Emergence of severe spondyloarthropathy-related entheseal pathology following successful vedolizumab therapy for inflammatory bowel disease

Dubash, Sayam; Marianayagam, Thiraupathy; Tinazzi, Ilaria; Al-Araimi, Tariq; Pagnoux, Christian; Weizman, Adam V.; Richette, Pascal; Minh, My-Linh Tran; Allez, Matthieu; Singh, Animesh; Ciccia, Francesco; Hamlin, John; Tan, Ai Lyn; Marzo‐Ortega, Helena; McGonagle, Dennis

doi:10.1093/rheumatology/key267

Cited by 53 publications

(22 citation statements)

References 15 publications

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“…While inhibition of IL-23 appears to be an effective strategy in IBD [ 70 ], this is not effective for axSpA [ 35 , 36 ]. Vedolizumab, an α4β7 integrin blocker licensed for the treatment of IBD [ 71 ], has been reported to precipitate enthesitis and sacroiliitis in some patients [ 72 ], so should be used with caution in patients with IBD and axSpA. The results for the JAK inhibitors in IBD have been more mixed, with tofacitinib failing to reach its primary end point in Crohn’s disease but effective in ulcerative colitis, while the JAK1 inhibitors filgotinib and upadacitinib have reported promising early-phase results [ 73 , 74 ].…”

Section: Biologic Dmards In Axspamentioning

confidence: 99%

Treatment strategies in axial spondyloarthritis: what, when and how?

Fragoulis

Siebert

2020

Rheumatology

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There have been major advances in the management of axial spondyloarthritis (axSpA) with the introduction of effective biologic agents targeting TNF and IL-17A. Clinicians now have more choice but, despite treatment recommendations, are still faced with significant uncertainty when deciding on the optimal treatment strategy for an individual patient in clinical practice. Management of axSpA typically requires both non-pharmacological and pharmacological interventions. NSAIDs remain the first line drug therapies for axSpA with proven efficacy for symptomatic management but uncertainty remains regarding their optimal long-term use relating to radiographic progression and safety in axSpA. To-date there are no head-to-head trials of biologics in axSpA. Clinicians need to consider other factors, including extra-articular manifestations, comorbidities, safety and radiographic progression when deciding on which biologic to recommend for an individual patient. This article will explore the evidence relating to these factors and highlight areas of unmet need.

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Section: Biologic Dmards In Axspamentioning

confidence: 99%

Treatment strategies in axial spondyloarthritis: what, when and how?

Fragoulis

Siebert

2020

Rheumatology

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“…publications described a number of patients with IBD having possible flares or new occurrence of rheumato logical SpA manifestations after treatment with vedolizumab 250,251 . In another IBD case series, an improvement in rheumatologic manifestations was described with vedolizumab; however, the follow-up period of these cases was very short 252,253 .…”

Section: Patients With Active Spa and Quiescent Ibdmentioning

confidence: 99%

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

et al. 2020

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Gut inflammation is strongly associated with spondyloarthritis (SpA), as exemplified by the high prevalence of inflammatory bowel disease (IBD) and the even higher occurrence of subclinical gut inflammation in patients with SpA. The gut-joint axis of inflammation in SpA is further reinforced by similarities in immunopathogenesis at both anatomical sites and by the clinical success of therapies blocking TNF and IL-23 in IBD and in some forms of SpA. Many genetic risk factors are shared between SpA and IBD, and changes in the composition of gut microbiota are seen in both diseases. Current dogma is that inflammation in SpA initiates in the gut and leads to joint inflammation; however, although conceptually attractive, some research does not support this causal relationship. For example, therapies targeting IL-17A are efficacious in the joint but not the gut, and interfering with gut trafficking by targeting molecules such as α4β7 in IBD can lead to onset or flares of SpA. Several important knowledge gaps remain that must be addressed in future studies. Determining the true nature of the gut-joint axis has real-world implications for the treatment of patients with co-incident IBD and SpA and for the repurposing of therapeutics from one disease to the other.

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“…Similarly, observations highlight the role of the gut as the primary site for the differentiation, expansion and priming of innate cells prior to recirculation to axSpA target sites [ 19 ]. Reported de novo severe SpA in ameliorated IBD following α4β7 integrin blockade is further clinical evidence of the intimate connection intertwined at the gut–joint axis and innate-driven mechanisms [ 20 ]. Perhaps upregulation of the mucosal vascular cell adhesion molecule 1 (MADCAM-1), the homing integrin (α4β7) ligand, in the gut and inflamed bone marrow of patients with axSpA provides additional evidence of the importance of recirculation of gut-primed innate cells [ 20 ].…”

Section: Gut Barrier Regulation and Axspamentioning

confidence: 99%

“…Reported de novo severe SpA in ameliorated IBD following α4β7 integrin blockade is further clinical evidence of the intimate connection intertwined at the gut–joint axis and innate-driven mechanisms [ 20 ]. Perhaps upregulation of the mucosal vascular cell adhesion molecule 1 (MADCAM-1), the homing integrin (α4β7) ligand, in the gut and inflamed bone marrow of patients with axSpA provides additional evidence of the importance of recirculation of gut-primed innate cells [ 20 ]. Finally, microbial products, also known as pathogen-associated molecular patterns, act as adjuvants, defined as substances enhancing antigen-specific immune response [ 21 ].…”

Section: Gut Barrier Regulation and Axspamentioning

confidence: 99%

Intestinal and enthesis innate immunity in early axial spondyloarthropathy

et al. 2020

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Axial SpA (axSpA), encompassing AS, is a multifactorial disease that localizes to sites of high spinal biomechanical stress. Much has been written on T cells and adaptive immunity in axSpA, which is understandable given the very strong HLA-B27 disease association. Extra-axial disease characteristically involves the anterior uveal tract, aortic root, lung apex and terminal ileum. Under recent classification, axSpA is classified as an intermediate between autoimmunity and autoinflammatory disease, with the latter term being synonymous with innate immune dysregulation. The purpose of this review is to evaluate the ‘danger signals’ from both the exogenous intestinal microbiotal adjuvants or pathogen-associated molecular patterns that access the circulation and endogenously derived damaged self-tissue or damage-associated molecular patterns derived from entheses and other sites of high biomechanical stress or damage that may serve as key drivers of axSpA onset, evolution, disease flares and eventual outcomes.

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Emergence of severe spondyloarthropathy-related entheseal pathology following successful vedolizumab therapy for inflammatory bowel disease

Abstract: Severe SpA, predominantly HLA-B27 negative, with osteitis/enthesitis may occur under successful VDZ treatment for IBD, including in subjects with prior anti-TNF therapy for intestinal disease.

Cited by 53 publications

References 15 publications

Treatment strategies in axial spondyloarthritis: what, when and how?

Treatment strategies in axial spondyloarthritis: what, when and how?

Revisiting the gut–joint axis: links between gut inflammation and spondyloarthritis

Intestinal and enthesis innate immunity in early axial spondyloarthropathy

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