Outcome of biological therapies in chronic antibiotic-refractory pouchitis: A retrospective single-centre experience

Abstract

Background: In limited retrospective series, infliximab, adalimumab and vedolizumab have demonstrated efficacy in chronic antibiotic-refractory pouchitis. Here, we report single-centre data of all biological therapies in refractory pouchitis.

Methods: We retrospectively assessed all records from patients with ulcerative colitis and ileal pouch -anal anastomosis who received infliximab, adalimumab or vedolizumab for pouchitis. Clinically relevant remission, defined as a modified Pouchitis Disease Activity Index <5 and a reduction of modified Pouchitis Disease Activity Index ≥2 points from baseline, was assessed at week 14.

Results: Thirty-three unique patients were identified. Prior to colectomy, patients had been exposed to cyclosporine (n = 14), infliximab (n = 12), adalimumab (n = 3), and/or vedolizumab (n = 3). All developed chronic antibiotic-refractory pouchitis, for which they received infliximab (n = 23), adalimumab (n = 13) or vedolizumab (n = 15). Clinically relevant remission was observed in 43.5% of patients in the infliximab group, and in 38.5% and 60.0% in the adalimumab and vedolizumab group, respectively. In the long-term, significantly more patients continued vedolizumab compared to anti-tumour necrosis factor (anti-TNF) therapy (hazard ratio 3.0, p = 0.04). Adverse events (mainly infusion reactions) explained 40.7% of the patients discontinuing anti-TNF therapy, whereas discontinuation of vedolizumab was only related to insufficient efficacy. Four patients eventually required a permanent ileostomy.

Conclusion: In this case series of chronic antibiotic-refractory pouchitis, biological therapy was effective in the majority of patients and only a minority eventually required a permanent ileostomy. The use of anti-TNF agents was hampered by a high rate of adverse events, partly related to immunogenicity as some patients had been exposed to anti-TNF prior to colectomy. Vedolizumab was also efficacious and may provide a safe alternative in these chronic antibiotic-refractory pouchitis patients.

Keywords: Chronic pouchitis; adalimumab; biological therapy; infliximab; ulcerative colitis; vedolizumab.

Figure 1.

Flowchart. CD: Crohn's disease.

Figure 2.

Evolution of the median (interquartile range) modified pouch disease activity index (mPDAI) during infliximab (a), adalimumab (b) and vedolizumab (c) therapy.

Figure 3.

Clinically relevant remission rates by week 14 in infliximab (n = 23), adalimumab (n = 13) and vedolizumab (n = 15) treated patients with chronic antibiotic-refractory disease.

Figure 4.

Histological changes in pouch biopsies of ulcerative colitis (UC) patients with chronic antibiotic-refractory pouchitis before and after biological therapy (H&E stain; original magnification (OM) ×100–200). (a) H&E stainings from a pouchitis patient before infliximab therapy: active pouchitis (polymorphonuclear infiltration 3, ulceration per low power field 3). (b) H&E stainings from a pouchitis patient after infliximab therapy: week 14, epithelial restoration (decrease of the polymorphonuclear infiltration 0, ulceration per low power field 0). (c) H&E stainings from a pouchitis patient before adalimumab therapy: active pouchitis (polymorphonuclear infiltration 2, ulceration per low power field 2). (d) H&E stainings from a pouchitis patient after adalimumab therapy: week 13, partial epithelial restoration (decrease of the polymorphonuclear infiltration 1, ulceration per low power field 1). (e) H&E stainings from a pouchitis patient before vedolizumab therapy: active pouchitis (polymorphonuclear infiltration 2, ulceration per low power field 1). (f) H&E stainings from a pouchitis patient after vedolizumab therapy: week 14, complete epithelial restoration (decrease of the polymorphonuclear infiltration 0, ulceration per low power field 0). H&E: heamtoxylin and eosin.

Figure 5.

Biological therapy discontinuation-free survival in patients with chronic antibiotic-refractory pouchitis, grouped by either anti-TNF or vedolizumab therapy. CI: confidence interval.