Recurrent giant cellulitis-like Sweet syndrome induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine.

Primary and booster vaccines for SARS-CoV-2 are the most effective methods of preventing infection and are generally considered safe. However, many cutaneous adverse events have been reported following vaccination. To date, there have been seven reported cases of Sweet syndrome occurring after the first dose of the SARS-CoV-2 vaccine. We describe a rare case of atypical giant-cellulitis like Sweet syndrome reemerging after receiving the SARS-CoV-2 booster vaccine.

Pityriasis Lichenoides-Like Mycosis Fungoides: A Case Report.

A rare subtype of mycosis fungoides (MF) known as pityriasis lichenoides-like mycosis fungoides (PL-like MF) manifests as recurrent crops of erythematous scaly papules with the histological findings of MF. We report a 64-year-old male with recurrent crops of psoriasiform papules with mild scales on his trunk and extremities. Skin biopsy results were consistent with CD8+ cutaneous T-cell lymphoma (CTCL). Our patient had clinical features of pityriasis lichenoides and histological findings consistent with CD8+ MF. A differential diagnosis of PL, lymphomatoid papulosis (LyP), and PL-like MF was considered. Counseling patients with CD8+ cutaneous T-cell lymphoma can be challenging, as there is an aggressive variant named primary cutaneous aggressive epidermotropic CD8+ CTCL. However, with the ability to recognize PL-like MF, a rare indolent type of CD8+ CTCL, physicians can counsel patients appropriately.

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.

Consistent response to guselkumab treatment between Hispanic and non-Hispanic patients with psoriasis: an analysis from VOYAGE 1 and VOYAGE 2.

INTRODUCTION: In VOYAGE 1 (NCT02207231) and VOYAGE 2 (NCT02207244), guselkumab, an interleukin-23 blocker, was safe and effective in patients with moderate-to-severe plaque psoriasis. METHODS: Patients who self-identified as Hispanic (n = 117) or non-Hispanic (n = 1686) were randomized to guselkumab, placebo, or adalimumab. Efficacy assessments included Psoriasis Area and Severity Index (PASI), Investigator's Global Assessment (IGA), and Dermatology Life Quality Index (DLQI). RESULTS: At week 16, treatment differences for guselkumab versus placebo in the Hispanic and non-Hispanic populations were 67.4 (95% confidence interval 50.4, 84.4) and 77.2 (73.5, 80.8) percentage points for IGA 0/1 and 59.2 (41.9, 76.4) and 69.2 (65.7, 72.7) percentage points for PASI 90, respectively. Treatment differences for guselkumab versus adalimumab were 25.9 (6.5, 45.3) and 17.5 (12.8, 22.3) percentage points for IGA 0/1 and 21.4 (-0.1, 42.9) and 23.5 (18.2, 28.9) percentage points for PASI 90, respectively. Week 24 results were similar. Adverse event frequency was greater in adalimumab- versus guselkumab-treated patients in the Hispanic population only through weeks 16 and 28. In both populations, DLQI 0/1 responses were greater in guselkumab-treated versus placebo- and adalimumab-treated patients at week 16 and versus adalimumab-treated patients at week 24. CONCLUSIONS: Guselkumab safety and efficacy were consistent between Hispanic and non-Hispanic populations.

Emerging drugs for the treatment of hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a severe, chronic inflammatory disorder that causes recurrent occlusion of hair follicles in the intertriginous regions of the skin. Mild to moderate HS has been successfully treated with oral antibiotics, topical therapy, and lifestyle modifications. However, moderate to severe HS is known to be refractory to conventional treatments. Wide excision surgery is a treatment option for severe HS, but often leads to functional impairments. Additionally, recurrence is common. The proper management of moderate to severe HS continues to be a challenge to practitioners. AREAS COVERED: A comprehensive literature search was conducted to identify published HS treatments using PubMed databases, in addition, ongoing studies were sought in clinicaltrials.gov. Search terms included 'hidradenitis suppurativa,' 'treatment,' and 'management.' EXPERT OPINION: Although adalimumab is currently the only biologic approved by the United States Food and Drug Administration for treatment of HS, there are many studies underway involving the development of drugs with a variety of immunological targets. Those potential HS therapies in either Phase II or Phase III trials show much promise. Since HS is a complicated disease that involves both pathological and environmental factors, treating HS continues to involve a multidisciplinary approach and monotherapy tends to not be efficacious.

Baseline Characteristics from UNITE: An Observational, International, Multicentre Registry to Evaluate Hidradenitis Suppurativa (Acne Inversa) in Clinical Practice.

BACKGROUND: Hidradenitis suppurativa (HS), also known as acne inversa, is a recurring, painful, chronic, and sometimes disfiguring inflammatory skin disease. OBJECTIVES: Our objective was to report the baseline clinical characteristics, natural history, and associated outcomes of patients with HS from the ongoing, prospective, non-interventional UNITE registry that is collecting data regarding the natural history and associated outcomes of HS. METHODS: Patients with inflammatory HS lesions were enrolled, including adolescents (aged 12 to < 18 years) and adults (aged ≥ 18 years). None had participated in previous or current originator-adalimumab studies/registries. Patients received treatment consistent with site-specific, routine clinical practice. HS disease status was assessed by HS lesions and disease flare; treatment and outcomes data were collected at enrolment and every 6 months for ≤ 4 years. RESULTS: Enrolment (N = 594; 89.1% adults; 10.9% adolescents) occurred from 29 October 2013 to 29 December 2015 at 73 sites in 12 countries. At baseline, the majority were female (69.7%) and White (81.2%), had moderate-to-severe disease (Hurley stage II or III; 93.3%), and had undergone prior procedures/surgery for HS (68.7%). In total, 61.6% of adults and 49.2% of adolescents were obese; 40.2% of patients reported current tobacco use. Scarring due to lesions occurred in 91.2% of patients. The prevalence of comorbidities of interest was as follows: depression (13.3%), other psychiatric disorders (9.6%), inflammatory bowel disease (2.7%), diabetes (9.1%), and polycystic ovary syndrome (5.2%). CONCLUSIONS: In this population from the UNITE HS registry, obesity and smoking were common, and disease burden was high, manifesting as multiple lesions, scarring, surgical history, and considerable comorbidities.

A Phase II Open-Label Study of Bermekimab in Patients with Hidradenitis Suppurativa Shows Resolution of Inflammatory Lesions and Pain.

The objective of this study was to evaluate the safety and efficacy of bermekimab, an IL-1α inhibitor, in the treatment of hidradenitis suppurativa (HS). This study was a phase II, multicenter, open-label study of two dose cohorts of bermekimab in patients with moderate-to-severe HS who are naïve to or have failed prior anti-TNF therapy. Patients with HS (n = 42) were divided into groups A and B based on whether or not they had previously failed an anti-TNF therapy. In group A (n = 24), bermekimab was administered subcutaneously at a dose of 400 mg weekly (13 doses) in patients who had previously failed anti-TNF therapy; in group B (n = 18), bermekimab was administered subcutaneously at a dose of 400 mg weekly (13 doses) in patients who were anti-TNF naïve. Bermekimab, previously found to be effective in treating HS, was evaluated using a subcutaneous formulation in patients with HS naïve to or having failed anti-TNF therapy. There were no bermekimab-related adverse events with the exception of injection site reactions. Bermekimab was effective despite treatment history, with 61% and 63% of patients naïve to and having failed anti-TNF therapy, respectively, achieving HS clinical response after 12 weeks of treatment. A significant reduction in abscesses and inflammatory nodules of 60% (P < 0.004) and 46% (P < 0.001) was seen in anti-TNF naïve and anti-TNF failure groups, respectively. Clinically and statistically significant reduction was seen in patients experiencing pain, with the Visual Analogue Scale pain score reducing by 64% (P < 0.001) and 54% (P < 0.001) in the anti-TNF naïve and anti-TNF failure groups, respectively. IL-1α is emerging as an important clinical target for skin disease, and bermekimab may represent a new therapeutic option for treating moderate-to-severe HS.

Lichenoid drug eruption after treatment with ixekizumab for plaque psoriasis.

Lichen Planus (LP), the prototype of lichenoid dermatoses, is an idiopathic, T cell-mediated, autoimmune, inflammatory disease. It may affect the skin, hair, nails, and mucous membranes. Many clinical variants of LP have been described, including lichenoid drug eruption or drug induced LP, associated with a myriad of culprit medications. We describe a 63-year-old woman with longstanding psoriasis effectively controlled with ixekizumab, who developed lichenoid drug eruption . Her lichen planus lesions improved after treatment discontinuation and the patient was started on an IL23 inhibitor to treat her psoriasis through an alternative mechanism of action. Our report adds to the literature and provides insight into the complex pathophysiology of lichen planus.

Multiple Facial Lesions of Recalcitrant Pyoderma Gangrenosum Successfully Treated with Adalimumab.

Pyoderma gangrenosum (PG) is a rare, ulcerative, inflammatory skin disease that most commonly presents on the lower legs. Development of PG on the head and neck is exceedingly rare. We present the case of a 52-year-old man with no known history of underlying systemic disease who developed multiple facial lesions of PG that were refractory to both standard and alternative treatment modalities. Clearance of disease was ultimately achieved using adalimumab.

Apremilast for the Treatment of Mild-to-Moderate Hidradenitis Suppurativa in a Prospective, Open-Label, Phase 2 Study

Background: Treatment options are limited for patients with hidradenitis suppurativa (HS). Apremilast, an oral phosphodiesterase 4 inhibitor, may offer an attractive therapeutic option for patients with mild-to-moderate HS. Methods: This open-label, phase 2 clinical trial enrolled adults (≥18 years of age) with mild-to-moderate HS. Patients received apremilast 30mg twice daily for 24 weeks after a 5-day titration period. Therapy was discontinued at week 24; data were collected up to week 28. Hidradenitis Suppurativa Clinical Response 30 (HiSCR30), ie, proportion of patients with a ≥30% reduction in abscesses and nodules at week 16, was the primary endpoint. HiSCR50, ie, ≥50% reduction, was also explored. Mean changes from baseline to week 24 in the modified Sartorius, Physician's Global Assessment, visual analog scale (VAS) for pain, and Dermatology Life Quality Index (DLQI) scores were analyzed using the Wilcoxon Rank-Sum test. Adverse events (AEs) were summarized. Results: Twenty patients (mean age, 32.5 years) were enrolled in the study. HiSCR30 was achieved in 65% of patients at weeks 16 and 24. A similar proportion of patients achieved HiSCR50. Significant mean improvements from baseline were observed for all assessments. At week 24, the overall Sartorius score improved from 35.6 to 13.9 (-21.7 change; P<0.001), the PGA score from 2.7 to 1.6 (-1.1 change; P<0.01), the VAS pain score from 27.6 to 10.9 (-16.8 change; P<0.05), and the DLQI score from 11.6 to 5.4 (-6.2 change; P<0.01). Diarrhea (20%), nausea (15%), and depression (10%) were the most commonly reported AEs. No serious AEs or deaths were reported. Conclusions: Apremilast was safe and effective in improving HS disease activity, pain, and QoL in patients with mild-to-moderate HS. These data suggest that apremilast may have a role in the early treatment of less severe HS. J Drugs Dermatol. 2019;18(2):170-176.

A phase 2, multicenter, double-blind, randomized, vehicle-controlled clinical study to compare the safety and efficacy of a halobetasol propionate 0.01% lotion and halobetasol propionate 0.05% cream in the treatment of plaque psoriasis.

Background: Halobetasol propionate (HP) 0.05% is a highly effective short-term treatment for plaque psoriasis. Objective: Compare efficacy and safety of once-daily HP 0.01% lotion and 0.05% cream (Ultravate®) in moderate-to-severe psoriasis. Methods: Multicenter, randomized, double-blind, vehicle-controlled Phase 2 study (N = 150). Patients randomized to HP 0.01% lotion, HP 0.05% cream, or vehicle, once-daily for 2 weeks. Efficacy assessments included treatment success; impact on erythema, plaque elevation, and scaling; and improvement in body surface area (BSA). Safety and treatment-emergent adverse events (TEAEs) were evaluated throughout. Results: 30.0% and 31.6% of patients were treatment successes with HP 0.01% lotion and HP 0.05% cream (p = .854). A 2-grade improvement in erythema, plaque elevation and scaling was achieved in 38.3%, 40.0%, and 43.3% of patients, compared with 31.6% (p = .446), 36.8% (p = .727), and 47.4% (p = .663) on HP 0.05% cream. BSA improved by 22.3% with HP 0.01% lotion compared with 20.9% (p = .787). There was one treatment-related application-site reaction with HP 0.01% lotion, and no AE reports of skin atrophy, striae, telangiectasia, or folliculitis. Conclusions: Halobetasol propionate 0.01% lotion was comparable to the higher concentration halobetasol propionate 0.05% cream; achieving treatment success, reducing psoriasis signs at the target lesion, and improving BSA following two weeks' daily-treatment. Both treatments were well-tolerated. Clinical Trials Registration: clinicaltrials.gov NCT02785185.

Safety and Efficacy of a Once-Daily Halobetasol Propionate 0.01% Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis: Results of Two Phase 3 Randomized Controlled Trials.

BACKGROUND: Topical corticosteroids (TCS) are the mainstay of psoriasis treatment; long-term safety concerns limiting consecutive use of potent TCS to 2-4 weeks. OBJECTIVE: Investigate safety and efficacy of halobetasol propionate 0.01% lotion in moderate-to-severe plaque psoriasis. METHODS: Two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N=430). Subjects randomized (2:1) to halobetasol propionate 0.01% lotion or vehicle once-daily for 8 weeks, 4-week posttreatment follow-up. Primary efficacy assessment: treatment success (at least a 2-grade improvement from baseline in Investigator Global Assessment [IGA] score and 'clear' or 'almost clear') at week 8. Safety and treatment emergent adverse events (AEs) evaluated throughout. RESULTS: Halobetasol propionate 0.01% lotion demonstrated statistically significant superiority over vehicle as early as week 2. By week 8, 36.5% (Study 1) and 38.4% (Study 2) of subjects were treatment successes compared with 8.1% and 12.0% on vehicle (P less than 0.001). Halobetasol propionate 0.01% lotion was also superior in reducing psoriasis signs and symptoms, body surface area (BSA), and improving quality of life. Halobetasol propionate 0.01% lotion was well-tolerated with no treatment-related AEs greater than 1%. LIMITATIONS: Study did not include subjects with BSA greater than 12. CONCLUSIONS: Halobetasol propionate 0.01% lotion was associated with significant reductions in the severity of the clinical signs of psoriasis, without the safety concerns of a longer treatment course. J Drugs Dermatol. 2018;17(10):1062-1069.

The Importance of Early Treatment in Psoriasis and Management of Disease Progression.

Psoriasis is a chronic, immune-mediated, inflammatory disease that if left untreated can result in prolonged subclinical inflammation that affects a variety of organs, including the heart, liver, kidney, and intestines, as well as joints and muscles. Relatedly, psoriasis significantly increases patients' risks for developing certain comorbidities. Disease progression in psoriasis is unpredictable, and some patients have mild disease that is stable for many years, while in others, mild disease quickly progresses to moderate-to-severe psoriasis. Adding to the complexity of this disease, subclinical systemic inflammation is present in patients with either mild or moderate-to-severe psoriasis. In this review, key factors in psoriasis progression, including the role that systemic inflammation has in psoriasis pathogenesis and the development of comorbidities, are highlighted along with the ability of various therapies to potentially stop or slow the progression of psoriasis and its associated comorbidities. Additionally, practical guidance is provided for physicians regarding treatment and monitoring of disease progression based on psoriasis severity and the risk of comorbidities. J Drugs Dermatol. 2018;17(7):737-742.

Evaluation of Risk of Major Adverse Cardiovascular Events With Biologic Therapy in Patients With Psoriasis.

BACKGROUND: Psoriasis is associated with increased risk of major adverse cardiovascular events (MACE). OBJECTIVES: Compare MACE risk with biologics vs topical/phototherapy use. METHODS: Psoriasis Longitudinal Assessment Registry (PSOLAR) is an international psoriasis registry of patients eligible to receive biologic/systemic treatments prospectively. MACE is defined as myocardial infarction, stroke, or cardiovascular death. Biologic cohorts, including tumor necrosis factor-alpha (TNF-α) inhibitors (ie, adalimumab, etanercept, and infliximab) and ustekinumab, combined and by class, were compared with a topical/phototherapy cohort. Incidence rates of MACE per 100-patient-years (100PY) with 95% confidence intervals (95% CI) are reported. Multivariate analyses were performed to evaluate the effect of treatment on the risk of MACE adjusting for confounders. RESULTS: Analyses included 7550 patients: 6767 in the combined biologics cohort (3949 and 2818 in the TNF-α inhibitors and ustekinumab cohorts, respectively) and 783 in the topical/phototherapy cohort. Mean duration of exposure was approximately 2.8 years (combined biologics) and 4.1 years (topical/phototherapy). A total of 52 MACE were reported; MACE incidence rates were 0.22/100PY (95% CI: 0.16, 0.30) for the combined biologics cohort (TNF-α inhibitors [0.20/100PY (0.12, 0.31)] and ustekinumab [0.24/100PY (0.15, 0.37]) and 0.34/100PY (0.17, 0.61) for the topical/phototherapy cohort. For the combined biologics (hazard ratio=0.92; 95% CI [0.426, 1.988]), TNF-α inhibitor (0.85 [0.373, 1.928]), and ustekinumab (1.03[0.440, 2.402]) cohorts, treatment was not associated with increased risk of MACE versus the topical/phototherapy cohort. CONCLUSION: Based on data accumulated to date in PSOLAR, treatment with biologics did not have an impact on the risk of MACE in patients with moderate-to-severe psoriasis.

J Drugs Dermatol. 2017;16 (10):1002-1013.

Long-Term Safety and Effectiveness of Adalimumab for Moderate to Severe Psoriasis: Results from 7-Year Interim Analysis of the ESPRIT Registry.

INTRODUCTION: ESPRIT (NCT00799877) is an ongoing 10-year international prospective observational registry evaluating the long-term safety and effectiveness of originator adalimumab in routine clinical practice for adult patients with chronic plaque psoriasis. Herein, we report the long-term safety, effectiveness, and patient-reported outcomes (PROs) following adalimumab treatment over the first 7 years of the ESPRIT registry. METHODS: All treatment-emergent (All-TE) adverse events (AE) since the initial (first ever) dose of adalimumab were assessed. Physician Global Assessment (PGA) and PROs (PROs for US patients only) were evaluated during registry participation. RESULTS: As of 30 November 2015, 6051 patients in the ESPRIT registry were analyzed, representing 23,660.1 patient-years (PY) of overall adalimumab exposure. The incidence rates for All-TE serious AEs, serious infections, and malignancies were 4.4, 1.0, and 1.0 events per 100 PY (E/100PY), respectively. The standardized mortality ratio for TE deaths in the registry was 0.27 (95% CI 0.18-0.38). During the registry's first 7 years, PGA "clear" or "minimal" was achieved by >50% of patients at each annual visit, and among US patients, the mean improvement from baseline in different PROs was maintained. CONCLUSION: No new safety signals were identified during the first 7 years of the registry, and safety was consistent with the known safety profile of adalimumab. The number of TE deaths was below the expected rate. During the registry's first 7 years, most of the patients remained free of All-TE cardiovascular events, serious infections, and malignancy. As-observed effectiveness of adalimumab and improvements from baseline in PROs were maintained through 7 years of registry participation. FUNDING: Abbvie. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00799877.