Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta-Analysis Gorski, Daniela Luna Lazo, Raul Edison de Assis de Souza, Dalton Lobo Borba, Helena Hiemisch Pontarolo, Roberto Stumpf Tonin, Fernanda CINeMA interleukin inhibitors monoclonal antibody 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, healthrelated 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 5mg/kg (SUCRA 98.6%), 10mg/kg (92%), and 20mg/kg intravenous (91.8%), the recently approved drugs guselkumab 1200mg (83.2%), 600mg (89.2%), and 200mg intravenous (90.1%), as well as mirikizumab 600mg (91.5%) and 1000mg 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. 2025-09-24T10:41:07Z 2025-09-24T10:41:07Z 2025-07-07 journal article Gorski, D., Lazo, R.E.L., de Souza, D.d.A., Borba, H.H.L., Pontarolo, R. and Tonin, F.S. (2025), Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta-Analysis. Pharmacotherapy, 45: 587-599. https://doi.org/10.1002/phar.70049 https://hdl.handle.net/10481/106597 10.1002/phar.70049 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Wiley Periodicals LLC