Prevalence and Real-World Management of Vedolizumab-Associated Enthesitis in Successfully Treated IBD Patients

Mirko Di Ruscio; Ilaria Tinazzi; Angela Variola; Andrea Geccherle; Antonio Marchetta; Dennis McGonagle

Disclosures

Rheumatology. 2021;60(12):5809-5813. 

In This Article

Abstract and Introduction

Abstract

Background: Some studies have reported the development of moderate and severe de novo SpA-associated disease under vedolizumab (VDZ) treatment for IBD. Herein, we report a case series who developed severe enthesitis under VDZ therapy from a cohort of 90 treated cases.

Methods: In a single Italian IBD Unit in which 90 cases were on VDZ therapy, we identified 11 cases who developed severe enthesitis. The onset of disease in relationship to VDZ initiation, clinical and sonographic imaging features, and outcomes (including therapy switches) was described.

Results: A total of 11 cases, including 8 prior anti-TNF failures, with new-onset entheseal pathology were identified: multifocal (n = 4), unifocal (n = 6), and enthesitis/synovitis/dactylitis (n = 1). The mean duration of symptoms was 46 weeks (range 6–119), the mean CRP was 5.1 mg/dl, and the majority were HLA-B27 negative and showed good clinical response for gut disease. Clinical features and US showed severe enthesitis, including power Doppler change in 7 patients. All patients were initially treated with NSAIDs, and 5 patients underwent local steroid injections. At 12 months, 5/7 cases continued VDZ and 2 were switched to ustekinumab. At 12 months follow-up of 7 cases, 5 patients were in clinical remission and 2 patients had mild enthesitis with minimal increase of power Doppler signal. In addition, 4/7 severe patients developed marked post-inflammatory entheseal calcifications

Conclusions: A predominant isolated severe enthesitis pattern of SpA may develop under VDZ therapy with severe disease in 8% of cases. Most cases continued VDZ therapy.

Introduction

The seronegative SpA group of diseases share overlapping immunogenetics, a link to gut inflammation and a skeletal microanatomical basis for disease localization to entheses and other sites of high mechanical stress.[1] The advent of the anti-TNF alpha class of drugs changed the management of the entire gamut of inflammatory disease associated with SpA, including PsA, AS, IBD uveitis and psoriasis.[2–4]

Translational therapeutics has taught us that these conditions have a different immunopathology, as some therapies work in certain situations but not others. For example, the TNF fusion protein etanercept is not effective for IBD or uveitis. The IL-17 blockers are not effective for IBD features of SpA, but work for psoriasis and musculoskeletal inflammation.[5,6] Remarkably, the converse is also true in that drugs that may work in IBD show no efficacy for SpA or may even be associated with de novo disease. One such agent is vedolizumab (VDZ), a humanized integrin antagonist approved for IBD therapy that selectively blocks gut-specific lymphocyte trafficking and recruitment.[7] Previous studies have shown new-onset SpA following VDZ therapy that is sometimes severe, with a reported prevalence of around 4%.[8]

Enthesitis is the cardinal lesion in SpA, and isolated peripheral enthesitis has previously been reported following VDZ therapy.[9–11] However, its management and follow-up has been poorly described. In our tertiary referral centre of 300 biologic-treated patients, 30% (90/300) of these were taking VDZ. We looked at the prevalence of peripheral enthesitis, its severity and its therapy in patients complaining of articular symptoms during VDZ therapy. Herein, we report on the prevalence and management of this complication, including switching to third-line biologic therapy in some cases to control disease.

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