Serious adverse events put a stop to ASTIClite trial for CD

The ASTIClite trial, developed to analyse the efficacy of haematopoietic stem cell transplantation (HSCT) on refractory Crohn’s disease (CD) patients, was halted due to unexpected serious events. Although the HSCT regimen was associated with regression of endoscopic ulcers in some patients, the adverse safety profile, including 2 deaths, rules out its future use in clinical practice.

Autologous HSCT has been associated with patient benefits in several autoimmune diseases, stated Prof. James Lindsay (Barts and The London School of Medicine, UK). He argued that there are CD patients with active disease who need non-surgical alternative therapies. Serious adverse events (AEs) that have been reported in the preceding ASTIC trial were suspected to be caused by high doses of cyclophosphamide. Therefore, the ASTIClite trial (ISRCTN17160440) aimed to investigate the efficacy and safety of and adapted low-intensity HSCT regimen compared with standard-of-care (SoC) in refractory CD patients in a 2:1 randomisation ratio [1]. The primary clinical endpoint was a simple endoscopic score (SES)-CD ulcer subscore of 0 at 48 weeks.

The trial was terminated due to unexpected serious adverse events, after 23 patients had been randomised into the study (SoC, n=10; HSCT, n=13). Only 13 patients contributed to the primary endpoint assessment. Although 3 out of 7 patients in the HSCT arm reached the primary endpoint versus 0 patients in the SoC arm, the number of serious AEs in the HSCT group (n=38) exceeded that of the SoC arm (n=16). Grade 4 serious AEs were exclusively reported in the HSCT group (n=8). Thrombotic microangiopathy resulted in several significant events in the HSCT arm. This complication was confirmed through biopsy in 3 patients who suffered from significant renal dysfunction. One patient died from refractory pulmonary hypertension secondary to pulmonary veno-occlusive disease. A second death occurred after the final endpoint of the trial, due to respiratory failure of the participant after HSCT.

1. Lindsay J. A randomised controlled clinical trial of autologous stem cell transplantation (HSCT) in patients with treatment refractory Crohn’s disease (low intensity therapy evaluation): ASTIClite. OP192, UEG Week Virtual Congress 2021, 03–05 October.

 

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Posted on 27 October, 20218 April, 2024