Efficacy and Safety of Azathioprine and 6-Mercaptopurine in Japanese Pediatric Patients with Ulcerative Colitis: A Survey of the Japanese Society for Pediatric Inflammatory Bowel Disease

Tajiri, Hitoshi; Tomomasa, Tsuyoshi; Yoden, Atsushi; Konno, Mutsuko; Sasaki, Mika; Maisawa, Shuniti; Sumazaki, Ryo; Shimizu, Tadayori; Toyoda, Shigeru; Etani, Yuri; Nakacho, Mariko; Ushijima, Kosuke; Kobayashi, Akio

doi:10.1159/000140974

Cited by 25 publications

(24 citation statements)

References 34 publications

(19 reference statements)

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“…Hepatitis was reported in 2 patients (10%) and leukopenia was reported in 1 patient (5%). Tajiri et al [11] reported that 14 patients (40%) of 35 UC patients experienced adverse drug effects to AZA or 6-MP treament in a study conducted in Japan. Leukopenia was reported reported in 11 patients (27.5%), aplastic anemia in 1 patient (2.5%), pancreatitis in 1 patient (2.5%) and liver dysfunction in 1 patient (2.5%).…”

Section: Discussionmentioning

confidence: 99%

Adverse Events Associated with Azathioprine Treatment in Korean Pediatric Inflammatory Bowel Disease Patients

Chun

Kang

Lee

et al. 2013

Pediatr Gastroenterol Hepatol Nutr

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PurposeThis study was aimed to evaluate the frequency and course of adverse events associated with azathioprine treatment in Korean pediatric patients with inflammatory bowel disease.MethodsTotal of 174 pediatric patients (age range, 1 to 19 years) with inflammatory bowel disease who received azathioprine in order to maintain remission at Samsung Medical Center (Seoul, Korea) from January 2002 through December 2012 were included in this study. Medical records of these subjects were retrospectively reviewed regarding the development of adverse events associated with azathioprine treatment.ResultsNinety-eight patients (56.3%) of 174 patients experienced 136 episodes of adverse events, requiring dose reduction in 31 patients (17.8%), and discontinuation in 18 patients (10.3%). The mean dose of azathioprine that had been initially administered was 1.32±0.42 mg/kg/day. Among the adverse reactions, bone marrow suppression developed in 47 patients (27.0%), requiring dose reduction in 22 patients (12.6%) and discontinuation in 8 patients (4.6%). Other adverse events that occurred were gastrointestinal disturbance (15.5%), hair loss (12.1%), pancreatitis (7.5%), arthralgia (6.9%), hepatotoxicity (2.9%), skin rash/allergic reactions (2.9%), headache/dizziness (2.3%), sepsis (0.6%), and oral mucositis (0.6%).ConclusionBone marrow suppression, especially leukopenia was most commonly associated with azathioprine treatment in Korean pediatric inflammatory bowel disease patients. Close observation for possible adverse events is required in this population with inflammatory bowel diseases who are under treatment with azathioprine.

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Section: Discussionmentioning

confidence: 99%

Adverse Events Associated with Azathioprine Treatment in Korean Pediatric Inflammatory Bowel Disease Patients

Chun

Kang

Lee

et al. 2013

Pediatr Gastroenterol Hepatol Nutr

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“…There appears to be a higher rate of adverse events in Asians compared with Caucasians prescribed thiopurines, particularly bone marrow suppression in up to 40% of Asian subjects 193,194 . Thiopurine methyltransferase (TPMT) polymorphisms alone may not be responsible for the development of toxicity in Asian patients 194,195 .…”

Section: Medical Therapymentioning

confidence: 99%

Inflammatory bowel disease in Asia: A systematic review

Prideaux

Kamm

Cruz

et al. 2012

J of Gastro and Hepatol

302

249

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The incidence and prevalence of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are lower in Asia than in the West. However, across Asia the incidence and prevalence of IBD has increased rapidly over the last two to four decades. These changes may relate to increased contact with the West, westernization of diet, increasing antibiotics use, improved hygiene, vaccinations, or changes in the gut microbiota. Genetic factors also differ between Asians and the Caucasians. In Asia, UC is more prevalent than CD, although CD incidence is rapidly increasing in certain areas. There is a male predominance of CD in Asia, but a trend towards equal sex distribution for UC. IBD is diagnosed at a slightly older age than in the West, and there is rarely a second incidence peak as in the West. A positive family history is much less common than in the West, as are extra-intestinal disease manifestations. There are clear ethnic differences in incidence within countries in Asia, and an increased incidence in IBD in migrants from Asia to the West. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.

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“…Azathioprine and 6‐MP are considered equivalent in efficacy at the equivalent doses. A survey of the efficacy and safety of AZA/ 6‐MP in a Japanese pediatric population with UC found that 40% developed adverse drug effects including aplastic anemia, leukopenia and hepatotoxicity 155 . Lower starting doses in Asian compared to Caucasian populations along with close monitoring of complete blood count and liver function is recommended 156 .…”

mentioning

confidence: 99%

The Asia‐Pacific consensus on ulcerative colitis

Ooi

Fock

Makharia

et al. 2010

J of Gastro and Hepatol

140

101

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Inflammatory bowel disease (IBD) is increasing in many parts of the Asia-Pacific region. There is a need to improve the awareness of IBD and develop diagnostic and management recommendations relevant to the region. This evidence-based consensus focuses on the definition, epidemiology and management of ulcerative colitis (UC) in Asia.A multi-disciplinary group developed the consensus statements, reviewed the relevant literature, and voted on them anonymously using the Delphi method. The finalized statements were reviewed to determine the level of consensus, evidence quality and strength of recommendation.Infectious colitis must be excluded prior to diagnosing UC. Typical histology and macroscopic extent of the disease seen in the West is found in the Asia-Pacific region. Ulcerative colitis is increasing in many parts of Asia with gender distribution and age of diagnosis similar to the West. Extra-intestinal manifestations including primary sclerosing cholangitis are rarer than in the West. Clinical stratification of disease severity guides management. In Japan, leukocytapheresis is a treatment option. Access to biologic agents remains limited due to high cost and concern over opportunistic infections. The high endemic rates of hepatitis B virus infection require stringent screening before initiating immune-suppressive agents. Vaccination and prophylactic therapies should be initiated on a case-by-case basis and in accordance with local practice. Colorectal cancer complicates chronic colitis.A recent increase in UC is reported in the Asia-Pacific region. These consensus statements aim to improve the recognition of UC and assist clinicians in its management with particular relevance to the region.

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Efficacy and Safety of Azathioprine and 6-Mercaptopurine in Japanese Pediatric Patients with Ulcerative Colitis: A Survey of the Japanese Society for Pediatric Inflammatory Bowel Disease

Cited by 25 publications

References 34 publications

Adverse Events Associated with Azathioprine Treatment in Korean Pediatric Inflammatory Bowel Disease Patients

Adverse Events Associated with Azathioprine Treatment in Korean Pediatric Inflammatory Bowel Disease Patients

Inflammatory bowel disease in Asia: A systematic review

The Asia‐Pacific consensus on ulcerative colitis

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