Predictors of Thiopurine Treatment Failure in Biologic-Naïve Ulcerative Colitis Patients.
BACKGROUND
Thiopurines (azathioprine and 6-mercaptopurine) have been used in the management of UC patients for over three decades. Nearly half of patients with UC treated with thiopurines fail to achieve remission or lose remission during treatment. Factors associated with thiopurine failure are poorly understood. The primary aim of our study was to investigate patient-related factors which are associated with thiopurine failure.


METHODS
TNF-alpha antagonist-naïve patients with histological diagnosis of UC, receiving thiopurine therapy, with follow-up data from 1 to 3 years were included in the study. Data regarding demographics, laboratory results, and disease characteristics were collected. The primary endpoint was failure of thiopurine therapy, defined as treatment with steroids, therapeutic escalation to TNF-alpha antagonist therapy, or need for surgery.


RESULTS
Of the 563 patients identified using ICD-9 codes, 78 TNF-alpha antagonist-naïve patients with a histological diagnosis of UC, receiving thiopurine treatment, were identified. Over the three-year follow-up period, 38 patients failed thiopurine treatment. On adjusted Cox regression, BMI < 25 kg/m(2) (HR 3, 95 % CI 1.55-5.83; p value = 0.001) was significantly associated with thiopurine failure. Furthermore, although not statistically significant, there was a strong trend toward thiopurine failure among patients with serum albumin level < 4 g/dL (HR 1.98, 95 % CI 0.97-4; p value = 0.06), non-smoking status (HR 2.2, 95 % CI 0.96-5.06; p value = 0.06), and higher degree of colon inflammation (HR 1.49, 95 % CI 0.96-2.32; p value = 0.08).


CONCLUSIONS
Our results show that low body mass index is associated with increased risk of failure of thiopurine treatment. Furthermore, there was a strong trend toward thiopurine failure among patients with low serum albumin level (<4gm/dL). These factors should be considered as markers of non-response to thiopurine monotherapy for patients with moderately severe ulcerative colitis.
Henry Ford Hospital, Madison Heights, MI, USA. dr.sdthapa@gmail.com.
Sudeep Dhoj
SD
Thapa
Henry Ford Hospital, Madison Heights, MI, USA.
Hiba
H
Hadid
Henry Ford Hospital, Madison Heights, MI, USA.
Mohammed
M
Usman
Henry Ford Hospital, Madison Heights, MI, USA.
Waseem
W
Imam
Henry Ford Hospital, Madison Heights, MI, USA.
Ahmad
A
Hassan
Henry Ford Hospital, Madison Heights, MI, USA.
Jason
J
Schairer
Henry Ford Hospital, Madison Heights, MI, USA.
Syed-Mohammed R
SM
Jafri
Henry Ford Hospital, Madison Heights, MI, USA.
Nirmal
N
Kaur
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D001688:Biological Products / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000601:surgery; D013505:Digestive System Surgical Procedures; D057915:Drug Substitution; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D034141:Hypoalbuminemia / Q000097:blood / Q000453:epidemiology; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D009752:Nutritional Status; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012709:Serum Albumin / Q000032:analysis; D000075462:Serum Albumin, Human; D012720:Severity of Illness Index; D013256:Steroids / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
C422455:ALB protein, human; D000893:Anti-Inflammatory Agents; D001688:Biological Products; D015415:Biomarkers; D005765:Gastrointestinal Agents; D012709:Serum Albumin; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D015122:Mercaptopurine; D001379:Azathioprine; D000075462:Serum Albumin, Human
Inflammatory bowel disease; Thiopurine; Ulcerative colitis