Ustekinumab Is Associated with Real-World Long-Term Effectiveness and Improved Health-Related Quality of Life in Crohn's Disease

Abstract

Background: Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce.

Aims: To assess the long-term effectiveness of ustekinumab in patients with active Crohn's disease (CD).

Methods: This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey-Bradshaw Index (HBI) ≤ 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (≥ 3-point-decrease in HBI among patients with initial HBI ≥ 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures.

Results: Of 114 included patients, 107 (94%) had previously failed ≥ 1 and 58 (51%) ≥ 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed.

Conclusions: In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care.

Keywords: Crohn’s disease; Inflammatory bowel disease; Observational study; Ustekinumab.

Fig. 1

Flowchart of ustekinumab treatment in the PROSE study population. In total, 114 patients with confirmed Crohn’s disease (CD) diagnosis were included. Treatment retention at weeks 16, 52 and 104 was seen in 105 (92%), 80 (70%) and 69 (61%) patients, respectively. Of these, 9 (8%) patients discontinued or were lost to follow-up (lack of response, n = 6; pregnancy, n = 1; lost to follow-up, n = 2) before week 16. Between weeks 16 and 52, a total of 25 (22%) patients discontinued, were lost to follow-up or withdrew consent (lack of response, n = 18; adverse event, n = 3; lost to follow-up, n = 1; withdrawal of consent, n = 3). Between weeks 52 and 104, 11 (10%) patients discontinued, were lost to follow-up or died (lack of response, n = 7; pregnancy, n = 1; death, n = 1; lost to follow-up, n = 2)

Fig. 2

Ustekinumab drug survival Kaplan–Meier probability plot of ustekinumab drug survival during follow-up (104 weeks)

Fig. 3

Clinical response and remission. Proportion of patients (%) with Harvey–Bradshaw Index (HBI) score ≥ 5 at baseline (n = 69) and response (≥ 3-point-decrease in HBI) at weeks 16, 52 and 104. Proportion of patients (%) in clinical remission (HBI score ≤ 4 points) at weeks 16, 52 and 104 among patients with HBI scores at baseline (n = 96)