POS0253 RITUXIMAB-BIOSIMILAR FOR ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODIES-ASSOCIATED VASCULITIS: EXPERIENCE OF A SINGLE ITALIAN CENTER
Authors: S. Sartorelli, A. Cariddi, L. Moroni, E. Baldissera, E. Bozzolo, L. Dagna
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rituximab (RTX), an anti-CD20 monoclonal antibody, represents a valuable treatment for anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). RTX biosimilar CT-P10 (RTX-B) has been approved in Europe in all indications held by RTX originator (RTX-O). As stated by recent international consensus-based recommendations, 1 there is evidence regarding safety and efficacy of biosimilars in the context of rheumatic diseases, but it is encouraged to gather additional data. 2,3 Objectives: To report the experience of a single Italian center with RTX-B in AAV in terms of safety and efficacy. Methods: We retrospectively reviewed the charts of all AAV patients followed up in our Small Vessel Vasculitis Clinic and we selected those who received RTX-B between October 2017 and May 2020, both naïve to RTX (RTX-Bn) or already treated with ≥1 course of RTX-O and switched to RTX-B (RTX-Bs). Baseline features, disease outcome, concomitant therapy and adverse events 6 (T6), 12 (T12) and 24 (T24) months after RTX-B introduction, when available, were collected. Non-parametric statistic tests were used. Results: Fifty-six AAV patients (44 [78.6%] granulomatosis with polyangiitis (GPA), 12 [21.4%)] microscopic polyangiitis (MPA)) received RTX-B with a median follow up of 20 (IQR 10-24) months. ANCA were positive in 49 (87.5%) patients. Ten (17.9%) patients were newly diagnosed with AAV, while 23 (41.1%) had refractory disease and another 23 had relapsing disease. Thirty-three (58.9%) patients were RTX-Bs, whereas 23 (41.1%) RTX-Bn. In 29 (51.8%) patients RTX was decided because of remission induction, while in 27 (48.2%) as maintenance regimen. Median cumulative RTX-B dose was 2.5 (2-3.875) grams with 3 (IQR 2-4) median courses. AAV activity, adverse events and concomitant therapy at T6, T12 and T24 are shown in Table 1. One GPA patient died of severe infection 3 months after a single infusion of RTX-B 500 mg as maintenance therapy. Table 1. AAV activity, concomitant therapy and adverse events at T0, T6, T12 and T24. T0 T6 T12 T24 n (%) 56 (100) 52 (92.6) 40 (71.4) 18 (32.1) Dose RTX-B, median (IQR) grams 1.75 (0.5-2) 0.5 (0.5-1) 0.5 (0.5-1) 0.5 (0.5-1) Concomitant prednisone therapy, n (%) 42 (75) 27 (48.2) 13 (32.5) 4 (22.2) Dose prednisone, median (IQR) milligrams/day 5 (5-15.625) 2.5 (2.5-5) 3.75 (2.75-7.5) 2.75 (1.56-4.5) Concomitant bDMARDs, n (%) 10 (17.9) 5 (9.6) 3 (7.5) 1 (5.6) Refractoriness NA 4 (7.7) 2 (5) 1 (5.6) Relapse NA 0 (0) 3 (7.5) 2 (11.1) Remission NA 48 (92.3) 35 (87.5) 15 (83.3) Suspension NA 10 (19.2) 9 (22.5) 4 (22.2) Infusion reaction, n (%) 1 (1.8) 1 (1.9) 0 (0) 0 (0) Infectious adverse events, n (%) NA 10 (19.2) 6 (15) 3 (16.7) Severe infectious adverse events, n (%) NA 2 (3.8) 1 (2.5) 0 (0) Considering the 52 (92.6%) patients who reached a 6 months-follow up, we marked a significant decrease of number of patients on steroid therapy (39 [75%] vs 27 [51.9%]; p=0.003), of median prednisone daily dose (5 [IQR 5-25] vs 2.5 [IQR 1.25-5 mg; p=0.001) and of number of patient on concomitant bDMARDs (10 [19.2%] vs 5 [9.6%]; p=0.003). Analysing the 40 (71.4%) patients who reached a 12 months-follow up, we confirmed the tendency with a decrease of number of patients on steroid therapy (29 [72.5%] vs 13 [32.5%]; p=0.007), of median prednisone daily dose (5 [IQR 5-12.5] vs 3.75 [IQR 2.75-7.5]; p=0.008) and of number of patient on concomitant bDMARDs (9 [22.5%] vs 3 [7.5%]; p=0.009). No statistically significant difference was found for the same variables comparing T0 versus T24. Conclusion: Our experience with RTX-B is limited; however, it represents an extensive report about the use of RTX-B in AAV patients and confirmed that it may be a well-tolerated and effective therapy in AAV setting, in agreement with previous evidence on RTX-O. Prospective and larger studies are needed to confirm this preliminary evidence. References: [1]Kay J, et al. Ann Rheum Dis 2018;77:165–74. [2]Kwon HC, et al. Yonsei Med J 2020;61:712-9. [3]Mittal S, et al. Clin Rheumatol 2021;40:645-51. Disclosure of Interests: Silvia Sartorelli: None declared, adriana cariddi: None declared, Luca Moroni: None declared, Elena Baldissera Speakers bureau: Pfizer, Roche, Sanofi-Genzyme, Consultant of: Novartis, Enrica Bozzolo: None declared, Lorenzo Dagna Consultant of: Abbvie, Amgen, Biogen, BristolMyers Squibb, Celltrion, Galapagos, GlaxoSmithKline, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unrestricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merk Sharp &amp; Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.