. Author manuscript; available in PMC: 2024 Mar 8.

Published in final edited form as: J Rheumatol. 2022 Dec 1;50(3):438–450. doi: 10.3899/jrheum.220317

Table 2.

Advanced therapy PBO-controlled RCTs in Crohn disease. Efficacy and safety results for new studies from February 2013 to August 2020

Medication Class vs PBO	Author, Year	N	(1) Primary and (2) Key Secondary Endpoints	Endpoints Met	Study Limitations

IFX	Regueiro 2016¹⁵	297	(1) Clinical recurrence at wk 76 (2) Endoscopic recurrence at wk 76 (2) Clinical recurrence at wk 104 (2) CDAI change at wk 104	IFX = PBO IFX > PBO IFX = PBO IFX = PBO	Entry restricted to CD cases who had had ileocolonic resection with ileocolonic anastomosis. Moderate-high risk of bias as domains poorly reported in the study.
UST	Feagan 2016¹⁶	761	(1) CDAI-100p or CDAI < 150 at wk 6 (2) CDAI remission at wk 8 (2) CDAI-70p at wk 8 (2) CRP decrease at wk 8 (2) Calprotectin decrease at wk 6	Both UST > PBO (UST 130 mg = UST 6 mg/kg) Both UST > PBO Both UST > PBO Both UST > PBO Both UST > PBO	-
	Sands 2018¹⁷	761	(2) IBDQ-MCID at wk 8 (2) SF-36 PCS at wk 8 (2) SF-36 MCS at wk 8	Both UST > PBO No difference UST 6 mg/kg > PBO	A paper focused on PROMs.
	Feagan 2016¹⁵	397	(1) CDAI < 150 at wk 44 (2) CDAI-70p at wk 44 (especially if remission after induction) (2) IBDQ decrease at wk 44 (2) IBDQ-MCID at wk 44	Both UST > PBO (UST Q8W = UST Q12W) Both UST > PBO UST Q8W = UST Q12W Both UST > PBO (UST Q8W = UST Q12W) UST Q8W > PBO	TNFi-IR mandated; otherwise, low risk of bias in the study.
	Sands 2018¹⁶	397	(2) SF-36 PCS-MCID at wk 44 (2) SF-36 MCS-MCID at wk 44	UST Q8W > PBO Both UST > PBO	A paper focused on PROMs.
RZB	Feagan 2017¹⁸	121	(1) CDAI ≤ 150 at wk 12 (2) CDAI-100p at wk 12 (2) CDEIS ≤ 4 at wk 12 (2) IBDQ at wk 12 (2) HRQOL at wk 12	600 mg > PBO (not 200 mg) 600 mg > PBO (not 200 mg) 600 mg > PBO (not 200 mg) 600 mg > PBO (not 200 mg) 600 mg > PBO (not 200 mg)	Low risk of bias in the study.
MEDI2070	Sands 2017¹⁹	121	CDAI-100p at wk 8 (1) CDAI ≤ 150 at wk 8 CRP decrease Calprotectin decrease	700 > PBO No difference 700 > PBO 700 > PBO	TNFi-IR mandated; otherwise, low risk of bias in the study.
BRO	Targan 2016²⁰	130	(1) CDAI ≤ 150 at wk 6 (2) CDAI-100p at wk 6 (2) CDAI-Δ at wk 6 (2) CRP (2) Calprotectin	PBO > all BRO groups No difference No difference No difference No difference	Several exclusions compared with other studies. Therefore, likely milder severity CD cohort than in clinical practice, consequently contributing to the risk of bias in the study.
PF-04236921	Danese 2019²¹	247	(1) CDAI-70p at wk 12 (2) CDAI remission (2) CRP decrease (2) Calprotectin decrease (2) IBDQ score (2) Change in EQ-5D	50 mg > PBO 50 mg > PBO All doses > PBO No difference No difference No difference	TNFi-IR mandated; otherwise, low risk of bias in the study.
TOF	Sandborn 2014²²	139	(1) CDAI-70p at wk 4 (2) CDAI-100p at wk 4 (2) CRP decrease at wk 4 (2) Calprotectin decrease at wk 4 (2) IBDQ-10 at wk 4	No difference No difference 15 mg > PBO 15 mg > PBO No difference	Moderate risk of bias: high screening fail rate (41%); very high PBO response rate leading to inadvertent selection bias.
	Panes 2017²³	180	(1) CDAI-100p or CDAI < 150 at wk 24 (2) CRP decrease at wk 24	No difference (either dose) TOF 10 > PBO	–
FILGO	Vermeire 2017²⁴	174	(1) CDAI at wk 10 (2) Histopathology (2) SES-CD (2) IBDQ-QoL (2) PRO2	FILGO 200 > PBO FILGO 200 > PBO No difference FILGO 200 > PBO FILGO 200 > PBO	Low risk of bias.
UPA	Mohamed 2020²⁵	220	(1) Dose-response at wk 16 (1) Safety	Dose-related response, especially 24 mg QID > PBO No dose-safety association observed	High attrition of 27% in PBO compared with UPA groups, contributing to risk of bias in the study.
	Sandborn 2020²⁶	220	(1) Clinical remission at wk 16 (1) Endoscopic remission at wk 12/16	All UPA doses = PBO Higher UPA doses > PBO

BRO: brodalumab; CD: Crohn disease; CDAI: Crohn’s Disease Activity Index; CDEIS: Crohn’s Disease Endoscopic Index of Severity; CRP: C-reactive protein; EQ-5D: EuroQol 5-dimension questionnaire; FILGO: filgotinib; HRQOL: health-related quality of life; IBDQ-10: 10-item Inflammatory Bowel Disease Questionnaire; IBDQ-MCID: Inflammatory Bowel Disease Questionnaire minimal clinically important difference; IBDQ-QoL: Inflammatory Bowel Disease Questionnaire quality of life; IFX: infliximab; MCS: mental component summary; NR: not reported; p: point; PBO: placebo; PCS: physical component summary; PRO2: patient-reported composite score; PROM: patient-reported outcome measure; Q12W: every 12 weeks; Q8W: every 8 weeks; QID: 4 times daily; RZB: risankizumab; SES-CD: Simplified Endoscopy Score for Crohn’s Disease; SF-36: 36-item Short Form Health Survey; TNFi-IR: inadequate response to tumor necrosis factor inhibitor; TOF: tofacitinib; UPA: upadacitinib; UST: ustekinumab.