Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology

Abstract

Background There is no consensus regarding dose and frequency of rituximab in Nephrology with extrapolation of dose used in treating lymphoproliferative disorders. There are no guidelines on targeting initial and subsequent doses based on CD19 + B cells. Methods 100 mg rituximab was given initially in 42 adults with steroid dependent (SDNS) and frequently relapsing nephrotic syndrome (FRNS), idiopathic membranous nephropathy (MN) and high immunologic risk kidney transplantation. Absolute and percentage CD19 B cells and clinical status were assessed at baseline, days 30, 90, 180 and 1 year. Subsequent doses of rituximab were based on CD19 B cell reconstitution and clinical response. Results CD19 B cell percentage decreased from 16.3+7.6 to 0.3±0.3 (P=<0.001), 1.9±1.7 (P=<0.001) and 4.0±4.5 (P=0.005) by 30, 90 and 180 days respectively. Suppression of CD 19 B cell count below 1% at day 30, 90 and 180 was 40/42 (95.2%), 18/42(42.9%) and 7/42(16.7%) respectively. Of 30 with SDNS and FRNS followed up for one year, 29(96.7%) went into remission at day 30. Remission was sustained in 23(76.6%) at day 180 and 21(70%) at 1 year. There was significant decrease [P <0.001] in the dose of steroids needed to maintain remission at 180 days following rituximab (0.27±0.02mg/Kg to 0.02±0.00mg/Kg). CD 19 B cell percentage at 90 days correlated with relapse (P=0.001, OR 1.422, 95% CI 1.246-2.574). Eighteen (60%) required an additional dose. Of five with MN, four achieved remission by 6 months which was sustained in three by 1 year. Of the 7 kidney transplant recipients, 2 had antibody mediated rejections though CD19 B cells were suppressed even at one year. Conclusions Low dose rituximab induces sustained depletion of CD19 B cells up to 90 days. Its role in preventing relapses in SDNS, FRNS, MN and rejection needs further studies.

Case series of low dose rituximab for membranous nephropathy; a single centre experience

“…One male patient received additional dose of rituximab based on CD 19 B cell count as a part of his treatment strategy. The need to repeat rituximab injection in our cases was based on the criteria of CD 19 B cell count being greater than five cells/µL, which was similar to the algorithm proposed by Jacob George et al (14). Higher PLA2R titre with more chronicity on renal biopsy can be considered as a possible explanation for poor response to rituximab as seen in patient 4 (15).…”

Perspective Chapter: Low Cost Immunosuppressive Strategies in Renal Transplantation

“…It may be possible to combine induction agents acting at different sites. ATG targets T cells and as Rituximab targets B cells, there may be a role in combining both [9,21,22]. Though a combination of ATG and IL2Ra has not been recommended [12], there are reports of combining ATG or IL2RA with rituximab in selected patients [9,21,22].…”

“…A single dose of 375 mg/m2 was effective in reducing the incidence of AMR in immunologically high-risk patients [31]. It has been shown that doses as low as 100 mg in renal transplantation while on other immunosupressants can produce prolonged CD19B cell suppression for even a year justifying avoiding the weekly doses used in lymphoproliferative disorders [22]. The cost of 100 mg Rituximab is INR3000 (US$40) making it one of the potentially cheapest induction agent.…”

“…INR 3000 (US$ 37.5). Monitoring CD19 counts suggests a lower initial dose may suffice and targeting subsequent doses depending on B cell repopulation can result in lesser boosters and at time intervals ranging from 6 to 12 months [22]. Targeting initial dose and deciding on need for further doses depending on the CD 19 count has been found to be effective with limiting state of immunosuppression [55].…”

“…Targeting initial dose and deciding on need for further doses depending on the CD 19 count has been found to be effective with limiting state of immunosuppression [55]. This could have significant cost advantages [22,56].…”