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.

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.

Adherence in Atopic Dermatitis.

Atopic dermatitis is a chronic dermatologic condition requiring extended treatment times with topical application of medications. While atopic dermatitis treatments can be highly effective when used as directed, oftentimes patients do not respond as expected, raising concern for nonadherence versus nonresponse. This chapter aims to describe what is currently known about adherence in atopic dermatitis and to discuss strategies to improve adherence in order to improve treatment outcomes. Whether intentional or unintentional, nonadherence to treatment can limit patient outcomes of this disease for a variety of reasons. These include frustration with medication efficacy, inconvenience, and fear of side effects. Other factors include forgetfulness, financial burden of treatment, lack of trust in the physician, dislike of prescribed medication, or lack of understanding of disease or treatment. Several interventions have been studied with the aim of improving adherence in atopic dermatitis-such as educational workshops for patients and caregivers, earlier follow-up visits, and text messages reminders-however, these are often limited by sample size and power. Further research is needed to study both specific patterns of nonadherence in atopic dermatitis, as well as methods to improve them.

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.

An effective patient-supporting intervention for topical treatment of psoriasis is also cost-effective.

BACKGROUND: A randomized controlled trial (RCT) of topical treatment combined with regular patient support provided by dermatological nurses in structured consultations of 20-min duration every fourth week improved psoriasis severity, quality of life and treatment adherence compared with topical treatment combined with standard patient support, which is seeing a dermatologist every third month. OBJECTIVES: To examine the economic impact of the patient support from a healthcare-sector perspective in the RCT. METHODS: Costs for primary care, secondary healthcare services and costs of prescription medication were compared for the intervention and nonintervention groups over 48 weeks. Health benefits were expressed in terms of quality-adjusted life-years (QALYs) measured by the EuroQoL five-dimension three-level questionnaire. Regression analyses were used to estimate incremental cost and QALYs. RESULTS: The incremental cost was estimated at £462, with an average increase of 0.08 QALYs per patients for participants receiving the intervention compared with those receiving standard care. The incremental cost-effectiveness ratio for patients was £5999/QALY. The intervention had an almost 100% probability of being cost-effective at a willingness-to-pay threshold of £30 000 per QALY. CONCLUSIONS: Addressing adherence issues is critical to improving outcomes for patients with psoriasis who use topical treatment. The personal support intervention was effective with an acceptable increase in costs.

A Review on the Use of Topical Ruxolitinib for the Treatment of Vitiligo.

BACKGROUND: This article describes the clinical trial, safety, and efficacy of ruxolitinib 1.5% cream or repigmentation in patients with vitiligo. DATA SOURCES: A systematic review was done using ruxolitinib or Opzelura in MEDLINE (PubMed) and EMBASE. CLINICALTRIALS: gov was used to identify ongoing or unpublished studies. STUDY SELECTION AND DATA EXTRACTION: Studies included were written in English and relevant to pharmacology, clinical trials, safety, and efficacy. DATA SYNTHESIS: In two 52-week phase 3 trials, 52.0% of subjects had at least 75% improvement in their Facial Vitiligo Area Scoring Index (F-VASI). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Ruxolitinib is a topical Janus kinase (JAK) inhibitor newly approved by the US Food and Drug Administration for repigmentation in patients with vitiligo. CONCLUSION: Topical ruxolitinib is the first medication approved for repigmentation in patients with vitiligo. It is a safe and effective treatment; however, cost may be a barrier to some patients when prescribing this medication. Trials to compare the efficacy and side effect profile of topical ruxolitinib with other topical treatments are still needed. Grossmann MC, Haidari W, Feldman SR. A Review on the use of topical ruxolitinib for the treatment of vitiligo. J Drugs Dermatol. 2023;22(7):664-667. doi:10.36849/JDD.7268.

Rethinking the Inflammatory Balance in Psoriasis and Atherosclerosis.

Guénin S, Kazemi A, Cline A, et al. Rethinking the inflammatory balance in psoriasis and atherosclerosis. J Drugs Dermatol. 2023;22(8):832-833. doi:10.36849/JDD.7082.

Patient Preferences in Topical Psoriasis Treatment.

BACKGROUND: Psoriasis is a common inflammatory skin condition that varies in severity. Most patients have limited disease amenable to topical treatment; however, poor treatment adherence limits efficacy. The purpose of this study was to assess patients’ psoriasis treatment experience, expectations, and preferences. METHOD: The National Psoriasis Foundation conducted a 17-question survey in March 2022 assessing psoriasis severity, bothersome signs and symptoms, current treatment modalities, frequency of topical therapy use, and vehicle preferences. Statistical analysis of the qualitative data was performed using descriptive analysis and calculations of relative frequencies. RESULTS: Most participants self-reported moderate psoriasis (83.9%). The most common bothersome symptoms were scaly appearance (78.8%), bleeding/oozing (60%), itch (55%), and flaking (37.4%). For treatment, 72.5% of participants disclosed using oral medication, while 8% used topical treatment alone. Most participants (76%) reported using topical therapy at least once weekly. Nearly 80% of participants said they would allow 2 weeks for a medication to become effective before considering discontinuation. Participants preferred water-based creams (75.7%), followed by oil-based foam (70.8%), gel (48.7%), solution (42.8%), lotion (21.2%), non-oil-based foam (17.5%), ointment (16.5%), and spray (6.3%). The formulation attributes rated most important were application feel (55.2%), non-staining (49.9%), quick absorption (46.7%), non-sticky texture (39.7%), ease of application (28.5%), no unpleasant smell (22.4%), non-greasy (16.8%), works quickly (14.1%), absent sting or burn (10%), no adverse skin reaction (9.7%), and once daily treatment (6.8%). If participants did not like a topical treatment's formulation, most (74.7%) said they would continue to use the medication for a week before discontinuation. CONCLUSION: Topical treatments continue to be a mainstay of psoriasis treatment. Patients expect to see rapid improvement with topical treatment; otherwise, they report that they will discontinue treatment. The characteristics of psoriasis treatment vehicles also affect patients’ reported willingness to use treatment and may be an important consideration in treatment planning. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7372 Citation: Curcio A, Kontzias C, Gorodokin B, et al. Patient preferences in topical psoriasis treatment. J Drugs Dermatol. 2023;22(4):326-329. doi:10.36849/JDD.7372.

The Patient-Physician Relationship and Adherence: Observations From a Clinical Study.

Improved patient-physician relationships (PPR) are associated with better patient satisfaction and disease outcomes, however, there is limited literature assessing how PPR affects adherence in dermatology. We recruited 30 subjects with a clinical diagnosis of rosacea. Subjects were instructed to use ivermectin 1% cream once daily for 3 months and adherence was measured using the Medication Event Monitoring System cap. The Patient-Doctor Relationship Questionnaire (PDRQ-9), a validated questionnaire assessing patients’ perceived strength of the relationship with their doctor, was completed. Mean adherence for all subjects over three months of the study was 62%. PDRQ-9 scores positively correlated with adherence rates for 3 months of treatment (r(26)=0.52; P=0.006). The perceived strength of the PPR may have a role in patients’ adherence to their medications. Improving the PPR, through empathy and effective communication, may facilitate better medication adherence and treatment outcomes. Perche PO, Singh R, Cook MK, et al. The patient-physician relationship and adherence: observations from a clinical study. J Drugs Dermatol. 2023;22(8):838-839. doi:10.36849/JDD.7103.

Efficacy, Convenience, and Safety of Calcipotriene-Betamethasone Dipropionate Cream in Skin of Color Patients With Plaque Psoriasis.

BACKGROUND: Psoriasis affects diverse racial and ethnic groups. In July 2021, the US Food and Drug Administration approved calcipotriene/betamethasone dipropionate (CAL/BDP) 0.005%/0.065% cream to treat plaque psoriasis in adults. The efficacy and safety of CAL/BDP in patients with skin of color (SOC) who have psoriasis is not well characterized. METHOD: A post hoc analysis of phase 3 clinical trial data (NCT03308799) was conducted to assess the efficacy, convenience, and safety of CAL/BDP cream versus CAL/BDP topical solution and vehicle cream in people with Fitzpatrick skin types IV to VI.   Results: This study included 784 participants, 280 (35.7%) of whom had Fitzpatrick skin types IV to VI. Patients treated with CAL/BDP cream had greater disease improvement, treatment convenience scores, and overall satisfaction than those treated with CAL/BDP topical solution in the subgroup with skin types IV to VI and the total study population.  Adverse event rates were similar between the subgroup with skin types IV to VI and the total study population for all treatment arms.  Conclusion: Psoriasis is associated with a greater physical and psychosocial impact in patients with SOC. While many effective topical therapies exist, it may be helpful to conduct separate analyses of patients with SOC to assess the efficacy and safety of treatment in this population. This sub-analysis of phase 3 clinical trial data supports the efficacy and safety of CAL/BDP cream in the treatment of plaque psoriasis in patients with SOC. CAL/BDP cream also had greater convenience, formula acceptability, and overall satisfaction in both the subgroup with SOC and the total trial population, which may improve adherence to topical therapy and treatment outcomes for people with SOC who have psoriasis. Kontzias CL, Curcio A, Gorodokin B, et al. Efficacy, convenience, and safety of calcipotriene-betamethasone dipropionate cream in skin of color patients with plaque psoriasis. J Drugs Dermatol. 2023;22(7):668-672. doi:10.36849/JDD.7497.

Abametapir for the Treatment of Head Lice: A Drug Review.

OBJECTIVE: This article reviews the pharmacology, safety, efficacy, and clinical importance of abametapir 0.74% (Xeglyze) for the treatment of head lice. DATA SOURCES: From 2020 to May 2021, a systematic review of the MEDLINE and EMBASE databases was conducted using the terms abametapir, Xeglyze, Ha44, and head lice. Bibliographies, Food and Drug Administration (FDA) drug package inserts, and ClinicalTrials.gov were searched for further information. STUDY SELECTION AND DATA EXTRACTION: All relevant full-text articles in English were considered for inclusion, with a final article date range of 1999 to 2020. DATA SYNTHESIS: Abametapir chelates heavy metal cations and inhibits metalloproteinases critical to louse ova development, hatching, and adult survival. In phase II, abametapir had direct ovicidal activity inhibiting 100% of treated louse eggs from hatching, compared with 64% in the vehicle-treated group. In two identical phase III clinical trials, subjects treated with a single 10-minute application of abametapir had greater treatment success compared with vehicle-treated subjects, with 81.1% success versus 50.9% in study 1 (P = 0.001) and 81.8% versus 47.2% in study 2 (P < 0.001). Abametapir was well tolerated, with only mild adverse effects. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Abametapir is a newly FDA-approved, single-application treatment for head lice in patients aged 6 months and older. This review highlights the safety and efficacy of abametapir in the treatment of head lice. CONCLUSIONS: In the wake of increasing widespread resistance to first-line treatment options, abametapir offers a safe and effective new treatment option for head lice infestations.

1% Tirbanibulin Ointment for the Treatment of Actinic Keratoses.

OBJECTIVE: Actinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new topical treatment for AKs, recently approved by the Food and Drug Administration. DATA SOURCES: The PubMed database was searched for articles published from 1960 to March 31, 2021, using the keywords tirbanibulin and Klisyri. DATA EXTRACTION: Phase 2 and phase 3 clinical trials were reviewed. DATA SYNTHESIS: In phase 2 clinical trials, 43% of patients treated with tirbanibulin experienced complete clearance by day 57 (43% [95% CI = 32, 54]). Across two phase 3 clinical trials (pooled data), complete (100%) clearance occurred in 49% of patients in tirbanibulin groups and in only 9% of the vehicle groups (difference, 41% points; 95% CI = 35 to 47; P < 0.001). Although no comparative studies are available, tirbanibulin is applied for a shorter duration (5 days) compared with diclofenac 3% gel, fluorouracil 5% cream, and imiquimod 3.75% cream. Adverse events were mild and included pruritus, application site pain, and local skin reactions. Systemic adverse events such as necrosis and angioedema, observed with other AK treatments such as fluorouracil and imiquimod, were not observed with tirbanibulin, thus giving tirbanibulin a favorable safety profile. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Tirbanibulin effectively reduces AK burden and recurrence and has a favorable safety profile with mild adverse events. In comparison, imiquimod, 5-flourouracil, and diclofenac can result in necrosis, angioedema, and arthralgias. CONCLUSION: With a favorable safety profile and short regimen, tirbanibulin is an efficacious treatment for clinicians to utilize in their treatment toolbox when treating AKs on the face and scalp.

Measuring and Improving Adherence to Crisaborole 2% Ointment in Patients With Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with dry, scaly, and intensely itchy skin. Treatment failure is the result of poor adherence. OBJECTIVE: In this study, we assessed the impact of an internet-based survey on adherence to topical crisaborole 2% ointment in patients with mild AD. METHODS: Participants were randomized to the intervention or control group. The intervention group received weekly email surveys regarding adherence for 6 weeks, then monthly for 12 months. All participants came in for 5 visits over the year. RESULTS: Twenty-eight subjects were recruited for the study (n=19 adults, n=9 pediatrics). Adherence for adults that remained in study (n=6) was 60%. Adherence of the adult control and intervention groups were 49% and 45%, respectively (P>0.05). Adherence for pediatric participants that remained in study (n=2) was 6%. The adherence of the pediatric control and intervention groups were 27% and 29%, respectively (P>0.05). DISCUSSION: Medication adherence was low. The survey intervention did not improve adherence. However, more participants in the intervention group completed the study than in the control group of adults. Regular communication from the provider may help patients feel supported and continue treatment. CLINICALTRIALS: gov identifier: NCT03250663 J Drugs Dermatol. 2022;21(10):1043-1048. doi:10.36849/JDD.6280.

Ixekizumab treatment and the impact on SF-36: results from three pivotal phase III randomised controlled trials in patients with moderate-to-severe plaque psoriasis.

PURPOSE: To assess improvements in health-related quality of life (HRQoL) with ixekizumab treatment in patients with moderate-to-severe psoriasis. METHODS: Adults with plaque psoriasis were enrolled in phase III, double-blind, randomised, controlled trials (UNCOVER-1, UNCOVER-2, or UNCOVER-3). All 3 protocols included a 12-week, placebo-controlled induction period; UNCOVER-2 and UNCOVER-3 also had an active-control group (50 mg etanercept) during induction. After induction, patients in UNCOVER-1 and UNCOVER-2 entered a 48-week withdrawal (maintenance) period (Weeks 12-60), during which Week-12 sPGA (0,1) responders were rerandomized to receive placebo, or 80 mg ixekizumab every 4 weeks (Q4W) or 12 weeks. As a secondary objective, HRQoL was measured by the generic Medical Outcomes Survey Short Form-36 (SF-36) at baseline and Weeks 12 and 60. Changes in mean SF-36 Physical and Mental Component Summary (PCS and MCS) and domain scores and proportions of patients reporting improvements ≥ minimal important differences in SF-36 scores were compared between groups. RESULTS: At Week 12, ixekizumab-treated patients (both dose groups in UNCOVER-1, -2, and -3) reported statistically significantly greater improvements in mean SF-36 PCS and MCS and all 8 SF-36 domain scores versus placebo. Further, more ixekizumab-treated patients than placebo-treated patients reported at least minimal treatment responses in SF-36 PCS and MCS scores and domain scores. Overall improvements in SF-36 PCS and MCS scores were maintained through Week 60. CONCLUSIONS: Ixekizumab-treated patients reported statistically significant improvements in HRQoL at 12 weeks that persisted through 1 year.

Publication rates on the topic of racial and ethnic diversity in dermatology versus other specialties.

BACKGROUND: The population of the U.S. is becoming more diverse every year. The field of dermatology is not following the same trend. OBJECTIVE: To assess the promotion of diversity in the field of dermatology by analyzing publications focused on diversity, compared to other specialties. METHODS: The PubMed database was systematically searched to identify publications focused on diversity from January 2008 to July 2019. The search criteria were as follows: dermatology/radiology/ophthalmology/ anesthesiology/orthopedic surgery/family medicine/ internal medicine/general surgery AND diversity/ diverse/racial/race/ethnic/ethnicity/cultural/culture/competency/competence. Comparisons were made using single-factor ANOVA and two-group t-tests. A qualitative analysis was performed for publications in the field of dermatology. RESULTS: From January 2016 to July 2019, there were 25 publications focused on diversity in dermatology (Mean=6.25, SD=2.06), compared to 6 in radiology (Mean=1.50, SD=1.29, P=0.01), two in ophthalmology (Mean=0.50, SD=0.58, P=0.01), two in anesthesiology (Mean=0.50, SD=1.00, P=0.01), 12 in orthopedic surgery (Mean=3.00, SD=1.41, P=0.04), 23 in family medicine (Mean=5.75, SD=2.22, P=0.75), 9 in internal medicine (Mean=2.25, SD=1.71, P=0.02), and 7 in general surgery (Mean=1.75, SD=0.50, P=0.02). CONCLUSIONS: Although the field of dermatology has suffered from a lack of racial/ethnic diversity, efforts to promote diversity via increased publications in the last four years have been stronger in dermatology compared to many other fields.

Resolution of Guttate Psoriasis Plaques After One-time Administration of Guselkumab

Guttate psoriasis is an acute subtype of plaque psoriasis characterized by eruption of small, scaly plaques, and papules, 5 to 10 mm in size over the trunk and proximal extremities.1 It often arises in children and young adults concomitantly with or shortly after a streptococcal throat infection or tonsillitis. Patients with chronic plaque psoriasis can also experience guttate flares following streptococcal throat infections.1,2 Controlling guttate psoriasis with topical corticosteroids is difficult to achieve due to numerous widespread lesions. Other treatment options include phototherapy and short term use of cyclosporine or methotrexate, as guttate variants of psoriasis can remit with these treatments.1,2 Guselkumab, an inhibitor of the p19 cytokine subunit of interleukin-23 and interleukin-39, produces dramatic resolutions of plaque psoriasis with long lasting effects.3 This case report describes a patient with a guttate variant of plaque psoriasis that resolved after a single administration of guselkumab and continues to remain clear more than 6 months after treatment with guselkumab.