TPMT PHENOTYPIC AND GENETIC ASSOCIATION WITH THIOPURINE TOXICITY

OutcomesPhenotypic associationGenotypic association (primary analysis)
Adverse EventI vs. NL vs. IL vs. NHeterozygotes vs. noncarriersHomozygotes vs. noncarriersHeterozygotes vs. homozygotes
Mortality, hospitalization, SAE and HQoL------
Infection---0.07 (0.00, 118.75) 3 studies, 154 patients--
Withdrawal due to adverse event(s)1.81 (0.89 – 3.67)--3.44 (0.78, 15.21)--
4 studies, 425 patients--3 studies, 150 patients--
Myelotoxicity1.58 (0.72, 3.50)14.53 (2.78, 76.01)19.12 (4.56, 80.24)0.37 (0.08, 1.66)1.36 (0.30, 6.16)-
5 studies, 902 patients3 studies, 92 patients3 studies, 403 patients4 studies, 187 patients2 studies, 55 patients-
Leukopenia1.12 (0.70, 1.78)*2.74 (1.54, 4.86)2.56 (1.41, 4.67)4.29 (2.67, 6.89)20.84 (3.42, 126.89)2.26 (0.26, 19.91)
8 studies, 762 patients4 studies, 257 patients4 studies, 397 patientsΩ18 studies, 1825 patients5 studies, 482 patients4 studies, 42 patients
Neutropenia------
Anemia1.66 (0.36, 7.64)--1.27 (0.30 – 5.45)--
2 studies, 246 patients--2 studies, 110 patients--
Thrombocytopenia---2.00 (0.34, 11.71)--
---3 studies, 253 patients--
Hepatotoxicity1.62 (0.75 – 3.51)1.19 (0.13, 11.11)2.17 (0.26, 18.29)0.43 (0.14, 1.34)2.89 (0.52, 16.02)-
7 studies, 775 patients2 studies, 68 patients2 studies, 433 patients11 studies, 1032 patients3 studies, 218 patients
Pancreatitis1.15 (0.38, 3.47)1.92 (0.19, 19.72)N/A0.40 (0.12, 1.32)0.80 (0.14, 4.57)-
6 studies, 1117 patients2 studies, 68 patients10 studies, 807 patients4 studies, 288 patients
Additional analysis
Inconclusive results for all outcomes, except:
  • withdrawal due to adverse events – heterozygotes versus noncarriers 5.55 (2.26, 13.63))
  • leukopenia -- heterozygotes versus noncarriers, 4.87 (3.34, 7.09)
  • leukopenia -- homozygotes versus noncarriers, 49.24 (10.23, 236.99)
  • leukopenia -- homozygotes versus heterozygotes, 7.54 (1.15, 49.57)
  • hepatotoxicity – homozygotes versus heterozygotes 29.00 (1.40, 600.54)

= I2 57%, and p-value >0.05;

Ω

= I2 79%, and p-value <0.05 I= intermediate activity; L = low activity

Estimates that lost statistical significance in the modified analysis;

= I2 57%, and p-value >0.05;

= I2 79%, and p-value <0.05 I= intermediate activity; L = low activity

From: Addendum—Updating the Report and Reanalysis

Cover of Assessment of Thiopurine Methyltransferase Activity in Patients Prescribed Azathioprine or Other Thiopurine-Based Drugs
Assessment of Thiopurine Methyltransferase Activity in Patients Prescribed Azathioprine or Other Thiopurine-Based Drugs.
Evidence Reports/Technology Assessments, No. 196.
Booth RA, Ansari MT, Tricco AC, et al.

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