Small molecule drugs in the treatment of inflammatory bowel diseases: which one, when and why? – a systematic review
| Autor: | Radu Seicean, Laura A. Lucaciu, Andrada Seicean |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Sphingosine 1 Phosphate Receptor Modulators
Oncology Ozanimod medicine.medical_specialty Filgotinib Integrin alpha4 Smad Proteins Inflammatory bowel disease law.invention Small Molecule Libraries 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Randomized controlled trial law Internal medicine medicine Humans Janus Kinase Inhibitors Tofacitinib Hepatology business.industry Gastroenterology Inflammatory Bowel Diseases medicine.disease Ulcerative colitis Clinical trial chemistry 030220 oncology & carcinogenesis 030211 gastroenterology & hepatology Phosphodiesterase 4 Inhibitors Janus kinase business |
| Zdroj: | European Journal of Gastroenterology & Hepatology. 32:669-677 |
| ISSN: | 0954-691X |
| DOI: | 10.1097/meg.0000000000001730 |
| Popis: | In the 'treat-to-target' era of inflammatory bowel disease (IBD) management, small molecule drugs (SMDs) represent a promising alternative to biomolecular drugs. Moreover, increasing failure rates of anti-tumor necrosis factor α agents have contributed to the development of new molecules with different mechanisms of action and bioavailability. This review focuses on the positioning of new, orally targeted therapies in the treatment algorithm of both Crohn's disease (CD) and ulcerative colitis (UC), with special consideration to their efficacy and safety. We performed a comprehensive search of PubMed and clinical trial registries to identify randomized controlled trials assessing SMDs in adult patients with moderate-to-severe IBD, irrespective of previous exposure to other biologics. In this review, we included 15 double-blind, placebo-controlled trials that assessed the efficacy and safety of Janus kinase inhibitors, sphingosine-1-phosphate modulators (S1P), SMAD blockers, phosphodiesterase 4 inhibitors and α-4 antagonists. The primary endpoints in UC were achieved for tofacitinib in the phase III OCTAVE study and AJM-300, with a favorable safety profile. S1P receptor agonists, such as etrasimod and ozanimod, demonstrated favorable results in induction studies. For CD, filgotinib and upadacitinib also met the primary outcome criteria. Available data have demonstrated so far that SMDs have an advantageous safety and efficacy profile. However, their use in a clinical setting will eventually require a personalized, mechanism-based therapeutic approach. |
| Databáze: | OpenAIRE |
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