Azathioprine with Allopurinol Is a Promising First‑Line Therapy for Infammatory Bowel Diseases Elsa L. S. A. van Liere, Ahmed B. Bayoumy, Chris J. J. Mulder, Ben Warner, Bu Hayee, Bilal A. Mateen, Jonathan D. Nolan, Nanne K. H. de Boer, Simon H. C. Anderson, Azhar R. Ansari Published Oct 2020, in the Digestive Diseases and Sciences.
Abstract
Background Benefcial response to frst-line immunosuppressive azathioprine in patients with infammatory bowel disease (IBD) is low due to high rates of adverse events. Co-administrating allopurinol has been shown to improve tolerability. However, data on this co-therapy as frst-line treatment are scarce.
Aim Retrospective comparison of long-term efectiveness and safety of frst-line low-dose azathioprine-allopurinol cotherapy (LDAA) with frst-line azathioprine monotherapy (AZAm) in patients with IBD without metabolite monitoring.
Methods Clinical beneft was defned as ongoing therapy without initiation of steroids, biologics or surgery. Secondary outcomes included CRP, HBI/SCCAI, steroid withdrawal and adverse events.
Results In total, 166 LDAA and 118 AZAm patients (median follow-up 25 and 27 months) were evaluated. Clinical beneft was more frequently observed in LDAA patients at 6 months (74% vs. 53%, p=0.0003), 12 months (54% vs. 37%, p=0.01) and in the long-term (median 36 months; 37% vs. 24%, p=0.04). Throughout follow-up, AZAm patients were 60% more likely to fail therapy, due to a higher intolerance rate (45% vs. 26%, p=0.001). Only 73% of the efective AZA dose was tolerated in AZAm patients, while LDAA could be initiated and maintained at its target dose. Incidence of myelotoxicity and elevated liver enzymes was similar in both cohorts, and both conditions led to LDAA withdrawal in only 2%. Increasing allopurinol from 100 to 200–300 mg/day signifcantly lowered liver enzymes in 5/6 LDAA patients with hepatotoxicity.
Conclusions Our poor AZAm outcomes emphasize that optimization of azathioprine is needed. We demonstrated a longterm safe and more efective profle of frst-line LDAA. This co-therapy may therefore be considered standard frst-line immunosuppressive.
Keywords Azathioprine · Allopurinol · Thiopurines · Infammatory bowel disease · Drug repositioning