Brodalumab: 5-Year US Pharmacovigilance Report.

INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. METHODS: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. RESULTS: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. CONCLUSION: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Brodalumab is an injectable treatment approved for moderate-to-severe plaque psoriasis in adults who lacked response to previous treatments. In the USA, brodalumab is only available under a Risk Evaluation and Mitigation Strategy for increased suicidality risks; however, findings from 5 years of real-world safety data have demonstrated a lack of association. In this report, we discuss safety findings reported by US patients and healthcare providers for 4744 patients treated with brodalumab over 5 years. Joint pain (known as arthralgia) was the most common safety finding, with 122 cases reported over 5 years. Other safety findings of interest across 5 years included 106 serious infections (defined as prolonged infections or infections requiring treatment), 54 cases of depression, 49 cases of cancer (in 42 patients), 40 confirmed cases of COVID-19, and 11 cases of major cardiovascular events (such as stroke or heart attack). No completed suicides occurred throughout 5 years, and no new suicidal attempts were reported in year 5. In indirect comparisons with safety data from patients with psoriasis receiving or eligible to receive similar treatments, brodalumab was not associated with an increased risk of serious infection, cancer, major cardiovascular events, or inflammatory bowel disease. Taken together, these data are consistent with safety findings from long-term clinical trials and previous safety reports of brodalumab.

Halobetasol Propionate 0.01% and Tazarotene 0.045% Lotion With a Ceramide-Containing Moisturizer in Adults With Psoriasis.

INTRODUCTION: Moisturizers are often used as adjuvant therapy for psoriasis to assist with rehydration and skin barrier restoration. Fixed-combination halobetasol propionate 0.01% and tazarotene 0.045% lotion (HP/TAZ) is indicated for the topical treatment of plaque psoriasis in adults, with a demonstrated clinical profile in two phase 3 trials. However, the effect of application order with HP/TAZ has yet to be explored. This study evaluated the clinical profile of HP/TAZ applied before versus after a ceramide-containing moisturizer in adults with mild-to-moderate plaque psoriasis. METHODS: Sixteen participants were randomized to apply HP/TAZ followed by moisturizer on one side and moisturizer followed by HP/TAZ on the other side once daily for 12 weeks. Tolerability, safety, efficacy, and quality of life endpoints were assessed.  Results: Significant Investigator's Global Assessment improvement was observed across all time points (P≤0.003) regardless of application order. Total Dermatology Life Quality Index scores significantly improved at all time points (P≤0.003), and visual analog scale for itch significantly improved at weeks 4, 8, and 12 (P<0.008). Four moderate adverse events were experienced by 3 participants. Two participants reported itching/irritation, which was worse when HP/TAZ was applied first. CONCLUSIONS: The application order of moisturizer did not decrease therapeutic efficacy of HP/TAZ. Moisturizer application before HP/TAZ may reduce incidence of application site adverse events, ultimately increasing tolerability and supporting the real-world recommendation that applying a ceramide-containing moisturizer before HP/TAZ, versus after, results in a safe and effective therapeutic option for plaque psoriasis. J Drugs Dermatol. 2024;23(2):50-53.     doi:10.36849/JDD.7928.

Fixed-combination halobetasol propionate and tazarotene topical lotion decreases TNF-α and IL-17A levels in psoriatic lesions.

OBJECTIVE: Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) is approved for the treatment of plaque psoriasis in adults, with a demonstrated efficacy and safety profile in phase 3 trials. This study examined the effect of HP/TAZ on the reduction of tumor necrosis factor alpha (TNF-α) and interleukin 17 A (IL-17A) and its correlation to psoriasis improvement. MATERIALS AND METHODS: Ten adults with mild-to-moderate plaque psoriasis and 2 symmetrical plaques self-applied HP/TAZ (treated plaque) or vehicle lotion (untreated plaque) for 12 weeks. At baseline and each study visit (weeks 2, 4, 8, and 12), Investigator's Global Assessment (IGA) score and erythema, scaling, and induration were assessed. Additionally, D-squame tape strips were utilized to quantify TNF-α and IL-17A in target lesions by enzyme-linked immunosorbent assay. RESULTS: Significant improvements in mean IGA score in HP/TAZ-treated compared with untreated plaques were evident at week 2 and maintained through week 12 (p < 0.003). HP/TAZ significantly reduced TNF-α levels at weeks 4 through 12 (p < 0.03) and IL-17A levels at weeks 2 through 8 (p < 0.05) in treated compared with untreated plaques. CONCLUSIONS: HP/TAZ was highly effective in treating psoriasis plaques and, although HP/TAZ is not a biologic, effectively reduced cytokine-associated inflammatory markers that drive psoriatic disease.

Brodalumab: 4-Year US Pharmacovigilance Report.

Brodalumab is an interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis in adults without response or with loss of response to other systemic therapies. Brodalumab carries a boxed warning in the United States regarding suicidal ideation and behavior, though no causal relationship has been established. Here, we summarize 4 years of pharmacovigilance data, from August 15, 2017, through August 14, 2021, reported to Ortho Dermatologics by US patients and healthcare providers. The most common AEs listed in the brodalumab package insert (incidence ≥1%) and AEs of special interest are described. Brodalumab exposure estimates were calculated using the time between the first prescription-dispensing authorization date and last prescription-dispensing authorization date. Data were collected from 4019 patients with an estimated brodalumab exposure of 4563 patient-years. The most common AE was arthralgia (115 events; 2.52 events per 100 patient-years). No completed suicides and no new suicidal attempts were reported. There were 102 cases with serious infections; however, no serious fungal infections (including no new cases of oral candidiasis) were reported. There were 26 COVID-19 cases, and 3 of the cases with comorbid conditions were fatal. There were no new cases of Crohn’s disease. Of 37 reported malignancies among 32 cases, none were deemed related to brodalumab. Four-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and 3-year pharmacovigilance data. J Drugs Dermatol. 2023;22(4) doi:10.36849/JDD.7344 Citation: Lebwohl M, Koo J, Leonardi C, et al. Brodalumab: 4-Year US pharmacovigilance report. J Drugs Dermatol. 2023;22(4):419-422. doi:10.36849/JDD.7344.

Breaking the Frustrating Cycle of Topical Steroids in Psoriasis: A Review of a Novel Vehicle for Fixed-Dose Combination Halobetasol Propionate/Tazarotene.

Topical therapies are commonly used to treat psoriasis, either as monotherapy for milder disease or as adjuncts to systemic and biologic drugs. Topical steroids and tazarotene are both options for topical psoriasis treatment, but as monotherapies, they are associated with adverse events (AEs) that make adherence to prescribed treatment challenging. In addition, the topical vehicles may have an unappealing appearance or texture that proves impractical for patients. Consequently, patients may not use treatments as prescribed. This noncompliance can lead to a frustrating cycle of treatment, discontinuation, and retreatment without achieving treatment goals. Psoriasis is a chronic disease; thus, topical treatment options are needed that address these barriers to use and promote long-term adherence, making satisfactory improvement of psoriasis more attainable. In this review, we discuss patient preferences for topical therapies with vehicles that are moisturizing, nongreasy, and quickly absorbed. We then introduce the vehicle formulation of fixed-dose combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion, which has a unique matrix mesh formulation that enhances uniform absorption, allows for efficient drug delivery, and aligns with patient preferences. In addition to vehicle benefits, the combination of HP and TAZ has been shown to minimize AEs seen with either monotherapy. In clinical trials, HP/TAZ was efficacious and associated with a low rate of AEs with long-term use. This evidence supports the use of HP/TAZ as a topical treatment for patients with psoriasis facing challenges adhering to prescribed treatments and looking to break the cycle of unsatisfactory treatment outcomes. J Drugs Dermatol. 2023;22(3):247-251. doi:10.36849/JDD.7399.

Challenges in Psoriatic Disease Addressed by Fixed-Combination Halobetasol Propionate 0.01% and Tazarotene 0.045% Lotion.

Objective: The fixed-dose corticosteroid/retinoid combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) is approved for topical treatment of plaque psoriasis in adults. In addition to its current indication for plaque psoriasis, a growing body of clinical data suggests that HP/TAZ may be a beneficial therapy for palmoplantar and scalp psoriasis. Here, we discuss the efficacy and safety of HP/TAZ in various psoriatic phenotypes and related conditions. Methods: Three studies (one post-hoc analysis, two open-label reports) of HP/TAZ were identified for this discussion. Results: A post-hoc analysis demonstrated that once-daily HP/TAZ was associated with sustained efficacy and clinically meaningful quality-of-life improvements in participants with psoriatic disease who had low quality of life and 3% to 5% affected body surface area at baseline. In open-label reports, HP/TAZ was associated with improvement in scalp psoriasis measures, as well as quality of life. Additionally, HP/TAZ was efficacious in patients with palmoplantar psoriasis and in one report of a patient with palmoplantar pustulosis. Limitations: Limitations include the small sample sizes of open-label reports of HP/TAZ; larger studies are needed to confirm findings. Conclusion: Taken together, this evidence suggests that HP/TAZ may address unmet needs in psoriatic disease as a therapy for patients with all levels of psoriasis severity who experience daily challenges associated with their disease and that it may be a candidate for treating a variety of forms of psoriasis.

Meeting Patient Expectations of Topical Psoriasis Treatment: Evidence Supporting the Use of Fixed-Combination Halobetasol/Tazarotene Lotion.

Discordance between patient and clinician treatment goals and expectations can present a challenge to implementation of effective therapeutic plans. Because topical treatments are commonly used for plaque psoriasis, both as monotherapy and adjuncts to other treatment modalities, providers need to understand the concerns of patients with psoriasis regarding use of topical products. Psoriasis is a complex and chronic disease with treatment needs that may change over time, influencing patient treatment goals and expectations of efficacy. When these expectations are not met and patient concerns are unaddressed, dissatisfaction may lead to nonadherence, which in turn can prevent patients from achieving relief from the signs and symptoms of psoriasis that affect their quality of life. Here, we detail how current topical treatments meet patient expectations and needs, with particular attention given to combination regimens using corticosteroids. This review shows that once-daily application of halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) not only has a rapid onset of treatment effect and proven efficacy, but also has a remittive effect. In addition, HP/TAZ has a favorable safety profile, with low rates of irritation and local skin reactions in clinical studies. The dual mechanisms of action related to 2 active ingredients, once-daily use, and the favorable clinical findings suggest that HP/TAZ may address patient concerns and promote treatment adherence.J Drugs Dermatol. 2023;22(2):132-138. doi:10.36849/JDD.7367.

Healthcare Provider Experience in Diagnosing and Treating Cutaneous T-Cell Lymphoma.

INTRODUCTION: Cutaneous T-cell lymphoma (CTCL) is a rare, heterogeneous group of non-Hodgkin lymphomas characterized by various clinical, molecular, and histopathologic features of the skin. Variants of CTCL share many clinical features with common inflammatory skin diseases such as atopic dermatitis and psoriasis, making accurate and early diagnosis challenging in clinical settings. Inappropriate treatment or a delay in diagnosis can lead to increased morbidity and mortality. Here, we report findings from an online survey that investigated dermatology community practice, knowledge, and education surrounding CTCL. METHODS: An electronic survey of ten questions was developed and approved by physician experts in CTCL to assess experiences in diagnosing and treating CTCL among healthcare providers (HCPs). The survey was deployed to 10,600 US dermatology HCPs, including medical doctors (MDs), doctors of osteopathic medicine (DOs), nurse practitioners (NPs), and physician assistants (PAs) and excluding HCPs associated with CTCL centers of excellence. RESULTS: Among 44 HCPs who responded and were eligible for inclusion, 82% had diagnosed between one and ten CTCL cases in the last 5 years. Most respondents (91%) reported that they include CTCL in their differential diagnoses after patients do not respond to treatment of more common conditions. Patients with CTCL were frequently diagnosed with other inflammatory dermatoses-most commonly dermatitis and psoriasis-before a CTCL diagnosis, and many were treated with ineffective therapies for years. The most common length of time before a CTCL diagnosis was made was between 1 and 3 years, though 16% of HCPs reported that patients were treated for other diseases or skin conditions for ≥ 5 years. Two-thirds of HCPs agreed that further education surrounding CTCL is needed. CONCLUSIONS: Given the infrequency of CTCL and its similar presentation to other common dermatologic conditions, increased education of CTCL is needed in the dermatology community to improve patient outcomes.

Onset of Plaque Psoriasis Treatment Responses With Anti-IL-17/IL-23 Biologic Therapies.

BACKGROUND: The impact of psoriasis on quality of life arises from both physical symptoms, such as pain and pruritus, and the psychosocial effects of the often highly visible lesions. For patients with moderate-to-severe psoriasis seeking amelioration of these symptoms, time to onset of treatment response is an important consideration when determining an appropriate therapeutic approach with their healthcare provider. METHODS: In this review, we discuss the fluidity of the definition of rapid response and time-to-response expectations of patients with psoriasis receiving biologic therapies. Next, we focus on time to response of brodalumab, a human anti–interleukin-17 receptor A monoclonal antibody, in patients with moderate-to-severe psoriasis, as measured by the psoriasis area and severity index and the psoriasis symptom inventory. Brodalumab previously exhibited efficacy and safety in treatment of moderate-to-severe psoriasis in three phase 3 trials (AMAGINE-1/-2/-3), warranting further characterization of its ability to meet patient needs regarding rapidity of treatment response. Finally, we place time to response of brodalumab in the context of the current treatment landscape of biologic therapies for psoriasis (particularly those targeting the interleukin-17/interleukin-23 axis). RESULTS: Direct and indirect comparisons with other interleukin-targeting drugs support brodalumab’s more rapid onset of treatment effects, including skin clearance and relief of itch and pain. CONCLUSION: Brodalumab induces a rapid treatment response in patients with moderate-to-severe psoriasis and may promote earlier improvements in quality of life. J Drugs Dermatol. 2022;21(8):854-860. doi:10.36849/JDD.6791.

Narrative Review of the Emerging Therapeutic Role of Brodalumab in Difficult-to-Treat Psoriasis.

Psoriatic involvement in areas of the body such as nails, palms and soles (palmoplantar), and scalp is associated with dramatically negative effects on quality of life relative to involvement elsewhere in the body. Although numerous evidence-based studies demonstrate the efficacy of biologics for overall skin clearance in moderate-to-severe plaque psoriasis (including tumor necrosis factor α [TNFα] inhibitors and interleukin [IL]-17A, IL-12/IL-23, IL-23, IL-17F, and IL-17A/F inhibitors), large, randomized, placebo-controlled clinical studies of psoriasis with nail, palmoplantar, and scalp involvement are needed to better inform decision-making in clinical practice. Moreover, biologic failure caused by drug ineffectiveness is a common occurrence in patients who do not respond, lose response, or are intolerant to treatment. Brodalumab is a fully human IL-17 receptor A antagonist that demonstrates high rates of skin clearance among the latest generation of biologic therapies for treatment of moderate-to-severe psoriasis. This review summarizes current literature on the efficacy of brodalumab and other therapies in difficult-to-treat psoriasis including psoriasis in difficult-to-treat locations (such as psoriasis with nail, palmoplantar, or scalp involvement) and psoriasis in patients whose disease did not respond to other biologics.

Long-Term Skin Clearance With Brodalumab in Patients With Psoriasis and Inadequate Response to Prior Biologics.

BACKGROUND: Despite the emergence of multiple biologic drug options for psoriasis, unmet treatment needs remain. Biologic therapies can vary in their effectiveness and adverse events, and many patients experience a loss of treatment effect over time. After lack of response, treatment may be switched to a biologic with a different mechanism of action. Brodalumab, a human interleukin-17 (IL-17) receptor A antagonist, is approved for the treatment of adult patients with moderate-to-severe psoriasis with inadequate response or loss of response to prior systemic therapies. Because brodalumab targets the IL-17 receptor instead of the ligand itself, it not only targets a broader set of IL-17 isoforms but also may be effective in patients who received prior IL-17 inhibitors or failed to respond to anti–IL-17 treatment. This is supported by long-term evidence from clinical trials and real-world studies of patients receiving brodalumab who were previously treated with IL-17 inhibitors. Additionally, brodalumab produces reliable treatment effects after use of biologics with other mechanisms of action, such as tumor necrosis factor α and IL-12/IL-23 inhibitors, as well as after the use of multiple biologic therapies. For patients with psoriasis with inadequate response to one or more biologic therapies, brodalumab is an option that has the ability to lead to long-term skin clearance. J Drugs Dermatol. 2022;21(3):364-370. doi:10.36849/JDD.6743.

Efficacy of brodalumab in the treatment of scalp and nail psoriasis: results from three phase 3 trials.

INTRODUCTION: We evaluated the efficacy of brodalumab in patients with nail or scalp psoriasis in three phase 3 studies (AMAGINE-1/-2/-3). METHODS: In AMAGINE-1, scalp clearance, measured by the psoriasis scalp severity index (PSSI), was reported for patients who received brodalumab 210 mg every 2 weeks (Q2W) or placebo through 12 weeks. In AMAGINE-2/-3, nail clearance, measured by the nail psoriasis severity index (NAPSI), was reported for patients receiving either brodalumab 210 mg Q2W or ustekinumab continuously through 52 weeks. RESULTS: At week 12, significantly more patients receiving brodalumab achieved 75% and 100% improvement rates from baseline PSSI and had lower mean PSSI across 12 weeks compared with placebo, with significant improvement in PSSI evident with brodalumab 210 mg Q2W vs placebo by week 2. Across 52 weeks, patients receiving brodalumab achieved significantly greater complete clearance of nail psoriasis (NAPSI 0), lower mean NAPSI, and higher mean percent improvement rates from baseline NAPSI than patients receiving ustekinumab. At week 52, 63.8% of patients receiving brodalumab achieved NAPSI 0 vs 39.1% of patients receiving ustekinumab. CONCLUSIONS: Brodalumab was associated with clearance of scalp psoriasis through 12 weeks and improvements in nail psoriasis, including complete nail clearance, through 52 weeks.

Posttreatment maintenance of therapeutic effect with fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% lotion for moderate-to-severe plaque psoriasis.

BACKGROUND: The topical corticosteroid halobetasol propionate (HP) and retinoid tazarotene (TAZ) are effective in psoriasis treatment. Fixed-combination HP 0.01%/TAZ 0.045% lotion has demonstrated efficacy and safety in moderate-to-severe plaque psoriasis. OBJECTIVE: To investigate the maintenance of therapeutic effects after cessation of once-daily HP/TAZ treatment. METHODS: In two phase 3 studies (NCT02462070; NCT02462122), adults with moderate-to-severe psoriasis received HP/TAZ for 8 weeks. Data at week 12 were analyzed post hoc to evaluate posttreatment maintenance of treatment success (clear/almost clear skin), improvements in signs of psoriasis (erythema, plaque elevation, scaling), and reductions in affected body surface area (BSA). In a 52-week open-label study (NCT02462083), participants stopped HP/TAZ treatment after achievement of treatment success; data were analyzed post hoc to assess time to retreatment. RESULTS: Across all studies, most participants who achieved treatment success maintained this effect for at least one month posttreatment. Treatment effects were similarly maintained for improvements in signs of psoriasis and reductions in BSA. Some participants continued to improve after cessation of treatment. Maintenance of treatment success and time to retreatment were greater for participants who achieved clear skin. CONCLUSION: HP/TAZ lotion provides therapeutic effects that persist after treatment cessation, supporting its use in long-term management of plaque psoriasis.

Fixed-Combination Halobetasol Propionate/Tazarotene Lotion for Psoriasis in Patients With 3%-5% Affected Body Surface Area.

INTRODUCTION: Patients with psoriasis and low body surface area (BSA) involvement often experience substantially reduced quality of life and may be candidates for topical therapies. Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) vs vehicle lotion was evaluated in participants with 3% to 5% BSA involvement. METHODS: In two phase 3, multicenter, double-blind, vehicle-controlled, 8-week studies (ClinicalTrial.gov identifiers: NCT02462070/NCT02462122), adults with moderate/severe investigator’s global assessment (IGA) score were randomized 2:1 to once-daily HP/TAZ or vehicle. Pooled post hoc analyses included participants with baseline BSA involvement of 3% to 5%. Measures included treatment success (≥2-grade IGA reduction, clear/almost clear score), reduction in affected BSA, and clinically meaningful improvement (reduction) of ≥4 points on dermatology life quality index (DLQI). RESULTS: Of 418 participants, 232 had baseline BSA involvement of 3% to 5% (HP/TAZ, n=149; vehicle, n=83). At week 8, 42.7% of HP/TAZ-treated participants achieved treatment success, compared with 11.4% of vehicle-treated participants (P< .001). Participants experienced significantly greater reductions in affected BSA at week 8 with HP/TAZ (-36.0%) vs vehicle (-1.6%; P< .001). Larger proportions experienced clinically meaningful DLQI improvements at week 8 with HP/TAZ (64.2%) vs vehicle (47.4%; P< .05). More participants achieved a ≥2-grade improvement in plaque elevation and scaling with HP/TAZ vs vehicle (each comparison, P< .001). Serious adverse events and discontinuations due to treatment-emergent adverse events were rare. CONCLUSIONS: In participants with plaque psoriasis and BSA involvement of 3% to 5%, HP/TAZ provided significantly improved effectiveness after 8 treatment weeks vs vehicle lotion, with clinically meaningful improvements in quality of life. J Drugs Dermatol. 2021;20(8):829-836. doi:10.36849/JDD.6217.

Three-year U.S. pharmacovigilance report of brodalumab.

Brodalumab, an interleukin-17 receptor A antagonist, is approved for treatment of moderate-to-severe plaque psoriasis in adults without response or with loss of response to other systemic therapies. In the United States, there is a boxed warning for brodalumab regarding suicidal ideation and behavior; however, no causal relationship between brodalumab and suicidality was established during pivotal trials. In the 2-year pharmacovigilance data, no completed suicides or suicide attempts were reported. The most frequent adverse event (AE) was arthralgia. The safety profile of brodalumab is now being updated after 3 years of pharmacovigilance data. Here, we outline pharmacovigilance data reported to Ortho Dermatologics by patients and healthcare professionals in the United States from August 15, 2017, to August 14, 2020. Brodalumab exposure estimates were obtained by calculating the time between first and last prescription-dispensing authorization dates. Data from 1854 patients were collected, and brodalumab exposure was estimated to be 2736 patient-years. The most frequent AE was arthralgia (111 events; 0.04 events per patient-year). One episode of suicide attempt was reported in a patient with a history of depression. No completed suicides were reported. There were 81 serious infections reported, none of which were fungal. Over the 3-year period, 30 malignancies occurred in 25 patients, none of which were determined to be related to brodalumab. Three-year pharmacovigilance data are consistent with the safety profile of brodalumab previously reported in long-term analyses of clinical trials and the 2-year pharmacovigilance data.

Fixed-Combination Halobetasol Propionate and Tazarotene Lotion for Psoriasis in Patients With Skin of Color.

BACKGROUND: Few studies have examined topical psoriasis therapies in patients with skin of color. Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) was investigated in two phase 3, multicenter, double-blind, vehicle-controlled trials (NCT02462070; NCT02462122). This post hoc analysis evaluated HP/TAZ in subgroups of non-White and White participants, including Hispanic/Latino participants, from these trials. METHODS: Adult participants were randomized (2:1) to receive HP/TAZ or vehicle lotion once daily for 8 weeks. Data were pooled and analyzed in non-mutually exclusive subgroups of self-identified non-White or White and Hispanic/Latino participants. Efficacy assessments included treatment success (≥2-grade improvement from baseline in investigator’s global assessment [IGA] and score of clear/almost clear), reduction from baseline in affected body surface area (BSA), and reduction in mean IGA × BSA. Safety was evaluated via treatment-emergent adverse events (TEAEs). RESULTS: Of 418 participants, 60 and 358 self-identified as non-White and White, respectively; 115 of 418 participants self-identified as Hispanic/Latino. At week 8, a higher percentage of HP/TAZ-treated participants achieved treatment success vs vehicle (non-White, 34.4% vs 19.0%; White, 41.8% vs 8.7%; Hispanic/Latino, 39.3% vs 9.3%); rates for White and Hispanic/Latino participants were statistically significant. Compared with vehicle, HP/TAZ-treated participants in each subgroup experienced numerically greater reductions in affected BSA and IGA × BSA at week 8. The most common TEAEs were contact dermatitis, pruritus, nasopharyngitis, and application-site pain; discontinuations due to TEAEs were few. CONCLUSIONS: HP/TAZ reduced disease severity in non-White, White, and Hispanic/Latino participants with psoriasis, with good tolerability and safety over 8 weeks of treatment. J Drugs Dermatol. 2021;20(7):735-744. doi:10.36849/JDD.6158.

Fixed-Combination Halobetasol Propionate and Tazarotene in the Treatment of Psoriasis: Narrative Review of Mechanisms of Action and Therapeutic Benefits.

Psoriasis is a lifelong disease associated with cycles of remission and relapse. Topical treatments are the front line of psoriasis therapy for most patients and have antiproliferative, anti-inflammatory, and immunosuppressive mechanisms of action. Novel fixed-dose combinations of topical therapeutic agents are becoming increasingly available, leveraging multiple mechanisms of action to improve safety and efficacy with formulations that are easier to use and may allow for the use of lower doses of active ingredients. A fixed-combination lotion containing the potent-to-superpotent corticosteroid halobetasol propionate (HP) and the retinoid tazarotene (HP 0.01%/TAZ 0.045%) was recently developed using polymeric emulsion technology. This new formulation technology allows for more uniform and efficient delivery of the active ingredients at lower doses than conventional monotherapy formulations of either ingredient while providing enhanced hydration and moisturization. This review provides an up-to-date overview of the therapeutic mechanisms of action of HP and TAZ, the rationale behind the development of HP 0.01%/TAZ 0.045% lotion, and clinical trials data on the efficacy, safety and tolerability, and maintenance of therapeutic effect with HP 0.01%/TAZ 0.045% lotion in the treatment of moderate-to-severe plaque psoriasis.

Once-Daily Halobetasol Propionate 0.01% Lotion for Moderate-to-Severe Plaque Psoriasis: Phase 3 Analysis of Hispanic Participants.

BACKGROUND: Psoriasis is a chronic, inflammatory disease that may differ in prevalence and clinical presentation among patients from various racial and ethnic groups. Two phase 3 studies demonstrated efficacy and safety of halobetasol propionate (HP) 0.01% lotion in the treatment of moderate-to-severe plaque psoriasis (NCT02514577, NCT02515097). These post hoc analyses evaluated HP 0.01% lotion in Hispanic participants. METHODS: Participants were randomized (2:1) to receive once-daily HP or vehicle lotion for 8 weeks, with a 4-week posttreatment follow-up. Post hoc efficacy assessments in Hispanic participants (HP, n=76; vehicle, n=43) included treatment success (≥2­grade improvement in Investigator’s Global Assessment and score of ‘clear’ or ‘almost clear’), psoriasis signs, and affected body surface area (BSA). Treatment-emergent adverse events (TEAEs) were evaluated. RESULTS: At week 8, 38.8% of participants achieved treatment success with HP versus 10.3% on vehicle (P=0.001). HP­treated participants achieved greater improvements in psoriasis signs, compared with vehicle (P<0.01 all). HP group had a greater reduction in affected BSA versus vehicle (P=0.001). Treatment-related TEAEs with HP were application site infection and dermatitis (n=1 each). CONCLUSIONS: Once-daily HP 0.01% lotion was associated with significant reductions in disease severity in Hispanic participants with moderate-to-severe psoriasis, with good tolerability and safety over 8 weeks. J Drugs Dermatol. 2021;20(3):252-258. doi:10.36849/JDD.5698.

Two-Year US Pharmacovigilance Report on Brodalumab.

INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. In the United States, brodalumab carries a boxed warning about suicidal ideation and behavior; however, no causal association was established between brodalumab and suicides reported during pivotal trials. We have previously reported results from an analysis of 1-year pharmacovigilance data in patients in the United States who took brodalumab, in which the most commonly reported adverse event was psoriasis flare. There were no completed suicides, suicide attempts, or serious fungal infections. Here, we provide a 2-year US pharmacovigilance report. METHODS: This analysis summarizes pharmacovigilance data reported to Ortho Dermatologics by US patients and healthcare providers from August 15, 2017, through August 14, 2019. The most common adverse events listed in the brodalumab package insert (incidence ≥ 1%; arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and tinea infections) and adverse events of special interest are reported. RESULTS: Data were collected from 2677 patients in the United States who took brodalumab, with an estimated exposure of 1656 patient-years. Arthralgia was the most commonly reported adverse event (73 events; 0.04 events per patient-year). No suicide attempts or completed suicides were reported; there were 25 reports of depression. There were 46 serious infections and no serious fungal infections. One event of Crohn's disease was reported, which led to discontinuation. There were 13 malignancies, with none deemed related to brodalumab. CONCLUSIONS: This pharmacovigilance report supports the safety profile of brodalumab previously reported from long-term analyses of clinical trials and 1-year pharmacovigilance data.