Crohn’s disease (CD) is a chronic condition characterized by segmental, transmural inflammation, which, although most common in the terminal ileum and right colon, can affect any part of the alimentary tract. In addition to the commonly observed signs and symptoms of Crohn’s disease, local complications as well as manifestations outside the digestive tract can also occur as a result of Crohn’s disease -associated inflammation, underscoring the importance of effective treatment options.
Subgroup analyses from prospective, randomised, controlled trials in patients with active Crohn’s disease have shown that patient demographics and disease characteristics such as disease duration and treatment history can impact clinical outcomes. Our retrospective study further evaluated the impact of patient baseline clinical and disease characteristics on the efficacy of mongersen, an oral, locally active Smad7 antisense oligonucleotide that targets Smad7 in the ileum and colon. In addition to the impact of human serum C-reactive protein (hsCRP) values, disease duration, and disease activity at baseline on mongersen over 10 weeks, our analysis also looked at how sex, body mass index, smoking status, history of Crohn’s disease-related intestinal resection, steroid status, and immunosuppressant use at baseline impacted treatment efficacy.
Our results showed that patients with Crohn’s Disease Activity Index (CDAI) scores ≤260 at baseline had significantly higher clinical remission rates (defined as a CDAI <150) with mongersen 40 mg/day and 160 mg/day treatment, whereas patients with CDAI scores >260 at baseline achieved clinical remission most frequently with the highest mongersen dose (160 mg/day), suggesting that greater disease activity can impact clinical benefit. Baseline disease characteristics such as hsCRP (<3 mg/L or ≥3 mg/L) and disease duration (<5 or ≥5 years) did not appear to significantly impact efficacy of mongersen treatment in our study.
Aliment Pharmacol Ther. 2016 ;43(6):717-24.
Monteleone G1, Di Sabatino A2, Ardizzone S3, Pallone F1, Usiskin K4, Zhan X4, Rossiter G4, Neurath MF5.[expand title=”Show Affiliations”]
- Department of Systems Medicine, University of Tor Vergata, Rome, Italy.
- First Department of Internal Medicine, St. Matteo Hospital Foundation, University of Pavia, Pavia, Italy.
- Department of Surgery, “L. Sacco” University Hospital, Milan, Italy.
- Celgene Corporation, Warren, NJ, USA.
- Department of Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
In a phase 2 study, mongersen, an oral antisense oligonucleotide targeting Smad7, was effective in inducing clinical remission in approximately 60% of patients with active Crohn’s disease (CD).
In a post hoc analysis to evaluate those patient disease characteristics that may have influenced the efficacy and safety of mongersen therapy.
Patients with steroid-dependent/resistant, active Crohn’s disease were randomised to mongersen 10, 40 or 160 mg/day or placebo for 2 weeks; patients were followed for 10 weeks. Clinical remission [Crohn’s Disease Activity Index (CDAI) score <150] and clinical response (CDAI score reduction ≥100 points) were assessed at weeks 2, 4 and 12 for these subgroups: disease duration <5/≥5 years, human serum C-reactive protein (hsCRP) <3/≥3 mg/L, and CDAI at baseline ≤260/>260. Additional patient baseline and disease characteristics were explored.
Clinical remission and response rates were significantly higher in patients receiving mongersen 40 and 160 mg/day but not 10 mg/day vs. placebo and independent of disease duration and hsCRP. Patients with baseline CDAI ≤260 had significantly higher remission rates with 40 and 160 mg/day. In patients with baseline CDAI >260, remission rates were statistically greater with 160 mg/day and numerically better with 40 mg/day vs. placebo. Adverse event rates were similar across treatment groups. Mongersen was safe and well tolerated.
Patients with higher CDAI scores achieved clinical remission most frequently with the highest mongersen dose. Disease duration and baseline human serum C-reactive protein did not appear to significantly impact efficacy of mongersen in this study (EudraCT Number: 2011-002640-27.).
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