Alimentary Tract
The effectiveness of ustekinumab and vedolizumab as third-line biologic therapy in patients with Crohn's disease

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Abstract

Background

The effectiveness of Ustekinumab (UST) and Vedolizumab (VDZ) in patients with Crohn's disease (CD) as third-line biologic therapies is unclear.

Aims

We performed a multicentre, real-world assessment of the effectiveness of UST and VDZ among highly-refractory patients with CD.

Methods

Data of consecutive patients with CD treated with UST and VDZ as third-line biologic therapy until December 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD).

Results

143 patients (UST: n = 113; VDZ: n = 30) were included. At the end of induction, the rates of clinical response (CR) were 61.9% for UST and 60.0% for VDZ (p = 1.00), with steroid-free clinical remission (SFCR) achieved in 38.1% of patients in the UST group and 43.3% of patients in the VDZ group (p = 0.75). After 52 weeks of observation, the rates of CR were 65.9% for UST and 71.4% for VDZ (p = 0.77), while the rates of SFCR were 51.8% for UST and 57.1% for VDZ (p = 0.78). At multiple Cox proportional hazard regression model, age (HR 0.98; p = 0.04) and need for systemic steroids at baseline (HR 3.29; p = 0.003) were found to be independent predictors of treatment discontinuation.

Conclusions

Both VDZ and UST showed high effectiveness as third-line biologic therapy in CD, without significant differences between them.

Introduction

Relevant improvements in the understanding of the molecular mechanisms of Crohn's disease (CD) have been achieved over the past years, leading to the development of novel targeted therapies [1]. Two biologics have been recently introduced in clinical practice for the treatment of CD, namely Ustekinumab (UST) [2] – a monoclonal antibody targeting the p40 subunit of IL-12 and IL-23 – and Vedolizumab (VDZ) [3] - a monoclonal antibody that targets the α4β7 integrin, typically expressed by gut-homing lymphocytes. Both drugs have joined to the already available inhibitors of TNF-α. This enlargement of the medical options led to the demand of a better understanding of the efficacy of these drugs among different lines of treatment. In other words, comparative data between drugs are needed, but this has clashed with the current paucity of head-to-head randomized controlled trials comparing different treatments. As a consequence, data from real-world experience are becoming more and more relevant to better clarify the positioning of drugs inside the therapeutic algorithms for CD [4].

Inhibitors of TNF-α are currently employed in CD mostly as first-line biologic therapy due to the current availability of effective and low-cost biosimilars of infliximab and adalimumab [5], [6], [7], while VDZ and UST are mainly used as second- or third-line therapies. The comparison between VDZ and UST as second-line agents in patients witch CD has been investigated by recent studies [8]. While most of the papers suggested that UST may be associated with higher long-term effectiveness than VDZ [9], [10], [11], [12], other studies did not find significant differences [13,14], or even favored the use of VDZ [15]. Conversely, the effectiveness of UST and VDZ as third-line biologic agents - i.e. after failure with at least one TNF-α inhibitor plus failure with either VDZ or UST - has been poorly investigated. In this regard, a recent multicentric study showed that both drugs were effective in more than half of the patients with CD as third-line treatment [16], and these encouraging results were confirmed by a French study assessing the effectiveness of third-line biological therapies among patients with CD [17].

On these premises, web-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a multicentre, real-world assessment of the effectiveness of UST and VDZ as third-line biologic treatment for CD.

Section snippets

Patients and treatment strategies

The SN-IBD is a regional group composed of all 16 centers licensed to prescribe biologics in Sicily (Italy). Since January 2013, these centers collect real-world, prospective data on patients with IBD treated with biologics via a web-based software, with the aim of monitoring efficacy and safety of these drugs. Each physician of the Network has its own access to the software, where the upload of the clinical data of the patients at the time of the clinical visit is required. This platform

Patients

One hundred forty-three patients were included: 113 were treated with UST, while 30 were treated with VDZ, with a median follow-up of 54.0 weeks (I.Q.R. 24.0–102.0 weeks). All patients in the VDZ group had been previously treated with one or two anti-TNFs as first-line biologic therapy and with UST as second-line agent. Regarding those in the UST group, 110 out of 113 (97.3%) had been treated with one or two anti-TNFs as first-line biologic therapy and with VDZ as second-line agent, while 3

Discussion

As therapeutic options for CD expand, there is an increased need to understand the effectiveness of the various drugs across different lines of treatment. This applies to first-line treatments but it's even more important for the biologic-experienced patients, when the surgical option should also be taken into account. In this regard, our study attempted to better clarify the real effectiveness of UST and VDZ as third-line biologic therapies. Overall, the results of our multicentre, real-world

Funding

None.

Disclosures

Fabio Salvatore Macaluso served as an advisory board member and/or received lecture grants from Biogen, Ferring, Galapagos, Janssen, MSD, Pfizer, and Takeda Pharmaceuticals. Maria Cappello served as an advisory board member for AbbVie, MSD, Takeda Pharmaceuticals, and received lecture grants from AbbVie, MSD, Chiesi, and Takeda Pharmaceuticals. Sara Renna served as an advisory board member/and or received lecture grants from AbbVie, Janssen, MSD, and Takeda Pharmaceuticals. Walter Fries served

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