Comment on: Prevalence and real-world management of vedolizumab-associated enthesitis in successfully treated IBD patients

Dear Editor, We read with great interest the report of Di Ruscio et al. [1] entitled ‘Prevalence and real-world management of vedolizumab-associated enthesitis in successfully treated IBD patients’.

The authors reported in this manuscript the development of severe enthesitis under vedolizumab (VDZ) therapy in patients with IBD. In this context, we would like to call attention to a few points. As clinicians who have been involved in elaborating a draft recommendation for the management of rheumatic disorders in IBD patients, we believe that dealing with this particular situation is a challenging task because of the lack of standardized guidelines [2].

VDZ, a gut-selective blocker inhibiting the α4β7 integrin and the leucocytes migration across inflamed intestinal tissue, has been recently approved as a part of the therapeutic arsenal to be used in IBD [3]. However, there has yet to be evidence of its effects on articular manifestations. The issue of whether VDZ can be prescribed in patients with coexisting spondylarthritis (SpA) and IBD has become a subject of lively debate, with some groups completely opposed to this therapeutic option and others supporting it. A potential benefit of VDZ on articular manifestations of IBD has been reported and explained by the previous demonstration of α4β7 in the joint [4]. Conversely, as reported in the present study, new onset or exacerbation of sacroiliitis, arthritis or enthesitis have been described upon VDZ therapy [5, 6]. Such findings have major implications in managing SpA associated with IBD and may reduce the therapeutic armamentarium; that is why we felt the need to discuss some results. The authors reported new-onset entheseal pathology in 11 cases among a total of 90 IBD patients.

The first point we want to draw attention to is that most of the patients developing active enthesitis (8/11) have been previously under anti-TNF agents, which may mask pre-existing quiescent articular disorders. Moreover, the authors reported a history of inactive axial SpA prior to VDZ therapy in one case. The discontinuation of anti-TNF alpha can be the cause of the SpA flare. Thus, it would be difficult to incriminate VDZ in such situations.

Second, the entheseal involvement, confirmed by clinical examination and/or positive Doppler ultrasound signals, may be found in IBD patients even when they do not fulfil the SpA items [7]. Enthesitis can be considered as a part of the natural course of the disease, regardless of the prescribed treatments.

Regarding the management of this complication, ustekinumab may not be the appropriate third-line biological therapy in axial SpA coexisting with CD (patient 6). Indeed, three multicentre studies in phase III showed a lack of clinical response or spine MRI improvement under ustekinumab in axial SpA [8]. Given its well-proven efficacy in both conditions, certolizumab pegol may be more suitable in this case. However, specific studies assessing its potential effect on enthesitis are missing.

To sum up, further investigations of the molecular mechanisms underlying the α4β7 blockade in the joints are still required before drawing firm conclusions on this issue.

Disclosure statement: The authors have declared no conflicts of interest.

Data availability statement

Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). All data relevant to the study are included in the article.

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