AB1202 SUCCESSFUL LONG-TERM TREATMENT OF SYSTEMIC SCLEROSIS BY HIGH-FREQUENT, LOW-DOSE B CELL DEPLETING THERAPY
Authors: F. Moazedi-Fuerst, A. Lackner, S. Kreuzer, K. Eller, G. Kovacs, H. Flick, O. Balazs, E. Talakic, J. Hermann, N. Venhoff, A. Venhoff, P. Jud, B. Yazdani-Biuki, M. Brodmann, W. Salmhofer, R. Husic, M. Stradner, W. Graninger, J. Thiel, H. P. Brezinsek
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic sclerosis (SSc) is a multiorgan disease, that frequently affects the skin and involves the lung in up to 70 percent of cases with a 10 years mortality rate in SSc up to 50 percent. B cell-depleting therapy with rituximab (RTX) seems to be effective in the treatment of SSc, but data from randomized controlled trials (RCTs) are missing and there is no consensus on frequency and dosage of RTX in SSc. [1-3] <h3>Objectives:</h3> We aimed to assess the long-term efficacy and safety of quarterly administered RTX in SSc. <h3>Methods:</h3> Retrospective analyses of 40 consecutive systemic sclerosis patients suffering from interstitial lung disease and progredient skin involvement treated with rituximab twice within 14 days every three months from 2010-2020. Of RTX-treated patients 42.5 % were treated with RTX monotherapy and 47.5 with RTX in combination with other immunosuppressants. The patients' fulfilled the LeRoy and the ACR/EULAR Criteria for SSc. (4) Modified Rodnan skin score (mRSS), lung function test results, laboratory values including serum immunoglobulin (IgG, IgA, IgM) concentrations.[5] The clinical parameters are included in the EScSGAI and have been documented over time.[6] (Figure 1) <h3>Results:</h3> In total 40 SSc patients received RTX as described above over a median time of 3.9 years (1-10 years). A significant improvement in median mRSS (baseline: 19, month 24: 16, p&lt;0.001), as well as a stable predicted forced vital capacity (FVC) were observed from baseline to month 24. There were no new or unexpected safety signals especially regarding treatment-related infectious adverse events. Immunoglobuline concentrations stayed within the normal range and specific antibodies to pneumococcal polysaccharides were preserved despite of long term B cell depleting therapy. During the observation period of up to ten years none of the patients died. <i>(A) European Scleroderma Study Group Activity Index, (B) modified Rodnan Skin Score (mRss), (C) forced vital capacity (FVC) in percent predicted, and (D) diffusing lung capacity of carbonmonoxide (DLCO) in percent during RTX treatment. The number of patients treated is indicated by n, the duration of treatment on the x-axis by months. Median + 95%CI Significance was calculated using paired Wilcoxon Test.</i> <h3>Conclusion:</h3> <i>Conclusion</i>: SSc can be effectively and safely treated by 3-monthly, low-dose RTX. Controlled, randomized studies are needed to validate the advantage of continuous B cell depletion by 3-monthly low dose RTX application compared to other application intervals. <h3>REFERENCES:</h3> [1] Katsumoto TR, Whitfield ML, Connolly MK. The pathogenesis of systemic sclerosis. Annu Rev Pathol. 2011 Feb 28;6:509–37. [2] Moazedi-Fuerst FC, Kielhauser SM, Brickmann K, Hermann J, Lutfi A, Meilinger M, et al. Rituximab for systemic sclerosis: arrest of pulmonary disease progression in five cases. Results of a lower dosage and shorter interval regimen. Scand J Rheumatol [Internet]. 2014 Jan [cited 2015 Feb 25];43(3):2. [3] Maher TM, Tudor VA, Saunders P, Gibbons MA, Fletcher S V, Denton CP, et al. Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial. Lancet Respir Med. 2022 Jan; [4] van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum [Internet]. 2013 Nov [cited 2016 Mar 23];65(11):2737–47. [5] Venhoff N, Effelsberg NM, Salzer U, Warnatz K, Peter HH, Lebrecht D, et al. Impact of rituximab on immunoglobulin concentrations and B cell numbers after cyclophosphamide treatment in patients with ANCA-associated vasculitides. PLoS One. 2012 May 21;7(5). [6] Valentini G, Bencivelli W, Bombardieri S, D'Angelo S, Della Rossa A, Silman AJ, et al. European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. III. Assessment of the construct validity of the preliminary activity criteria. Ann Rheum Dis [Internet]. 2003 Sep [cited 2018 Oct 10];62(9):901–3. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>