Advancements in Inflammatory Bowel Disease Management: From Traditional Treatments to Monoclonal Antibodies and Future Drug Delivery Systems
Abstract
1. Introduction
2. Gut Barrier in IBD
3. Traditional Treatments of IBD
3.1. Aminosalicylates
3.2. Corticosteroids
3.3. Immunomodulators
4. Monoclonal Antibodies in IBD
4.1. Tumor Necrosis Factor-Alpha (TNF-α) Blockers
4.2. Integrin Blockers
4.3. Interleukins Blockers
4.4. Monoclonal Antibodies in Development
Drugs | Mechanism of Action | Administration Route | Doses | Adverse Effects | Ref. |
---|---|---|---|---|---|
Infliximab (REMICADE®) | Anti-TNF-α | Intravenous | 5 mg/kg Induction doses: 0, 2, and 6 weeks. Maintenance doses: 8-weekly intervals. | Hypersensitivity reactions. | [44] |
Infliximab (ZYMFENTRA®) | Anti-TNF-α | Subcutaneous | Maintenance doses only: 120 mg at week 10, 2-weekly intervals. | COVID-19, anemia, arthralgia, injection site reaction, increased alanine aminotransferase, and abdominal pain (for UC). COVID-19, headache, upper respiratory tract infection, injection site reaction, diarrhea, increased blood creatine phosphokinase, arthralgia, increased alanine aminotransferase, hypertension, urinary tract infection, neutropenia, dizziness, and leukopenia (for CD). | [54] |
Adalimumab (HUMIRA®) | Anti-TNF-α | Intramuscular | Induction doses: 80/160 mg at week 0 and 40/80 mg at week 2 (for CD); 80/160 mg at week 0, 40/80 mg at week 1, and 40/80 mg at week 2 (for UC). Maintenance doses: 20/40 mg every week starting from week 4 (for CD); 40/80 mg every week starting from week 4 or 20/40 mg every week (for UC). | Infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash. | [55] |
Golimumab (SIMPONI®) | Anti-TNF-α | Subcutaneous | Induction doses: 200 mg week 0 and 100 mg at week 2. Maintenance doses: 50/100 mg 4-weekly intervals. | Paraesthesia, cutaneous infection, pneumonitis, and the recurrence of cervical neoplasia. | [58] |
Certolizumab pegol (CIMZIA®) | Anti-TNF-α | Subcutaneous | Induction doses: 400 mg at 0, 2, and 4 weeks. Maintenance doses: 400 mg 4-weekly intervals. | Upper respiratory tract infection, rash, and urinary tract infection. | [61] |
Natalizumab (TYSABRI®) | Integrin blocker | Intravenous | 300 mg 4-weekly intervals. | Headache, the exacerbation of CD, nausea, nasopharyngitis, and progressive multifocal leukoencephalopathy. | [69,70] |
Vedolizumab (ENTYVIO®) | Integrin blocker | Intravenous and subcutaneous | Induction doses: 300 mg at weeks 0, 2, and 6. Maintenance doses: 300 mg 8-weekly intervals. | Nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, rash, pruritus, sinusitis, oropharyngeal pain, pain in extremities, and injection site reactions with subcutaneous administration. | [72,73] |
Etrolizumab | Integrin blocker | Subcutaneous | 105 mg every 4 weeks for 14 weeks (phase 3 clinical program). | UC flare, appendicitis, and anemia. | [75] |
Ustekinumab (STELARA®) | Interleukin blocker | Intravenous and subcutaneous | Induction doses: depends on the patient’s body weight. Maintenance doses: 90 mg 8–12-weekly intervals. | Headache, nasopharyngitis, inflammation of the nose and throat, and hypersensitivity (allergic reaction). | [79] |
Mirikizumab (OMVOH®) | Interleukin blocker | Intravenous and subcutaneous | Induction doses: 300 mg at weeks 0, 4, and 8; 4-weekly intervals. Maintenance doses: 200 mg 4-weekly intervals. | Infections (active tuberculosis). | [83] |
Briakinumab | Interleukin blocker | Intravenous and subcutaneous | Induction doses: 200, 400, and 700 mg at weeks 0, 4, and 8. Maintenance doses: 200, 400, and 700 mg after 12 weeks (phase 2 clinical program). | Upper respiratory tract infection, nausea, abdominal pain, and headache. | [84] |
Ontamalimab | Integrin blocker | Subcutaneous | Induction doses: 25/75 mg once 4-weekly intervals to week 12. Maintenance doses: 25/75 mg once at 4-weekly intervals to week 52 (phase 3 clinical program). | Serious infections, gastroenteritis, pelvic abscess, pneumonia, arthralgia, and nasopharyngitis. | [85] |
Risankizumab (SKYRIZI®) | Interleukin blocker | Intravenous and subcutaneous | Induction doses: 600 mg at weeks 0, 4, and 8. Maintenance doses: 360 mg at week 12, 8-weekly intervals. | Upper respiratory infection, tinea infection, folliculitis, headache, pruritus, rash, urticaria, fatigue, and injection site reactions. | [86] |
Brazikumab | Interleukin blocker | Intravenous and subcutaneous | Induction doses: 700 mg at weeks 0 and 4. Maintenance doses: 210 mg from week 12. (Phase 2 clinical program.) | Nasopharyngitis, headache, and abdominal pain. | [86] |
Guselkumab (TREMFYA®) | Interleukin blocker | Intravenous | Induction doses: 200 mg at weeks 0, 4, and 8 for 12 weeks. | Headache, joint pain, upper respiratory infections, diarrhea, and stomach pain. | [88] |
4.5. Other Treatments
5. Drug Delivery Systems
5.1. General Features of DDSs in the IBD
5.2. Antibody-Loaded DDSs
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Traditional Drugs | Class of Drugs | Administration Route | Mechanism of Action | Refs. |
---|---|---|---|---|
Sulfasalazine | Aminosalicylates | Oral | The inhibition of IL-1, TNF-α production, NF-kB, and lipoxygenase pathways | [21,22,23,24,25,26] |
Prednisone | Corticosteroids first generation | Oral or parenteral | The inhibition of the immune system | [29] |
Beclomethasone dipropionate | Corticosteroids second generation | Oral or topical | The inhibition of the immune system | [30,31] |
Azathioprine | Thiopurines | Oral | The inhibition of T lymphocyte proliferation and activation | [32] |
Methotrexate | Antimetabolites | Parenteral | Decreasing pro-inflammatory cytokine production and leading to the apoptosis of T cells | [33,34] |
Cyclosporine | Immunosuppressives | Oral or intravenous | Calcineurin inhibition | [35] |
Tacrolimus | Immunosuppressives | Oral or intravenous | Calcineurin inhibition | [36,37] |
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Di Rienzo, A.; Marinelli, L.; Dimmito, M.P.; Toto, E.C.; Di Stefano, A.; Cacciatore, I. Advancements in Inflammatory Bowel Disease Management: From Traditional Treatments to Monoclonal Antibodies and Future Drug Delivery Systems. Pharmaceutics 2024, 16, 1185. https://doi.org/10.3390/pharmaceutics16091185
Di Rienzo A, Marinelli L, Dimmito MP, Toto EC, Di Stefano A, Cacciatore I. Advancements in Inflammatory Bowel Disease Management: From Traditional Treatments to Monoclonal Antibodies and Future Drug Delivery Systems. Pharmaceutics. 2024; 16(9):1185. https://doi.org/10.3390/pharmaceutics16091185
Chicago/Turabian StyleDi Rienzo, Annalisa, Lisa Marinelli, Marilisa Pia Dimmito, Eleonora Chiara Toto, Antonio Di Stefano, and Ivana Cacciatore. 2024. "Advancements in Inflammatory Bowel Disease Management: From Traditional Treatments to Monoclonal Antibodies and Future Drug Delivery Systems" Pharmaceutics 16, no. 9: 1185. https://doi.org/10.3390/pharmaceutics16091185
APA StyleDi Rienzo, A., Marinelli, L., Dimmito, M. P., Toto, E. C., Di Stefano, A., & Cacciatore, I. (2024). Advancements in Inflammatory Bowel Disease Management: From Traditional Treatments to Monoclonal Antibodies and Future Drug Delivery Systems. Pharmaceutics, 16(9), 1185. https://doi.org/10.3390/pharmaceutics16091185