Corticosteroid-Free Kidney Transplantation Improves Growth: 2-Year Follow-up of the TWIST Randomized Controlled Trial
Webb NJ, Douglas SE, Rajai A, et al.Transplantation. 2015 Jun; 99(6): 1178-85
Aims
This is a follow up to the Tacrolimus and Withdrawal of Steroids (TWIST) study, with the aim to ascertain whether the improved growth observed at 6 months was sustained at 1 and 2 years, and whether early corticosteroid withdrawal was associated with more acute rejection or other adverse events.
Interventions
The initial 6-month study involved the randomisation of participants to receive either early corticosteroid withdrawal (tacrolimus, MMF, daclizumab (x2) and corticosteroids until day 4), or corticosteroid continuation (tacrolimus, MMF and on-going corticosteroids). This study collects data from the participants at 1 year and 2 year follow-ups.
Participants
200 paediatric subjects (aged 2-18 years) were randomised in the initial 6-month study. All 168 subjects who completed the initial 6-month study were eligible for inclusion in this follow-up study. Complete 1 year follow-up data was available for 113 subjects; 2-year follow-up data was available for
Outcomes
The primary outcome measured was change in height standard deviation score (SDS) from baseline assessed at 1 and 2 years after transplantation with a nominal 3-month window for data inclusion. The secondary outcomes measured included the incidence of acute rejection, patient and graft survival, change in BMI SDS, kidney function and incidence of adverse effects, including hypertension, dyslipidemia, obesity, abnormal glucose metabolism, malignancy and infection.
Follow-up
2 years
CET Conclusions
This manuscript reports the two-year results of the TWIST study, in which 200 paediatric renal transplant recipients were randomised to early steroid withdrawal (day 4) or steroid continuation, in conjunction with IL2RA induction, tacrolimus and MMF. There were no differences in efficacy or safety outcomes between the two arms of the study at 2 years, but a significant growth improvement was seen in the withdrawal arm. These results suggest that early steroid withdrawal is likely safe and may have some growth benefit in this low-risk population. It is worth noting that the study was powered to detect differences in growth, and may be under-powered to show differences in efficacy variables such as rejection or graft survival. The clinical significance of a 1.8cm difference in growth is also uncertain, even though statistically significant.
Data analysis
Strict intention-to-treat analysis
Quality notes
Previously assessed as Grenda, R., A. Watson, et al. (2010). "A randomized trial to assess the impact of early steroid withdrawal on growth in pediatric renal transplantation: the TWIST study." American Journal of Transplantation 10(4): 828-836.
Trial registration
EudraCT 2005 - 001348022