Crohn’s disease is an inflammatory, chronic bowel disease, and very disabling. Ustekinumab is a recently approved drug, a monoclonal antibody, indicated for patients experiencing moderate to severe Crohn’s disease, and for patients already refractory to multiple previous lines of treatments. The FDA approved administration of Ustekinumab is an intravenous injection followed by a maintenance phase of subcutaneous injections every 8 or 12 weeks. Unfortunately, many patients experience loss of response, and require a dose optimization of the treatment, in a personalized and off-label manner. Recent studies have focused on the influence of previous treatments on the effectiveness of Ustekinumab, on potential predictors of response to Ustekinumab, on Therapeutic Drug Monitoring and on dose optimizing the administration of Ustekinumab (interval shortening and reinduction).
The main results of these studies are fourfold : i) the prediction of response to Ustekinumab prior to the start of the treatment is difficult (1), and most of them resulted in negative predictors of response (2); ii) anti-TNFa naïve patients achieve a better response to Ustekinumab than anti-TNFa refractory patients ; iii) the multiple results regarding Therapeutic Drug Monitoring (TDM) are heterogeneous, however, clinical relevance of TDM is agreed upon (3) in different situations, and more trials are warranted iv) dose optimization of the treatment is efficient and seems to be a reliable option, according the majority of the further detailed studies.
The conclusion of this thesis consists of a series of potential new treatment guidelines, taking into consideration all the studies referenced and their interpretations. The posology of Ustekinumab is a complex brainteaser, which needs to be solved in the name of patients in dire need of regaining their quality of life.