Table 2.
Summary and take home messages
| 1. The pathogenesis of IBD is not completely understood yet, and all therapies currently available are aimed at downstream steps of the complex inflammatory process. Specific targets when treating children with IBD are achieving satisfactory growth and nutritional status. |
| 2. Paediatric pharmacometric approaches are increasingly applied to drugs already in use but that remain unlicensed and off-label in children due to missing information on age appropriate dosing, efficacy and safety. |
| 3. Corticosteroids can be used to induce remission in CD (when exclusive enteral nutrition is not possible) and are first-line therapy for induction of remission in UC, particularly in case of non-response to 5-ASA or with severe presentation. |
| 4. One of the targets of current research is to customise therapy to a patient’s predictive biomarker profile in order to personalise treatments and to maximise response. |
| 5. 5-ASA are used in induction and maintenance of remission in UC. They are not recommended in CD except from post-operative maintenance of remission. |
| 6. Thiopurines include AZA and 6-MP and are steroid sparing agents. They are effective in maintaining disease remission in patients with CD and UC as well as post-surgical remission in CD. The use of TPMT activity and 6-TGN level measurements helps avoiding nearly a quarter of episodes of myelosuppression as well as to monitor non-compliance, under-dosing, drug-resistance or refractory state. |
| 7. An increase in mean 6-TGN blood level has been reported in patients on 6-MP or AZA co-treated with 5-ASA, with a higher rate of myelotoxicity in respect to patients treated with the thiopurine alone. |
| 8. MTX is effective in 50%-80% of the children who fail to respond or are intolerant to thiopurines. It is particularly suitable to patients who have coexistent inflammatory arthritis. |
| 9. In CD, anti-TNF agents are used to treat moderate to severe disease with inadequate response, or contraindication to, or intolerance to, conventional therapy including corticosteroids and immunomodulators. They are also indicated in children with active perianal fistulising disease. Therapeutic drug monitoring of IFX has improved response rates and is increasingly used in clinical practice as a tool for the management of secondary failure to IFX. |
| 10. ADA is a fully human IgG1k monoclonal antibody, which represents a treatment option in patients who have lost response or are intolerant to IFX. ADA achieves remission rates of 45% at 1 yr in anti-TNF naïve children and is effective in nearly 2/3 of patients with IFX failure. |
| 11. Vedolizumab is an anti-integrin therapy which inhibits the migration of intestinal T lymphocytes. The mechanism of action of Vedolizumab is restricted to the GI tract, mitigating the risks of systemic immunosuppression such as infections and malignancies. The clinical response rate for induction with vedolizumab is 50% in UC patients. Vedolizumab is approved for treatment of CD and UC in adults and there is increasing off-label use in children. |
| 12. Thalidomide is an immunosuppressant drug used infrequently off-label in the treatment of refractory CD and UC. Induction of remission is achieved in aroud 50% cases and clinical response in 70%. |
| 13. Drug therapies that interfere selectively with lymphocyte trafficking (e.g., etrolizumab, ozanimod) are emerging treatment options for UC. |
UC: Ulcerative colitis; IBD: Inflammatory bowel disease; ADA: Adalimumab; IFX: Infliximab; TPMT: Thiopurine methyl transferase; 5-ASA: Aminosalicylates; CD: Crohn’s disease; 6-MP: 6-mercaptopurine; AZA: Azathioprine; MTX: Methotrexate; GI: Gastrointestinal.