Dermatology and Therapy最新文献

Introduction: Roflumilast cream 0.3% contains a selective, highly potent phosphodiesterase 4 inhibitor approved to treat plaque psoriasis. The Psoriasis Area and Severity Index (PASI)-High Discrimination (PASI-HD) is more precise than PASI when psoriasis involves < 10% of the area of an anatomic region. Clinical trials of roflumilast utilized PASI and its modified version, PASI-HD, to assess disease improvement. The objective of this analysis was to demonstrate the effect of topical roflumilast in patients with psoriasis and to compare PASI-HD with PASI.

Methods: DERMIS-1 and DERMIS-2 were phase III, 8-week, randomized, vehicle-controlled trials of once-daily roflumilast cream 0.3% in patients aged ≥ 2 years with psoriasis involving 2-20% body surface area. PASI and PASI-HD were clinical endpoint measures.

Results: At week 8, statistically significantly more roflumilast- than vehicle-treated patients achieved ≥ 75% reduction in PASI (40.3% vs 6.5%; P < 0.0001) and PASI-HD (59.9% vs 17.9%; P < 0.0001). Evaluations using PASI-HD resulted in larger effect sizes compared with PASI at higher levels of response.

Conclusions: Roflumilast-treated patients experienced greater improvements in disease severity than vehicle-treated patients. The PASI-HD can more accurately assess disease changes compared with PASI.

Trial registration: ClinicalTrials.gov Identifiers: DERMIS-1, NCT04211363; DERMIS-2, NCT04211389.

Introduction: Evidence for moderate to severe chronic hand eczema (CHE) treatments in clinical practice is limited. The objective was to investigate treatment patterns in patients with moderate to severe CHE, and in those with an inadequate response to topical corticosteroids (TCS) or in whom TCS were contraindicated.

Methods: This was a multinational retrospective physician chart review. Physicians who routinely diagnosed and treated CHE were recruited in Canada, France, Germany, Italy, Spain, and the UK and provided data on adult patients with moderate to severe CHE treated with TCS over the past 12 months or for whom TCS were contraindicated.

Results: A total of 292 physicians provided data on 1939 patients. Worst severity of CHE in the 12-month study period was judged by the physician to be moderate in 56.8% and severe in 43.2% of patients. Overall, 6.7% of patients received topical calcineurin inhibitors, 3.9% phototherapy, 6.8% alitretinoin, 11.1% traditional orals (acitretin, azathioprine, oral corticosteroids, cyclosporine, methotrexate), 8.0% biologics, and 1.7% oral Janus kinase (JAK) inhibitors. An inadequate response or contraindication to TCS was reported in 39.9% of patients (27.4% progressed to phototherapy/systemics; 12.1% with adverse events or an inadequate response to high/ultra-high potency TCS, and 0.4% contraindicated). Among these patients, the highest line of treatment during the 12-month period was biologics in 29.2%, alitretinoin in 22.3%, oral JAK inhibitors in 5.1%, traditional orals in 33.3%, and phototherapy in 9.6% of patients. There were no significant differences in phototherapy/systemic treatments between patients with moderate and severe disease in this subgroup.

Conclusions: Despite being a first-line treatment, 40% of patients with CHE were inadequately treated with or contraindicated to TCS. Over one-quarter of patients progressed to phototherapy or systemic therapy. These results suggest a lack of effective and well-tolerated topical treatment options in CHE. Graphical Abstract available for this article.

Introduction: Aquagenic pruritus (AP) is an underrecognized condition in which patients perceive itch following contact with water on clinically non-lesional skin. AP is frequent in patients suffering from myeloproliferative neoplasms (MPN) such as polycythemia vera and may manifest several years prior to MPN diagnosis. To date, there is no validated patient-reported outcome measure (PROM) assessing AP and its association with MPN.

Methods: In this multiphase study, eight questions relevant to AP were developed and validated in 77 patients with AP and 50 patients with chronic non-aquagenic pruritus (CP). After reduction to those questions relevant for distinguishing between AP with and without MPN, the resulting questionnaire was validated in 76 patients with AP (37 with MPN) and 76 with CP. The predictive power of the questionnaire's score was retrospectively tested in the first cohort.

Results: Four key questions were identified as central to differentiating MPN in AP, forming the basis of the AP questionnaire (APQ). Sensitivity and specificity of the score reached 97.3% and 79.5%, respectively. The APQ classified five patients with AP with MPN who were diagnosed with MPN at a later stage.

Conclusion: APQ is the first validated PROM for patients with AP, detecting a potential relationship to MPN with high sensitivity. APQ is a useful addition to standard of care in patients suffering from AP, potentially shortening the delay of MPN diagnosis.

Trial registration: German Clinical Trials Registry, DRKS 00006075.

Introduction: Nemolizumab is a humanized monoclonal antibody targeting interleukin-31 receptor A. It has shown efficacy in treating patients with prurigo nodularis (PN). In this study, we characterized the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of nemolizumab in patients with PN and compared its efficacy with that of another approved treatment, dupilumab, using a model-based meta-analysis (MBMA).

Methods: We updated an existing population PK (PopPK) model developed for patients with atopic dermatitis (AD) by incorporating data from four clinical studies. The updated model validated the PK of nemolizumab in patients with PN, confirming its relevance and precision. Furthermore, we developed a population PD (PopPD) model to characterize treatment response and assessed changes in the weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) over time. To conduct an MBMA, we performed a systematic literature search of public databases to identify studies for modeling the success rate of achieving a ≥ 4-point improvement in the PP-NRS and a ≥ 2-point decrease in the Investigator's Global Assessment (IGA).

Results: The updated PopPK model adequately described the serum concentration profile of nemolizumab in patients with PN, suggesting a similarity in the PK characteristics between AD and PN. The PopPD model successfully described the effects of the placebo and nemolizumab on PP-NRS. Six individual randomized controlled trials were eligible for the MBMA. Model simulations indicated that the success rates for PP-NRS and IGA were consistently higher for nemolizumab compared with dupilumab, up to 24 weeks.

Conclusion: The PopPK and PopPD models well described the PK and PD profiles of nemolizumab in patients with PN. MBMA demonstrated that nemolizumab was superior to dupilumab in improving response rates in patients with PN. These findings, derived from pharmacometrics modeling and indirect comparison, may help inform future clinical studies and support the ongoing evaluation of nemolizumab in PN.

Introduction: Cardiovascular disease is a leading co-morbidity in psoriasis patients. The cutaneous benefits of biologic therapies for severe plaque psoriasis are well-established, but the impact of biologics on major adverse cardiovascular events (MACE) in psoriatic patients requires further elucidation. This study aimed to investigate the impact of biologic therapies on the risk of MACE in patients with chronic plaque psoriasis.

Methods: We conducted a systematic review and meta-analysis on 10 May 2022, using Medline, PubMed, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR) and EMBASE databases for relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) methodology was applied, and all studies were critically appraised. All studies selected for inclusion were randomised control trials (RCTs) that contained data on MACE and compared licensed biologic therapies with placebo or other biologics in adults with moderate-severe plaque psoriasis.

Results: The search of the databases revealed 36 papers (reporting on 43 RCTs) which met the inclusion criteria. No statistically significant difference in the risk for MACE between biologic therapies and placebo was found [Peto odds ratio (POR) 1.26, 95% confidence interval (CI) 0.53-3.01, P = 0.59]. A comparison of specific types of biologics also revealed no significant effect in adult patients with moderate-to-severe plaque psoriasis: tumour necrosis factor (TNF)-alpha inhibitors (adalimumab, infliximab, etanercept) (POR 1.13, 95% CI 0.29-4.32 P = 0.86), interleukin (IL)-17 inhibitors (secukinumab, ixekizumab, brodalumab, bimekizumab) (POR 0.60, 95% CI 0.16-2.25, P = 0.45); IL 12/23 inhibitors (usetekinumab) (POR 3.80, 95% CI 0.37-39.44, P = 0.26) and IL-23 (guselkumab, risankizumab, tildrakizumab) (POR 1.75, 95% CI 0.25-12.43 P = 0.58).

Conclusions: Anti-psoriatic biologics were not associated with an increased risk of MACE in psoriasis patients. Given that most included RCTs were of relatively short duration, longer-term studies and post-marketing surveillance are needed to clarify the cardiovascular safety profile of biologic therapies. Further large-scale studies with extended follow-up are warranted.

Study registration: This study was prospectively registered on PROSPERO (identification number CRD42022325792).

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin condition commonly associated with other dermatologic comorbidities, which can complicate management and affect treatment outcomes. This review aims to analyse the dermatologic comorbidities of AD, their underlying mechanisms, and therapeutic implications, with a focus on their management in clinical practice.

Methods: A narrative review was conducted by searching PubMed, Embase, Cochrane and ClinicalTrials.gov, using terms related to AD and its comorbidities, including allergic contact dermatitis, alopecia areata, prurigo nodularis, psoriasis, hidradenitis suppurativa and chronic spontaneous urticaria.

Results: The literature highlights a strong association between AD and several dermatologic comorbidities, including allergic contact dermatitis, alopecia areata, chronic spontaneous urticaria, hidradenitis suppurativa, psoriasis, prurigo nodularis and vitiligo. Promising therapeutic effects were observed with JAK inhibitors, dupilumab and other biologics across multiple comorbid condition.

Conclusion: Recognizing comorbidities in AD is critical for effective management. Tailored therapies targeting both AD and its comorbidities, based on shared immunological mechanisms, may improve outcomes. Further research is needed to optimize treatment strategies and explore combination therapies for patients with both AD and comorbid dermatological conditions.

Introduction: Despite recent advancements in treating severe alopecia areata (AA), many patients do not achieve target efficacy with approved therapies. Ritlecitinib is an oral Janus kinase 3 (JAK3)/tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor approved to treat severe AA at a dose of 50-mg once daily (QD). A new phase 3 clinical trial (NCT06873945) described herein evaluates a higher dose of ritlecitinib (100-mg QD) in patients with AA. The study employs an innovative design using patient-level data from patients with similar baseline characteristics from previous AA ritlecitinib studies to form an external placebo control group, a synthetic placebo control group (extrapolating for outcomes over a longer timeframe than captured previously), and an external ritlecitinib 50-mg nonresponders group, eliminating the need to randomize patients to placebo.

Methods: This randomized, double-blind clinical trial investigates the efficacy and safety of ritlecitinib in patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss. Patients are randomized to ritlecitinib 100-mg or 50-mg QD. Those randomized to ritlecitinib 100-mg continue the 100-mg dose through week 48. Patients randomized to ritlecitinib 50-mg with a Severity of Alopecia Tool (SALT) score ≤ 20 at week 24 (responders) continue ritlecitinib 50-mg through week 48; nonresponders at week 24 are rerandomized 2:1 to increase to ritlecitinib 100-mg or continue ritlecitinib 50-mg through week 48.

Planned outcomes: The primary end point is a SALT score ≤ 20 at week 24 for ritlecitinib 100-mg versus external placebo. Key secondary end points include SALT score ≤ 20 at week 24 for ritlecitinib 50-mg versus external placebo and week 36 for ritlecitinib 100-mg versus synthetic placebo, and SALT score change from baseline at week 24 for ritlecitinib 100-mg versus 50-mg. An external ritlecitinib 50-mg nonresponders control group augments the ritlecitinib 50-mg nonresponders at week 24 rerandomized to ritlecitinib 50-mg to support comparative analyses at week 48.

Clinicaltrials:

Gov registration: NCT06873945. Video Abstract (MP4 303790 kb).

Introduction: Ruxolitinib cream demonstrated superior repigmentation versus vehicle at week 24 with continued improvement through week 104 in phase 3 studies of patients (aged ≥ 12 years) with nonsegmental vitiligo. Here, we evaluated long-term safety of ruxolitinib cream in an integrated analysis of phase 3 vitiligo studies.

Methods: Reported incidence and exposure-adjusted incidence rates (EAIRs) of treatment-emergent adverse events (TEAEs) were determined.

Results: Over 104 weeks, 673 patients with vitiligo applied either ruxolitinib cream (n = 637; 867.9 person-years [PY]) or vehicle (n = 270; 131.1 PY). TEAEs (EAIR, patients/100 PY) with ruxolitinib cream versus vehicle occurred in 62.6% (46.0) versus 37.0% (76.3) of patients, most commonly nasopharyngitis (7.2% [5.3] vs 2.6% [5.3]) and application site acne (6.0% [4.4] vs 1.1% [2.3]). No serious treatment-related TEAEs were reported with ruxolitinib cream. EAIRs (patients/100 PY) were low for acne-related TEAEs (7.1), skin and subcutaneous tissue infections (4.0), cytopenias (2.4), and liver enzyme elevations (2.2). Malignancies, serious infections, and thromboembolic events were rare (0.7, 0.5, and 0.2 patients/100 PY, respectively), and none were considered related to treatment. No major adverse cardiovascular events or deaths occurred.

Conclusion: Ruxolitinib cream demonstrated tolerability, with no unexpected safety findings through 2 years in patients with vitiligo. Graphical Plain Language Summary available for this article.

Trial registration: Clinicaltrials.gov identifiers, NCT04052425 (registered on August 8, 2019), NCT04057573 (registered on August 14, 2019), and NCT04530344 (registered on August 25, 2020).

Introduction: Ablative fractional CO₂ laser treatment (AFCO₂) can cause immediate erythema, pain, and complications such as prolonged erythema and post-inflammatory hyperpigmentation. This study investigated whether the use of a serum before and after AFCO₂ could accelerate skin recovery and relieve complications.

Methods: This randomized controlled trial included 72 healthy Chinese women with acne scars who intended to undergo AFCO₂; 64 (32 in each group) completed the study and were included in the analysis. The participants in the serum group applied the study serum for 2 weeks in the preoperative (D0 and D14) and post-treatment stages (D32 and D39), with additional product usage of standard products, including standard cleanser, moisturizer, and sunscreen, for all participants (both groups). Transepidermal water loss (TEWL), skin hydration, and skin qualities were evaluated throughout the entire study. Clinical assessment was conducted at D0 (baseline and time immediately after product application); D14; D15 (directly after procedure treatment); D16, D18, D22, and D25 (1 day, 3 days, 7 and 10 days after CO₂ laser treatment); and during the post-treatment period at D32 and D39 (1 and 2 weeks after self-recovery).

Results: TEWL improvement was significantly better in the serum group than in the control group throughout the study (p < 0.001), including pre-treatment (p = 0.043), self-recovery (D15-D31) (p < 0.001), and post-treatment (p = 0.027) stages. In the post-treatment stage, the improvement in skin hydration with the serum was significantly better than in the control group (p < 0.001). The serum group showed significantly better improvements in smoothness (p = 0.001), brightness (p = 0.016), and overall healthy appearance (p = 0.001) compared with controls.

Conclusion: Peri-AFCO₂ application of the serum can facilitate faster postoperative recovery and can help reduce postoperative erythema and discomfort with satisfying tolerance. The use of the serum can enhance effectiveness and satisfaction with AFCO₂ treatment.

Trial registration: This trial was retrospectively registered on 30 June 2025: ISRCTN identifier ISRCTN60519611.