Association of risk of incident acne and treatment with systemic Janus kinase inhibitors in atopic dermatitis: a systematic review and meta-analysis

Sun, Chen; Su, Zheng; Zeng, Yue-Ping

doi:10.1007/s00011-023-01789-x

Cited by 9 publications

(2 citation statements)

References 33 publications

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“…Induction of acne lesions through inhibition of immune signaling by JAK inhibitors has also been suggested. However, overexpression of JAK1 and JAK3 has also been reported in acne vulgaris lesions suggesting a complex interplay of immune modulation and the potential that acne represents a paradoxical reaction to JAK inhibition [ 29 , 31 ]. For the other dermatological adverse reactions associated with JAK inhibitors, there is no clear understanding of the pathogenic mechanisms that drive or exacerbate these events during JAK inhibitor treatment.…”

Section: Discussionmentioning

confidence: 99%

“…All events of acne, urticaria, and folliculitis were mild to moderate in severity. Acne has been reported as a common or very common adverse drug reaction for all JAK inhibitors approved for dermatological conditions [25][26][27][28][29][30]. While no clear mechanism of action is known for this, it has been suggested that JAK inhibitors may be associated with skin dysbiosis, including microbial colonization of Demodex folliculorum.…”

Section: Discussionmentioning

confidence: 99%

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Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program

King,

Soung,

Tziotzios

et al. 2024

Am J Clin Dermatol

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Background The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA). Objective The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA. Methods Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size–adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported. Results In the placebo-controlled cohort ( n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2–75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort ( n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events. Conclusions Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available). Trial Registries ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019). Supplementary Information The online version contains supplementary material available at 10.1007/s40257-024-00846-3.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program

King,

Soung,

Tziotzios

et al. 2024

Am J Clin Dermatol

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Small Molecules, Big Results: How JAK Inhibitors Have Transformed the Treatment of Patients with IBD

Fansiwala,

Sauk

2024

Dig Dis Sci

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Fungal Head and Neck Dermatitis: Current Understanding and Management

Chong,

Navarro-Triviño,

et al. 2024

Clinic Rev Allerg Immunol

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Head and neck dermatitis (HND) is a form of atopic dermatitis (AD) that affects the seborrheic areas of the body and causes greater quality of life detriments than other types of AD. HND can be challenging to treat since first-line topical therapies may be ineffective or intolerable for long-term use on areas affected by HND while dupilumab may cause dupilumab-associated HND (DAHND). Current evidence implicates fungi, particularly Malassezia spp., in the pathogenesis of HND. Penetration of fungal antigens through the defective AD skin barrier activates the innate and adaptive immune systems to cause cutaneous inflammation via the T helper (Th)17 and/or Th2 axes. Malassezia sensitization may distinguish HND from other forms of AD. Multiple double-blind, placebo-controlled trials have shown antifungals to benefit HND, yet the persistence of symptom relief with sustained use remains unclear. Oral antifungals appear more effective than topical antifungals but may be harmful with long-term use. DAHND may also be fungal-mediated given improvement with antifungals and evidence of an overactive immune response against Malassezia in these patients. Janus kinase inhibitors are effective for HND, including DAHND, but may cause significant side effects when administered systemically. OX40/OX40L inhibitors and tralokinumab may be promising options for HND on the horizon. Demographic and environmental factors influence the host mycobiome and should be considered in future precision-medicine approaches as microbiome composition and diversity are linked to severity of HND.

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Association of risk of incident acne and treatment with systemic Janus kinase inhibitors in atopic dermatitis: a systematic review and meta-analysis

Cited by 9 publications

References 33 publications

Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program

Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program

Small Molecules, Big Results: How JAK Inhibitors Have Transformed the Treatment of Patients with IBD

Fungal Head and Neck Dermatitis: Current Understanding and Management

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