Background: Enthesitis is a key feature of peripheral Spondyloarthritis (SpA). Several pro-inflammatory cytokines including Interleukin-17 and Interleukin-23 are found within the enthesis (1). Dupilumab is a recombinant human monoclonal antibody that inhibits signalling of Interleukin-4 and Interleukin-13, approved for use in patients with moderate- to –severe atopic eczema. Here we describe a cohort of patients with severe atopic eczema who have developed a new peripheral SpA/ enthesitis after receiving Dupilumab.

Objectives: To describe the clinical and imaging details of this cohort.

Methods: All patients in St John’s Institute of Dermatology who exhibited new arthralgias on Dupilumab therapy were referred for assessment in Guy’s Rheumatology Department. These patients had a focussed history, examination, ultrasound and/or MRI of affected joints and entheseal sites.

Results: To date we have seen 12 patients with a history of new inflammatory peripheral SpA type symptoms following onset of Dupilumab therapy. There were 7 males and 5 females all of whom have longstanding severe atopic Eczema. All patients had raised baseline IgE levels of mainly >10000. All patients exhibited a positive response to Dupilumab with a marked improvement in eczema as measured by the EASI score. All patients had normal inflammatory markers and negative immunological screening bloods. Musculoskeletal symptom onset was between 2 and 20 weeks after starting treatment. Typically, these patients had inflammatory symptoms affecting both the small joints and the entheseal sites. 2/12 patients developed inflammatory sounding spinal pain. 2/12 patients had ultrasound evidence of arthritis. 11/12 patients had radiological findings of enthesitis as seen on MRI or ultrasound (power doppler ultrasound signal). 9/12 patients were treated with non-steroidal anti-inflammatories with variable improvement.1 patient required no treatment and 1 patient received low dose prednisolone.

Conclusion: In our centre approximately 200 patients have received Dupilumab. These musculoskeletal findings have not been reported previously in clinical trials. We hypothesise that the profound inhibition of IL- 4/13 may allow an inflammatory response at the enthesis presenting with a peripheral SpA pattern. IL-4 has been shown to suppress delayed type hypersensitivity reactions (DTHRs) and psoriasis in both human and mice studies (2). These findings and the demonstratation that IL-23 transcription and secretion can be suppressed by IL-4 with resultant reduction in Th17 function (3) may be key factors as to why a SpA type response is seen in certain subjects.

REFERENCES:

[1]Bridgewood et al. Immunol Rev 2020 [Epub]

[2]Ghoreschi et al. Nat Med. 2003;9:40-6.

[3]Guenova et al. PNAS. 2015;112:2163-8.

Disclosure of Interests: Catherine Hughes Speakers bureau: Lilly, Bina Menon Speakers bureau: Novartis, Richard Woolf: None declared, Zena Willsmore: None declared, Catherine Smith: None declared, Andrew Pink: None declared, L Bruce Kirkham Grant/research support from: Eli Lilly Novartis, Consultant of: Eli Lilly Gilead Janssen Novartis