Moon, Won Kyu

SummaryBackgroundAzathioprine and mercaptopurine have a pivotal role in the treatment of inflammatory bowel disease (IBD). However, because of their complex metabolism and potential toxicities, optimal use of biomarkers to predict adverse effects and therapeutic response is paramount.AimTo provide a comprehensive review focused on pharmacogenetics and pharmacokinetics for safe and effective thiopurine therapy inIBD.MethodsA literature search up to July 2015 was performed in PubMed using a combination of relevant MeSHterms.ResultsPre‐treatment thiopurine S‐methyltransferase typing plus measurement of 6‐tioguanine nucleotides and 6‐methylmercaptopurine ribonucleotides levels during treatment have emerged with key roles in facilitating safe and effective thiopurine therapy. Optimal use of these tools has been shown to reduce the risk of adverse effects by 3‐7%, and to improve efficacy by 15–30%. For the introduction of aldehyde oxidase (AOX) into clinical practice, the association betweenAOXactivity andAZAdose requirements should be positively confirmed. Inosine triphosphatase assessment associated with adverse effects also shows promise. Nucleoside diphosphate‐linked moiety X‐type motif 15 variants have been shown to predict myelotoxicity on thiopurines in East Asian patients. However, the impact of assessments of xanthine oxidase, glutathione S‐transferase, hypoxanthine guanine phosphoribosyltransferase and inosine monophosphate dehydrogenase appears too low to favour incorporation into clinical practice.ConclusionsMeasurement of thiopurine‐related enzymes and metabolites reduces the risk of adverse effects and improves efficacy, and should be considered part of standard management. However, this approach will not predict or avoid all adverse effects, and careful clinical and laboratory monitoring of patients receiving thiopurines remains essential.

SummaryBackgroundCertolizumab pegol (CZP) is Food and Drug Administration (FDA)‐approved to treat Crohn's disease (CD). However, the efficacy and safety of CZP outside clinical trials are not well established.AimTo report the efficacy, safety and predictors of response to CZP in CD patients treated during a 6‐year period since FDA‐approval at a tertiary care centre.MethodsAll CD patients who received CZP at our institution between 2008 and 2013 were evaluated through retrospective medical record‐based review of steroid‐free complete response (SCR), loss of response and safety.ResultsA total of 358 patients were included. One hundred twelve patients (31.3%) and 189 (52.8%) received CZP as their second and third biological agent, respectively. The probability of SCR at 26 week was 19.9% (95% CI, 15.9–24.5). The probability of survival free of loss of response at 2 year was 45.7% (95% CI, 32.5–59.5). A predictor of SCR was age at CD diagnosis of >40 years old (hazard ratio, HR relative to those <17, 4.69; 95% CI, 1.75–12.61). Negative predictors included present perianal fistula (HR, 0.39; 95% CI, 0.16–0.98) and prior primary nonresponse to adalimumab (ADA; HR relative to secondary loss of response, 0.18; 95% CI, 0.04–0.76). Twenty‐three patients (6.4%) experienced serious adverse events and 19 patients (5.3%) discontinued CZP due to adverse events.ConclusionsCertolizumab pegol was both effective and well tolerated for the treatment of Crohn's disease in this large tertiary care centre enriched with biologics‐exposed patients. It may be more effective in patients without early‐aged Crohn's disease diagnosis, prior primary nonresponse to adalimumab and present perianal fistula.