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Background: Janus kinase 1 inhibitor upadacitinib is therapeutically effective for atopic dermatitis (AD). However, predictive factors for high responders to upadacitinib have not been established in real-world clinical practice. Objectives: To identify predictive factors for responders to upadacitinib 15mg or 30mg, defined as achievers of investigator’s global assessment (IGA) 0/1 with ≥ 2-point improvement from basal IGA. Methods: A retrospective study was conducted from August 2021 to July 2023 on 159 AD patients treated with upadacitinib 15mg and 52 patients with 30mg. Patients in each group were categorized into responders (achievers of IGA 0/1 at week 12) and non-responders (non-achievers). We compared baseline values of clinical and laboratory parameters between responders and non-responders. Logistic regression analysis was used to detect variables predicting responders. Receiver-operating characteristic curves were used for evaluating prediction capabilities of the variables. Results: In logistic regression analysis, responders to 15mg upadacitinib were associated with lower total EASI and higher age whereas responders to 30mg were associated with lower LDH and lower IgE. Conclusions: Lower total EASI and higher age may predict responders to upadacitinib 15mg while lower IgE and lower LDH may predict responders to 30mg. [ABSTRACT FROM AUTHOR]

Background: Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52weeks for moderate-to-severe atopic dermatitis (AD). Objectives: To assess the effectiveness and safety of upadacitinib through 48weeks in real-world clinical practice for Japanese AD patients (aged ≥12years). Methods: This retrospective study included 287 patients with moderate-to severe AD treated with 15mg (n=216) or 30mg (n=71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator’s global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events. Results: From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15mg group, and 77.4, 54.8, and 3.2% in 30mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred. Conclusions: Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48weeks in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Background: Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not examined. Objectives: This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases. Methods: This retrospective study involved 105 patients with moderate-to-severe AD treated with upadacitinib 15mg/day. Eczema area and severity index (EASI), atopic dermatitis control tool, and achievement rate of EASI 100 were evaluated at weeks 4, 12, and 24. The threshold of early peak pruritus-numerical rating scale (PP-NRS) predicting later skin clearance was assessed by area under the receiver-operating characteristic curve, and predictors for EASI 100 achievement were determined by logistic regression analysis. Results: The rate of achieving EASI 100 at week 24 was extremely higher in patients who achieved week 2 PP-NRS ≤ 1 (42.9%) than in non-achievers (1.4%). The logistic regression analysis showed that the achievement of week 2 PP-NRS ≤ 1 and low body mass index were associated with achievement of EASI 100 at weeks 12 and 24. Conclusions: The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment. [ABSTRACT FROM AUTHOR]

Purpose: For individuals with atopic dermatitis (AD), interpreting scientific papers that present clinical outcomes including the Eczema Area and Severity Index (EASI) and Investigators Global Assessment may be difficult. When compared to tabulated data and graphs, images from before and after treatment are often far more meaningful to these patients that ultimately will be candidates for the treatment. This systematic review focused on determining the frequency of clinical image sharing in AD research. Materials and methods: Conducted in accordance with PRISMA guidelines, the review concentrated on randomized controlled trials that investigated predefined and available systemic treatments for AD. The search was performed in the MEDLINE database for studies published from the inception until 21 December 2023. Results: The review included 60 studies, encompassing 17,799 randomized patients. Across these studies, 16 images representing 6 patients were shared in the manuscripts, leading to a sharing rate of 0.3‰. Conclusions: The almost missing inclusion of patient images in clinical trial publications hinders patient understanding. Adding images to scientific manuscripts could significantly improve patients’ comprehension of potential treatment outcomes. This review highlights the need for authors, the pharmaceutical industry, study sponsors, and publishers to enhance and promote patient information through increased use of visual data. [ABSTRACT FROM AUTHOR]

AbstractPurpose: For individuals with atopic dermatitis (AD), interpreting scientific papers that present clinical outcomes including the Eczema Area and Severity Index (EASI) and Investigators Global Assessment may be difficult. When compared to tabulated data and graphs, images from before and after treatment are often far more meaningful to these patients that ultimately will be candidates for the treatment. This systematic review focused on determining the frequency of clinical image sharing in AD research.Materials and methods: Conducted in accordance with PRISMA guidelines, the review concentrated on randomized controlled trials that investigated predefined and available systemic treatments for AD. The search was performed in the MEDLINE database for studies published from the inception until 21 December 2023.Results: The review included 60 studies, encompassing 17,799 randomized patients. Across these studies, 16 images representing 6 patients were shared in the manuscripts, leading to a sharing rate of 0.3‰.Conclusions: The almost missing inclusion of patient images in clinical trial publications hinders patient understanding. Adding images to scientific manuscripts could significantly improve patients’ comprehension of potential treatment outcomes. This review highlights the need for authors, the pharmaceutical industry, study sponsors, and publishers to enhance and promote patient information through increased use of visual data.

AbstractIn this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. Our case report highlights a novel therapeutic option for an eczematous cirAE: the topical JAK 1/2 inhibitor, ruxolitinib. CirAEs can occur in up to 55% of patients on ICIs, a class of medications seeing rapidly increasing use in cancer therapy, and prior research has demonstrated that ICI-induced dermatitis may involve different pathways than traditionally observed in their spontaneous counterparts. Specifically, marked Th1 skewing is noted in ICI-induced dermatitis, as opposed to a predominant Th2 response which typically characterizes spontaneous atopic dermatitis. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population.

In this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. Our case report highlights a novel therapeutic option for an eczematous cirAE: the topical JAK 1/2 inhibitor, ruxolitinib. CirAEs can occur in up to 55% of patients on ICIs, a class of medications seeing rapidly increasing use in cancer therapy, and prior research has demonstrated that ICI-induced dermatitis may involve different pathways than traditionally observed in their spontaneous counterparts. Specifically, marked Th1 skewing is noted in ICI-induced dermatitis, as opposed to a predominant Th2 response which typically characterizes spontaneous atopic dermatitis. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population. [ABSTRACT FROM AUTHOR]

Ruxolitinib is a JAK1/2 inhibitor, which inhibits the signal transduction of interferon-gamma, a cytokine implicated in the pathogenesis of atopic dermatitis (AD). In this before-after single group phase IIA pilot study, we investigated the efficacy of topical nanoliposomal ruxolitinib phosphate (RuxoLip) emulgel in mild AD. Clinical evaluation was conducted on 10 patients with mild AD. The efficacy of the product as well as patient satisfaction was evaluated by local scoring atopic dermatitis (SCORAD) of AD. In addition, trans-epidermal water loss (TEWL), stratum corneum (SC) hydration, sebum, erythema, melanin content, and ultrasonographic parameters were measured before, and two and four weeks after treatment. Four weeks of treatment reduced SCORAD, itching, and burning (p =.001,.001, and.001, respectively) and increased hydration, sebum, and epidermal density (p =.001,.018, and.037, respectively). SCORAD and other skin biophysical parameters improved within two weeks of treatment and then were in plateau for up to four weeks. The topical ruxolitinib emulgel has good short-term efficacy and tolerability. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is one of the serious global problems. There were wide concerns about whether Janus kinase (JAK) inhibitor was an alternative treatment for AD. Eight databases were searched from the earliest publication date available to January 2, 2021. We included randomized controlled trials comparing JAK inhibitors with control treatment for AD. Data were pooled using Stata.14 software and performed as mean differences (MD) and risk ratios (RR) with 95% CIs. We did subgroup analysis based on specific outcomes. A total of studies, ten randomized controlled trials, with 2583 patients were included in the final synthesis. This meta-analysis showed JAK inhibitor resulted in significant improvement on EASI total score (MD = −0.31; 95%CI, −0.46 to –0.17; p =.000; I2 = 90.0%, p =.000) and pruritus numerical rating scale (NRS) score (MD = −1.15; 95%CI, −1.48 to –0.83; p =.000; I2 = 95.9%, p =.000), without the higher risk of total adverse effects (RR = 1.02; 95%CI, 0.90–1.16; p =.745; I2 =27.9%, p =.206). JAK inhibitor was a promising option for atopic dermatitis. More data and surveillance will be needed to identify efficacy, safety, and the risk of adverse effects. [ABSTRACT FROM AUTHOR]

Background: Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52 weeks for moderate-to-severe atopic dermatitis (AD)., Objectives: To assess the effectiveness and safety of upadacitinib through 48 weeks in real-world clinical practice for Japanese AD patients (aged ≥12 years)., Methods: This retrospective study included 287 patients with moderate-to severe AD treated with 15 mg ( n  = 216) or 30 mg ( n  = 71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator's global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events., Results: From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15 mg group, and 77.4, 54.8, and 3.2% in 30 mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred., Conclusions: Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48 weeks in real-world clinical practice.

Background: Janus kinase 1 inhibitor upadacitinib is therapeutically effective for atopic dermatitis (AD). However, predictive factors for high responders to upadacitinib have not been established in real-world clinical practice., Objectives: To identify predictive factors for responders to upadacitinib 15 mg or 30 mg, defined as achievers of investigator's global assessment (IGA) 0/1 with ≥ 2-point improvement from basal IGA., Methods: A retrospective study was conducted from August 2021 to July 2023 on 159 AD patients treated with upadacitinib 15 mg and 52 patients with 30 mg. Patients in each group were categorized into responders (achievers of IGA 0/1 at week 12) and non-responders (non-achievers). We compared baseline values of clinical and laboratory parameters between responders and non-responders. Logistic regression analysis was used to detect variables predicting responders. Receiver-operating characteristic curves were used for evaluating prediction capabilities of the variables., Results: In logistic regression analysis, responders to 15 mg upadacitinib were associated with lower total EASI and higher age whereas responders to 30 mg were associated with lower LDH and lower IgE., Conclusions: Lower total EASI and higher age may predict responders to upadacitinib 15 mg while lower IgE and lower LDH may predict responders to 30 mg.

Background: Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not examined., Objectives: This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases., Methods: This retrospective study involved 105 patients with moderate-to-severe AD treated with upadacitinib 15 mg/day. Eczema area and severity index (EASI), atopic dermatitis control tool, and achievement rate of EASI 100 were evaluated at weeks 4, 12, and 24. The threshold of early peak pruritus-numerical rating scale (PP-NRS) predicting later skin clearance was assessed by area under the receiver-operating characteristic curve, and predictors for EASI 100 achievement were determined by logistic regression analysis., Results: The rate of achieving EASI 100 at week 24 was extremely higher in patients who achieved week 2 PP-NRS ≤ 1 (42.9%) than in non-achievers (1.4%). The logistic regression analysis showed that the achievement of week 2 PP-NRS ≤ 1 and low body mass index were associated with achievement of EASI 100 at weeks 12 and 24., Conclusions: The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment.

Background: A few anecdotal case reports demonstrated that tofacitinib improved nail changes associated with AA. Objective: To investigate nail changes in patients with AA treated with tofacitinib and evaluate the relationship between nail and hair responses to tofacitinib. Methods: This is a retrospective study of 33 adult patients with moderate-to-severe AA treated with oral tofacitinib monotherapy for at least 4 months. Results: Fifteen patients had nail involvement and demonstrated more severe hair loss than those without nail involvement (p = .040). However, there was no significant difference in hair regrowth between two groups. Of 15 patients with nail involvement, 11 (73.3%) showed improvement regardless of type of nail change; the first improvement was observed at a median of 5 months (range, 1-11) after administration. Nail improvement was associated with neither initial severity of hair loss nor hair response to tofacitinib. Nail improvement tended to occur later than hair regrowth. Conclusions: Oral tofacitinib monotherapy improves nail involvement associated with AA. Nail involvement is not a poor prognosis factor in hair regrowth with tofacitinib treatment and there is no evident relationship between nail and hair responses. [ABSTRACT FROM AUTHOR]

Janus kinase family (JAKs) has recently attracted the attention of many researchers, and several JAK inhibitor drugs have been developed targeting different members of the JAK family. Tofacitinib and ruxolitinib are US FDA approved drugs in this family for rheumatoid arthritis and myeloproliferative diseases, respectively. Dysregulation of JAK/STAT pathway is also involved in many skin diseases, specifically inflammatory disorders. The JAK/STAT signaling pathway and its involvement in skin diseases are overviewed in this study. We also review clinical studies of JAK inhibitors in field of dermatology, including psoriasis, atopic dermatitis, alopecia areata and vitiligo. Although the available evidence shows promising results, it is still too early to draw a firm conclusion about the place of these drugs in dermatological treatment. [ABSTRACT FROM PUBLISHER]