Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta‐Analysis
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Wiley
2025
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| author | Daniela Gorski Raul Edison Luna Lazo Dalton de Assis de Souza Helena Hiemisch Lobo Borba Roberto Pontarolo Fernanda Stumpf Tonin |
| author_facet | Daniela Gorski Raul Edison Luna Lazo Dalton de Assis de Souza Helena Hiemisch Lobo Borba Roberto Pontarolo Fernanda Stumpf Tonin Daniela Gorski Raul Edison Luna Lazo Dalton de Assis de Souza Helena Hiemisch Lobo Borba Roberto Pontarolo Fernanda Stumpf Tonin |
| collection | Wiley Open Access |
| contents | Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta‐Analysis Daniela Gorski Raul Edison Luna Lazo Dalton de Assis de Souza Helena Hiemisch Lobo Borba Roberto Pontarolo Fernanda Stumpf Tonin Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy ABSTRACT First‐line therapeutic approaches for Crohn's disease include immunosuppressants, aminosalicylates, and corticosteroids. However, more than one‐third of patients are resistant to these treatments and require second‐line therapies. Our goal was to synthesize the evidence on the efficacy and safety of biologics and small molecules for inducing remission in patients with moderate‐to‐severe Crohn's disease. A systematic review was conducted by searching for randomized controlled trials on the target population in PubMed, Scopus, and Web of Science (March 2025). Data synthesis for the outcomes of remission, health‐related quality of life (HRQoL), and safety was performed using network meta‐analyses and surface under the cumulative rating curve (SUCRA) analyses. The results were presented as risk ratios with 95% credible intervals. We included 55 trials ( n = 16,113 patients) evaluating 26 biological drugs across 83 doses and six small molecules across 15 doses. Similar results were obtained in the sensitivity analyses conducted across different measurement time points. Alongside infliximab 5 mg/kg (SUCRA 98.6%), 10 mg/kg (92%), and 20 mg/kg intravenous (91.8%), the recently approved drugs guselkumab 1200 mg (83.2%), 600 mg (89.2%), and 200 mg intravenous (90.1%), as well as mirikizumab 600 mg (91.5%) and 1000 mg intravenous (82.4%) presented higher probabilities of disease remission and were associated with increased HRQoL. Drugs such as certolizumab, andecaliximab, fontolizumab, abatacept, and etanercept ranked low for remission (SUCRA < 40%) and presented high probabilities of serious adverse events (over 60%). Small molecules presented an intermediate profile. Inhibitors of interleukin‐23 appear to be promising alternatives for the treatment of moderate‐to‐severe Crohn's disease. Given their safety profile, some anti‐TNF drugs should be avoided in practice. Trial Registration: PROSPERO: CRD42024519150 10.1002/phar.70049 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/phar.70049 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_phar_70049 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta‐Analysis Daniela Gorski Raul Edison Luna Lazo Dalton de Assis de Souza Helena Hiemisch Lobo Borba Roberto Pontarolo Fernanda Stumpf Tonin Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta‐Analysis Daniela Gorski Raul Edison Luna Lazo Dalton de Assis de Souza Helena Hiemisch Lobo Borba Roberto Pontarolo Fernanda Stumpf Tonin Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy ABSTRACT First‐line therapeutic approaches for Crohn's disease include immunosuppressants, aminosalicylates, and corticosteroids. However, more than one‐third of patients are resistant to these treatments and require second‐line therapies. Our goal was to synthesize the evidence on the efficacy and safety of biologics and small molecules for inducing remission in patients with moderate‐to‐severe Crohn's disease. A systematic review was conducted by searching for randomized controlled trials on the target population in PubMed, Scopus, and Web of Science (March 2025). Data synthesis for the outcomes of remission, health‐related quality of life (HRQoL), and safety was performed using network meta‐analyses and surface under the cumulative rating curve (SUCRA) analyses. The results were presented as risk ratios with 95% credible intervals. We included 55 trials ( n = 16,113 patients) evaluating 26 biological drugs across 83 doses and six small molecules across 15 doses. Similar results were obtained in the sensitivity analyses conducted across different measurement time points. Alongside infliximab 5 mg/kg (SUCRA 98.6%), 10 mg/kg (92%), and 20 mg/kg intravenous (91.8%), the recently approved drugs guselkumab 1200 mg (83.2%), 600 mg (89.2%), and 200 mg intravenous (90.1%), as well as mirikizumab 600 mg (91.5%) and 1000 mg intravenous (82.4%) presented higher probabilities of disease remission and were associated with increased HRQoL. Drugs such as certolizumab, andecaliximab, fontolizumab, abatacept, and etanercept ranked low for remission (SUCRA < 40%) and presented high probabilities of serious adverse events (over 60%). Small molecules presented an intermediate profile. Inhibitors of interleukin‐23 appear to be promising alternatives for the treatment of moderate‐to‐severe Crohn's disease. Given their safety profile, some anti‐TNF drugs should be avoided in practice. Trial Registration: PROSPERO: CRD42024519150 10.1002/phar.70049 http://creativecommons.org/licenses/by/4.0/ |
| title | Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta‐Analysis |
| topic | Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy |
| url | https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.70049 |