P942 Real-world data on outcomes of treatment with ustekinumab in patients with Ulcerative Colitis
Authors: Chalakatevaki K , Kokkotis G , Chatzinikolaou M L , Anagnostopoulou E , Argiriou K , Viazis N , Galanopoulos M , Gerasimatos G , Giouleme O , Zampeli E , Zacharopoulou E , Theodoropoulou A , Theocharis G , Kalogirou M , Karatzas P , Karmiris K , Kapsoritakis A , Koustenis K , Koutroumpakis I , Kiriakos N , Lazou D , Liatsos C , Mantaka A , Mantzaris G , Michalopoulos G , Michopoulos S , Orfanidou A , Papathanasiou E , Polymeros D , Potamianos S , Sotiropoulos C , Soufleris K , Tzouvala M , Foteinogiannopoulou K , Chatzidakis A , Psistakis A , Bamias G 
Published: January 2024

Background

Ustekinumab (UST), a monoclonal antibody against the shared p40 subunit of IL-12/IL-23, has been approved for the treatment of moderate to severe ulcerative colitis (UC). The aim of this ambi-directional study is to collect and analyze data from a large cohort of Greek patients with UC treated with UST.

Methods

Data from UC patients treated with UST in 15 Greek hospitals were analyzed to evaluate rates of clinical response (CR, 50% reduction in UC-PRO2 compared to baseline) at week 16 of treatment, steroid-free clinical remission (SFCRem, pMAYO score &lt;3 with UC PRO2=0) at weeks 16 and 54, and endoscopic healing (EH, endoscopic MAYO=0 and/or UCEIS=0-1, with 1 allowed only for vascular score) at week 54.

Results

Characteristics of the 132 enrolled patients are shown in Table 1. Most patients, 98/ 74% commenced UST treatment for active disease despite treatment and 92/ 72% had been exposed to biologic agents prior to UST (anti-TNFs, 66/50%, vedolizumab (VDZ) 57/43%). Fifty-three (40%) and 29 (22%) had received a single or two biologics (IFX and VDZ, 18/14%), respectively. By week 54, 19 had discontinued treatment due to no response. A sum of 116 patients have reached week 16, out of whom 104 have enough data to be analyzed. SFCRem was achieved in 49/47% patients. Analysis of patients with active disease at induction (87 in total with adequate data) showed that CR was achieved in 64/74%. Of 49 patients who completed 54 weeks of treatment, 25/51% were in SFCRem. Of 38 patients with adequate endoscopic data 14 /37% achieved EH. Patients who achieved SFCRem at week 16 were more likely to maintain SFCRem at week 54 (OR=3.89 [1.10-13.76], P=0.035). CR at week 16 was not associated with SFCRem at week 54. In univariate analysis SFCRem at week 54 was negatively associated with baseline disease activity (pMAYO score OR=0.78 [0.61-0.99], P=0.047; UCEIS OR=0.55 [0.36-0.85], P=0.007; WBC/1000: OR=0.65 [0.49-0.87], P=0.003), refractoriness to IFX (OR=0.27 [0.08-0.85], P=0.026), and positively associated with concomitant use of 5-ASA at UST initiation (OR=3.69 [1.05-12.96], P=0.041) but not at week 54 (P=0.757). EH at week 54 was negatively associated with refractoriness to IFX (OR=0.13 [0.02-0.71], P=0.019) and VDZ (OR=0.19 [0.05-0.79], P=0.022).

Conclusion

UST is mostly used as 2nd or 3rd line treatment for moderate to severe UC. By the end of induction, patients' majority showed CR, while at year 1 SFCRem was achieved in 51% and EH in almost 40% of patients. Negative predictive factors of SFCRem at week 54 included baseline disease activity, WBC count and resistance to prior treatment with IFX, while concomitant use of 5-ASA at baseline had positive effect. Negative predictive factors for EH at week 54 were refractoriness to IFX or VDZ.