Successful use of secukinumab in a 4-year-old patient with deficiency of interleukin-36 antagonist

Prelog, Martina; Almanzar, Giovanni; Fesq, Heike; Haas, Johannes‐Peter; Hügle, Boris

doi:10.1093/rheumatology/kex510

Cited by 28 publications

(39 citation statements)

References 8 publications

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“…However, its safety and efficacy in children have remained unknown. Successful treatment with secukinumab has been reported in only two non‐adult cases of DITRA presenting with GPP, including one adolescent (of unknown age) with a homozygous mutation at c.115+6T>C in the IL36RN gene and another 4‐year‐old Moroccan boy with a homozygous mutation at c.80T>C (Table ) . Both cases showed rapid defervescence and improvement of skin lesions with the latter 4‐year‐old case started with only 75 mg of secukinumab per week .…”

Section: Discussionmentioning

confidence: 99%

“…Successful treatment with secukinumab has been reported in only two non‐adult cases of DITRA presenting with GPP, including one adolescent (of unknown age) with a homozygous mutation at c.115+6T>C in the IL36RN gene and another 4‐year‐old Moroccan boy with a homozygous mutation at c.80T>C (Table ) . Both cases showed rapid defervescence and improvement of skin lesions with the latter 4‐year‐old case started with only 75 mg of secukinumab per week . However, different from a successful treatment with secukinumab monotherapy in our case, combined treatment with either oral methotrexate or oral corticosteroids had been used concurrently with secukinumab in these two cases .…”

Section: Discussionmentioning

confidence: 99%

“…In the lesions of GPP, infiltrates of innate immune cells contribute to the dominant cytokines such as IL-1, IL-36, tumor necrosis factor (TNF)-a and interferon (IFN)-a, 8 which may explain the rationale of treating GPP with aforementioned anti-TNF-a agents and IL-1 receptor antagonist (anakinra). 3,8 However, neutrophils may play a more important role in the pathogenesis of GPP compared with plaque-type psoriasis, because they are more profound in GPP than in psoriasis vulgaris. 9 Neutrophils in active psoriatic lesions are the largest fraction of infiltrating cells containing IL-17, which is preformed by T-helper 17 cells (or possibly derived from neutrophils themselves) and also highly expressed in the lesion of GPP.…”

Section: Discussionmentioning

confidence: 99%

“…8,13 Both cases showed rapid defervescence and improvement of skin lesions with the latter 4-year-old case started with only 75 mg of secukinumab per week. 8,13 However, different from a successful treatment with secukinumab monotherapy in our case, combined treatment with either oral methotrexate or oral corticosteroids had been used concurrently with secukinumab in these two cases. 8,13 Clearance and volume of secukinumab have been shown to vary with bodyweight allometrically and the influence of age (in adult patients) was considered clinically irrelevant.…”

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confidence: 96%

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Successful treatment of refractory juvenile generalized pustular psoriasis with secukinumab monotherapy: A case report and review of published work

Tsai

2018

The Journal of Dermatology

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Juvenile generalized pustular psoriasis (GPP) is rare and often resistant to conventional systemic therapy such as methotrexate, retinoic acid and cyclosporin A. GPP can be induced by deficiency of interleukin (IL)-36 receptor antagonist (DITRA). No standardized guidelines are available for juvenile GPP or DITRA, and a uniformly safe and effective biologic agent has not been identified. However, multiple biologics approved for use in plaque-type psoriasis have also been used in GPP. Herein, we report a case of a 6-year-old Taiwanese boy with GPP and homozygous mutation at c.115+6T>C within the IL-36 receptor antagonist (IL36RN) gene, who was treated successfully with secukinumab after failure of prior methotrexate, acitretin, cyclosporin A, etanercept and adalimumab. Similar to two previously reported non-adult cases of GPP successfully treated with secukinumab, our case also demonstrated a history of repeated treatment failures with several conventional oral systemic agents and biologics. Different from these two cases, however, ours is the first of juvenile GPP successfully treated with secukinumab monotherapy, without using other systemic agent concurrently during the use of secukinumab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

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Successful treatment of refractory juvenile generalized pustular psoriasis with secukinumab monotherapy: A case report and review of published work

Tsai

2018

The Journal of Dermatology

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“…The binding of IL-36Ra to IL-36R prevents the association of IL1RAcP and downstream signalling. While there have been four case reports of the successful treatment of DITRA with anakinra therapy [35–38], therapeutic benefit has also resulted from TNF inhibition [39–41], IL-17 inhibition with secukinumab [42] and IL-12/IL-23 inhibition with ustekinumab [43–45]. This suggests that these agents may be targeting cytokines that are downstream of IL-36 [38].…”

Section: Classificationmentioning

confidence: 99%

The classification, genetic diagnosis and modelling of monogenic autoinflammatory disorders

Moghaddas

Masters

2018

Clinical Science

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Monogenic autoinflammatory disorders are an increasingly heterogeneous group of conditions characterised by innate immune dysregulation. Improved genetic sequencing in recent years has led not only to the discovery of a plethora of conditions considered to be ‘autoinflammatory’, but also the broadening of the clinical and immunological phenotypic spectra seen in these disorders. This review outlines the classification strategies that have been employed for monogenic autoinflammatory disorders to date, including the primary innate immune pathway or the dominant cytokine implicated in disease pathogenesis, and highlights some of the advantages of these models. Furthermore, the use of the term ‘autoinflammatory’ is discussed in relation to disorders that cross the innate and adaptive immune divide. The utilisation of next-generation sequencing (NGS) in this population is examined, as are potential in vivo and in vitro methods of modelling to determine pathogenicity of novel genetic findings. Finally, areas where our understanding can be improved are highlighted, such as phenotypic variability and genotype–phenotype correlations, with the aim of identifying areas of future research.

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Efficacy and safety of secukinumab for the treatment of severe ABCA12 deficiency‐related ichthyosis in a child

Yogarajah

Gouveia

Iype

et al. 2021

Skin Health and Disease

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Background: Patients with severe autosomal recessive congenital ichthyosis (ARCI) show a T helper 17/interleukin 17 (Th17/IL17) skewing in their skin and serum, resembling the inflammatory profile of psoriatic patients. Secukinumab, an IL-17A inhibitor, has shown clinical efficacy in patients with moderate-to-severe plaque psoriasis. Aims: To test the clinical efficacy and safety of secukinumab in a paediatric patient with ATP-binding cassette subfamily A member 12 deficiencyrelated severe erythrodermic ARCI.Materials & Methods: 6-months therapeutic trial. During the first 4-weeks induction period, the patient received weekly subcutaneous injections of 150 mg secukinumab (five injections in total). During the following 20weeks maintenance period, the patient was given a subcutaneous injection of 150 mg secukinumab every 4 weeks. Result & Discussion: After the 6-months therapy period, there was a 48% reduction from the baseline Ichthyosis-Area-Severity-Index (-Erythema/-Scaling) score. The treatment was well tolerated. Moreover, cytokine analysis revealed a reduction of keratinocyte-derived proinflammatory cytokines and an abrogation of Th17-skewing during therapy. Conclusion: Further studies are needed to evaluate the effects of the use of IL-17A inhibition in ARCI patients. J. Yogarajah and C. Gouveia contributed equally to this study.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Successful use of secukinumab in a 4-year-old patient with deficiency of interleukin-36 antagonist

Cited by 28 publications

References 8 publications

Successful treatment of refractory juvenile generalized pustular psoriasis with secukinumab monotherapy: A case report and review of published work

Successful treatment of refractory juvenile generalized pustular psoriasis with secukinumab monotherapy: A case report and review of published work

The classification, genetic diagnosis and modelling of monogenic autoinflammatory disorders

Efficacy and safety of secukinumab for the treatment of severe ABCA12 deficiency‐related ichthyosis in a child

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