Commentary: salvage medical therapy for acute severe colitis - ciclosporin or infliximab?

The article by Croft et al., compared outcomes of 83 patients from a single centre treated with either ciclosporin or infliximab as salvage therapy for acute severe ulcerative colitis (UC).1 The authors demonstrated significantly better colectomy-free rates for patients treated with infliximab compared with ciclosporin at discharge (84% vs. 56%), 3 months (76% vs. 53%) and 12 months (65% vs. 42%). Although these data provide an interesting comparison of the two therapies, there are several limitations to this study, many addressed by the authors themselves. First, there is no randomisation, and therefore inherent bias with regard to drug selection. Secondly, the colectomy-free rates for infliximab were higher than in other published data, including the only RCT to examine this issue. The GETAID group demonstrated equal efficacy for ciclosporin and infliximab in preventing colectomy,2 findings that are supported by a meta-analysis of six eligible nonrandomised trials.3 Thirdly, although Cox regression demonstrated no significant effect of duration of disease and colectomy rates, it is an interesting observation that median disease for the infliximab arm was shorter than for those receiving ciclosporin. Finally, only one infusion of infliximab was administered, which may underestimate the efficacy of this treatment strategy, although a recent retrospective review of outcomes of 211 infliximab-treated patients suggested no difference in colectomy rates between single-dose and three-dose induction.4 The majority of patients in both groups in this study were not taking immunosuppressants (IS) on initiation of rescue therapy, whilst >90% in both groups were discharged on IS. Whilst numbers in the non-IS maintenance group are small, it would be interesting to know if ‘bridging’ to IS therapy reduced colectomy compared with non-IS (naive/intolerant) patients. Reduced colectomy rates with bridging have been reported with ciclosporin previously, and in our own group with infliximab for acute severe UC.5 However, a larger infliximab cohort demonstrated no difference in colectomy rates with maintenance IS at 12 months.4 All patients responding to ciclosporin or infliximab in the GETAID trial were treated with azathioprine (93% were IS naive previously).2 Thus, it would be interesting if this group report any longer term data on bridging to azathioprine beyond the 98 days of reported follow-up for either drug. This study provides clinically useful data; however, questions remain regarding the use of salvage therapy, in particular, the role of ongoing anti-TNF and/or IS maintenance therapy in this clinical setting. Declaration of personal interests: Dr John Hamlin has participated in advisory boards for MSD. Declaration of funding interests: None.