S Singh1,2, M Fumery1,3, W J Sandborn1, M H Murad4. 1. Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA. 2. Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA. 3. Gastroenterology Unit, Amiens University and Hospital, Université de Picardie Jules Verne, Amiens, France. 4. Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
Abstract
BACKGROUND: There are limited data to inform positioning of agents for treating moderate-severe Crohn's disease (CD). AIM: We assessed comparative efficacy and safety of first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor [TNF]-α) agents) biologic therapy for moderate-severe CD, through a systematic review and network meta-analysis, and appraised quality of evidence (QoE) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. METHODS: We identified randomised controlled trials (RCTs) in adults with moderate-severe CD treated with approved anti-TNF agents, anti-integrin agents and anti-IL12/23 agents, first-line or second-line, and compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of clinical remission; safety outcomes were serious adverse events and infections. Network meta-analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities. RESULTS: No head-to-head trials were identified. In biologic-naïve patients, infliximab (SUCRA,0.93) and adalimumab (SUCRA,0.75) were ranked highest for induction of clinical remission (moderate QoE). In patients with prior anti-TNF exposure, adalimumab (SUCRA, 0.91; low QoE, in patients with prior response or intolerance to anti-TNF agents) and ustekinumab (SUCRA, 0.71) were ranked highest for induction of clinical remission. In patients with response to induction therapy, adalimumab (SUCRA, 0.97) and infliximab (SUCRA, 0.68) were ranked highest for maintenance of remission. Ustekinumab had lowest risk of serious adverse events (SUCRA, 0.72) and infection (SUCRA, 0.71; along with infliximab, SUCRA, 0.83) in maintenance trials. CONCLUSION: Indirect comparisons suggest that infliximab or adalimumab may be preferred first-line agents, and ustekinumab a preferred second-line agent, for induction of remission in patients with moderate-severe CD. Head-to-head trials are warranted.
BACKGROUND: There are limited data to inform positioning of agents for treating moderate-severe Crohn's disease (CD). AIM: We assessed comparative efficacy and safety of first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor [TNF]-α) agents) biologic therapy for moderate-severe CD, through a systematic review and network meta-analysis, and appraised quality of evidence (QoE) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. METHODS: We identified randomised controlled trials (RCTs) in adults with moderate-severe CD treated with approved anti-TNF agents, anti-integrin agents and anti-IL12/23 agents, first-line or second-line, and compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of clinical remission; safety outcomes were serious adverse events and infections. Network meta-analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities. RESULTS: No head-to-head trials were identified. In biologic-naïve patients, infliximab (SUCRA,0.93) and adalimumab (SUCRA,0.75) were ranked highest for induction of clinical remission (moderate QoE). In patients with prior anti-TNF exposure, adalimumab (SUCRA, 0.91; low QoE, in patients with prior response or intolerance to anti-TNF agents) and ustekinumab (SUCRA, 0.71) were ranked highest for induction of clinical remission. In patients with response to induction therapy, adalimumab (SUCRA, 0.97) and infliximab (SUCRA, 0.68) were ranked highest for maintenance of remission. Ustekinumab had lowest risk of serious adverse events (SUCRA, 0.72) and infection (SUCRA, 0.71; along with infliximab, SUCRA, 0.83) in maintenance trials. CONCLUSION: Indirect comparisons suggest that infliximab or adalimumab may be preferred first-line agents, and ustekinumab a preferred second-line agent, for induction of remission in patients with moderate-severe CD. Head-to-head trials are warranted.
Authors: Tiziana Larussa; Antonio Basile; Caterina Palleria; Chiara Iannelli; Ada Vero; Lidia Giubilei; Caterina De Sarro; Evelina Suraci; Raffaella Marasco; Maria Imeneo; Emilio Russo; Ludovico Abenavoli; Giovambattista De Sarro; Francesco Luzza Journal: Med Pharm Rep Date: 2021-07-29
Authors: Michał Łodyga; Piotr Eder; Magdalena Gawron-Kiszka; Agnieszka Dobrowolska; Maciej Gonciarz; Marek Hartleb; Maria Kłopocka; Ewa Małecka-Wojciesko; Piotr Radwan; Jarosław Reguła; Edyta Zagórowicz; Grażyna Rydzewska Journal: Prz Gastroenterol Date: 2021-11-19
Authors: Philipp Schreiner; Markus F Neurath; Siew C Ng; Emad M El-Omar; Ala I Sharara; Taku Kobayashi; Tadakazu Hisamatsu; Toshifumi Hibi; Gerhard Rogler Journal: Inflamm Intest Dis Date: 2019-07-09