Long-term Safety and Efficacy of Low-dose Azathioprine and Allopurinol Cotherapy in Inflammatory Bowel Disease: A Large Observational Study.
Low-dose azathioprine with allopurinol (LDAA) has been proposed as a potent therapy in inflammatory bowel disease (IBD) with the benefit of overcoming side effects regularly associated with thiopurine monotherapy and poor responses. Concerns regarding safety remain, while a layer of complexity has been added by the trend toward treatment directed by red cell thioguanine nucleotide (TGN) profiling. We report on the clinical efficacy and safety of LDAA use in IBD undirected by metabolite profiling.



Observational study of clinical practice from a single IBD center. Patient outcomes were defined clinically based on established activity scores and corticosteroid withdrawal. Red cell TGN was monitored only for suspected nonadherence.



Overall, 113/164 (69%) patients with Crohn's disease and 83/136 (61%) patients with ulcerative/unclassified colitis had a clinical response by the end of follow-up (median 19 months), while 85 (52%) patients with Crohn's disease and 74 (54%) patients with ulcerative/unclassified colitis were in clinical remission. Clinical response was seen in 45/57 (79%) patients with Crohn's disease and 34/53 (64%) patients with ulcerative/unclassified colitis who were thiopurine naive, had active IBD, and received LDAA as the first line immunomodulator, while in 35 (61%) and 28 (53%), respectively, remission was achieved. LDAA was stopped in 20/300 (7%) patients because of side effects, all of which resolved on drug cessation.



This is the largest cohort supporting the favorable safety profile and high efficacy of LDAA in IBD. It presents 2 advances in therapy: prescribing LDAA for thiopurine-naive patients, and bypassing TGN monitoring in favor of clinical monitoring (blood counts, etc.), which will make it more accessible for clinics without access to TGN assays.
*Surrey and Sussex Healthcare NHS Trust, East Surrey Hospital, Redhill, United Kingdom; †Department of Gastroenterology, King's College Hospital NHS Foundation Trust, King's Health Partners; ‡East Surrey Clinical Commissioning Group Assistant Chair; and §School of Pharmacy and Mater Research Institute, The University of Queensland, Brisbane, Australia.
Polychronis
P
Pavlidis
Panagiotis
P
Stamoulos
Answar
A
Abdulrehman
Patrick
P
Kerr
Claire
C
Bull
John
J
Duley
Azhar
A
Ansari
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000009:adverse effects / Q000627:therapeutic use*; D000963:Antimetabolites / Q000009:adverse effects / Q000627:therapeutic use*; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007413:Intestinal Mucosa; D008297:Male; D008780:Methyltransferases / Q000097:blood; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D000963:Antimetabolites; D007166:Immunosuppressive Agents; D000493:Allopurinol; D002097:C-Reactive Protein; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine