Successful treatment of ulcerated pyoderma gangrenosum with baricitinib, a novel JAK inhibitor

Scheinberg, Morton; Machado, Luís Antonio de Paula; Castro, Luiz G M; Ferreira, Sineida Berbert; Michalany, Nílceo Schwery

doi:10.1016/j.jtauto.2021.100099

Cited by 22 publications

(26 citation statements)

References 9 publications

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“…The role of JAK inhibitors as a treatment option for PG is yet to be thoroughly assessed. Baricitinib has been trialled for two patients with ulcerative PG involving the scalp and the legs, with complete regression seen in 5 weeks in one patient and 3 months in the other, at a dose of 4 mg a day 46 . JAK inhibitors may be effective as a treatment for PG given that they target multiple cytokine receptors involved in PG pathogenesis such as IL‐23R, IL‐12R and IL‐10R.…”

Section: Discussionmentioning

confidence: 99%

Pyoderma gangrenosum: A systematic review of the molecular characteristics of disease

Flora

Kozera

Frew

2022

Experimental Dermatology

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Pyoderma gangrenosum is a painful recurrent ulcerative neutrophilic dermatosis in which the pathogenesis is incompletely defined. Current evidence suggests that PG is associated with dysregulation of components of both the innate and adaptive immune system with dysregulation of neutrophil function and contribution of the Th17 immune axis. PG can be present in numerous heterogeneous clinical presentations and be associated with multiple inflammatory conditions including rheumatoid arthritis, inflammatory bowel disease and hidradenitis suppurativa. However, no critical evaluation of the observed molecular characteristics in PG studies in association with their clinical findings has been assessed. Additionally, emerging evidence suggests a potential role for other cell types and immune pathways including B cells, macrophages, autoantibodies and the complement system in PG, although these have not yet been integrated into the pathogenesis of disease. This systematic review aims to critically evaluate the current molecular observations regarding the pathogenesis of PG and discuss associations with clinical characteristics as well as the evidence supporting novel cell types and immune pathways in PG.

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Section: Discussionmentioning

confidence: 99%

Pyoderma gangrenosum: A systematic review of the molecular characteristics of disease

Flora

Kozera

Frew

2022

Experimental Dermatology

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“…9 Another report described two patients who showed complete remission upon treatment with baricitinib (JAK1/2 inhibitor). 10 Finally, successful treatment of a patient with concomitant polycythemia vera with ruxolitinib (JAK1/2 inhibitor) has been reported. 11 Baricitinib is currently being investigated for PG in a phase II trial.…”

Section: Discussionmentioning

confidence: 99%

“…One group reported 10 cases of tofacitinib (JAK1/3 inhibitor), of whom 4 achieved full healing of the ulcers 9 . Another report described two patients who showed complete remission upon treatment with baricitinib (JAK1/2 inhibitor) 10 . Finally, successful treatment of a patient with concomitant polycythemia vera with ruxolitinib (JAK1/2 inhibitor) has been reported 11 .…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of pyoderma gangrenosum with Janus kinase 1/2 inhibition

Sitaru

Biedermann

Lauffer

2022

JEADV Clinical Practice

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Pyoderma gangrenosum (PG) is a rare, autoinflammatory disease leading to painful, hard‐to‐treat ulcers. Besides systemic glucocorticoids, a plethora of classic immunosuppressants, biologics and small molecules have been reported to improve PG disease course. However, often several treatment strategies fail or cannot be applied due to comorbidities or side effects. We herein report the case of an 85‐year‐old woman with rheumatoid arthritis, lymphopenia and lower leg ulceration due to PG. After multiple steroid‐sparing therapies failed, including methotrexate, mycophenolate mofetil, intravenous immunoglobulins and infliximab, we initiated treatment with baricitinib, a Janus kinase (JAK) 1/2 inhibitor. In combination with intravenous immunoglobulins, we achieved complete remission first of the inflamed margin and second, of the ulceration. Our report suggests that JAK 1/2 inhibition might be a promising therapy option in refractory PG even in elderly patients with comorbidities.

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“…Two patients with polycythemia vera experienced PG resolution after treatment with ruxolitinib [ 156 , 157 ]. Baricitinib 4 mg daily has led to complete ulcer healing in isolated reports [ 158 ] and is currently under investigation in a phase II clinical trial (NCT04901325) in combination with prednisone [ 159 ].…”

Section: Small Moleculesmentioning

confidence: 99%

Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments

Maronese

Pimentel

et al. 2022

Am J Clin Dermatol

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Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous-violaceous edges. Pyoderma gangrenosum pathogenesis is complex and involves a profound dysregulation of components of both innate and adaptive immunity in genetically predisposed individuals, with the follicular unit increasingly recognized as the putative initial target. T helper 17/T helper 1-skewed inflammation and exaggerated inflammasome activation lead to a dysregulated neutrophil-dominant milieu with high levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1α, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. Low-evidence studies and a lack of validated diagnostic and response criteria have hindered the discovery and validation of new effective treatments for pyoderma gangrenosum. We review established and emerging treatments for pyoderma gangrenosum. A therapeutic algorithm based on available evidence is also provided. For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum.

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Successful treatment of ulcerated pyoderma gangrenosum with baricitinib, a novel JAK inhibitor

Cited by 22 publications

References 9 publications

Pyoderma gangrenosum: A systematic review of the molecular characteristics of disease

Pyoderma gangrenosum: A systematic review of the molecular characteristics of disease

Successful treatment of pyoderma gangrenosum with Janus kinase 1/2 inhibition

Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments

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