus, varicella, measles, mumps, rubella, diphtheria, and influenza while having a clear impact on autoantibody levels. References: [1.] McWilliams EM. Blood Adv 2019;3(3):447-60. [2.] Dörner T. Ann Rheum Dis 2024;83:956-7. [3.] Darce JR. J Immunol 2007;179(11):7276-86.