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P573 Assessment of serum C-reactive protein, faecal lactoferrin, and faecal calprotectin in patients with Crohn’s disease: results from the UNITI-1 and UNITI-2 Ustekinumab induction studies

C. Gasink*1, Y. Lang1, D. Jacobstein1, J. Johanns1, P. Rutgeerts2, W. de Villiers3, J.-F. Colombel4

1Janssen R & D, LLC, Spring House, Pennsylvania, United States, 2University Hospital Gasthuisberg, Department of Haematology, Leuven, Netherlands, 3Universiteit Stellenbosch University, Stellenbosch, South Africa, 4Mount Sinai, Icahn School of Medicine, New York, New York, United States

Background

Inflammatory markers including serum C-reactive protein (CRP), faecal lactoferrin (fLac), and faecal calprotectin (fCal) are important markers of objective inflammation in patients with moderate-severe Crohn’s disease (CD). Therefore, these were carefully assessed in the recently presented UNITI-1& 2 induction studies of intravenous (IV) ustekinumab (UST).

Methods

The UNITI-1 & 2 Phase 3 induction trials enrolled 741 anti-TNF failure patients (UNITI-1) and 628 conventional therapy failure patients (UNITI-2) with moderate-severe CD. Patients were randomised to receive a single IV dose of placebo (PBO) or UST ~ 6 mg/kg, or UST 130 mg at week 0. Secondary endpoints included changes from baseline in CRP, fLac, and fCal, as well as normalisation of each of these markers.

Results

In UNITI-1 & 2, each of these 3 markers of inflammation was elevated in 60%–87% of patients at baseline; UNITI-1 (CRP 78.3%, fCal 63.4%, and fLac 86.9 %) and UNITI-2 (76.8%, fCal 62.9%, and fLac 83.6%). The median CRP at baseline was greater in UNITI-1 compared with UNITI-2 (9.88 mg/L vs 8.05 mg/L). In both studies, significantly greater reductions from baseline in CRP concentration at weeks 3, 6, and 8 were observed in both the UST~6 mg/kg and 130 mg groups vs PBO (p < 0.001 for all). By week 8 in both studies, whereas both UST groups had greater reductions than PBO, the UST~6 mg/kg group had greater median reductions in CRP than the UST 130 mg group, UNITI-1 (-2.38 vs -1.42 [PBO 0.06]) and UNITI-2 (-2.39 vs -1.29 [PBO 0.0]). At week 8, proportions of pts achieving normalised CRP levels (amongst those ≥ 3mg/L at baseline) were greater for the UST~6mg/kg, 130mg, vs PBO, respectively, UNITI-1 (21.3%, 16.8% vs 8.3%; p < 0.001, p = 0.012); UNITI-2 (26.1%, 21.0% vs 9.4%; p < 0.001, p = 0.004). In UNITI-1 & 2 at week 6, there was a significantly greater reduction in fCal and fLac concentration in both the ~6 mg/kg and 130 mg UST groups compared with the PBO group, and greater proportions of pts also achieved normalised levels in these markers with both doses in both UNITI-1 & 2 (Table 1).

Conclusion

UST was efficacious in reducing both serum based markers of inflammation (CRP), as well as faecal based markers (fLac and fCal). Reduction in or normalisation of CD inflammatory biomarkers with induction treatment shows that UST, besides decreasing clinical activity of CD, improves biological activity both in pts who have already failed anti-TNF, as well as after conventional therapy failure.

Table 1 UST CRP, fLac, fCal UNITI 1 and UNITI 2