Inflammatory bowel disease events after exposure to interleukin 17 inhibitors secukinumab and ixekizumab: Postmarketing analysis from the RADAR (“Research on Adverse Drug events And Reports”) program

Orrell, Kelsey A.; Murphrey, Morgan; Kelm, Ryan C.; Lee, Harrison H.; Pease, David R.; Laumann, Anne E.; West, Dennis P.; Nardone, Beatrice

doi:10.1016/j.jaad.2018.06.024

Cited by 35 publications

(27 citation statements)

References 4 publications

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“…Biologic medications and their effects on the immune system have been shown to have multiple unanticipated effects on the skin. [4][5][6] We are not insinuating that dupilumab was the cause of our patients having developed CTCL, but we do propose that the underlying interplay of dupilumab with the immune system might have accelerated progression of underlying CTCL, resulting in the lymphoma presenting itself clinically and histopathologically. We also must mention that all 3 cases could represent a "true, true, and unrelated" phenomenon.…”

Section: Commentmentioning

confidence: 87%

Long-standing Dermatitis Treated With Dupilumab With Subsequent Progression to Cutaneous T-cell Lymphoma

Hollins¹,

Wirth²,

Fulchiero³

et al. 2020

Cutis

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This case series discusses 3 patients with long-standing eczematous or psoriasiform dermatitis, demonstrated by multiple biopsies. Following off-label treatment with dupilumab, all 3 patients had clinical expansion of disease, with histopathologic features consistent with cutaneous T-cell lymphoma (CTCL) on subsequent biopsy. We postulate that this expansion likely was secondary to an exacerbation of extant CTCL following exposure to dupilumab. A proposed mechanism of promotion of CTCL is based on the functional increase in IL-13 available for binding at the upregulated IL-13 receptor (IL-13R) α2 site on cells, following blockade of the α1 receptor with dupilumab. This progression merits further investigation.

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Section: Commentmentioning

confidence: 87%

Long-standing Dermatitis Treated With Dupilumab With Subsequent Progression to Cutaneous T-cell Lymphoma

Hollins¹,

Wirth²,

Fulchiero³

et al. 2020

Cutis

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“…13,14 In addition to the lack of response in existing IBD, new onset of IBD cases following treatment with anti-IL-17 agents have been reported in both case reports, [15][16][17] clinical trials 7,10,18 and post-marketing surveillance. 19 These findings therefore suggest that IL-17 may paradoxically play a protective role in the pathogenesis of IBD and that anti-IL-17 agents may be causing new onset or exposing subclinical IBD. However, patients with autoimmune diseases are known to have increased risk of IBD as there is overlap between susceptibility genes.…”

Section: Introductionmentioning

confidence: 91%

“…However, clinical trials of anti‐IL‐17 agents not only have failed to demonstrate clinical efficacy, but findings also suggested that they may actually cause exacerbations of symptoms and clinical relapses in patients with CD . In addition to the lack of response in existing IBD, new onset of IBD cases following treatment with anti‐IL‐17 agents have been reported in both case reports, clinical trials and post‐marketing surveillance . These findings therefore suggest that IL‐17 may paradoxically play a protective role in the pathogenesis of IBD and that anti‐IL‐17 agents may be causing new onset or exposing subclinical IBD.…”

Section: Introductionmentioning

confidence: 99%

Systematic review with meta‐analysis: risk of new onset IBD with the use of anti‐interleukin‐17 agents

Yamada

Wang

Komaki

et al. 2019

Aliment Pharmacol Ther

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Summary Background New onset IBD has been reported with the use of anti‐IL‐17 agents, but it remains unclear to what extent this is attributed to treatment or to underlying disease. Aim To evaluate the risk of new onset IBD with the use of anti‐IL‐17 agents Methods Electronic databases were searched for randomised controlled trials (RCT) of anti‐IL‐17 agents (brodalumab, ixekizumab and secukinumab). Risk of new onset IBD was compared to placebo by Mantel‐Haenszel (MH) risk difference (RD). Sensitivity analyses including meta‐analysis using fixed‐effect model, MH and Peto odds ratio and MH risk ratio were performed due to incidence of rare adverse events. The risk of diarrhoea was also assessed due to the possibility of underdiagnosis of IBD. Results Thirty‐eight RCTs including 16 690 patients treated with anti‐IL‐17 agents were included. Twelve cases of new onset IBD were reported with anti‐IL‐17 agents in five studies, whereas no cases were reported with placebo. There was no difference in the risk of developing new onset IBD with anti‐IL‐17 agents compared to placebo (MH RD 0.00062, 95% CI −0.00072‐0.0021, P = 0.35). Sensitivity analyses demonstrated no consistent risk with any method. There was no difference in the risk of diarrhoea (MH RD 0.0013, 95% CI −0.0014‐0.0041, P = 0.34). Conclusions New onset IBD with the use of anti‐IL‐17 agents was rare. Interpretation of the results needs caution due to the presence of many zero‐event studies.

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“…4,5 Interestingly, IL-17 inhibitors are well known to induce or worsen Crohn's disease (CD), in which granuloma formation is common. [6][7][8] These observations suggest that in some patients, IL-17 inhibition might promote, rather than treat, granulomatous inflammation. We also found that IL-17 blockade results in downregulation of NOD2, a familial sarcoidosis and CD gene, in skin and may relate to this observation.…”

Section: Development or Worsening Of Sarcoidosis Associated With Il-1mentioning

confidence: 92%

Development or worsening of sarcoidosis associated with IL‐17 blockade for psoriasis

Hornick

Wang

Lim

et al. 2020

Acad Dermatol Venereol

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app for risk assessment of pigmented and non-pigmented skin lesions-a study on sensitivity and specificity in detecting malignancy. Telemed J E Health 2017; 23: 948-954. 7 SkinVision. [WWW document]. URL https://www.skinvision.com/news/ skinvision-to-join-nhs-innovation-accelerator (last accessed: 26 May 2020). 8 Freeman K, Dinnes J, Chuchu N et al. Algorithm based smartphone apps to assess risk of skin cancer in adults: systematic review of diagnostic accuracy studies. BMJ 2020; 368: m127.

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Inflammatory bowel disease events after exposure to interleukin 17 inhibitors secukinumab and ixekizumab: Postmarketing analysis from the RADAR (“Research on Adverse Drug events And Reports”) program

Cited by 35 publications

References 4 publications

Long-standing Dermatitis Treated With Dupilumab With Subsequent Progression to Cutaneous T-cell Lymphoma

Long-standing Dermatitis Treated With Dupilumab With Subsequent Progression to Cutaneous T-cell Lymphoma

Systematic review with meta‐analysis: risk of new onset IBD with the use of anti‐interleukin‐17 agents

Development or worsening of sarcoidosis associated with IL‐17 blockade for psoriasis

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