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Gut. 2007 April; 56(4): 576.
PMCID: PMC1856868


Further evidence that thiopurines are safe in pregnancy

[filled triangle] Langagergaard V, Pedersen L, Gislum M,et al. Birth outcome in women treated with azathioprine or mercaptopurine during pregnancy: a Danish nationwide cohort study. Aliment Pharm Ther 2007;25:73–81.

The placenta forms a relative barrier to thiopurines and their metabolites; 6‐thioguanine crosses the placenta, but 6‐methylmercaptopurine does not. Although animal studies show teratogenicity, most human data are limited to case reports and series. The only controlled studies have shown conflicting results.

The authors, therefore, conducted a nationwide cohort study, using the Danish fertility database, linked to the national prescription database and investigated pregnancies from 1996 to 2001 inclusive. They selected 64 pregnancies where the women had been treated with a prescription for azathioprine or mercaptopurine in the 30 days before conception and up to the end of the first trimester (early pregnancy) to look for congenital abnormalities. In addition, the authors selected 65 pregnancies for women who had been treated between the first and the third trimester (entire pregnancy), to look for preterm birth and low birthweight at term (76 births from 69 women were included in both groups). Overall, 41 births were from women with ulcerative colitis or Crohn's disease (the remainder had liver disease, renal transplant or other systemic disorders). The comparison groups were women who had taken no prescription drugs during these periods, and were matched for age and county of residence, with 1243 and 1274 live births for the two groups. Only live births were studied. In addition, a disease control group included 174 births from women treated with the drugs at least three months before the pregnancy, but not during.

In the entire pregnancy group, there were 26.2% preterm births, 4.2% low birthweight. This gives a relative risk (RR) of 1.9 (CI 1.1 to 3.3) and 1.7 (CI 0.3 to 8.7) in comparison with the healthy controls. In the early pregnancy group, there were 9.4% congenital abnormalities, with RR 1.1 (CI 0.5 to 2.9). However, when compared with the disease control group, there was a less significant increase in risk of preterm birth (RR 1.9 (CI 1.1 to 3.3)), and no increase in risk of low birthweight (RR 1.7 (CI 0.3 to 8.7)) or congenital abnormality (RR 1.1 (CI 0.5 to 2.9)). It seems, therefore, that the risk of fetal damage is primarily related to the underlying disease process, and not to the thiopurine drugs. This population‐based study provides further strong and reassuring evidence of the safety of using thiopurines during pregnancy.

Statins and colorectal cancer: another prevention strategy bites the dust

[filled triangle] Coogan PF, Smith J, Rosenberg L. Statin use and risk of colorectal cancer. J Natl Cancer Inst 2007;99:32–40.

Statins lower cholesterol through the inhibition of the HMG‐CoA reductase enzyme. This enzyme is also over expressed in colorectal cancer cells and statins have been shown to have anticancer effects in vitro and in animal models. A case‐control study suggested that the use of statins for at least five years was associated with a reduced risk of developing colorectal cancer (Poynter JN, et al. NEJM 2005;352:2184–92), although post hoc analyses of randomised controlled trials have yielded conflicting results. Coogan et al report a large study of 1809 cases of colorectal cancer and 1809 population age, sex and geographical area matched controls. Statin use was not associated with a reduced risk of colorectal cancer (adjusted odds ratio (OR) 0.92; 95% CI 0.78 to 1.09). There was no association between cumulative standardised dose or duration of statin treatment and risk of colorectal cancer. In a subgroup analysis, there was a reduced risk of stage IV cancer (OR 0.49; 95% CI 0.26 to 0.91). Continued regular use of non‐steroidal anti‐inflammatory drugs was associated with a reduced risk of colorectal cancer (OR 0.67; 95% CI 0.53 to 0.85). Statins are expensive drugs and these data do not support their use in chemoprevention for colorectal cancer.

Minding the gap

[filled triangle] Jeffrey GP, MacQuillan G, Chua F, et al. Hepatitis C virus eradication in intravenous drug users maintained with subcutaneous naltrexone implants. Hepatology 2007;45:111–17.

Much of the gap that exists between the reported efficacy of combination treatment in clinical trials and its impact — or lack of it — on the burden of chronic hepatitis C in the population is due to barriers preventing access to hepatitis C virus (HCV) treatment. Current intravenous drug users (IDUs) are often not considered for HCV treatment until after a period of abstinence. Jeffrey et al recruited IDUs maintained on subcutaneous naltrexone implants (replaced every 3 to 6 months) for the study. The first 50 patients to commence combination treatment (α‐interferon plus ribavirin) and complete at least 6 months' follow‐up were prospectively studied. The treatment in this community‐based clinic resulted in a 62% sustained virological response ((SVR), intention‐to‐treat) at 6 months post‐treatment; quite comparable with that reported in hospital‐based patient groups and non‐IDU patients. Patients who showed SVR included 22/33 patients with genotype 2 or 3 and 9/17 with genotype 1. The side effect profile of combination treatment in this group was no worse than those reported in non‐IDU patients. All 22 patients that had 12 months or longer follow‐up after completing treatment had remained HCV RNA negative. Irrespective of whether lack of inhibition of endogenous interferon with naltrexone (in contrast with methadone) was independently responsible for the high SVR reported by this study, results encourage increased use of HCV treatment in current IDUs.

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