A randomized, double-blind, phase III study assessing clinical similarity of SB17 (proposed ustekinumab biosimilar) to reference ustekinumab in subjects with moderate-to-severe plaque psoriasis.

BACKGROUND: Ustekinumab (UST) is a safe and effective treatment for moderate-to-severe psoriasis. OBJECTIVES: To compare efficacy, safety, pharmacokinetics (PK), and immunogenicity of the proposed UST biosimilar SB17 with reference UST in subjects with moderate-to-severe plaque psoriasis. METHODS: In this randomized double-blind study, subjects were randomized to receive 45 mg of SB17 or UST subcutaneously at week 0, 4, and every 12 weeks. The primary endpoint was the percent change from baseline in Psoriasis Area and Severity Index at week 12 with an equivalence margin of [-15%, 15%]. Other secondary efficacy, safety, PK, and immunogenicity endpoints were measured through week 28. RESULTS: Two hundred forty-nine subjects were randomized to SB17, 254 to UST. Adjusted difference of Psoriasis Area and Severity Index change from baseline at week 12 of -0.6% (95% confidence interval; -3.780, 2.579) was within the equivalence margin. Physician's Global Assessment and Dermatology Life Quality Index were also comparable. Overall treatment-emergent adverse events were comparable (SB17: 48.2%, UST: 48.8%). The overall incidence of antidrug antibodies up to Week 28 was 13.3% with SB17 and 39.4% with UST. LIMITATIONS: Data were only through week 28. CONCLUSION: SB17 was clinically biosimilar to UST up to week 28.

Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Choosing Systemic Agents for Psoriasis.

Treatment options for moderate-to-severe psoriasis depend on drug efficacy and safety, patient preferences, comorbidities, and cost-no drug dominates across all dimensions. Interleukin (IL)-17 inhibitors may be preferred for fast-acting treatment, while the 3-month schedule of risankizumab, ustekinumab, or tildrakizumab may be attractive for patients who prioritize fewer injections. Phototherapy is suitable for patients who wish to avoid systemic agents or when cost is a concern. For patients with poor adherence, infliximab or tildrakizumab may be well suited as they require in-office administration. Dermatologists can educate patients on available therapies to find a regimen best suited to their needs.

A Review of Topical Tapinarof for the Treatment of Plaque Psoriasis.

OBJECTIVE: This article reviews the efficacy and safety of 1% tapinarof cream for plaque psoriasis. DATA SOURCES: A literature search was conducted from August 2022 to February 2023. The terms tapinarof, VTAMA, benvitimod, GSK2894512, DMVT-505, and WBI-1001 were queried in PubMed. ClinicalTrials.gov was searched to identify ongoing or unpublished studies. STUDY SELECTION AND DATA EXTRACTION: All clinical trials written in English and relevant to pharmacology, efficacy, and safety were included. DATA SYNTHESIS: In two 12-week phase III clinical trials, disease severity assessed by a Physician's Global Assessment (PGA) score of clear or almost clear and a 2-point PGA improvement was 35.4% and 40.2% at week 12 in the 2 trials, respectively. In the 40-week, open-label extension trial, the efficacy and safety results were similar: 40.9% of patients achieved a PGA of 0 at least once during the trial, and 58.2% of patients with PGA ≥ 2 achieved PGA 0/1 at least once. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Tapinarof is a topical aryl hydrocarbon receptor agonist and a first-in-class, potentially promising treatment for plaque psoriasis recently approved by the U.S. Food and Drug Administration. CONCLUSION: Compared with placebo, tapinarof may be an effective and safe topical treatment for mild to severe plaque psoriasis. Head-to-head trials to compare the efficacy and adverse effect profile of tapinarof to other topical treatments are still needed, as are investigation in patients with recent or current use of phototherapy or biologic or nonbiologic systemics. Cost and adherence to treatment may be barriers for treatment efficacy.

A Review of Topical Sirolimus for the Treatment of Facial Angiofibromas in Tuberous Sclerosis Complex.

OBJECTIVE: This article assesses the efficacy, safety, pharmacology, and clinical applications of topical sirolimus 0.2% gel for the treatment of tuberous sclerosis complex (TSC)-associated facial angiofibromas. DATA SOURCES: A review of the literature was conducted using the Medline (PubMed) and EMBASE databases using the keywords topical sirolimus, rapamycin, Hyftor, and tuberous sclerosis. STUDY SELECTION AND DATA EXTRACTION: Articles written in English and relevant to the topic were included. DATA SYNTHESIS: In the phase 2 trial, the mean improvement factor, a composite measure of improved tumor size and redness, was achieved in all patient groups (P < 0.001) with significant responses among the adult and pediatric subgroups at week 12. There were no serious adverse events recorded. In the phase 3 trial, 60% of participants responded to treatment in the sirolimus group compared with 0% in the placebo group with different response rates between the adult and pediatric subgroups at week 12. Sirolimus gel had no serious adverse events, and dry skin was the most common adverse reaction. Patients who had completed the 12-week trials were then enrolled in a long-term trial; angiofibromas had response rates of 78.2% to 0.2% sirolimus gel. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Topical sirolimus 0.2% is a first-in-class, newly Food and Drug Administration (FDA)-approved, mammalian target of rapamycin (mTOR) inhibitor that is a promising and safe, noninvasive alternative to surgical procedures for TSC-associated angiofibromas. CONCLUSIONS: Topical sirolimus 0.2% gel is a moderately effective treatment for TSC-associated facial angiofibromas with an adequate safety profile.

Spesolimab: A Review of the First IL-36 Blocker Approved for Generalized Pustular Psoriasis.

OBJECTIVE: This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP). DATA SOURCES: A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023. STUDY SELECTION AND DATA EXTRACTION: Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included. DATA SYNTHESIS: In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 (P = 0.0005), 0.35 (P = 0.0057), and 0.47 (P = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents. CONCLUSION: Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents.

Qualitative investigation of disease course, characteristics and lived experience of generalized pustular psoriasis.

BACKGROUND: Generalized pustular psoriasis (GPP) is a relapsing-remitting chronic disease characterized by painful pustules with systemic symptoms that negatively impacts quality of life. The psychosocial and economic burden of this rare condition is not well characterized. OBJECTIVES: To qualitatively characterize the cumulative burden of generalized pustular psoriasis on patients' quality of life and psychosocial wellbeing. METHODS: A retrospective chart review of patients with generalized pustular psoriasis was performed to collect demographic information, followed by prospective semi-structured clinical interviews. Interview transcripts were analyzed using thematic analysis. RESULTS: Three major themes were revealed: (1) Burden of having a chronic disease with an unpredictable course, (2) an inability to fulfill societal roles results in a loss of identity, and (3) a physician-patient relationship grounded in trust and transparency can be invaluable in helping patients endure chronic disease. CONCLUSION: GPP has a negative impact on patients' quality of life and psychosocial wellbeing. Impairments in daily function and mental health primarily affects patients during flares and influences behavior during periods of quiescence. A strong patient-physician relationship may help mitigate the impact of GPP.

Dermatologists' Perspectives on Biosimilars.

BACKGROUND: Biosimilars are biologic agents the Food and Drug Administration (FDA) has deemed to have no clinical difference from their reference biologics. In dermatology,  biosimilars are approved for the treatment of psoriasis and hidradenitis suppurativa. Although dermatologists are high prescribers of biologics, they are more reluctant to prescribe biosimilars than other specialists. This survey-based study sought to characterize dermatologists’ current perspectives on biosimilars.  Methods: A 27-question survey was distributed via email to dermatologists between September and October of 2022.  Results: Twenty percent of respondents would not prescribe a biosimilar for an FDA-approved indication. When asked about the greatest barriers to biosimilar adoption, 61% had concerns about biosimilar safety and efficacy, 24% reported uncertainty about state laws for interchangeability and substitutions, and 20% had concerns about biosimilar safety without concerns about efficacy. Thirty-five percent of respondents felt moderately or extremely knowledgeable about biosimilar interchangeability.  Conclusion: Biosimilars are safe and effective for treating approved dermatological conditions and may lower patient costs compared to their reference products. Patients are not always offered biosimilar therapy as an option, which may be due to unfamiliarity among dermatologists.  This survey suggests a need for more research and educational initiatives, such as modules and workshops that focus on biosimilar safety, efficacy, and interchangeability guidelines. J Drugs Dermatol. 2024;23(4):doi:10.36849/JDD.7755.

Number of Affected Nails Is the Primary Determinant of Efinaconazole 10% Solution Usage for Onychomycosis.

Good adherence to treatment is necessary for the successful treatment of onychomycosis and requires that an appropriate amount of medication be prescribed. Most prescriptions for efinaconazole 10% solution, a topical azole antifungal, are for 4 mL per month but there are no data on patient factors or disease characteristics that impact how much medication is needed. Data from two phase 3 studies of efinaconazole 10% solution for the treatment of toenail onychomycosis were pooled and analyzed to determine monthly medication usage based on the number of affected toenails, percent involvement of the target toenail, body mass index (BMI), and sex. Participants with two or more affected nails required, on average, >4 mL of efinaconazole per month, with increasing amounts needed based on the number of nails with onychomycosis (mean: 4.39 mL for 2 nails; 6.36 mL for 6 nails). In contrast, usage was not greatly impacted by target toenail involvement, BMI, or sex. Together, these data indicate that the number of affected nails should be the major consideration when determining the monthly efinaconazole quantity to prescribe. J Drugs Dermatol. 2024;23(2):110-112.    doi:10.36849/JDD.7676.

Benefit of Topical Combination Therapy for Acne: Analyzing Effect Size Using Number Needed to Treat.

BACKGROUND: Topical acne trials often are confounded by high vehicle response rates and differing outcome measures, making it difficult to compare treatments. Number needed to treat (NNT) can be a simple, clinically meaningful way to indirectly compare treatment options without head-to-head data. NNT is the number of patients who need to be treated with an intervention to observe one additional patient successfully achieving a desired outcome versus vehicle/placebo. While treatment attributes such as adverse events may not be captured, lower NNT is a good indicator of a more effective treatment. METHODS: Following a search of combination topical treatments for acne vulgaris, all treatments that reported pivotal trial efficacy data consistent with the 2018 FDA definition of success were included in NNT analyses.  Results: Of 13 treatments, 7 reported 12-week treatment success rates in 11 phase 3 trials, with similar baseline demographics/disease severity. Treatment success ranged from 26.8% with tretinoin 0.1%/benzoyl peroxide (BPO) 3% cream to 50% with triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel. NNTs for the triple-combination gel were 4 and 5 (from 2 pivotal trials). Adapalene 0.3%/BPO 2.5% gel had an NNT of 5. Tretinoin/BPO had the largest range between trials, with NNTs of 4 and 9. The other 4 treatments had NNTs ranging from 6 to 8. CONCLUSION: A comparison of combination topical acne treatment trial data, using the same treatment outcome and similar patient populations, resulted in triple-combination clindamycin phosphate/adapalene/BPO gel and adapalene/BPO gel having the most favorable NNTs.J Drugs Dermatol. 2024;23(2):42-49.  doi:10.36849/JDD.7927.

Biologics for Treatment of Pityriasis Rubra Pilaris: A Literature Review.

OBJECTIVE: To describe the published efficacy and adverse event rates associated with existing biologics for the treatment of pityriasis rubra pilaris (PRP). DATA SOURCES: A literature review using the PubMed database (January 1990-July 2023) was conducted. Multiple search combinations were conducted using "pityriasis rubra pilaris" and various biologics as keywords to identify relevant articles. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria included all study types that were published within the past 30 years in English and mentioned at least one biologic and PRP. A preliminary search yielded a total of 499 results. After screening using inclusion and exclusion criteria, 77 relevant articles (69 case reports, 5 case series, 2 clinical trials, and 1 retrospective analysis) were analyzed. DATA SYNTHESIS: TNF-α inhibitors have been evaluated and are effective in treating PRP. However, recent treatment with anti-interleukin (IL)-17 and anti-IL-23 therapies such as ustekinumab, secukinumab, and ixekizumab are emerging as new treatment options with a mean improvement in PRP Area and Severity Index scores, change in severity of erythema, scaling, and thickness of PRP lesions. From initial clinical trials, secukinumab and ixekizumab are promising treatment options for achieving remission. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review compares the efficacy for numerous biologics and a discussion to guide clinicians on benefits and risks in choosing a biologic for PRP patients. CONCLUSIONS: Biologics may be a favourable treatment option leading to greater patient adherence due to reduced dosing frequencies, improvement in quality of life, and reduction in frequency and severity of flares.

Non-Systemic Medication for the Treatment of Prurigo Nodularis: A Systematic Review.

Prurigo nodularis (PN) is a skin disease characterized by firm, itchy, erythematous lesions. Treatment consists of systemic and non-systemic modes of therapy. Non-systemic forms of treatment are first-line and include topical corticosteroids, topical steroid-sparing agents, and phototherapy. The objective was to review the efficacy of non-systemic treatment used to treat PN. A systematic search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with PROSPERO (CRD42023412012). The search consisted of keywords and Medical Subject Heading (MeSH) terms and translated to Ovid MEDLINE, Embase, and Scopus. Google Scholar was also searched for the first 200 articles. Article quality of evidence was scored using GRADE criteria. The search yielded 1151 results; 37 met criteria for inclusion. There were 14 studies on phototherapy, and 11 studies on topical corticosteroids, most of which were also combined with topical antihistamines, antipruritics, and/or phototherapy. There were 2 studies each on topical antipruritics used in isolation, vitamin D analogues, and intralesional triamcinolone acetonide. There was 1 study each on topical pimecrolimus, tacrolimus, 2% dinitrochlorobenzene, cryotherapy, acupuncture, and the Paul Gerson Unna boot. Most were case reports and case series, although 2 randomized controlled trials on phototherapy and topical pimecrolimus were included. Corticosteroids had varying levels of positive response in patients and appeared more effective when used in combination or under occlusive dressing. Phototherapy is likely effective, but the risk of relapse is high. Cryotherapy may also be a lesion-directed agent to circumvent challenges to adherence and avoidance of systemic medication.

Overview of Dermatological Manifestations Associated with the COVID-19 Infection.

COVID-19 is an infectious disease caused by SARS-CoV-2 that is characterized by respiratory symptoms, fever, and chills.[1] While these systemic symptoms are widely known and well understood, there have also been reports of dermatological manifestations in patients with COVID-19. These manifestations include chilblain-like lesions, maculopapular lesions, urticarial lesions, necrosis, and other varicella-like exanthems.[2] The pathogenesis of these lesions are not well understood, but the procoagulant and pro-inflammatory state induced by COVID-19 infections may be contributing to varied cutaneous manifestations.[3] Drug interactions and concurrent hypersensitivity reactions have also been postulated.[4] This review aims to compile and analyze various retrospective studies and case reports to summarize the clinical presentation of dermatological lesions associated with COVID-19 infections and suggest further areas of research.

Bromhidrosis treatment modalities: A literature review.

BACKGROUND: Treatment options for Bromhidrosis include botulinum toxin therapy, microwave-based therapy, laser therapy, and surgical intervention. Limited studies compare their efficacies. OBJECTIVE: The purpose of this literature review is to compare the efficacy and safety of these treatments for bromhidrosis. METHODS: A PubMed search included terms bromhidrosis and bromhidrosis AND treatment. RESULTS: A total of 25 articles were reviewed. Botulinum toxin therapy shows consistent benefit but requires repeated therapies. Microwave therapies have shown promising results but require larger cohort sizes with bromhidrosis. Similarly, laser therapy has shown promise with biopsy-proven results, but long-lasting effects remain unknown. Surgery has the best long-term prognosis, but the ideal surgical method remains unknown. LIMITATIONS: Each study varied in their treatment interval and method of assessing bromhidrosis, making direct comparisons difficult. CONCLUSIONS: Managing bromhidrosis requires shared decision making with the patient. Mild-to-moderate symptoms may be treated initially with botulinum toxin therapy. In cases that are refractory, laser therapy should be considered, as it is better studied than microwave therapy currently. Lastly, if the condition is severe and refractory to other options, surgery can be considered, although the ideal method remains unknown.

Review of Ruxolitinib in the Treatment of Atopic Dermatitis.

OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of a newly approved topical Janus kinase 1 (JAK) inhibitor, ruxolitinib (RUX), in patients with atopic dermatitis (AD). DATA SOURCES: A literature search was completed May 1, 2022. The term RUX and AD was queried in MEDLINE (PubMed) and EMBASE databases. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed articles written in English and published prior to May 1, 2022 were included. DATA SYNTHESIS: In the phase II clinical trial, more patients treated with 1.5% topical RUX twice a day had a mean percentage improvement in Eczema Area and Severity Index (EASI) scores from baseline to 4 weeks, when compared to vehicle (71.6% vs 15.5%; P < 0.001). In phase III clinical trials, greater percentage of patients who received 0.75% topical RUX (TRuE-AD1 50.0% and TRuE-AD2 39.0%) or 1.5% topical RUX (TRuE-AD1 53.8% and TRuE-AD2 51.3%) achieved an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and had a ≥2-grade improvement from baseline to 8 weeks, when compared to vehicle (TRuE-AD1 15.1% and TRuE-AD2 7.6%; P < 0.001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Atopic dermatitis is a highly prevalent long-term inflammatory skin condition. Pruritus is the main contributor of decreased quality of life in patients with AD. Topical RUX inhibits JAK1 and JAK2 producing antiinflammatory and antipruritic effects. Patients experienced a reduction in pruritus within 2 days. This decreased pruritus translated to increased quality of life and less sleep disturbances. CONCLUSION: Data from phase II and III clinical trials in adult patients suggest RUX is an effective and safe therapy for AD.

Review of Calcipotriene and Betamethasone Dipropionate Cream in the Treatment of Psoriasis.

OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of recently approved calcipotriene and betamethasone dipropionate (C-BD) cream. DATA SOURCES: A literature review was conducted using MEDLINE (PubMed) and ClinicalTrials.gov from 2002 to mid-May 2022. STUDY SELECTION AND DATA EXTRACTION: Articles in English discussing the use of C-BD cream in the treatment of psoriasis were included. DATA SYNTHESIS: In 2 phase I trials, there was no phototoxic or photoallergic skin reaction at irradiated C-BD cream sites at baseline, 24 hours, 48 hours, and 72 hours postirradiation. In 2 phase III trials, after 8 weeks of treatment, more subjects treated with C-BD cream achieved Physician's Global Assessment treatment success (37.4%), compared to C-BD topical suspension (TS) (22.8%, P < 0.0001) and vehicle (3.7%, P < 0.0001). More subjects had greater mean percentage decline in Modified Psoriasis Area Severity Index (Trial 1: 52.9% and Trial 2: 64.6%), when compared to C-BD TS (Trial 1: 51.3%, P < 0.0001 and Trial 2: 56.4%, P < 0.0001) and vehicle (Trial 1: 22.9%, P < 0.0001 and Trial 2: 20.0%, P < 0.0001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Psoriasis has a multifactorial pathogenesis and topical treatments are considered first line. Poor adherence is a major hurdle in management; the combination of 2 separate first-line drugs may address this by decreasing the complexity of treatment regimens. A cream formulation can be preferred, and C-BD is now Food and Drug Administration (FDA) approved as one. CONCLUSIONS: Newly FDA-approved C-BD cream with novel polyaphron dispersion (PAD) technology provides a safe efficacious combination therapy for mild-to-moderate psoriasis which may be preferred by some patients.

Tretinoin 0.1% and Benzoyl Peroxide 3% Cream for the Treatment of Facial Acne Vulgaris.

OBJECTIVE: To assess the efficacy, safety, and clinical application of tretinoin 0.1%-benzoyl peroxide 3% cream for the topical treatment of acne vulgaris. DATA SOURCES: A systematic review of the literature was performed using the terms Twyneo OR tretinoin and benzoyl peroxide OR S6G5T-3 in MEDLINE (PubMed) and EMBASE. ClinicalTrials.gov was searched to obtain completed clinical trial results not published elsewhere. STUDY SELECTION AND DATA EXTRACTION: All human studies published in English prior to November 2022 related to pharmacology, clinical trials, safety, and efficacy were evaluated for inclusion. DATA SYNTHESIS: In two 12-week, phase 3, randomized, vehicle-controlled clinical trials, tretinoin 0.1%-benzoyl peroxide 3% cream significantly reduced inflammatory and noninflammatory facial acne lesions and significantly improved Investigator Global Assessment (IGA) rating to clear or almost clear. The cream has a suitable safety profile, with application site pain and dryness as the most common adverse events. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS: Tretinoin-BPO had similar IGA success compared to other topical retinoid and retinoid-BPO treatments for acne vulgaris. Compared to individual tretinoin and benzoyl peroxide therapy, the combination product streamlines application, which will improve medication adherence; however, the cost of tretinoin-BPO cream may be prohibitive. CONCLUSIONS: Tretinoin 0.1%-benzoyl peroxide 3% cream is safe and effective for the treatment of moderate-to-severe acne. Long-term trial data on efficacy and tolerability are not yet available.

A Review of Topical Roflumilast for the Treatment of Plaque Psoriasis.

OBJECTIVE: This article reviews clinical trials to assess the efficacy, safety, and clinical application of once-daily roflumilast 0.3% cream for the treatment of plaque psoriasis. DATA SOURCES: A systematic review of the literature was performed using the terms roflumilast OR Zoryve OR ARQ-151 in MEDLINE (PubMed) and EMBASE databases between January 2012 and October 2022. Bibliographies and the ClinicalTrials.gov website were also searched to identify further studies. STUDY SELECTION AND DATA EXTRACTION: Studies written in English and relevant to pharmacology, clinical trials, and safety were considered for inclusion. DATA SYNTHESIS: In two 8-week phase III clinical trials, disease severity as assessed by a score of "clear" or "almost clear" and a 2-point improvement on Investigator Global Assessment (IGA) was 42.4% and 37.5% at week 8 in DERMIS-1 and DERMIS-2, respectively, compared to 6.1% and 6.9% in the control groups. In the 52-week phase III trial, treatment success rates for plaque psoriasis and intertriginous psoriasis were similar to the 8-week data with 45% of patients in the treatment group were evaluated as an IGA of "clear" or "almost clear" at week 52. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Roflumilast is a new US Food and Drug Administration (FDA)-approved topical phosphodiesterase inhibitor that shows promise for the treatment of mild-severe plaque psoriasis. It is an effective and safe topical nonsteroidal alternative to currently available topical corticosteroids, but there are currently no comparative studies with other psoriasis treatments. CONCLUSION: Roflumilast is effective and safe for the treatment of plaque psoriasis and intertriginous psoriasis. Future trials should compare its efficacy and tolerability with that of the older, clinically established topical corticosteroids. Prohibitive factors may include limited patient adherence to topical treatments and cost.

Abrocitinib: A New FDA-Approved Drug for Moderate-to-Severe Atopic Dermatitis.

OBJECTIVE: The objective of this article is to review abrocitinib, an oral Janus kinase (JAK) 1 inhibitor, for the treatment of patients with moderate-to-severe atopic dermatitis (AD). DATA SOURCES: A literature search of MEDLINE (PubMed) was performed for articles from inception through end-March 2022 using the following search terms: atopic dermatitis, abrocitinib, PF-04965842, methotrexate, cyclosporine, dupilumab, ruxolitinib, and JAK-STAT pathway. STUDY SELECTION AND DATA EXTRACTION: English articles relating to pharmacology, pharmacokinetics, efficacy, and safety of abrocitinib, and other conventional systemic medications for AD, were included. DATA SYNTHESIS: Across phase IIb and phase III clinical trials, abrocitinib was efficacious with an average of 47.5% patients on 200 mg abrocitinib and 32.0% on 100 mg abrocitinib achieving an Investigator's Global Assessment (IGA) of 0 or 1 at 12 weeks. In comparison with dupilumab 300 mg subcutaneously every other week, patients on abrocitinib 200 mg once daily had improved disease severity and itch response. The majority of adverse events were not severe and self-limited. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Prior to Food and Drug Administration (FDA) approval of abrocitinib, prednisone was the only FDA-approved oral medication for AD. Although biologics such as dupilumab have revolutionized care, some patients prefer oral medications. Compared with clinical trials of conventional AD treatments, abrocitinib appears more effective. CONCLUSIONS: Abrocitinib is an efficacious oral JAK 1 inhibitor recently FDA-approved for patients ≥ 18 years old with moderate-to-severe AD who have not responded to systemic medications or when contraindicated otherwise.

Review of Tralokinumab in the Treatment of Atopic Dermatitis.

OBJECTIVE: To review pharmacokinetics, efficacy, and safety of tralokinumab in treatment of atopic dermatitis (AD). DATA SOURCES: Literature review was conducted using MEDLINE (PubMed), EMBASE, and ClinicalTrials.gov for articles published between January 2010 and May 2022. STUDY SELECTION AND DATA EXTRACTION: Articles in English discussing tralokinumab in AD were included. DATA SYNTHESIS: In one phase 2 trial, more subjects treated with tralokinumab 150 and 300 mg achieved an Investigator's Global Assessment (IGA) of 0/1 with minimum ≥2 point IGA reduction (23%), versus placebo (11.8%, P = 0.10). During 2 phase 3 trials, more subjects treated with tralokinumab achieved IGA success (ECZTRA 1: 15.8% and ECZTRA 2: 22.2%), versus placebo (7.1% and 10.9%, respectively; P = 0.002 and P < 0.001). During one phase 3 trial, in conjunction with topical corticosteroids (TCS), more subjects treated with tralokinumab 300 mg achieved IGA success (ECZTRA 3: 38.9%), versus placebo (26.2%, P = 0.015). During another phase 3 trial in subjects with resistance or contraindication to oral cyclosporine, more subjects treated with tralokinumab 300 mg achieved an Eczema Area Severity Index 75 (64.2%), versus placebo (50.5%, P = 0.018). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Tralokinumab is efficacious for moderate-to-severe AD, as monotherapy, in conjunction with TCS, and resistance or contraindication to cyclosporine. Although IL-4 and IL-13 are both implicated in AD's pathogenesis, IL-13 is overexpressed, and head-to-head trials are needed to assess efficacy of tralokinumab, versus dupilumab. Compared with upadacitinib and abrocitinib, tralokinumab is not associated with black-box warnings. CONCLUSIONS: Tralokinumab is an efficacious and safe systemic treatment for moderate-to-severe AD.