Clinical utility of ustekinumab in Crohn’s disease

Figures & data

Figure 1 Structures of IL-12 and IL-23, their receptors and the site of action of UST.

Notes: IL-12 is composed of both p40 and p35 subunits, while IL-23 is composed of p40 and p19 subunits. IL-12 receptor is composed of two subunits, such as IL-12Rβ1 and IL-12Rβ2. IL-23 receptor is composed of two subunits, such as IL-12Rβ1 and IL-23R.

Abbreviations: IL, interleukin; IL-23R, IL-23 receptor; UST, ustekinumab.

Figure 2 Clinical response in Phase IIa trial of UST in population 1 (n=104 randomized patients).

Notes: The primary endpoint (clinical response at week 8) was not met, and the trial was considered negative. However, a significant difference in clinical response was observed at weeks 4 and 6. Data from Sandborn et al.¹⁸

Abbreviation: UST, ustekinumab.

Figure 3 Clinical response rates at week 6 (induction) in the CERTIFI trial (primary outcome).

Notes: Statistical significance reached in the UST 1 and 6 mg/kg groups. Data from Sandborn et al.¹⁹

Abbreviation: UST, ustekinumab.

Figure 4 Primary endpoint results of the UNITI-1 and UNITI-2 studies.

Notes: Clinical response at week 6 was more prevalent in the UST-treated groups. In UNITI-1, P-values as compared to placebo were 0.002 (UST 130 mg) and 0.003 (UST 6 mg/kg). In UNITI-2, P-values as compared to placebo were <0.001 for both UST 130 mg and UST 6 mg/kg. Data from Feagan et al.¹⁷

Abbreviation: UST, ustekinumab.

Figure 5 Clinical remission rates at week 44 of the IM-UNITI maintenance study.

Notes: In the pooled overall UST group, P=0.040 (q12 weeks) and P=0.005 (q8 weeks) for UST as compared to placebo. Among patients derived from the UNITI-1 induction trial, P=0.14 (q12 weeks) and P=0.10 (q8 weeks). Among patients derived from UNITI-2 trial, P=0.15 (q12 weeks) and P=0.02 (q8 weeks). Data from Feagan et al.¹⁷

Abbreviation: UST, ustekinumab.

Table 1 Summary of open-label cohorts of UST for Crohn’s disease

Study	Relevance	Weakness
Batista et al (2014)^Citation43	First reported OLC experience with UST Reported mucosal healing experience	Limited sample size (n=18) Abstract only
Kopylov et al (2014)^Citation48	Uniform population of anti-TNF failure patients First OLC to evaluate efficacy of dose escalation of UST	Absence of validated clinical scores for disease activity Heterogeneity in dosing regimens
Wils et al (2016)^Citation51	Multicenter cohort (GETAID) Composite endpoint including surgery, corticosteroid weaning, and avoidance of rescue immunosuppressants	Absence of validated clinical scores for disease activity Heterogeneity in dosing regimens
Khorrami et al (2016)^Citation47	Multicenter cohort (Spanish USTEK) Evaluated predictors of long-term UST failure	Minimal evaluation of objective endpoints (endoscopy, fecal calprotectin) Heterogeneity in dosing regimens
Harris et al (2016)^Citation46	Fixed dosing regimen, administered SC but designed to mimic IV dosing Outcome evaluation using both HBI and short IBD questionnaire	Limited sample size (n=45) Missing data from retrospective collection
Ma et al (2017)^Citation49,Citation50 (two studies)	Evaluated both short- and long-term outcomes, both endoscopic, radiographic, and clinical outcomes Largest sample size (n=167)	Heterogeneity in dosing regimens Nonvalidated definitions of endoscopic and radiographic endpoints
Battat et al (2017)^Citation44	Evaluated effect of therapeutic drug monitoring for UST levels Evaluated clinical, biomarker, and endoscopic endpoints	Limited sample size (n=62) Off-label SC induction dosing regimen
Greenup et al (2017^)45	Evaluated type of preceding anti-TNF response as predictors of short-term UST response Evaluated combination of short-term and long-term, symptomatic and objective responses	Missing data from retrospective collection Off-label SC induction dosing regimen

Abbreviations: GETAID, [Therapeutic Study Group for Inflammatory Disorders of the Digestive Tube]; HBI, Harvey-Bradshaw Index; IBD, inflammatory bowel disease; IV, intravenous; SC, subcutaneous; TNF, tumor necrosis factor; UST, ustekinumab; USTEK, Spanish Ustekinumab Study group; OLC, open label cohort; IQR, interquartile range; CT, computed tomography; MR, magnetic resonance.

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