American Journal of Clinical Dermatology最新文献

Background

Two phase III trials, ECZTRA 1 and 2, confirmed the efficacy and safety of tralokinumab versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To further explore the long-term efficacy of tralokinumab for AD, a pooled analysis of these trials was conducted.

Methods

ECZTRA 1 and 2 patients (n = 1596 total) were randomized to tralokinumab 300 mg or placebo every 2 weeks (q2w) over 16 weeks. Patients achieving Investigator’s Global Assessment of clear/almost clear skin (IGA 0/1) and/or 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 16, were re-randomized to tralokinumab q2w, every 4 weeks (q4w), or placebo (tralokinumab withdrawal) for another 36 weeks. Patients not achieving the response criteria at Week 16 received open-label tralokinumab q2w plus optional topical corticosteroids (TCS). A pooled, prespecified analysis assessed the proportions of Week 16 responders that maintained IGA 0/1 and/or EASI-75 at Week 52. Pooled data from all patients initiated with tralokinumab, regardless of the response at Week 16 or dosing regimen received thereafter, were analyzed post hoc.

Results

In patients who achieved the primary endpoints at Week 16, IGA 0/1 responses were maintained at Week 52 without rescue treatment (including TCS) by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, or placebo (tralokinumab withdrawal), respectively, while EASI-75 responses were maintained by 57.3%, 50.4%, and 26.4%, respectively (prespecified analysis). In a post hoc analysis of all patients initiated with tralokinumab, response rates improved over time with continued tralokinumab treatment beyond Week 16 to Week 52 for EASI-50 (63.1–82.7%), EASI-75 (37.6–61.8%), EASI-90 (20.4–37.3%), and IGA 0/1 (23.0–36.2%).

Conclusions

Tralokinumab treatment provides progressive and sustained improvement over 1 year in the extent and severity of AD in patients with moderate-to-severe AD.

Clinical Trial Registration

NCT03131648 (ECZTRA 1); study start date: 30 May 2017; primary completion date: 7 August 2018; study completion date: 10 October 2019. NCT03160885 (ECZTRA 2); study start date: 12 June 2017; primary completion date: 4 September 2019; study completion date: 14 August 2019.

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Background

Histopathologic characteristics (HC) are a mainstay in melanoma prognosis; gene expression profiling (GEP) has emerged as a potential additional independent value.

Objective

To elucidate HC predictive of groups obtained via GEP of malignant melanoma.

Methods

A retrospective study analyzing HC of 265 melanomas submitted for GEP over the course of 8 years. GEP was conducted as a part of regular clinicopathologic workup through Castle Biosciences Decision Dx^®.

Results

Of the 265 cases, the major HC found to have an association with reported gene expression profiles were melanoma histology subtype, depth of invasion, and presence of ulcer.

Limitations

This study is limited by its cross-sectional nature. Causation and long-term related outcomes of the use of GEP versus American Joint Committee on Cancer histopathologic staging cannot be ascertained by this design.

Conclusions

An association, but no definitive prediction, exists between histopathologic categories of depth of invasion, melanoma subtype, and presence or absence of ulcer and gene expression profiles. GEP adds valuable data to the evaluation of malignant melanomas that cannot be definitively predicted by conventional models. The findings add to needed groundwork for comparison of traditional markers and molecular genotyping and begins to build a robust predictive model for better outcomes in patients with malignant melanoma.

Background

Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis.

Objective

The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial.

Methods

A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep.

Results

The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4–6, and 10 were associated with 0 days, 3–4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0–1, 4–5, and 10 were associated with 0–10%, 20–30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep.

Conclusion

These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity.

Clinical Trial Registration

NCT03575871

Alopecia areata is an autoimmune hair loss disease that is non-scarring and is characterized by chronic inflammation at the hair follicle level. Clinically, patients’ presentation varies from patchy, circumscribed scalp involvement to total body and scalp hair loss. Current management is guided by the degree of scalp and body involvement, with topical and intralesional steroid injections as primarily first-line for mild cases and broad immunosuppressants as the mainstay for more severe cases. Until recently, the limited number of blinded, randomized, placebo-controlled clinical trials for this disease had made establishing an evidence-based treatment paradigm challenging. However, growing insights into the pathogenesis of alopecia areata through blood and tissue analysis of human lesions have identified several promising targets for therapy. T-helper (Th) 1/interferon skewing has traditionally been described as the driver of disease; however, recent investigations suggest activation of additional immune mediators, including the Th2 pathway, interleukin (IL)-9, IL-23, and IL-32, as contributors to alopecia areata pathogenesis. The landscape of alopecia areata treatment has the potential to be transformed, as several novel targeted drugs are currently undergoing clinical trials. Given the recent US FDA approval of baricitinib and ritlecitinib, Janus kinase (JAK) inhibitors are a promising drug class for treating severe alopecia areata cases. This article will review the efficacy, safety, and tolerability of current treatments for alopecia areata, and will provide an overview of the emerging therapies that are leading the revolution in the management of this challenging disease.

There is an ongoing epidemic of chronic, relapsing dermatophytoses caused by Trichophyton indotineae that are unresponsive to one or multiple antifungal agents. Although this new species may have originated from the Indian subcontinent, there has been a notable increase of its reporting in other countries. Based on current literature, antifungal susceptibility testing (AFST) showed a large variation of terbinafine minimum inhibitory concentrations (MICs) (0.04 to ≥ 32 µg/ml). Elevated terbinafine MICs can be attributed to mutations in the squalene epoxidase gene (single mutations: Leu393Phe, Leu393Ser, Phe397Leu, and double mutations: Leu393Phe/Ala448Thr, Phe397Leu/Ala448Thr). Itraconazole MICs had a lower range when compared with that of terbinafine (0.008–16 µg/ml, with most MICs falling between 0.008 µg/ml and < 1 µg/ml). The interpretation of AFST results remains challenging due to protocol variations and a lack of established breakpoints. Adoption of molecular methods for resistance detection, coupled with AFST, may provide a better evaluation of the in vitro resistance status of T. indotineae. There is limited information on treatment options for patients with confirmed T. indotineae infections by molecular diagnosis; preliminary evidence generated from case reports and case series points to itraconazole as an effective treatment modality, while terbinafine and griseofulvin are generally not effective. For physicians working outside of endemic regions, there is currently an unmet need for standardized clinical trials to establish treatment guidelines; in particular, combination therapy of oral and topical agents (e.g., itraconazole and ciclopirox), as well as with other azoles (i.e., fluconazole, voriconazole, ketoconazole), warrants further investigation as multidrug resistance is a possibility for T. indotineae.

Background

Alopecia areata (AA) is a complex autoimmune condition resulting in nonscarring hair loss. In recent years, many studies have provided new evidence on comorbid diseases present in patients with AA. However, some studies have conflicting results, and analyses conducting a comprehensive approach are lacking.

Objective

The aim of our study was to provide an updated systematic review and meta-analysis of medical comorbidities associated with AA.

Methods

We searched PubMed, Embase, and Web of Science for case-control, cross-sectional, and cohort studies investigating medical comorbidities in AA published from inception through 1 February 2023.

Results

We screened 3428 abstracts and titles and reviewed 345 full text articles for eligibility. Ultimately, 102 studies were analyzed, comprising 680,823 patients with AA and 72,011,041 healthy controls. Almost all included studies (100 of 102 studies) were of satisfactory to high quality (Newcastle–Ottawa scale score ≥ 4). Among patients with AA, comorbidities with the highest odds ratios (OR) compared with healthy controls and data available from more than one study included vitamin D deficiency (OR 10.13, 95% CI 4.24–24.20), systemic lupus erythematous (OR 5.53, 95% CI 3.31–9.23), vitiligo (OR 5.30, 95% CI 1.86–15.10), metabolic syndrome (OR 5.03, 95% CI 4.18–6.06), and Hashimoto’s thyroiditis (OR 4.31, 95% CI 2.51–7.40). AA may be a protective factor for certain disorders, for which the AA group had lower odds compared with healthy controls, such as irritable bowel syndrome (OR 0.38, 95% CI 0.14–0.99) and colorectal cancer (OR 0.61, 95% CI 0.42–0.89).

Conclusion

These findings corroborate and contextualize the risks across comorbidities for patients with AA. Further work should be done to identify the underlying pathophysiology and understand appropriate screening criteria.

The advent of protein kinase inhibitors and immunotherapy has profoundly improved the management of advanced melanoma. However, with these therapeutic advancements also come drug-related toxicities that have the potential to affect various organ systems. We review dermatologic adverse events from targeted (including BRAF and MEK inhibitor-related) and less commonly used melanoma treatments, with a focus on diagnosis and management. As immunotherapy-related toxicities have been extensively reviewed, herein, we discuss injectable talimogene laherparepvec and touch on recent breakthroughs in the immunotherapy space. Dermatologic adverse events may severely impact quality of life and are associated with response and survival. It is therefore essential that clinicians are aware of their diverse presentations and management strategies.