THU0554 Rituximab (RTX) in paediatric diseases: describing its pharmacodynamics with a focus on b-cell depletion and repopulation, infections and anti-drug antibodies
Authors: A. Nassar-Sheikh Rashid, R. Kampinga, M. Peters, M. Oosterveld, T.W. Kuijpers, J.M. van den Berg, D. Schonenberg-Meinema
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rituximab (RTX) is increasingly used in rheumatologic,<sup>1, 2</sup> hematologic<sup>3</sup> and renal diseases.<sup>4</sup> The induced B cell depletion can lead to hypogammaglobulinemia and thus an increased risk of infection.<sup>5</sup> B cell depletion is not always achieved, and this has a negative effect on therapeutic response.<sup>6</sup> Anaphylaxis is a frequent side effect of RTX and has been associated with the occurrence of anti-drug antibodies (ADA) against RTX.<sup>7</sup> <h3>Objectives</h3> To describe in different paediatric patient groups the pharmacodynamics of RTX in children by outcome variables, i.e. success of B-cell depletion and time of B cell repopulation, as well as the risk factors for severe infections and anaphylaxis. <h3>Methods</h3> Patient data of children who received RTX between 2008 and 2017 at our centre were retrospectively collected. Three patient subgroups were defined: autoimmune diseases (AID), immune dysregulation (ID) and renal diseases (RD). B cell repopulation was defined as a number above the cut-off value of B cell depletion (=0.050*10^6/l or &lt;2% of the total amount of lymphocytes). <h3>Results</h3> B cell measurements were performed in 53/55 patients. B cell depletion was not achieved in 9 patients. In the 35 patients with B cell repopulation, median time until repopulation was 155 days (IQR 105–222): in the AID group (n=12) 129 days (IQR 77.5–243, p=0.363), in the ID group (n=5) 172 days (IQR 154–181, p=0.574) and in the RD group (n=18) 163 days (IQR 121–229, p=0.847). After RTX treatment, in 36 patients IgG levels were measured of which 14 (39%) had low IgG levels on at least one occasion (median 7 g/L [range 0.6–38.1 g/L]). Severe infections leading to hospitalisation occurred in 15 (27%) cases. An allergic reaction during or directly after RTX infusion was observed in 27 patients (49%). Anaphylaxis, defined as a systemic allergic reaction, characterised by impairment of airway, breathing, circulation or consciousness, occurred in 10 of these patients (18% of total cohort). Seven patients were tested for anti-RTX antibodies of whom 6 tested positive: 5 patients in the AID-group and one patient with renal disease. Allergic reactions occurred in all 6 while RTX failed to induce B cell depletion in 4 of these. <h3>Conclusions</h3> Time-to-B-cell-repopulation after RTX did not significantly differ between different paediatric patients groups. Severe infections were common (27%) in the cohorts studied. It is unclear from our data whether this is merely related to RTX treatment. Presence of ADA against RTX seems to predict failure of B-cell depletion and/or anaphylaxis after RTX treatment. <h3>References</h3> [1] de Lemos LL, et al. Rev Bras Reumatol2014;54(3):220–30. [2] Sanz I. Nat Rev Rheumatol2016;12(12):700–2. [3] Omri HE, et al. Clin Med Insights Blood Disord2015;8:1–7. [4] Fervenza FC, et al. Clin J Am Soc Nephrol2010;5(12):2188–98. [5] Lahiri M, et al. Best Pract Res Clin Rheumatol2015;29(2):290–305. [6] Thiel J, et al. Arthritis Res Ther2017;19(1):101. [7] Einarsson JT, et al. Clin Rheumatol2017; Dec;36(12):2743–2750. <h3>Disclosure of Interest</h3> None declared