Development of inflammatory arthritis and enthesitis in patients on dupilumab: a case series

Willsmore, Zena; Woolf, Richard; Hughes, Christopher R.; Menon, Bina; Kirkham, Bruce; Smith, Catherine; Pink, Andrew E.

doi:10.1111/bjd.18031

Cited by 53 publications

(42 citation statements)

References 8 publications

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“…Arthralgia has recently been added to the Summary of Product Characteristics for dupilumab as a result of post marketing reporting [15]. Willsmore et al [38] reported a series of three patients who developed generalised seronegative arthritis and enthesitis during dupilumab treatment. The pathogenesis of arthralgia in these patients remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Real-World Experience and Laboratory Monitoring of Dupilumab in Patients with Moderate to Severe Atopic Dermatitis in a Tertiary Centre

Kreeshan

Al‐Janabi

Warren

et al. 2020

Dermatol Ther (Heidelb)

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Introduction Dupilumab is a biologic therapy approved for treatment of moderate to severe atopic dermatitis (AD). Our objective was to assess the real-world effectiveness, safety and laboratory monitoring practices for dupilumab in a tertiary centre. Methods A retrospective review of medical records of all patients receiving dupilumab between September 2017 and October 2019 was undertaken. Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) were collected at weeks 0, 12–16 and 26–30. Data on laboratory tests undertaken for dupilumab screening and monitoring were also collected. Results At 12–16 weeks, 58.9% and 37.3% of patients achieved ≥ EASI 75 and ≥ EASI 90, respectively ( n = 156). Ninety-four patients underwent further analysis at weeks 26–30 with those achieving ≥ EASI 75 increasing from 61.7% (12–16 weeks) to 75.31%, and EASI 90 increasing from 35.8% (12–16 weeks) to 49.8%. The most common side effects were eye symptoms occurring in 43.1% of patients, with 16.3% developing conjunctivitis. The mean treatment duration was 255 days, during which an average of three sets of blood tests were performed ( n = 149). Of all laboratory abnormalities recorded, 24% started after initiation of dupilumab, and 93% were classified as ‘mild’. Dupilumab was not documented as causative in any of the cases, nor was treatment stopped on account of laboratory abnormalities. Conclusion Dupilumab provides an effective and safe treatment option for patients with AD. Clinical response continued to improve past 16 weeks in this real-world population. No laboratory abnormalities were felt to be secondary to dupilumab; screening and monitoring tests did not influence dupilumab prescribing. Electronic supplementary material The online version of this article (10.1007/s13555-020-00469-6) contains supplementary material, which is available to authorised users.

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Section: Discussionmentioning

confidence: 99%

Real-World Experience and Laboratory Monitoring of Dupilumab in Patients with Moderate to Severe Atopic Dermatitis in a Tertiary Centre

Kreeshan

Al‐Janabi

Warren

et al. 2020

Dermatol Ther (Heidelb)

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“…Dupilumab is approved for moderate‐to‐severe atopic dermatitis. Recently, cases of new‐onset seronegative arthropathy and enthesitis have been reported within 16 weeks of starting dupilumab, thus re‐affirming the potential of IL‐13 in enthesitis immunopathology. These findings are still preliminary but nevertheless intriguing.…”

Section: Animal Models Showing a Role For Il‐23 In Enthesitismentioning

confidence: 75%

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

Bridgewood

Sharif

Sherlock

et al. 2020

Immunological Reviews

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The inflammatory disorders collectively termed the seronegative spondyloarthropathies (SpA) include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, the arthritis associated with inflammatory bowel disease including Crohn's disease and ulcerative colitis, the arthritis related to anterior uveitis, and finally, somewhat controversially Behcet's disease. All of these diseases are associated with SNPs in the IL‐23R or the interleukin‐23 (IL‐23) cytokine itself and related downstream signaling JAK pathway genes and the interleukin‐17 (IL‐17) pathway. In rheumatoid arthritis, the target of the immune response is the synovium but the SpA disorders target the tendon, ligament, and joint capsule skeletal anchorage points that are termed entheses. The discovery that IL‐23R–expressing cells were ensconced in healthy murine enthesis, and other extraskeletal anchorage points including the aortic root and the ciliary body of the eye and that systemic overexpression of IL‐23 resulted in a severe experimental SpA, confirmed a fundamentally different immunobiology to rheumatoid arthritis. Recently, IL‐23R–expressing myeloid cells and various innate and adaptive T cells that produce IL‐17 family cytokines have also been described in the human enthesis. Blockade of IL‐23 pathway with either anti‐p40 or anti‐p19 subunits has resulted in some spectacular therapeutic successes in psoriasis and PsA including improvement in enthesitis in the peripheral skeleton but has failed to demonstrate efficacy in AS that is largely a spinal polyenthesitis. Herein, we discuss the known biology of IL‐23 at the human enthesis and highlight the remarkable emerging story of this unique skeletal tissue.

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“…7 Conversely, there have been reports of psoriasiform eruptions, psoriasis, and inflammatory arthritis developing after initiating dupilumab, which could indicate upregulation of Th1/ Th17 cytokines. 3,4,[8][9][10] The etiology of seborrhoeic dermatitis is multifactorial, involving the interaction between intrinsic susceptibility, immunological defects, and fungal colonization. 11 Introducing cytokine imbalances might influence the immune response to Malassezia, leading to the development of seborrhoeic dermatitis in susceptible patients.…”

Section: Discussionmentioning

confidence: 99%

“…In the psoriasis literature, atopic dermatitis has been reported as an adverse event to biologics, and it has been speculated that Th17 pathway inhibition allows upregulation of Th2‐mediated immunity 7 . Conversely, there have been reports of psoriasiform eruptions, psoriasis, and inflammatory arthritis developing after initiating dupilumab, which could indicate upregulation of Th1/ Th17 cytokines 3,4,8‐10 . The etiology of seborrhoeic dermatitis is multifactorial, involving the interaction between intrinsic susceptibility, immunological defects, and fungal colonization 11 .…”

Section: Discussionmentioning

confidence: 99%

Seborrhoeic dermatitis and sebopsoriasis developing in patients on dupilumab: Two case reports

Al‐Janabi

Marsland

2020

Clinical Case Reports

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Development of inflammatory arthritis and enthesitis in patients on dupilumab: a case series

Cited by 53 publications

References 8 publications

Real-World Experience and Laboratory Monitoring of Dupilumab in Patients with Moderate to Severe Atopic Dermatitis in a Tertiary Centre

Real-World Experience and Laboratory Monitoring of Dupilumab in Patients with Moderate to Severe Atopic Dermatitis in a Tertiary Centre

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

Seborrhoeic dermatitis and sebopsoriasis developing in patients on dupilumab: Two case reports

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