Session Information
Date: Sunday, November 8, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Azathioprine (AZA) is a commonly used immunosuppressive agent for a number of systemic rheumatic diseases. Although it is regarded to be relatively safe to prescribe in daily clinical practice, untoward rare side effects, especially gastrointestinal adverse events (GIAE) are sporadic, severe and troublesome. There is currently no test or guideline to help predict or prevent this event.
Methods: We reviewed medical records of patients followed at a rheumatology outpatient clinic in a single center (2012.3.1-2015.2.28, SMG-SNU BRMH). Clinical parameters including demographic data, underlying conditions, AZA dose and duration of use, concomitant medications, and laboratory exams were analyzed. Patients with AZA GIAE were defined as those having severe nausea, vomiting or diarrhea, and malaise during AZA ingestion unexplained otherwise. In total, 12 patients with GIAE and 37 control patients (with no side effects after 6 months of AZA) were identified, and among those, whole blood was drawn from 10 GIAE patients and 23 age/gender-matched controls for thiopurine methyltransferase (TPMT) testing (Green Cross Labs).
Results: The baseline data of AZA GIAE patients showed mean age of 58.4 years, and 58% were females. Mean disease duration of the underlying condition was 29.9 months. The initial dose of AZA was 56.3 mg/d, and GIAE was detected after 57.9 days, when on 85.4 mg/d (all mean values). Around that same period, the control group was on 66.7 mg/d of AZA (p= 0.057). Other clinical parameters between the two groups were comparable. TPMT genotype all GIAE patients were that of wild type, and mean TPMT enzymatic activity of GIAE patients and controls were 34.42 U, 34.23 U, respectively (p= 0.97). Notable laboratory results are described below (table).
Conclusion: These results suggest that early prediction of AZA GIAE is still challenging; physician’s awareness, gradual AZA dose increment, early follow-up of liver function tests are conventional, yet important principles to follow.
Table. Selected notable laboratory findings at the period of the adverse event of azathioprine
|
Laboratory test |
GIAE (n=12) |
Controls* (n=35) |
p-value |
|
White blood cells, mm3 |
8055 ± 856.0 |
7120 ± 523.7 |
p= 0.367 |
|
Aspartate aminotransferase, IU/L |
115.2 ± 28.7 |
24.9 ± 2.3 |
p< 0.001 |
|
Alanine aminotransferase, IU/L |
171.7 ± 46.3 |
20.5 ± 2.3 |
p < 0.001 |
|
Alkaline phosphatase, IU/L |
260.3 ± 83.5 |
83.7 ± 11.5 |
p= 0.0014 |
|
Erythrocyte sedimentation rate, mm/hr |
32.2 ± 7.3 |
19.4 ± 3.5 |
p= 0.0854 |
|
C-reactive protein, mg/dL |
1.0 ± 0.3 |
0.4 ± 0.1 |
p= 0.0505 |
*Laboratory value at 57.9 ± 14 days after starting azathioprine
GIAE, gastrointestinal adverse event
To cite this abstract in AMA style:
Ahn EY, Kwon HM, Park SH, Song YW, Shin K. Gastrointestinal Adverse Events of Azathioprine in Daily Clinical Practice: Independent of Thiopurine Methyltransferase Activity [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/gastrointestinal-adverse-events-of-azathioprine-in-daily-clinical-practice-independent-of-thiopurine-methyltransferase-activity/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/gastrointestinal-adverse-events-of-azathioprine-in-daily-clinical-practice-independent-of-thiopurine-methyltransferase-activity/