Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders

Corbella-Bagot, L.; Loughlin, Constanza Riquelme‐Mc; Morgado-Carrasco, D.

doi:10.1016/j.ad.2023.06.012

Cited by 7 publications

(8 citation statements)

References 96 publications

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“…There are currently two published cases of oral/esophageal ELP that have been successfully treated with Upadacitinib as well as six published cases of LP that have been successfully treated with Tofacitinib. 1,12 We therefore report the third documented case of oral LP that has been successfully treated with Upadacitinib and the only case to be complicated by malignant transformation of oral ELP to oral SCC. This particular case demonstrates that JAKi's, particularly Upadacitinib may offer a potential new therapeutic option in those with recalcitrant ELP.…”

Section: Discussionmentioning

confidence: 95%

Successful treatment of erosive lichen planus with Upadacitinib complicated by oral squamous cell carcinoma

Landells,

Goudie,

McGrath

et al. 2023

SAGE Open Medical Case Reports

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Erosive lichen planus is a chronic auto-inflammatory disease which affects the stratified squamous epithelia resulting in painful ulcerations of both the skin and mucosal surfaces, and has a known malignant potential. Management of erosive lichen planus has proven to be difficult; however, recent reports of treatment with Janus kinase inhibitors such as Upadacitinib, are encouraging. This report outlines the third reported case of erosive lichen planus to be successfully treated with Upadacitinib in a 70-year-old woman with treatment-resistant disease. In addition, we report the complication of oral squamous cell carcinoma which became apparent once the extensive erosive lichen planus had healed. This case report highlights the importance of monitoring for mucosal squamous cell carcinoma in areas affected by erosive lichen planus, as squamous cell carcinoma can mimic the erosions of erosive lichen planus.

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Section: Discussionmentioning

confidence: 95%

Successful treatment of erosive lichen planus with Upadacitinib complicated by oral squamous cell carcinoma

Landells,

Goudie,

McGrath

et al. 2023

SAGE Open Medical Case Reports

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“…Currently, atopic dermatitis, alopecia areata, vitiligo and psoriasis are dermatological conditions for the treatment of which JAKi have been officially approved by the FDA or EMA. In Table 2, we have provided a brief summary of the JAKi and dermatological diseases for which they have been approved by the FDA or EMA [24,27,28]. Figure 3 shows a schematic presentation of Janus kinases together with the STAT proteins with which they interact and the site of action of individual Janus kinase inhibitors [10,12].…”

Section: Janus Kinase Inhibitorsmentioning

confidence: 99%

Section: Janus Kinase Inhibitorsmentioning

confidence: 99%

Novel Janus Kinase Inhibitors in the Treatment of Dermatologic Conditions

Ryguła,

Pikiewicz,

Kaminiów

2023

Molecules

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Janus kinase inhibitors, also known as JAK inhibitors, JAKinibs or JAKi, are a new group of disease-modifying drugs. They work by inhibiting enzymes involved in the transmission of information from receptors located in the cell membrane to the cell interior, specifically to the cell nucleus, thus disrupting the JAK-STAT pathway. This pathway plays a role in key cellular processes such as the immune response and cell growth. This feature is used in the treatment of patients with rheumatological, gastroenterological and hematological diseases. Recently, it has been discovered that JAK-STAT pathway inhibitors also show therapeutic potential against dermatological diseases such as atopic dermatitis, psoriasis, alopecia areata and acquired vitiligo. Studies are underway to use them in the treatment of several other dermatoses. Janus kinase inhibitors represent a promising class of drugs for the treatment of skin diseases refractory to conventional therapy. The purpose of this review is to summarize the latest knowledge on the use of JAKi in dermatological treatment.

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“…Currently, six molecules have been approved for use in dermatology: upadacitinib, baricitinib, abrocitinib, ritlecitinib, deucravacitinib, and topical ruxolitinib. Off-label uses have been reported for multiple dermatoses, and the approval of these drugs for diverse inflammatory dermatoses is anticipated (Table 1 ) [ 8 ]. As JAKi block intracellular signaling, they could theoretically reduce systemic AEs, when compared to conventional immunosuppressants [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…In September 2021, the Food and Drug Administration (FDA) reviewed the post-marketing safety trial results comparing tofacitinib with anti-TNF in rheumatoid arthritis (RA), and concluded that tofacitinib posed a higher risk of major cardiovascular events (MACE), thromboembolic events, malignant neoplasms, and death. Based on these results, a boxed warning was issued, which also extended to other JAKi [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Biologics Versus JAK Inhibitors. Part I: Cancer Risk. A Narrative Review

Mansilla-Polo,

Morgado-Carrasco

2024

Dermatol Ther (Heidelb)

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Introduction Biological drugs (BD) and Janus kinase inhibitors (JAKi) have revolutionized the treatment of diverse dermatoses. However, there are concerns regarding their safety, especially the risk of cancer and opportunistic infections. Here, we discuss the risk of cancer associated with the BD and JAKi used in dermatology. Methods A narrative review was carried out. All relevant articles evaluating the risk of cancer associated with BD or JAKi and published between January 2010 and February 2024 were selected. Results Multiple large studies have evaluated the association between BD, JAKi and cancer risk. However, there is a lack of prospective, comparative studies. Overall, patients undergoing BD and JAKi present a cutaneous cancer incidence similar to that in the general population. The drugs more strongly associated with non-skin cancer risk were anti-tumor necrosis factor (anti-TNFs) agents and JAKi (especially tofacitinib and oral ruxolitinib). This risk appears to increase with age, the presence of other factors (such as chronic immunosuppression from previous drugs or other comorbidities), and specific diseases such as rheumatoid arthritis (RA) and myelodysplastic syndrome. Conversely, BD such as interleukin (IL)-17 and IL-23 inhibitors may even reduce the risk of some visceral and hematological malignancies. In patients with dermatological conditions such as psoriasis and atopic dermatitis, the risk of malignancies may be lower than in other subgroups, and probably comparable to the general population. Conclusions The incidence of cancer in patients undergoing BD or JAKi is generally low. This incidence can be higher in elderly patients with RA or myelodysplastic syndrome, and in those undergoing prolonged therapy with tofacitinib or ruxolitinib (oral), or anti-TNF agents.

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Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders

Cited by 7 publications

References 96 publications

Successful treatment of erosive lichen planus with Upadacitinib complicated by oral squamous cell carcinoma

Successful treatment of erosive lichen planus with Upadacitinib complicated by oral squamous cell carcinoma

Novel Janus Kinase Inhibitors in the Treatment of Dermatologic Conditions

Biologics Versus JAK Inhibitors. Part I: Cancer Risk. A Narrative Review

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