Long-term effectiveness of ustekinumab comparable to antitumor necrosis factor agents in patients with Crohn's disease

Abstract

Background: Ustekinumab (UST), an antibody against the p40 subunit of interleukin-12/23, has been proven to be effective in patients with Crohn's disease (CD). However, large, long-term comparative studies of UST against anti--tumor necrosis factor (TNF) agents are lacking. We compared the effectiveness of anti-TNF agents and UST in CD patients without prior use of biologics.

Methods: We used a large nationwide anonymized Japanese database containing administrative medical claims data and various related patient data. In a propensity score-matched cohort with similar clinical characteristics, 2-year effectiveness was compared between patients treated with infliximab or adalimumab (anti-TNF group) and those treated with UST (UST group). Primary outcomes were cumulative rates of hospitalization, surgery, and persistence.

Results: Among 53 540 CD patients, 7047 were extracted for eligibility, of which 5665 were treated with an anti-TNF agent and 1382 with UST. After propensity score matching, the cumulative hospitalization rates were comparable between anti-TNF and UST groups (P = 0.85; 25.3% vs 26.5% at 1 year, 33.8% vs 39.8% at 2 years). The cumulative surgery rates were also comparable between these groups (P = 0.46; 5.5% vs 5.1% at 1 year, 8.3% vs 8.4% at 2 years). The persistence rate at 1 year was higher in UST group (90.8% vs 92.5%), and that at 2 years was higher in anti-TNF group (81.2% and 74.6%); however, there was no significant difference in the cumulative persistence rate (P = 0.55).

Conclusions: Anti-TNF agents and UST appear to have comparable effectiveness for CD patients without prior use of biologics.

Keywords: Crohn's disease; adalimumab; anti-tumor necrosis factor; infliximab; ustekinumab.

Figure 1

Patient flow in this study. From the 53 540 patients with confirmed diagnoses of Crohn's disease (CD), we excluded patients with comorbidities that might warrant the use of biologics, patients history of biologic use during the observation period, and patients with a history of any type of biologic use within 6 months prior to the study entry. After further excluding 172 patients treated with vedolizumab, 7047 patients were eligible for this analysis.

Figure 2

Cumulative hospitalization rates. The cumulative hospitalization rate in patients treated with anti‐tumor necrosis factor (TNF) agents were 25.3% at 1 year and 33.8% at 2 years; that in patients treated with ustekinumab (UST) were 26.5% at 1 year and 39.8% at 2 years. There was no significant difference in the cumulative hospitalization rates between the two groups (P = 0.849). Anti‐TNF group. UST group.

Figure 3

Cumulative surgery rates. The cumulative surgery rate in patients treated with anti‐‐tumor necrosis factor (TNF) agents were 5.5% at 1 year and 8.3% at 2 years; that in patients treated with ustekinumab (UST) were 5.1% at 1 year and 8.4% at 2 years. The cumulative surgery rates were comparable between the two groups (P = 0.458). Anti‐TNF group. UST group.

Figure 4

Cumulative persistence rates. The treatment persistence rate at 1 year was higher in the ustekinumab (UST) group (92.5%) than in the antitumor necrosis factor (TNF) agent group (90.8%), and that at 2 years was higher in the anti‐TNF agent group (81.2%) than in the UST group (74.6%); however, there was no significant difference in the cumulative persistence rates between the two groups (P = 0.549). Anti‐TNF group. UST group.

Figure 5

Cumulative hospitalization, surgery, and persistence rates analyzed separately for patients with and without immunomodulators. In 1955 (70.9%) patients without concomitant immunomodulators, there were no significant differences in the cumulative hospitalization (a), surgery (b), and persistence (c) rates between the antitumor necrosis factor (TNF) and ustekinumab (UST) groups (P = 0.782, 0.153, and 0.757, respectively). Similarly, in 803 (29.1%) patients with concomitant immunomodulators, the cumulative hospitalization (d), surgery (e), and persistence (e) rates were not significantly different between the anti‐TNF and UST groups (P = 0.518, 0.552, and 0.536, respectively). Anti‐TNF group. UST group.

Figure 6

Cumulative hospitalization, surgery, and persistence rates analyzed dividing the anti‐TNF group into the IFX and ADA groups. Dividing the anti‐tumor necrosis factor (TNF) group into patients treated with infliximab (IFX) and adalimumab (ADA), we compared the treatment courses between the IFX, ADA, and ustekinumab (UST) groups. There were no significant differences in the cumulative hospitalization (a), surgery (b), and persistence (c) rates among the three groups (P = 0.970, 0.515, and 0.571, respectively). IFX group. ADA group. UST group.