TY - JOUR
T1 - Sustained effectiveness, safety and therapeutic drug monitoring of tioguanine in a cohort of 274 IBD patients intolerant for conventional therapies
AU - Simsek, Melek
AU - Deben, Debbie S.
AU - Horjus, Carmen S.
AU - Bénard, Melanie V.
AU - Lissenberg-Witte, Birgit I.
AU - Buiter, Hans J.C.
AU - van Luin, Matthijs
AU - Seinen, Margien L.
AU - Mulder, Chris J.J.
AU - Wong, Dennis R.
AU - de Boer, Nanne K.H.
AU - van Bodegraven, Adriaan A.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Background: Tioguanine (or thioguanine) is an alternative drug for IBD patients who fail prior conventional immunomodulating therapy. Aim: To report effectiveness, safety and therapeutic drug monitoring in a cohort of patients with prolonged tioguanine maintenance therapy. Methods: In this nationwide, multicentre study, medical records of tioguanine- using IBD patients were retrospectively reviewed. Response to therapy was defined as clinical effectiveness without (re)initiation of corticosteroids, concurrent biological therapy or surgical intervention. All adverse events that occurred during the follow-up were listed and graded according to the common terminology criteria (CTC). Results: Two hundred and seventy-four patients (female 63%, Crohn's disease in 68%) were included with median treatment duration of 51 months, 1567 patient-years of follow-up and median 20 mg/d tioguanine dosage. Tioguanine was tolerated in 79%, clinical effectiveness at 6 months was documented in 66% and sustained clinical effectiveness during 12 months in 51% of patients. Forty-one per cent of patients developed adverse events: 5% were graded as severe. Adverse events comprised infection requiring hospitalisation in three and skin cancer in eight patients (two melanomas). Asymptomatic nodular regenerative hyperplasia of the liver occurred in two out of 52 patients with liver biopsies (3.8%) and portal hypertension in three whereof one potentially associated with tioguanine (0.4%). Clinical effectiveness was correlated with 6-thioguanine nucleotide threshold concentrations >682 pmol/8×108RBC (P < 0.05). Conclusions: Long-term tioguanine therapy for at least 12 months was effective in 51% and well tolerated as a maintenance treatment for IBD in about 70% of patients. Adverse events were common, but mainly mild or moderate. 6-Thioguanine nucleotide threshold concentration ≥ 700 pmol/8×108RBC is proposed as target level with higher odds for clinical effectiveness.
AB - Background: Tioguanine (or thioguanine) is an alternative drug for IBD patients who fail prior conventional immunomodulating therapy. Aim: To report effectiveness, safety and therapeutic drug monitoring in a cohort of patients with prolonged tioguanine maintenance therapy. Methods: In this nationwide, multicentre study, medical records of tioguanine- using IBD patients were retrospectively reviewed. Response to therapy was defined as clinical effectiveness without (re)initiation of corticosteroids, concurrent biological therapy or surgical intervention. All adverse events that occurred during the follow-up were listed and graded according to the common terminology criteria (CTC). Results: Two hundred and seventy-four patients (female 63%, Crohn's disease in 68%) were included with median treatment duration of 51 months, 1567 patient-years of follow-up and median 20 mg/d tioguanine dosage. Tioguanine was tolerated in 79%, clinical effectiveness at 6 months was documented in 66% and sustained clinical effectiveness during 12 months in 51% of patients. Forty-one per cent of patients developed adverse events: 5% were graded as severe. Adverse events comprised infection requiring hospitalisation in three and skin cancer in eight patients (two melanomas). Asymptomatic nodular regenerative hyperplasia of the liver occurred in two out of 52 patients with liver biopsies (3.8%) and portal hypertension in three whereof one potentially associated with tioguanine (0.4%). Clinical effectiveness was correlated with 6-thioguanine nucleotide threshold concentrations >682 pmol/8×108RBC (P < 0.05). Conclusions: Long-term tioguanine therapy for at least 12 months was effective in 51% and well tolerated as a maintenance treatment for IBD in about 70% of patients. Adverse events were common, but mainly mild or moderate. 6-Thioguanine nucleotide threshold concentration ≥ 700 pmol/8×108RBC is proposed as target level with higher odds for clinical effectiveness.
UR - http://www.scopus.com/inward/record.url?scp=85066996013&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/apt.15280
DO - https://doi.org/10.1111/apt.15280
M3 - Article
C2 - 31094013
SN - 0269-2813
VL - 50
SP - 54
EP - 65
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 1
ER -