Background Rituximab (RTX) is increasingly used in rheumatologic,^{1, 2} hematologic³ and renal diseases.⁴ The induced B cell depletion can lead to hypogammaglobulinemia and thus an increased risk of infection.⁵ B cell depletion is not always achieved, and this has a negative effect on therapeutic response.⁶ Anaphylaxis is a frequent side effect of RTX and has been associated with the occurrence of anti-drug antibodies (ADA) against RTX.⁷

Objectives 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.

Methods 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 <2% of the total amount of lymphocytes).

Results 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.

Conclusions 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.

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[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.

Disclosure of Interest None declared