PMID- 31359480
OWN - NLM
STAT- MEDLINE
DCOM- 20200515
LR  - 20200515
IS  - 1365-2036 (Electronic)
IS  - 0269-2813 (Linking)
VI  - 50
IP  - 4
DP  - 2019 Aug
TI  - Real-life study of safety of thiopurine-allopurinol combination therapy in 
      inflammatory bowel disease: myelotoxicity and hepatotoxicity rarely affect 
      maintenance treatment.
PG  - 407-415
LID - 10.1111/apt.15402 [doi]
AB  - BACKGROUND: Low-dose thiopurine-allopurinol (LDTA) combination therapy is a 
      commonly applied optimisation strategy in IBD patients with a skewed thiopurine 
      metabolism. AIM: To assess continued LDTA maintenance treatment at annual 
      intervals and explore risk factors for treatment cessation METHODS: Adult IBD 
      patients treated with LDTA between 2009 and 2016 were retrospectively included. 
      Data on the incidence of clinical and laboratory adverse events (AEs), including 
      hepatotoxicity and myelotoxicity resulting in imposing LDTA therapy cessation and 
      associated risk factors were collected. RESULTS: In total, 221 IBD patients (46% 
      male, median age 42 years) were included. Maintenance LDTA treatment was 
      continued in 78% of patients at 1 year (n = 145), 66% at 2 years (n = 83), 57% at 
      3 years (n = 52) and 52% at 4 years (n = 33). Treatment in patients receiving 
      LDTA therapy for AEs during thiopurine monotherapy was more often continued than 
      in patients initiating LDTA for other indications (eg, ineffectiveness of 
      thiopurine monotherapy, routinely discovered skewed metabolism) (P = 0.016). 
      Myelotoxicity during thiopurine monotherapy resolved in 87% and hepatotoxicity in 
      86% after median of 1.2 and 1.4 months after LDTA initiation. Cumulative 
      incidence of AEs during LDTA resulting in therapy cessation within total 
      follow-up of 449 treatment-years was 7% for clinical AEs, 4% for myelotoxicity 
      and 1% for hepatotoxicity. CONCLUSION: LDTA therapy is a safe and beneficial 
      optimisation strategy in IBD patients. Continued maintenance LDTA treatment is 
      52% after 4 years of treatment and most commonly affected by ineffectiveness of 
      LDTA rather than LDTA-attributed toxicity. LDTA optimisation strategy is most 
      advantageous in patients failing thiopurine monotherapy due to AEs.
CI  - (c) 2019 John Wiley & Sons Ltd.
FAU - Kreijne, Joany E
AU  - Kreijne JE
AUID- ORCID: 0000-0002-4015-5571
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center, Rotterdam, The Netherlands.
FAU - de Veer, Rozanne C
AU  - de Veer RC
AUID- ORCID: 0000-0003-1604-0931
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center, Rotterdam, The Netherlands.
FAU - de Boer, Nanne K
AU  - de Boer NK
AD  - Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit 
      Amsterdam, AG&M Research Institute, Amsterdam, The Netherlands.
FAU - Dijkstra, Gerard
AU  - Dijkstra G
AD  - Department of Gastroenterology and Hepatology, University Medical Center 
      Groningen and University of Groningen, Groningen, The Netherlands.
FAU - West, Rachel
AU  - West R
AD  - Department of Gastroenterology and Hepatology, Sint Franciscus Gasthuis & 
      Vlietland, Rotterdam, The Netherlands.
FAU - Moorsel, Sofia A W
AU  - Moorsel SAW
AUID- ORCID: 0000-0003-1947-8971
AD  - Department of Pharmacology, Zuyderland Medical Center, Heerlen-Sittard-Geleen, 
      The Netherlands.
FAU - de Jong, Dirk J
AU  - de Jong DJ
AD  - Department of Gastroenterology and Hepatology, Radboud University Medical Center, 
      Nijmegen, The Netherlands.
FAU - van der Woude, C Janneke
AU  - van der Woude CJ
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center, Rotterdam, The Netherlands.
FAU - de Vries, Annemarie C
AU  - de Vries AC
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center, Rotterdam, The Netherlands.
CN  - of the Dutch Initiative on Crohn, Colitis (ICC)
LA  - eng
GR  - Erasmus MC Medical Research Advisory Comittee (Mrace 2016) program/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Aliment Pharmacol Ther
JT  - Alimentary pharmacology & therapeutics
JID - 8707234
RN  - 0 (Immunosuppressive Agents)
RN  - 63CZ7GJN5I (Allopurinol)
RN  - E7WED276I5 (Mercaptopurine)
SB  - IM
MH  - Adult
MH  - Allopurinol/administration & dosage/*adverse effects
MH  - Bone Marrow Diseases/*chemically induced/*epidemiology
MH  - Chemical and Drug Induced Liver Injury/*epidemiology
MH  - Drug Therapy, Combination
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/adverse effects
MH  - Inflammatory Bowel Diseases/*drug therapy/epidemiology
MH  - Male
MH  - Medication Adherence/statistics & numerical data
MH  - Mercaptopurine/administration & dosage/*adverse effects
MH  - Middle Aged
MH  - Netherlands/epidemiology
MH  - Retrospective Studies
MH  - Withholding Treatment/*statistics & numerical data
OTO - NOTNLM
OT  - adverse events
OT  - allopurinol
OT  - hepatotoxicity
OT  - inflammatory bowel disease
OT  - myelotoxicity
OT  - thiopurine
EDAT- 2019/07/31 06:00
MHDA- 2020/05/16 06:00
CRDT- 2019/07/31 06:00
PHST- 2019/01/22 00:00 [received]
PHST- 2019/02/12 00:00 [revised]
PHST- 2019/06/16 00:00 [accepted]
PHST- 2019/07/31 06:00 [entrez]
PHST- 2019/07/31 06:00 [pubmed]
PHST- 2020/05/16 06:00 [medline]
AID - 10.1111/apt.15402 [doi]
PST - ppublish
SO  - Aliment Pharmacol Ther. 2019 Aug;50(4):407-415. doi: 10.1111/apt.15402.