These findings suggest that the combination of intravenous immune globulin and rituximab may prove effective as a desensitization regimen for patients awaiting a transplant from either a living donor or a deceased donor. Larger and longer trials are needed to evaluate the clinical efficacy and safety of this approach. (ClinicalTrials.gov number, NCT00642655.)
IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).
BACKGROUND.: We have shown that high-dose intravenous immune globulin (IVIG; 2 g/kg x2 doses)+rituximab (1 g x2 doses) was effective in lowering anti-human leukocyte antigen (HLA) antibodies and improving rates of transplantation. The aim of this report was to evaluate the efficacy of IVIG+rituximab on reduction of anti-HLA antibodies to a level that was permissive for living donor (LD) or deceased donor (DD) transplantation without incurring the risk of antibody-mediated rejection and immediate graft loss. METHODS.: From July 2006 to February 2009, 76 HLA-sensitized (HS) patients who met strict sensitization criteria received kidney transplants after desensitization using IVIG 2 g/kg (days 1 and 30)+rituximab (1 g, day 15). Parameters evaluated included rates of transplantation, previous transplants, panel reactive antibodies, donor specific antibody, crossmatches (CMXs), patient and graft survival, acute rejection, serum creatinines, and infections. RESULTS.: Seventy-six HS CMX treated patients (31 LD/45 DD) were transplanted. For LD and DD recipients, significant reductions were seen in T-cell flow cytometry CMXs from pretreatment (T cell 183.5+/-98.4 mean channel shifts (MCS) for LD and 162.8+/-41 MCS for DD) to time of transplant (T cell 68.2+/-58 MCS for LD [P<0.00006] and 125+/-49 for DD [P=0.05]), respectively. Time on wait list for DD recipients was reduced from 95+/-46 months to 4.2+/-4.5 months after treatment. Twenty-eight patients (37%) experienced acute rejection (29% C4d/8% C4d). Patient and graft survival up to 24 months was 95% and 84%, respectively. The mean serum creatinines, at 12 and 24 months were 1.5+/-1.1 and 1.3+/-0.3 mg/dL, respectively. Viral infections were seen in six patients. CONCLUSIONS.: IVIG and rituximab seems to offer significant benefits in reduction of anti-HLA antibodies allowing improved rates of transplantation for HS patients, especially those awaiting DD, with acceptable antibody-mediated rejection and survival rates at 24 months.
Tocilizumab and IVIg appear to be safe. From this pilot trial, we are cautiously optimistic that targeting the IL-6/IL-6R pathway could offer a novel alternative for difficult to desensitize patients. Larger controlled studies are essential to prove efficacy
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