The results of the “UC SUCCESS” trial show that combination therapy with infliximab and azathioprine is more effective than either medication as monotherapy in ulcerative colitis (UC) (Gastroenterol 2014; 146: 392-400). This study findings are similar to the SONIC trial in Crohn’s disease (CD).
Study Design: randomized, double-blind trial with evaluation at 16 weeks with a total of 239 patients. In patients assigned to infliximab (IFX) alone, they were given daily oral placebo pills. In patients with azathioprine monotherapy (AZA), dosed at 2.5 mg/kg/day, they also received placebo infusions. Patients had moderate to severe UC as defined by Mayo scores at baseline and had not responded adequately to a course of corticosteroids. All patients were naive to tumor necrosis factor α antagonists (anti-TNFα). Mean age was approximately 40 years.
- IFX/AZA had a 39.7% corticosteroid-free remission at week 16 compared with 22.1% with IFX monotherapy and 23.8% with AZA monotherapy.
- Mucosal healing at week 16 was evident in 62.8% of combination group compared with 54.6% IFX monotherapy and 36.8% with AZA monotherapy.
- Serious adverse events were noted more frequently in the AZA monotherapy group, though this did not reach statistical significance.
- A subset of patients had antibodies to infliximab (ATIs) measured. ATI-positivity was more common with IFX monotherapy (19%, 7 of 37) than for IFX/AZA combination (3%, 1 of 31)
While this study indicates that for moderate to severe UC combination therapy with IFX/AZA was superior in this age group, there were several limitations. Given the slow onset of action of azathioprine, more patients may have responded to this therapy if longer treatment duration was studied.
Take-home message: Combination therapy for UC, like CD, is more effective. In this small study population, the adverse events were not increased. In the pediatric population, particularly males, the concern for malignancy in patients (especially males) treated with combination therapy may limit the frequency of combination therapy.
Related blog posts:
- Infliximab for children with Ulcerative Colitis | gutsandgrowth
- Predicting Remission in Pediatric Ulcerative Colitis | gutsandgrowth
- Predictors of colectomy in pediatric UC | gutsandgrowth
Other recent IBD articles of interest:
Inflamm Bowel Dis 2014; 20: 291-300. “Malignancy and Mortality in Pediatric Patients with Inflammatory Bowel Disease” This article presented the results of a survey of 20 European countries and Israel. Key finding: 18 cases of cancer and 31 deaths in 44 children. 5 of the deaths were due to cancer; the most common cause of mortality was infectious (n=14). In this cohort, all HSTCL or EBV-positive lymphomas were treated with thiopurine monotherapy.
Inflamm Bowel Dis 2014; 20: 196-212. “Opportunistic Infections Due to Inflammatory Bowel Disease Therapy” This review article covers a broad range of pathogens and includes recommendations for prophylaxis and treatment (Table 3). In addition the authors provide suggestions for checking for several infections prior to treatment and vaccinations.