Journal of the American Academy of Dermatology最新文献

Background: Iberdomide, a cereblon modulator, promotes degradation of transcription factors Ikaros and Aiolos.

Objective: Evaluate iberdomide efficacy and safety in cutaneous lupus erythematosus (CLE) in a phase 2 study.

Methods: Patients were randomized (2:2:1:2) to iberdomide 0.45 (n=81), 0.30 (n=82), or 0.15 mg (n=42) or placebo (n=83) daily while continuing background lupus medications.

Results: The mean (SD) baseline Cutaneous Lupus Area and Severity Index Activity (CLASI-A) score was 6.9 (7.0); 28% of patients had a score ≥8; 56% had acute CLE, 29% chronic CLE, and 16% subacute CLE. Mean CLASI-A improvement in patients with baseline score ≥8 was 39.7% for iberdomide 0.45 mg versus 20.1% for placebo at week 4 (P=0.032), with continued improvement through week 24 (66.7% vs 54.2%; P=0.295). Proportions of patients achieving ≥50% CLASI-A reduction from baseline at week 24 were significantly greater for iberdomide 0.45 mg versus placebo for patients with subacute (91.7% vs 52.9%, P=0.035) and chronic (62.1% vs 27.8%; P=0.029) CLE but not for the overall population (55.6% vs 44.6%) or patients with baseline CLASI-A ≥8 (66.7% vs 50.0%).

Limitations: Small patient subgroups of CLE subtypes.

Conclusions: Iberdomide showed beneficial effects when added to background lupus medications in patients with subacute and chronic CLE.

Background: Cicatricial alopecias (CA) are chronic, progressive scarring hair-loss conditions. Molecular dysregulation is not fully understood, hindering treatment development. Th1/IFNγ signaling and JAK dysregulation has shown involvement, providing rationale for this phase 2a trial with TYK2/JAK1 inhibitor brepocitinib.

Methods: Randomized, placebo-controlled phase 2a trial spanning 52 weeks. Adults (18≥years of age) with lichen planopilaris, frontal fibrosing alopecia, or central centrifugal cicatricial alopecia diagnosis were randomized 3:1 to brepocitinib 45mg daily or placebo for 24 weeks, after which all patients received brepocitinib for another 24 weeks, with a safety follow up 4 weeks later. Lesional scalp biopsies were collected at baseline, week 24, and week 48. Co-primary endpoints were changes in lesional expression of CCL5, changes in lesional expression of fibrosis-related markers, and safety at week 24.

Results: Patients receiving brepocitinib showed significant downregulation in CCL5 expression at week 24 (p=0.004). Enrichment analysis of a subset of fibrosis markers showed trending upregulation in placebo patients (p<0.1). Brepocitinib was well tolerated and improved clinical severity scores.

Limitations: Single-dose regimen, small placebo group.

Conclusion: Brepocitinib significantly reduces CCL5 expression and was well tolerated at week 24, meeting co-primary endpoints. Brepocitinib reduces inflammatory biomarker expression and improves clinical severity, while maintaining favorable safety profile.

Background: We observed many preterm infants with unexpectedly thick infantile hemangiomas (IH), a subtype known to be associated with increased risk of scarring.

Objective: To compare the clinical features of localized IH in preterm versus term infants.

Methods: A retrospective study at three tertiary referral centers was conducted on 830 consecutive patients with localized IH.

Results: Preterm infants had a significantly higher incidence of superficial IH (75% in <33weeks, 57% in 33-<37 weeks, and 50% in term infants, p=0.007). Overall, their IH had thicker superficial components (p<0.001) and more stepped borders (p<0.001). These features correlated with the degree of prematurity. The average chronological age at presentation to the specialist was 5.6 (SD=6.2) months, with no difference between gestational age.

Limitations: The retrospective design and use of non-standardized clinical photographs. There may be biases introduced toward more severe IH types because the study sites were tertiary referral centers.

Conclusion: Preterm infants have features of IH that have obvious implication for systemic therapies. Most of these infants were seen beyond the typical proliferative phase when irreversible skin changes may have already occurred.

Lentigo Maligna (LM) arises on chronically-sun damaged skin and can have extensive subclinical spread, often in functionally and cosmetically challenging areas. This two-part continuing medical education (CME) series reviews LM. Part I reviews epidemiology, risk factors, clinical presentation, diagnostic tools, biopsy technique, and histopathology of LM. Part II reviews both surgical and non-surgical treatment options. Surgical approaches - including conventional excision, Mohs micrographic surgery, and staged excision - remain first-line therapy to achieve cure. Some patients may be poor surgical candidates or elect for alternative treatments. Non-surgical modalities, such as topical and radiation therapy, are also reviewed. Finally, surveillance recommendations are discussed.

Background: Baricitinib, an oral selective Janus kinase inhibitor, is approved to treat adults with severe alopecia areata (AA).

Objective: To report the week 152 efficacy results from the phase 3 trial BRAVE-AA2 down-titration substudy.

Methods: BRAVE-AA2 enrolled 546 adults with severe AA (Severity of Alopecia Tool [SALT] score ≥50). Baricitinib 4-mg-treated patients achieving a clinical response (SALT score ≤20) at week 52 were rerandomized 1:1 to stay on 4-mg or down-titrate to 2-mg. The last observation carried forward was used to impute missing or censored data.

Results: At week 52, 86/234 (36.8%) baricitinib 4-mg-treated patients were eligible for down-titration; 44 remained on 4-mg while 42 down-titrated to 2-mg. At week 152, 39/44 (88.6%) 4-mg-treated patients had maintained clinical response, compared to 24/41 (58.5%) down-titrated patients. Among down-titrated patients, loss of treatment benefit was less frequent in those with sustained response and SALT score ≤5 at week 52.

Limitations: Method and timing of down-titration were prespecified in the protocol based on week 52 responder status and not on other clinical factors.

Conclusion: More than half of down-titrated patients maintained response. Sustained treatment response and/or near-total regrowth may be associated with a greater likelihood of response maintenance after down-titration.