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Abstract: SA-OR33

Antibodies Anti-Rituximab Do Not Affect Response to Rituximab in Idiopathic Nephrotic Syndrome

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Angeletti, Andrea, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Bruschi, Maurizio, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Lugani, Francesca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Colucci, Manuela, Ospedale Pediatrico Bambino Gesu, Roma, Lazio, Italy
  • Vivarelli, Marina, Ospedale Pediatrico Bambino Gesu, Roma, Lazio, Italy
  • Emma, Francesco, Ospedale Pediatrico Bambino Gesu, Roma, Lazio, Italy
  • Caridi, Gianluca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Verrina, Enrico E., Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Ghiggeri, Gian Marco, Istituto Giannina Gaslini, Genova, Liguria, Italy
Background

Previous studies reported how infusion of the chimeric anti-CD20 rituximab results in production of antibodies anti-rituximab, that may limit the efficacy of further infusions. Among other reasons, the reduced immunogenicity of fully humanized anti-CD20 antibodies should increase their efficacy. In a randomized clinical trial, we compared the efficacy of ofatumumab vs. rituximab in children and young adults with steroid dependent nephrotic syndrome. As secondary endpoints, we evaluated possible role of anti-CD20 rituximab.

Methods

We randomized 140 children treated with single infusion of rituximab or ofatumumab, with a follow up of 24 months. We measured anti-rituximab antibodies IgG at the enrolment in 64/140 (46%) patients who have previously received rituximab and at 6 months in patients in the rituximab arm. Median time of the previous rituximab was 36 (12-51) months before enrolment.

Results

As primary endpoint, ofatumumab was not superior to rituximab in maintaining remission (Fig 1a). Serum anti-rituximab IgG were undetectable at baseline in 64 participants who had previously received rituximab. Six months following rituximab infusion, anti-rituximab antibody levels increased in 14 (42%) of the 33/64 patients who were randomized in the rituximab arm (Fig 1b). Among patients with relapse in rituximab arm, the efficacy of a second infusion of rituximab, infused in accordance with the protocol, was not affected by the presence of anti-rituximab antibodies (Fig 1c).

Conclusion

Previous exposure to rituximab results in production of anti-rituximab antibodies, which persist for a limited time. Presence of circulating anti-rituximab antibodies does not affect response to rituximab in steroid dependent nephrotic syndrome.