Favourable Tolerability and Drug Survival of Tioguanine Versus Methotrexate After Failure of Conventional Thiopurines in Crohn's Disease.

BACKGROUND AND AIMS: Both methotrexate and tioguanine can be considered as treatment options in patients with Crohn's disease after failure of conventional thiopurines. This study aimed to compare tolerability and drug survival of methotrexate and tioguanine therapy after failure of conventional thiopurines in patients with Crohn's disease. METHODS: We conducted a retrospective, multicentre study, including patients with Crohn's disease initiating monotherapy methotrexate or tioguanine after failure [all causes] of conventional thiopurines. Follow-up duration was 104 weeks or until treatment discontinuation. The primary outcome was cumulative therapy discontinuation incidence due to adverse events. Secondary outcomes included total number of [serious] adverse events, and ongoing monotherapy. RESULTS: In total, 219 patients starting either methotrexate [n = 105] or tioguanine [n = 114] were included. In all 65 [29.7%] patients (methotrexate 43.8% [46/105 people], tioguanine 16.7% [19/114 people], p <0.001) discontinued their treatment due to adverse events during follow-up. Median time until discontinuation due to adverse events was 16 weeks (interquartile range [IQR] 7-38, p = 0.812). Serious adverse events were not significantly different. Patients treated with methotrexate experienced adverse events more often [methotrexate 83%, tioguanine 46%, p <0.001]. Total monotherapy drug survival after 104 weeks was 22% for methotrexate and 46% for tioguanine [p <0.001]. CONCLUSIONS: We observed a higher cumulative discontinuation incidence due to adverse events for methotrexate [44%] compared with tioguanine [17%] in Crohn's disease patients after failure of conventional thiopurines. The total adverse events incidence during methotrexate use was higher, whereas serious adverse events incidence was similar. These favourable results for tioguanine treatment may guide the selection of immunosuppressive therapy after failure of conventional thiopurines.

Renin-induced hypertension in Wilms tumor patients.

BACKGROUND: Since the report that hypertension associated with Wilms tumor (WT) may be renin-induced, no larger series than 13 patients have been published. Nevertheless, angiotensin converting enzyme (ACE) inhibitors have become treatment of choice for hypertension in WT patients. The purpose of this study was to investigate the correlation between plasma renin levels and blood pressure in a larger cohort of WT patients. PROCEDURE: In this retrospective, single-center study, data on blood pressure and plasma renin were analyzed in 86 WT patients treated according to the consecutive SIOP protocols 6, 9, 93-01, and 2001. RESULTS: At diagnosis, 47 WT patients suffered from hypertension (55%). In 31 of these patients plasma renin levels were analyzed; increased plasma renin levels were found in 25/31 patients (81%). In contrast, normal plasma renin levels were measured in 8/13 of the patients with a normal blood pressure (P = 0.012). Twenty-eight children received antihypertensive treatment before surgery, in 25 of them blood pressure normalized before surgery. Blood pressure was normal directly after surgery in all patients but 4, in whom blood pressure recovered to normal within a few weeks. CONCLUSIONS: This retrospective study shows that hypertension in WT patients is associated with elevated plasma renin levels, indicating that ACE inhibitors may be a good therapeutic option in at least a subset of WT patients with hypertension before nephrectomy.