Skip to Main content Skip to Navigation
Master Thesis

Safety and efficacy of dual biologic therapy in severe and refractory inflammatory bowel disease treatment: DB-RA trial

Abstract : Background: Inflammatory Bowel Diseases (IBD) are characterized by chronic intestinal inflammation. Despite the optimization of biologic therapies, a significant proportion of patients have a secondary loss-of-response or are primary non-responders to therapy. Until recently, dual biologic or small molecule therapy (DBT and SBT) was rarely reported in literature. We aim to assess the safety and effectiveness of DBT and SBT (Dual Targeted Therapy DTT) IBD patients across the various individual combinations. Methods : From January 2016 to February 2021, we performed a medical record–based, multicenter retrospective study of established CD or UC patients who were treated with anti-TNF agents, vedolizumab, ustekinumab or tofacitinib in combination at 3 academic IBD centers and 1 general hospital. Indications for combination therapy were: a) uncontrolled active severe IBD patients according to ECCO criteria with ungoing worsening luminal disease or with complicated behaviour disease b) increased uncontrolled active severe perianal disease not controlled by the treatment c) uncontrolled extra intestinal manifestations (EIM). Primary outcomes included M3-6 rates of adverse events, rates of serious adverse events, infections, malignancy, need for hospitalizations and for surgery for each combination Secondary outcomes included M3-6 clinical remission, steroid-free remission, and biomarkers response. Results: 19 severe IBD patients receiving DTT in 4 french IBD referral centers were identified. 16 patients (88,9%) started DTT due to uncontrolled active severe IBD with ungoing worsening luminal disease or with complicated behaviour disease (group a), while 2 started DTT for increased uncontrolled active severe perinanal disease (group b). The most frequently used drug was vedolizumab (15 patients, 79%) and most common combination was vedolizumab + ustekinumab [9 patients, 47.4%]. Only one UC patient experienced at least one AE (5,8%) and 2 SAEs involving the same CD patient were recorded during follow-up (5,8%). 10 out of 15 (66,7%) remaining patients were considered in remission, according to PMS and HBI scores (p =0,002). 6 months after DTT introduction, 100% of patients (n=15) were able to discontinue steroids (p = 0.008). Median levels of inflammatory markers were lower after 6 months of DBT (p= 0,001 and <0,001 for CRP and fecal calprotectin. Conclusion: Our study suggest that DTT is an attractive therapeutic option and may be an opportunity to better tailor and personalize the therapies for patients. Further studies, as randomized control trials, are needed.
Document type :
Master Thesis
Complete list of metadata

https://dumas.ccsd.cnrs.fr/dumas-03409347
Contributor : Jean-Hugues Morneau Connect in order to contact the contributor
Submitted on : Friday, October 29, 2021 - 4:04:37 PM
Last modification on : Sunday, October 31, 2021 - 3:29:28 AM

File

2021GRAL5199_merle_sylvain_dif...
Files produced by the author(s)

Identifiers

  • HAL Id : dumas-03409347, version 1

Citation

Sylvain Merle. Safety and efficacy of dual biologic therapy in severe and refractory inflammatory bowel disease treatment: DB-RA trial. Human health and pathology. 2021. ⟨dumas-03409347⟩

Share

Metrics

Record views

40

Files downloads

6