Another study revealed a significant induction of regulatory macrophages in patients receiving infliximab/azathioprine combination treatment. This might be an explanation for the better outcome of this combination treatment regime in clinical practice and as demonstrated in the SONIC trial. However, in our study combination therapy with anti-TNF-alpha antibody and thiopurines was not associated with a higher rate of MH. Other important mechanisms by which anti-TNF-alpha antibodies may promote MH are downregulation of proinflammatory cytokines/chemokines, matrix-metalloproteinases, tissue inhibitors of metalloproteinases and apoptosis/necroptosis. One may speculate if early start of anti-TNF-alpha antibody treatment could have improved the rates of MH in our study cohort, since most of the patients in our study underwent step-up strategies and were treated with an anti-TNF-alpha antibody only 7 years after the first diagnosis of IBD. In the large anti-TNFalpha antibody landmark trials, MH rates are varying with the different time points of assessment. In CD patients, infliximab induced MH rates ranging from 29% to 45% and 27% with adalimumab. In studies with UC patients, MH rates are higher and ranged from 47% with adalimumab and 60% with infliximab. However, in contrast to these anti-TNF-alpha antibody studies, in which patients have routine colonoscopy after a defined time point after initiation of anti-TNF-alpha antibody treatment, in clinical practice patients without clinical symptoms are often not willing to undergo colonoscopy. Accordingly, data from these patients are missing and in a real life situation there might be higher rates of MH in anti-TNF-alpha antibody-treated patients who have no colonoscopy after start of anti-TNF-alpha antibody therapy, since clinical activity was obviously low and there was no need for routine diagnostic colonoscopy. There are some limitations of our study, mostly due to its retrospective nature: first, there were limited data on clinical scores like CDAI/CAI. However, there is evidence that CDAI and CAI as subjective scoring systems are not suitable to determine MH. Moreover, only in a few patients neutrophil-derived fecal stool markers like calprotectin were available to be correlated with MH. Second, time periods between baseline and follow-up colonoscopy were varying. However, there was no significant difference in the time interval between baseline and follow-up colonoscopy among patients with and without MH. In the majority of our patients, the main reason for second colonoscopy was routine control of ongoing anti-TNFalpha antibody therapy, and only few colonoscopies were performed due to flare of the disease. Accordingly, CRP values at baseline colonoscopy were not significantly different in both groups, which suggest similar clinical disease activity. As noted above, colonoscopy as an invasive procedure has a low acceptance rate in asymptomatic IBD patients.