First exposure to rituximab is associated to high rate of anti-drug antibodies in systemic lupus erythematosus but not in ANCA-associated vasculitis

Arthritis Research & Therapy

Anna Fogdell-Hahn¹  Nastya Kharlamova¹  Nicky Dunn¹  Malin Ryner¹  Annette Bruchfeld²  Vivianne Malmström³  Francesca Faustini⁴  Iva Gunnarsson⁴ 

[1] Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden;Center for Molecular Medicine, Stockholm, Sweden;Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden;University Hospital and Department of Renal Medicine, Karolinska University Hospital and CLINTEC Karolinska Institutet, Stockholm, Sweden;Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden;Center for Molecular Medicine, Stockholm, Sweden;Department of Medicine Solna, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden;Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden;

关键词: Rituximab;    Anti-drug antibodies (ADA);    Systemic lupus erythematosus;    ANCA-associated vasculitis;    Disease activity;    B cell counts;    ADA-screening;   

DOI  :  10.1186/s13075-021-02589-6

来源: Springer

【 摘 要 】

BackgroundAnti-drug antibodies (ADAs) can impact on the efficacy and safety of biologicals, today used to treat several chronic inflammatory conditions. Specific patient groups may be more prone to develop ADAs. Rituximab is routinely used for ANCA-associated vasculitis (AAV) and as off-label therapy for systemic lupus erythematosus (SLE), but data on occurrence and predisposing factors to ADAs in these diseases is limited.ObjectivesTo elucidate the rate of occurrence, and risk factors for ADAs against rituximab in SLE and AAV.MethodsADAs were detected using a bridging electrochemiluminescent (ECL) immunoassay in sera from rituximab-naïve (AAV; n = 41 and SLE; n = 62) and rituximab-treated (AAV; n = 22 and SLE; n = 66) patients. Clinical data was retrieved from medical records. Disease activity was estimated by the SLE Disease Activity Index-2000 (SLEDAI-2 K) and the Birmingham Vasculitis Activity Score (BVAS).ResultsAfter first rituximab cycle, no AAV patients were ADA-positive compared to 37.8% of the SLE patients. Samples were obtained at a median (IQR) time of 5.5 (3.7–7.0) months (AAV), and 6.0 (5.0–7.0) months (SLE). ADA-positive SLE individuals were younger (34.0 (25.9–40.8) vs 44.3 (32.7–56.3) years, p = 0.002) and with more active disease (SLEDAI-2 K 14.0 (10.0–18.5) vs. 8.0 (6.0–14), p = 0.0017) and shorter disease duration (4.14 (1.18–10.08) vs 9.19 (5.71–16.93), p = 0.0097) compared to ADA-negative SLE. ADAs primarily occurred in nephritis patients, were associated with anti-dsDNA positivity but were not influenced by concomitant use of corticosteroids, cyclophosphamide or previous treatments.Despite overall reduction of SLEDAI-2 K (12.0 (7.0–16) to 4.0 (2.0–6.7), p < 0.0001), ADA-positive individuals still had higher SLEDAI-2 K (6.0 (4.0–9.0) vs 4.0 (2.0–6.0), p = 0.004) and their B cell count at 6 months follow-up was higher (CD19 + % 4.0 (0.5–10.0) vs 0.5 (0.4–1.0), p = 0.002). At retreatment, two ADA-positive SLE patients developed serum sickness (16.7%), and three had infusion reactions (25%) in contrast with one (5.2%) serum sickness in the ADA-negative group.ConclusionsIn contrast to AAV, ADAs were highly prevalent among rituximab-treated SLE patients already after the first course of treatment and were found to effect on both clinical and immunological responses. The high frequency in SLE may warrant implementations of ADA screening before retreatment and survey of immediate and late-onset infusion reactions.

【 授权许可】

CC BY