Roflumilast

斑块状银屑病是一种慢性炎症性皮肤病，头皮是其常见的受累部位之一，约有50%的患者头皮会受到影响。瘙痒是此类患者的主要症状，对患者的生活质量造成了严重影响。目前，头皮银屑病的局部治疗面临一定的挑战。现有外用药物（如乳膏和软膏）因受头发阻挡难以有效施用，且其乳状质地和明显的外观往往影响日常护发，从而导致患者的治疗依从性降低。此外，对于身体和头皮均受银屑病困扰的患者，往往需要多种药物联合治疗。 罗氟司特（roflumilast）是一种高效、选择性磷酸二酯酶4（PDE4）抑制剂，通过调节炎症因子（如IL-17、TNF-α）以及抑制感觉神经元的激活，从而有效改善瘙痒，且对表皮屏障功能障碍具有潜在改善作用。罗氟司特泡沫剂是一种每日一次、不含刺激成分的外用剂，适用于头皮和身体，便于涂抹。早期研究结果表明，0.3%罗氟司特泡沫剂在治疗头皮和身体银屑病方面安全有效。 近期，JAMA Dermatology发表的3期ARRECTOR研究结果显示，在12岁及以上青少年和成人中，在治疗第8周时，0.3%罗氟司特泡沫剂相较于赋形剂，显著改善了头皮和身体银屑病的体征和症状，其中达到头皮-研究者总体评估（S-IGA）成功的患者比例显著更高，为66.4%，而赋形剂为27.8%，且0.3%罗氟司特泡沫剂表现出良好的安全性和耐受性。 赋形剂：指不含活性药物成分的制剂，其他成分与试验药物完全一致，以此作为对照，确保试验结果的差异仅由活性药物引起。 文章指出，值得注意的是，0.3%罗氟司特泡沫剂有效缓解了瘙痒症状，而这是银屑病患者面临的一大负担。与赋形剂相比，0.3%罗氟司特泡沫剂在首次使用后24小时内就显示出显著的改善效果。这些结果表明，0.3%罗氟司特泡沫剂具有作为头皮和身体银屑病患者单一疗法的潜力。截图来源：JAMA Dermatology这是一项平行组、双盲、赋形剂对照、3期随机临床试验，于2021年8月24日至2022年6月3日在北美的49个医学中心开展。该研究纳入了432例患者。这些患者符合以下条件：年龄≥12岁（平均年龄47.3岁），其中56.3%为女性；患有斑块状银屑病且皮损累及范围不超过头皮和身体总面积的25%（其中头皮受累面积≥10%，非头皮区域不超过20%）；S-IGA评分至少为3分（中度），身体-研究者总体评估（B-IGA）评分至少为2分（轻度）。 入组患者被按照2：1的比例随机分配到罗氟司特（281例）组或赋形剂（151例）组，接受每日一次0.3%罗氟司特泡沫剂或赋形剂治疗，持续8周。有376例（87.0%）患者完成了研究。结果显示：0.3%罗氟司特泡沫剂治疗对皮损改善更明显。在第8周时，与使用赋形剂的患者相比，接受0.3%罗氟司特泡沫剂治疗的患者达到S-IGA和B-IGA成功的比例显著更高。具体来看，罗氟司特组和赋形剂组患者的S-IGA成功率分别为66.4%和27.8%（比例差37.1%[97.5% CI，25.7%-48.6%]；P＜0.001）；罗氟司特组和赋形剂组患者的B-IGA成功率分别为45.5%和20.1%（比例差24.8%[97.5% CI，13.6%-36.0%]；P＜0.001）。这两个指标也是研究的主要终点。 S-IGA和B-IGA：评分范围为5分，数字越大代表皮肤症状越严重；S-IGA成功和B-IGA成功定义为：评分达到皮损清除[0分]或几乎清除[1分]且较基线改善至少2级。 在治疗的其他时间节点，也观察到0.3%罗氟司特泡沫剂对皮损的明显改善：在第2周和第4周时，相较于赋形剂组，罗氟司特组达到S-IGA成功的患者比例均显著更高。第2周时，罗氟司特组和赋形剂组患者的S-IGA成功率分别为30.4%和11.7%（P＜0.001）；在第4周时，上述两组患者S-IGA成功率分别为53.8%和19.5%（P＜0.001）。在第4周时，罗氟司特组达到B-IGA成功的患者比例也显著高于赋形剂组（32.8% vs 12.1%；P＜0.001）。 0.3%罗氟司特泡沫剂治疗对瘙痒改善也更明显：在第2周、第4周和第8周时，相较于赋形剂组，罗氟司特组达到SI-NRS（通过头皮瘙痒数字评定量表测量）成功的患者比例均显著更高。在第2周时，罗氟司特组和赋形剂组患者的SI-NRS成功率分别为25.2%和8.0%（P＜0.001）；在第4周时分别为46.2%和16.8%（P＜0.001）；在第8周时分别为65.3%和30.3%（P＜0.001）。 此外，在第2周、第4周和第8周时，与赋形剂组相比，罗氟司特组达到WI-NRS（通过最严重瘙痒数字评分量表测量）成功的患者比例均显著更高。在第2周时，罗氟司特组和赋形剂组患者的WI-NRS成功率分别为23.2%和10.9%（P＜0.001）；在第4周时，分别为46.5%和18.1%（P＜0.001）；在第8周时，则分别为63.1%和30.1%（P＜0.001）。 SI-NRS和WI-NRS：评分范围为11分，数字越大表示头皮瘙痒程度越严重；达到SI-NRS和WI-NRS成功定义为：基线评分为≥4分的患者，其瘙痒评分胶济线改善至少4分。 0.3%罗氟司特泡沫剂对瘙痒的改善作用可谓“立竿见影”。与赋形剂组相比，罗氟司特组在首次评估（首次用药后24小时）开始，就观察到SI-NRS方面的显著改善（P＜0.02），在第1周时每周平均SI-NRS和WI-NRS的改善幅度均显著更大（P＜0.005）。 此外，0.3%罗氟司特泡沫剂对头皮、身体银屑病面积和严重程度的改善作用也很明显。在第8周时，与赋形剂组相比，罗氟司特组达到PSSI-75（银屑病头皮严重指数，相较于基线至少改善75%）、PASI-75（银屑病面积和严重程度指数，相较于基线至少改善75%）的患者比例均显著更高，分别为50.1%和16.8%、70.9%和31.3%。 从安全性来看，两个治疗组的不良事件发生率均较低，且耐受性良好。罗氟司特组有16例患者（5.7%），赋形剂组有3例患者（2.0%）报告了治疗相关不良事件。导致研究终止的不良事件的发生率较低，并且在罗氟司特组（1.8%）和赋形剂组（1.3%）之间相似。研究者评估的局部耐受性在罗氟司特组和赋形剂组之间也相似，研究者报告在所有时间点至少99.2%的患者均无刺激症状。 总之，该研究表明，在12岁及以上青少年和成人患者中，每日一次的0.3%罗氟司特泡沫剂，作为单药治疗时，可改善头皮和身体银屑病患者的多个疗效指标，且不良事件发生率低，耐受性良好。点击文末“阅读原文/Read more”，即可访问JAMA Dermatology官网阅读完整论文。推荐阅读欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。参考资料[1] Gooderham MJ, Alonso-Llamazares J, Bagel J, et al. Roflumilast Foam, 0.3%, for Psoriasis of the Scalp and Body: The ARRECTOR Phase 3 Randomized Clinical Trial. JAMA Dermatol. Published online May 07, 2025. doi:10.1001/jamadermatol.2025.1136免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医学新视点」微信公众号留言联系。如有其他合作需求，请联系wuxi_media@wuxiapptec.com分享，点赞，在看，传递医学新知

Once-daily, investigational ZORYVE foam 0.3%, rapidly improved psoriasis of the scalp and body, including itch, when used as a monotherapy 66.4% of individuals treated with ZORYVE foam achieved Scalp-Investigator Global Assessment (S-IGA) Success at Week 8 45.5% of individuals treated with ZORYVE foam achieved Body-Investigator Global Assessment (B-IGA) Success at Week 8 Efficacy and safety results were consistent with Phase 2 results of ZORYVE foam 0.3% in adults and adolescents 12 years of age and older Supplemental New Drug Application (sNDA) for investigational ZORYVE foam 0.3% for psoriasis is under review with U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) action date of May 22, 2025 More than half of the nearly 9 million people in the United States with plaque psoriasis experience scalp involvement WESTLAKE VILLAGE, Calif., May 07, 2025 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT), a commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, today announced that the Journal of American Medical Association (JAMA) Dermatology published the positive results from a pivotal Phase 3 study evaluating the efficacy and safety of ZORYVE® (roflumilast) foam 0.3% as a once-daily monotherapy treatment for psoriasis of the scalp and body. The study showed that treatment with investigational ZORYVE foam resulted in significant improvements across multiple efficacy endpoints, including the co-primary efficacy endpoints of S-IGA Success and B-IGA Success, as well as key secondary endpoints. The data also show improvement in pruritus (itch) was observed as early as 24 hours after the first application. “Plaque psoriasis is a chronic and burdensome disease that often leaves people searching for relief from thick scales, itch, and discomfort – especially when it affects the scalp, where treatment can be particularly challenging,” said Melinda Gooderham, MD, MSc, FRCPC, dermatologist and medical director at the SKiN Centre for Dermatology, principal investigator at the SKiN Research Centre, and lead author on the paper. “These compelling results demonstrate that ZORYVE foam 0.3% may provide rapid and significant relief of plaques anywhere on the body and is well-tolerated according to both investigator and patient-reported assessments. The foam formulation is particularly beneficial for its versatility in treating hair-bearing and non-hair-bearing skin, which could ultimately help patients adhere to their treatment.” A Randomized tRial Employing topiCal roflumilasT foam to treat scalp psORiasis (ARRECTOR), was a Phase 3, randomized, double-blinded, vehicle-controlled trial which enrolled 432 adults and adolescents aged 12 years and older with plaque psoriasis affecting the scalp and body, across 49 sites in the United States and Canada. Significantly greater proportions of individuals treated with ZORYVE foam 0.3% achieved the co-primary efficacy endpoints of S-IGA Success and B-IGA Success, defined as an IGA score of ‘clear’ or ‘almost clear’ plus a 2-point improvement from baseline. At Week 8, 66.4% of individuals treated with ZORYVE foam 0.3% achieved S-IGA success compared to 27.8% for vehicle (P<0.0001). At Week 8, 45.5% of patients treated with ZORYVE foam achieved B-IGA success compared to 20.1% for vehicle (P<0.0001). Other key findings include: ZORYVE foam provided a clinically meaningful improvement in scalp itch. 65.3% of individuals treated with ZORYVE achieved a clinically significant reduction in itch compared to 30.3% of individuals treated with vehicle at Week 8 (P<0.0001) as measured by a ≥ 4-point change from baseline in Scalp Itch-Numeric Rating Scale (SI-NRS). Significant improvement was seen in the ZORYVE treatment group as early as Week 2. The data also demonstrated improvement in body itch as measured by the Worst Itch-Numeric Rating Scale (WI-NRS) at Week 8, with 63.1% of those treated with ZORYVE foam 0.3% achieving a ≥ 4-point reduction in WI-NRS compared to 30.1% of those treated with vehicle (P<0.0001). Significant improvement was seen in the ZORYVE treatment group as early as Week 2. Importantly, there was a greater improvement in itch observed with ZORYVE within 24 hours after the first application compared to vehicle (as measured by mean SI-NRS change from baseline, relative to vehicle; P=0.0164). This improvement over vehicle within 24 hours after the first application was also observed in body itch (as measured by WI-NRS change from baseline, relative to vehicle; nominal P=0.0094). At Week 8, 70.9% of those treated with ZORYVE foam versus 31.3% treated with vehicle achieved at least 75% improvement in Psoriasis Scalp Severity Index (PSSI-75) (P<.001), another secondary endpoint. Similarly, 50.1% of people treated with ZORYVE foam 0.3% achieved at least 75% improvement in Psoriasis Area and Severity Index (PASI-75), a key secondary endpoint, as compared to 16.8% of those treated with vehicle at Week 8 (P<.001). ZORYVE foam was well-tolerated. The incidence of Treatment Emergent Adverse Events (TEAEs) was low and similar in both active treatment and vehicle arms. The most frequent adverse events in the ZORYVE foam arm (≥1%) included headache, diarrhea, and nausea. Investigator-rated application-site tolerability was similar between ZORYVE and vehicle groups, with investigators reporting no evidence of irritation for at least 99.2% of all patients at all time points. Patient-rated application-site tolerability was also similar between ZORYVE and vehicle with at least 94.4% of patients reporting no or mild sensation on local tolerability assessments at all time points. “We are thrilled that JAMA Dermatology, a premier medical journal, has published the positive results of our pivotal ARRECTOR study. These data demonstrate that investigational ZORYVE foam rapidly relieved psoriasis symptoms, including the most troublesome symptom of itch,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. “As an effective, safe, and well-tolerated once-daily treatment, ZORYVE foam 0.3%, if approved, will offer those living with psoriasis a potential new treatment option for use anywhere on the body with no limitations on duration of use. Having a single agent that effectively treats psoriasis on both the scalp and body, with a safe and tolerable profile, is an important therapeutic benefit for both clinicians and the people they treat. We look forward to the FDA’s potential approval of ZORYVE foam 0.3% for the treatment of plaque psoriasis of the scalp and body anticipated later this month.” About Plaque Psoriasis Psoriasis is a common, chronic, inflammatory skin disease that affects approximately nine million people in the United States. Symptoms include itch, scaling, redness, and flaking. On darker skin tones, plaques may appear more grayish, purplish, or brown. Psoriasis can appear anywhere on the body, including the knees, elbows, torso, and areas where the skin is thin, like the face, genitals, and intertriginous areas, which are areas where skin touches skin, such as the armpits, under the breasts, stomach folds, between the buttocks, and in the groin area. In addition, scalp psoriasis occurs in more than half of all psoriasis sufferers, and sometimes extends to the forehead, back of the neck, or behind or inside the ears. About ZORYVE (roflumilast) ZORYVE is a next generation topical phosphodiesterase-4 (PDE4) inhibitor. PDE4 – an established target in dermatology – is an intracellular enzyme that increases the production of pro-inflammatory mediators and decreases production of anti-inflammatory mediators. ZORYVE (roflumilast) topical foam 0.3% is indicated for treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older. ZORYVE foam is under review for the treatment of scalp and body psoriasis by the FDA with a PDUFA target action date of May 22, 2025. ZORYVE® (roflumilast) cream 0.3% is approved by the FDA for the topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. ZORYVE® (roflumilast) cream 0.15% is approved by the FDA for the topical treatment of mild to moderate atopic dermatitis in patients 6 years of age and older. In 2024, ZORYVE cream 0.15% was awarded Glamour’s Beauty and Wellness Award for “Eczema Product.” ZORYVE® (roflumilast) cream 0.05% is under review for the treatment of atopic dermatitis in children ages 2 to 5 by the FDA, with a PDUFA target action date of October 13, 2025. INDICATIONS ZORYVE cream, 0.3%, is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in adult and pediatric patients 6 years of age and older. ZORYVE cream, 0.15%, is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 6 years of age and older. ZORYVE foam, 0.3%, is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older. IMPORTANT SAFETY INFORMATIONZORYVE is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C). Flammability: The propellants in ZORYVE foam are flammable. Avoid fire, flame, and smoking during and immediately following application. The most common adverse reactions (≥1%) for ZORYVE cream 0.3% for plaque psoriasis include diarrhea (3.1%), headache (2.4%), insomnia (1.4%), nausea (1.2%), application site pain (1.0%), upper respiratory tract infection (1.0%), and urinary tract infection (1.0%). The most common adverse reactions (≥1%) for ZORYVE cream 0.15% for atopic dermatitis include headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%). The most common adverse reactions (≥1%) for ZORYVE foam 0.3% for seborrheic dermatitis include nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%). Please see full Prescribing Information for ZORYVE foam and full Prescribing Information for ZORYVE cream. About Arcutis Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT) is a commercial-stage medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions. With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio of advanced targeted topicals approved to treat three major inflammatory skin diseases. Arcutis’ unique dermatology development platform coupled with our dermatology expertise allows us to invent differentiated therapies against biologically validated targets, and has produced a robust pipeline with multiple follow-on clinical programs for a range of inflammatory dermatological conditions including atopic dermatitis and alopecia areata. For more information, visit www.arcutis.com or follow Arcutis on LinkedIn, Facebook, Instagram, and X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. For example, statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on The Company’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding the potential real-world use results of ZORYVE foam in scalp and body psoriasis, the potential for ZORYVE foam to advance the standard of care in plaque psoriasis, atopic dermatitis and other inflammatory dermatological conditions, as well as potential regulatory approvals and associated timing of such approvals. These statements are subject to substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. Risks and uncertainties that may cause our actual results to differ include risks inherent in our business, reimbursement and access to our products, the impact of competition and other important factors discussed in the “Risk Factors” section of our Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) on February 25, 2025, as well as any subsequent filings with the SEC. Any forward-looking statements that the company makes in this press release are made pursuant to the Private Securities Litigation Reform Act of 1995, as amended, and speak only as of the date of this press release. Except as required by law, we undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. Contacts: Media Amanda Sheldon, Head of Corporate Communications media@arcutis.com Investors Latha Vairavan, Chief Financial Officer ir@arcutis.com