Recurrence of Non-melanoma Skin Cancer in Inflammatory Bowel Disease Patients Who Continue Thiopurines After Developing Incident Non-melanoma Skin Cancer While on a Thiopurine

Abstract

Introduction: The use of thiopurines (TP) in patients with inflammatory bowel disease (IBD) is associated with an increased risk of developing non-melanoma skin cancer (NMSC). There is however, paucity of data on the recurrence rate of NMSC if TP are continued after the incident NMSC. Our aim was to determine the rate, number and complications of such recurrences if TP were continued. Methods: We conducted a retrospective study on nationwide data obtained from Veterans Affairs (VA) healthcare system. Veterans who were seen and followed up in the VA healthcare system from January 01, 2001 to June 30, 2016 were identified using the International Classification of Diseases (ICD-9 and ICD-10 codes) for IBD and NMSC. The exposure of interest was patients with IBD who were on TP, developed NMSC while on therapy and continued TP after the development of NMSC. The outcome of interest was one or more recurrence of NMSC. The patients were followed up until the last date of TP use, death or lost to follow up. Our definition of NMSC was based on pathology, diagnostic and surgical treatment codes. A manual chart review was performed by two individual reviewers to ascertain the NMSC diagnosis based on the surgical pathological reports. All recurrences were confirmed by surgical pathology reports.Figure: Time to first recurrence of NMSC.Figure: Number of recurrences.Table: Table. Death due to NMSC complicationsResults: A total of 263 patients had NMSC while on a TP. Median age of the population was 67 (IQR 62-73) years at time of first recurrence of NMSC with majority of population being male (98.1%) and Caucasian (97.7%). Amongst them, 257 (97.7%) patients continued TP medication after NMSC diagnosis. Median duration of follow up was 3.24 years (IQR 1.72-5.83). At least one NMSC recurrence was present in 149 (56.6%) patients, while 125 (47.5%) had two or more recurrences with a median number of recurrences being 3 (IQR 2-5). The median dose of azathioprine (AZA) at the first and the last recurrence was 1.44 (IQR 1.09- 1.82) mg/kg/day and 1.42mg/kg/day (IQR 0.94-1.77) respectively. The median dose of 6-mercaptopurine at the first and the last recurrence was 1 (IQR 0.67-1.28) mg/kg/day and 0.91mg/kg/day (IQR 0.31-2.29) respectively. A total of 66 (25.1 %) patients died during the follow up out of which 8 (3%) died due to NMSC complications. Conclusion: In patients who developed NMSC while on TP therapy there was a high rate of recurrence with continuation of therapy. More importantly the majority of patients who recurred had multiple recurrences and 3% of the patients died of complications of the recurrence.