Comparative onset of effect of biologics and small molecules in moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis
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Comparative onset of effect of biologics and small molecules in moderate-to-severe ulcerative colitis : a systematic review and network meta-analysis. / Attauabi, Mohamed; Dahl, Emilie Kristine; Burisch, Johan; Gubatan, John; Nielsen, Ole Haagen; Seidelin, Jakob Benedict.
In: EClinicalMedicine, Vol. 57, No. 3, 101866, 2023.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Comparative onset of effect of biologics and small molecules in moderate-to-severe ulcerative colitis
T2 - a systematic review and network meta-analysis
AU - Attauabi, Mohamed
AU - Dahl, Emilie Kristine
AU - Burisch, Johan
AU - Gubatan, John
AU - Nielsen, Ole Haagen
AU - Seidelin, Jakob Benedict
N1 - PMID: 36864986
PY - 2023
Y1 - 2023
N2 - BackgroundOnset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but comparative data are lacking. Therefore, we aimed to assess the comparative onset of efficacy of biological therapies and small molecules for this patient population.MethodsIn this systematic review and network meta-analysis, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 24 August 2022, for randomised controlled trials or open-label studies assessing the efficacy of biologics or small molecule drugs within the first six weeks of treatment in adults with UC. The co-primary outcomes were the induction of clinical response and clinical remission at week 2. Network meta-analyses was conducted under the Bayesian framework. This study is registered with PROSPERO: CRD42021250236.FindingsThe systematic literature search identified 20,406 citations, of which 25 studies comprising 11,074 patients fulfilled the eligibility criteria. Upadacitinib ranked highest for induction of clinical response and clinical remission at week 2 and was significantly superior to all agents but tofacitinib, which ranked second highest. Although the rankings remained consistent, no differences between upadacitinib and biological therapies were demonstrated in the sensitivity analyses of partial Mayo clinic score response or resolution of rectal bleeding at week 2. Tumor necrosis factor-α (TNF) inhibitors were significantly superior to vedolizumab and ustekinumab for patient-reported outcome-2 (PRO-2) remission at week 2 in bio-naïve patients. Filgotinib 100 mg, ustekinumab, and ozanimod ranked lowest across all endpoints.InterpretationIn this network meta-analysis, we found upadacitinib to be significantly superior to all agents but tofacitinib for the induction of clinical response and clinical remission two weeks after treatment initiation. In contrast, ustekinumab and ozanimod ranked lowest. Our findings help to establish the evidence regarding the onset of efficacy of advanced therapies.
AB - BackgroundOnset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but comparative data are lacking. Therefore, we aimed to assess the comparative onset of efficacy of biological therapies and small molecules for this patient population.MethodsIn this systematic review and network meta-analysis, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 24 August 2022, for randomised controlled trials or open-label studies assessing the efficacy of biologics or small molecule drugs within the first six weeks of treatment in adults with UC. The co-primary outcomes were the induction of clinical response and clinical remission at week 2. Network meta-analyses was conducted under the Bayesian framework. This study is registered with PROSPERO: CRD42021250236.FindingsThe systematic literature search identified 20,406 citations, of which 25 studies comprising 11,074 patients fulfilled the eligibility criteria. Upadacitinib ranked highest for induction of clinical response and clinical remission at week 2 and was significantly superior to all agents but tofacitinib, which ranked second highest. Although the rankings remained consistent, no differences between upadacitinib and biological therapies were demonstrated in the sensitivity analyses of partial Mayo clinic score response or resolution of rectal bleeding at week 2. Tumor necrosis factor-α (TNF) inhibitors were significantly superior to vedolizumab and ustekinumab for patient-reported outcome-2 (PRO-2) remission at week 2 in bio-naïve patients. Filgotinib 100 mg, ustekinumab, and ozanimod ranked lowest across all endpoints.InterpretationIn this network meta-analysis, we found upadacitinib to be significantly superior to all agents but tofacitinib for the induction of clinical response and clinical remission two weeks after treatment initiation. In contrast, ustekinumab and ozanimod ranked lowest. Our findings help to establish the evidence regarding the onset of efficacy of advanced therapies.
U2 - 10.1016/j.eclinm.2023.101866
DO - 10.1016/j.eclinm.2023.101866
M3 - Review
C2 - 36864986
VL - 57
JO - EClinicalMedicine
JF - EClinicalMedicine
SN - 2589-5370
IS - 3
M1 - 101866
ER -
ID: 337393320