Transplant Evidence Alert

The Transplant Evidence Alert provides a monthly overview of the 10 most important new clinical trials in organ transplantation, selected and reviewed by the Peter Morris Centre for Evidence in Transplantation (Oxford University).

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Efficacy and Safety of Iguratimod Supplement to the Standard Immunosuppressive Regimen in Highly Mismatched Renal Transplant Recipients: A Pilot Study

Front Immunol. 2021 Nov 23;12:738392 doi: 10.3389/fimmu.2021.738392.
Abstract

Iguratimod (IGU) can mitigate the symptoms of rheumatoid arthritis through its anti-inflammatory effects. The objective of this study was to investigate the clinical efficacy and safety of IGU in highly HLA-mismatched renal transplant recipients, in combination with standard immunosuppressive regimen. This pilot study was designed as an open-label, blank-control, randomized clinical trial on patients recruited from a single transplant center in China. Patients who met the inclusion criteria were randomized to the IGU (n=27) and blank control (n=27) groups. IGU was administrated with the conventional triple immunosuppressive protocol for 52 weeks after kidney transplantation. The incidence of biopsy-proven acute rejection rate was 14.8% (4/27) in the IGU group and 29.6% (8/27) in the control group, P = 0.19. The clinical rejection rate was also substantially reduced in the IGU group (3.7% vs. 18.5%, P = 0.08). De novo donor-specific antibody also showed a decline trend in the IGU group after 52 weeks. The graft function and incidence of adverse events were similar between the two groups. In addition, IGU intervention significantly decreased the number of NK cells throughout the follow-up. In conclusion, our study has shown the possibility that IGU could reduce the allograft rejection rate and de novo DSA with appreciable safety in combination with conventional immunosuppressants. Formal clinical trials were warranted based on current findings.

CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This small pilot RCT investigated whether the addition of the disease-modifying anti-rheumatoid drug (DMARD) Iguratimod (IGU) can improve outcomes in poorly-mismatched renal transplant recipients. The study itself was unblinded, but nephrologists scoring protocol biopsies were blinded to treatment allocation. Both modified intent-to-treat and per-protocol analyses are reported. Patients receiving IGU had numerically lower incidence of biopsy-proven acute rejection, although not achieving statistical significance due to the small sample size. The results presented do show some promise for the use of IGU following renal transplantation, but larger studies will be required to confirm any benefit. It should be noted that the baseline rate for biopsy-proven acute rejection was relatively high for a Tac/MMF/Pred based regimen (29.6%). Another potential limitation is that patients were only eligible at least 2 weeks post-transplant – anti-inflammatory drugs of this nature may be most effective if given from the day of transplant.
Methodological quality
Jadad score 3
Allocation concealment NO
Data analysis MODIFIED INTENTION TO TREAT
Study Details
Aims: This study aimed to assess the effect and safety of Iguratimod (IGU) combined with standard immunosuppressive regimen in highly HLA-mismatched kidney transplant patients.
Interventions: Patients were randomised to either the IGU or non-IGU group.
Participants: 60 highly HLA-mismatched renal transplant recipients.
Outcomes: The primary outcomes were biopsy-proven acute rejection and functional allograft survival. The secondary outcomes were the safety profile, donor-specific antibody (DSA) and other indicators.
Follow Up: 52 weeks
Metadata
Funding: Non-industry funding
Publication type: Randomized Controlled Trial, Randomised Controlled Trial
Trial registration: ClinicalTrials.gov - NCT02839941
Organ: Kidney
Language: English
Author email: lancetgu@aliyun.com
MeSH terms: Adult; Allografts; Antibody Specificity; China; Chromones; Drug Therapy, Combination; Female; Graft Rejection; HLA Antigens; Histocompatibility Testing; Humans; Immunosuppressive Agents; Isoantibodies; Kidney Transplantation; Killer Cells, Natural; Male; Middle Aged; Pilot Projects; Sulfonamides; Tissue Donors; 0 (Chromones); 0 (HLA Antigens); 0 (Immunosuppressive Agents); 0 (Isoantibodies); 0 (Sulfonamides); 4IHY34Y2NV (Iguratimod)