Mongersen, an Oral SMAD7 Antisense Oligonucleotide, and Crohns Disease. Giovanni Monteleone et al. N Engl J Med 2015;372:1104-13.
Adults with moderate to severe inflammation due to Crohn’s disease took part in this study performed in Italy to test the effect of different doses of a new drug, mongersen. Mongersen is a drug, taken by mouth, which modifies the production of TGF Beta. TGF Beta helps to reduce inflammation and is known to be low in patients with Crohn’s disease. It is hoped that mongersen would increase the level of TGF Beta and therefore decrease gut inflammation.
Patients already taking most other disease treatments could take part in the study but patients taking Infliximab or other biologic agents were excluded. The 166 patients who took part were randomly selected to receive one of three doses of mongersen (10, 40, or 160 mg per day) or placebo. Patients only took the treatment for 2 weeks and were followed up for 12 weeks.
The proportions of patients whose disease entered remission (according to clinical scores) after two weeks treatment were significantly higher in the 160-mg group (65%) and 40-mg group (55%) than in the 10-mg group (12%) and placebo group (10%). Change in CRP (a blood marker of inflammation) was not as dramatic as the change seen in clinical scores with only 18% of patients in the 160-mg group achieving a normal CRP. In most results there was no significant difference between the 160-mg and 40-mg groups but outcomes were better than in the 10-mg and placebo groups. Six patients had adverse reactions to the drug (3.6%) these were mainly thought to be effects of Crohn’s rather than the drug itself.
These results are clearly very exciting as the potential for a new treatment. However, the authors do not report the rates of healing of inflammation seen at endoscopy which is now a widely accepted trial outcome for IBD studies and the change in CRP is disappointing compared to the clinical score. In addition the length of time patients were followed up for was very short (12 weeks) as most studies follow patients for at least one year. It is also worth noting that Mongersen is released in the ileum and right side of the colon so is only likely to be of use in patients who have inflammation in that part of their gut.
We will have to wait for more studies to be done to understand how this drug would be included into standard protocols for treatment of Crohn’s disease and as yet it is untested in children.