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Letter: faecal calprotectin and lactoferrin – accurate biomarkers in post‐operative Crohn's disease – authors' reply

SIRS, We welcome the comments from Bodini et al. in response to our review. This letter highlights the confusion clinicians face when considering the heterogeneous evidence for post-operative prophylaxis in patients with Crohn’s disease (CD). It also highlights the difficulties clinicians face in predicting which patients are at highest risk of recurrence. While our review had focused on randomised controlled studies, other data are now available, as Savarino et al. discuss. In these, reported endoscopic recurrence (ER) rates with adalimumab (ADA) vary widely. Aguas et al. reported a 21% ER (Rutgeerts score i ≥2) at 12 months in 29 patients treated with 160/80/40 mg ADA every other week (eow). It is of interest that only two of the pre-requisite ‘high risk’ inclusion criteria predicted recurrence, neither of which was smoking. Papamichael et al. reported a 25% recurrence rate at 24 months (Rutgeerts score i ≥2) in eight patients treated with ADA 180/60/40 mg eow after curative resection, with Savarino et al. reporting 6.3% ER over the same period. On further literature review, we note the modest total of 59 ADA treated patients in 4 uncontrolled studies assessing efficacy in post-operative recurrence. We feel it is difficult therefore to position anti-TNF as first line therapy for post-operative recurrence, notwithstanding the health economic considerations of a treatment 80 times more expensive than, for example, azathioprine (£9295 per year ADA 40 mg eow, £114 per year Azathioprine 150 mg/day). Safety issues are also worthy of consideration in the asymptomatic post-operative setting, especially as drug withdrawal is problematic, and there is an increasing body of opinion favouring indefinite duration of therapy. We think it is very likely that anti-TNF medications will be an important part of future treatment algorithms, but the use and combination of existing immunomodulators in such an algorithm is yet to be established. It remains vital for the treatment stratification of patients that indices, such as biomarkers be utilised to detect the evolution of post-operative recurrence as Yamamoto et al. have suggested. We agree that faceal calprotectin represents an attractive monitoring modality in this area, and look forward to the publication of the trial of prevention of post-operative Crohn’s disease (TOPPIC) that employs this as a defined end-point. Accepting the limitations of current published data we agree with the assertion that there is emerging evidence for anti-TNF efficacy in this setting, but that further confirmation in larger cohorts is required, particularly in identifying those most likely to benefit. We look forward to the imminent publication of the post-operative Crohn’s endoscopic recurrence study (POCER) and of the future PREVENT trial (NCT01190839).