Infliximab may lead to higher infection rate, no improvement in transplant outcomes
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The use of infliximab in patients with a deceased donor kidney transplant led to increased infections and did not improve allograft survival, according to data presented at the American Transplant Congress.
“The intervention had no effect on allograft function or acute rejection,” Peter S. Heeger, MD, a professor of medicine and immunology at the Icahn School of Medicine at Mount Sinai Medical Center in New York, told Healio. “Unexpectedly, we observed higher rates of infection with the BK virus, a virus that can contribute to graft dysfunction and graft loss.”
In the randomized, double-blind, placebo-controlled phase 2 trial, Heeger and colleagues studied the induction therapy of infliximab (Remicade; Janssen Pharmaceuticals) in deceased donor kidney transplant recipients to determine whether infliximab reduced inflammation post-transplant and lower the risk of tumor necrosis factor-alpha (TNF-a) production.
“TNF is a potent inflammatory mediator that plays key roles in many diseases, including rheumatoid arthritis and inflammatory bowel disease,” Heeger told Healio. “Inflammation is induced immediately after transplantation of deceased donor organs and has been hypothesized to be one of the causes of early graft dysfunction and rejection that can contribute to organ failure.”
Researchers enrolled 242 deceased donor transplant recipients from 14 U.S. transplant centers and randomized 225 patients to receive either 3 mg/kg of infliximab (IFX) or saline intraoperatively, initiated prior to kidney reperfusion. Patients in both arms of the study received antithymocyte globulin induction therapy and maintenance immunosuppression.
Primary endpoint was the difference in the mean eGFR between the infliximab and placebo groups. Secondary endpoints included the proportions of patients who developed biopsy proven acute rejection, donor-specific antibody and delayed graft function. Safety endpoints included hospitalization rates and incidences of cytomegalovirus viremia or BK viremia.
Analysis of plasma at 7 days post-transplant showed 10-fold lower TNF-a (P<0.001) and lower cytokine interleukin-1 (IL-1b) (P =0.003), IL-6 (P =0.017) and IL-8 (P =0.002) levels in eGFR vs. the control patient group. BK viremia was seen in 28.9% in the IFX group vs. 13.4% in the control group.
“This unexpected [increase in] infectious disease is important because it shows that targeting inflammation with this agent and possibly others not yet tested can lead to adverse effects and thus may not be an ideal approach to improving kidney transplant outcomes,” Heeger said.
Heeger told Healio more research in the use of biologics that can reduce inflammation post-transplant is warranted.
“We, with collaborators, are testing the efficacy of various other biologics targeting inflammatory cytokines in kidney, heart or lung transplant recipients to determine their efficacy and off target effects,” he said.
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Heeger PS, et al. Abstract 9002. Presented at: American Transplant Congress; June 4-8, 2022; Boston (hybrid meeting).
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