Model-Based Meta-Analysis on the Efficacy of Biologics and Small Targeted Molecules for Crohn’s Disease
Information on comparative drug efficacy is of great importance for drug development as well as clinical practice. Up to now, the relative efficacy of biologics and small targeted molecules for Crohn’s disease (CD) remains unclear. The objective of this study was to quantify the relative efficacy of...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-03-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.828219/full |
| _version_ | 1818287516197847040 |
|---|---|
| author | Boran Yu Boran Yu Libo Zhao Siyao Jin Siyao Jin Huan He Jing Zhang Xiaoling Wang |
| author_facet | Boran Yu Boran Yu Libo Zhao Siyao Jin Siyao Jin Huan He Jing Zhang Xiaoling Wang |
| author_sort | Boran Yu |
| collection | DOAJ |
| description | Information on comparative drug efficacy is of great importance for drug development as well as clinical practice. Up to now, the relative efficacy of biologics and small targeted molecules for Crohn’s disease (CD) remains unclear. The objective of this study was to quantify the relative efficacy of investigational and approved biological treatments for CD measured in Crohn’s Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), and C-reactive protein (CRP). The analysis dataset was composed of summary-level data from 46 trials, containing 12,846 patients, with treatment of 24 drugs. Six mathematical models with non-parametric placebo estimations were developed to describe the time course and dose–response of six efficacy measures. The effects of covariate were further evaluated. Time–response relationships were found in outcomes measured in CDAI. The patients’ age, disease duration, baseline CDAI, and CRP showed an impact on the efficacy. Model simulations were performed to compare the efficacies across different drugs. The most achievement in clinical remission (defined as CDAI less than 150) and clinical response (defined as the reduction in CDAI for 100 or 70) was observed in the simulation for PF-04236921 and infliximab, respectively. The most improvement in IBDQ was shown in tofacitinib. In general, tumor necrosis factor (TNF)-α inhibitors were the most effective biologics, and the highest efficacy of small targeted molecules was observed in janus kinase (JAK) inhibitors. These findings have important implications for clinical practice in CD. |
| first_indexed | 2024-12-13T01:41:44Z |
| format | Article |
| id | doaj.art-39da1894051b4c06a4c10e7eea276dae |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T01:41:44Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-39da1894051b4c06a4c10e7eea276dae2022-12-22T00:03:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-03-011310.3389/fimmu.2022.828219828219Model-Based Meta-Analysis on the Efficacy of Biologics and Small Targeted Molecules for Crohn’s DiseaseBoran Yu0Boran Yu1Libo Zhao2Siyao Jin3Siyao Jin4Huan He5Jing Zhang6Xiaoling Wang7Clinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaSchool of Pharmacy, Capital Medical University, Beijing, ChinaClinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaClinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaSchool of Pharmacy, Capital Medical University, Beijing, ChinaClinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaDepartment of Gastroenterology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaClinical Research Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaInformation on comparative drug efficacy is of great importance for drug development as well as clinical practice. Up to now, the relative efficacy of biologics and small targeted molecules for Crohn’s disease (CD) remains unclear. The objective of this study was to quantify the relative efficacy of investigational and approved biological treatments for CD measured in Crohn’s Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), and C-reactive protein (CRP). The analysis dataset was composed of summary-level data from 46 trials, containing 12,846 patients, with treatment of 24 drugs. Six mathematical models with non-parametric placebo estimations were developed to describe the time course and dose–response of six efficacy measures. The effects of covariate were further evaluated. Time–response relationships were found in outcomes measured in CDAI. The patients’ age, disease duration, baseline CDAI, and CRP showed an impact on the efficacy. Model simulations were performed to compare the efficacies across different drugs. The most achievement in clinical remission (defined as CDAI less than 150) and clinical response (defined as the reduction in CDAI for 100 or 70) was observed in the simulation for PF-04236921 and infliximab, respectively. The most improvement in IBDQ was shown in tofacitinib. In general, tumor necrosis factor (TNF)-α inhibitors were the most effective biologics, and the highest efficacy of small targeted molecules was observed in janus kinase (JAK) inhibitors. These findings have important implications for clinical practice in CD.https://www.frontiersin.org/articles/10.3389/fimmu.2022.828219/fullmodel-based meta-analysisCrohn’s diseasebiologicssmall targeted moleculesrelative efficacy |
| spellingShingle | Boran Yu Boran Yu Libo Zhao Siyao Jin Siyao Jin Huan He Jing Zhang Xiaoling Wang Model-Based Meta-Analysis on the Efficacy of Biologics and Small Targeted Molecules for Crohn’s Disease Frontiers in Immunology model-based meta-analysis Crohn’s disease biologics small targeted molecules relative efficacy |
| title | Model-Based Meta-Analysis on the Efficacy of Biologics and Small Targeted Molecules for Crohn’s Disease |
| title_full | Model-Based Meta-Analysis on the Efficacy of Biologics and Small Targeted Molecules for Crohn’s Disease |
| title_fullStr | Model-Based Meta-Analysis on the Efficacy of Biologics and Small Targeted Molecules for Crohn’s Disease |
| title_full_unstemmed | Model-Based Meta-Analysis on the Efficacy of Biologics and Small Targeted Molecules for Crohn’s Disease |
| title_short | Model-Based Meta-Analysis on the Efficacy of Biologics and Small Targeted Molecules for Crohn’s Disease |
| title_sort | model based meta analysis on the efficacy of biologics and small targeted molecules for crohn s disease |
| topic | model-based meta-analysis Crohn’s disease biologics small targeted molecules relative efficacy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.828219/full |
| work_keys_str_mv | AT boranyu modelbasedmetaanalysisontheefficacyofbiologicsandsmalltargetedmoleculesforcrohnsdisease AT boranyu modelbasedmetaanalysisontheefficacyofbiologicsandsmalltargetedmoleculesforcrohnsdisease AT libozhao modelbasedmetaanalysisontheefficacyofbiologicsandsmalltargetedmoleculesforcrohnsdisease AT siyaojin modelbasedmetaanalysisontheefficacyofbiologicsandsmalltargetedmoleculesforcrohnsdisease AT siyaojin modelbasedmetaanalysisontheefficacyofbiologicsandsmalltargetedmoleculesforcrohnsdisease AT huanhe modelbasedmetaanalysisontheefficacyofbiologicsandsmalltargetedmoleculesforcrohnsdisease AT jingzhang modelbasedmetaanalysisontheefficacyofbiologicsandsmalltargetedmoleculesforcrohnsdisease AT xiaolingwang modelbasedmetaanalysisontheefficacyofbiologicsandsmalltargetedmoleculesforcrohnsdisease |