Treatment sequence network meta-analysis in Crohn’s disease: a methodological case study

Abstract

Objective: Several biologic therapies are available for the treatment of mild-to-moderate Crohn's disease (CD). This network meta-analysis (NMA) aimed to assess the comparative efficacy of ustekinumab, adalimumab, vedolizumab and infliximab in the maintenance of clinical response and remission after 1 year of treatment. Methods: A systematic literature search was performed to identify relevant randomized controlled trials (RCTs). Key outcomes of interest were clinical response (CD activity index [CDAI] reduction of 100 points; CDAI-100) and remission (CDAI score under 150 points; CDAI < 150). A treatment sequence Bayesian NMA was conducted to account for the re-randomization of patients based on different clinical definitions, the lack of similarity of the common comparator for each trial and the full treatment pathway from the induction phase onwards. Results: Thirteen RCTs were identified. Ustekinumab 90 mg q8w was associated with statistically significant improvement in clinical response relative to placebo and vedolizumab 300 mg. For clinical remission, ustekinumab 90 mg q8w was associated with statistically significant improvement relative to placebo and vedolizumab 300 mg q8w. Findings from sub-population analyses had similar results but were not statistically significant. Conclusions: The NMA suggest that ustekinumab is associated with the highest likelihood of reaching response or remission at 1 year compared with placebo, adalimumab and vedolizumab. Results should be interpreted with caution because this is a novel methodology; however, the treatment sequence analysis may be the most methodologically sound analysis to derive estimates of comparative efficacy in CD in the absence of head-to-head evidence.

Efficacy of ustekinumab vs. advanced therapies for the treatment of moderately to severely active ulcerative colitis: a systematic review and network meta-analysis

“…There is potential for further heterogeneity due to differences in the carry-over effects of the different active induction therapies. While the induction placebo rates are similar across trials, the heterogeneity of the placebo arms across maintenance trials has been demonstrated (see Supplementary Appendix 3), which was also the case in Crohn's disease 15 . Thus, the PBO arms across maintenance trials are not true common comparators, and it was therefore not considered appropriate to conduct a standard NMA of maintenance phase results only.…”

Early prescription of biological agents for immune-mediated inflammatory diseases: opportunities and prospects. An expert’s opinion

“…Инфликсимаб и адалимумаб эффективны при Пс, ПсА, БК, ЯК (уровень доказательности 1А), устекинумаб -при Пс, ПсА, БК (уровень доказательности 1А), ЯК (уровень доказательности 1В); этанерцепт, секукинумаб, иксекизумаб оказывают положительное действие при Пс, ПсА (уровень доказательности 1А), однако неэффективны и даже способствуют повышению риска обострения при ВЗК [119,120]. При назначении ГИБП пациентам с ИВЗ следует руководствоваться принципами персонифицированного подхода и управления рисками для достижения долгосрочных и безопасных результатов терапии [104,105,121,122].…”

Early administration of genetically engineered biological agents for immune-mediated inflammatory diseases: opportunities and prospects. An experts’ opinion

“…При назначении ГИБП пациентам с ИВЗ следует руководствоваться принципами персонифицированного подхода и управления рисками для достижения долгосрочных и безопасных результатов терапии [101,103,119,120].…”