JAK inhibition treating allograft pancreatitis & ischaemia reperfusion
Research type
Research Study
Full title
Safety and efficacy of Tofacitinib in ameliorating ischaemia reperfusion injury and allograft pancreatitis in solid organ transplantation – a pilot study
IRAS ID
221443
Contact name
Peter Friend
Contact email
Sponsor organisation
Clinical Trials and Research Governance
Eudract number
2017-002784-18
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Summary of Research
47% of patients who have a pancreas transplant develop an inflammatory condition called pancreatitis. This condition causes complications that cause patients to stay in hospital longer and remain more unwell. It also reduces graft survival. To prevent this complication, we want to use an anti inflammatory therapy, blocking a key molecular switch that drives the inflammation. We believe we will be able to dampen the effect,which will improve the outcome for patients and improve graft survival.
Safety and efficacy of Tofacitinib in ameliorating ischaemia reperfusion injury and allograft pancreatitis in solid organ transplantation – a pilot studyBackground: Allograft pancreatitis (AGP) is a major complication following whole organ pancreas transplantation. Tyrosine kinase is involved in key signaling pathways: its central role in cytokine-driven inflammation makes this an attractive target for pharmacological intervention. Tofacitinib, a potent tyrosine kinase inhibitor (TKI) of the Janus Kinase family, was used in the early post-operative period to evaluate safety and efficacy in ameliorating graft pancreatitis after pancreas transplantation.
Study design and methodology: In this phase 2 single arm trial, a total of 21 simultaneous kidney and pancreas transplant (SPK) patients were recruited to receive tofacitinib at a dose of 10mg twice daily for 7 days starting preoperatively. Data from 40 SPK recipients were compared to the treatment group.
Inflammatory markers were measured during and after reperfusion of the pancreas and daily for the first 7 days post-surgery. All patient underwent post-operative day 5 computed tomography (CT) angiogram pancreas to assess radiological evidence of pancreatitis. Clinical outcomes including reoperation, graft loss and length of stay were reported.
Results: The incidence of pancreatitis was 14.3% in the treatment group and 23% in the control group. Two patients (9.5%) required reoperation on for pancreatitis-related complications, compared to seven (17.5%) in the control group. Early graft loss occurred in three (14.3%) and two (5%) of patients in the study and control groups respectively: two of the graft losses in the treatment group were ascribed to non-pancreatitis causes. The median length of hospital stay, 11 (IQR 6) days in the treatment group and 11.5 (IQR 12) days in the control group. Serious adverse events occurred in 4 patients (incidence rate 0.19) in the study group and in 16 (incidence rate 0.40) control group. One patient died in the control group and none in the intervention group.
Conclusion: Tofacitinib administration led to a lower incidence of graft pancreatitis and reoperation. Tofacitinib is safe to administer in early post-transplant period.Summary of Results
Safety and efficacy of Tofacitinib in ameliorating ischaemia reperfusion injury and allograft pancreatitis in solid organ transplantation – a pilot studyBackground: Allograft pancreatitis (AGP) is a major complication following whole organ pancreas transplantation. Tyrosine kinase is involved in key signaling pathways: its central role in cytokine-driven inflammation makes this an attractive target for pharmacological intervention. Tofacitinib, a potent tyrosine kinase inhibitor (TKI) of the Janus Kinase family, was used in the early post-operative period to evaluate safety and efficacy in ameliorating graft pancreatitis after pancreas transplantation.
Study design and methodology: In this phase 2 single arm trial, a total of 21 simultaneous kidney and pancreas transplant (SPK) patients were recruited to receive tofacitinib at a dose of 10mg twice daily for 7 days starting preoperatively. Data from 40 SPK recipients were compared to the treatment group.
Inflammatory markers were measured during and after reperfusion of the pancreas and daily for the first 7 days post-surgery. All patient underwent post-operative day 5 computed tomography (CT) angiogram pancreas to assess radiological evidence of pancreatitis. Clinical outcomes including reoperation, graft loss and length of stay were reported.
Results: The incidence of pancreatitis was 14.3% in the treatment group and 23% in the control group. Two patients (9.5%) required reoperation on for pancreatitis-related complications, compared to seven (17.5%) in the control group. Early graft loss occurred in three (14.3%) and two (5%) of patients in the study and control groups respectively: two of the graft losses in the treatment group were ascribed to non-pancreatitis causes. The median length of hospital stay, 11 (IQR 6) days in the treatment group and 11.5 (IQR 12) days in the control group. Serious adverse events occurred in 4 patients (incidence rate 0.19) in the study group and in 16 (incidence rate 0.40) control group. One patient died in the control group and none in the intervention group.
Conclusion: Tofacitinib administration led to a lower incidence of graft pancreatitis and reoperation. Tofacitinib is safe to administer in early post-transplant period.REC name
London - City & East Research Ethics Committee
REC reference
18/LO/0560
Date of REC Opinion
10 May 2018
REC opinion
Further Information Favourable Opinion