Efficacy and safety of guselkumab compared with placebo and adalimumab in Korean patients with moderate-to-severe psoriasis: post-hoc analysis from the phase III, double-blind, placebo- and active-comparator-controlled VOYAGE 1/2 trials.

BACKGROUND: The phase 3 studies, VOYAGE 1 and 2, were conducted to assess guselkumab in the treatment of patients with moderate-to-severe psoriasis. OBJECTIVES: To investigate the efficacy and safety of guselkumab in Korean patients. METHODS: The Korean sub-population of VOYAGE 1 and 2 study patients were included in this analysis. Efficacy and safety were evaluated through Weeks 24 and 28, respectively. RESULTS: Of 126 randomized Korean patients, 30, 63, and 33 received placebo, guselkumab, and adalimumab, respectively. At Week 16, guselkumab was superior to placebo in achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (cleared or minimal; 90.5 vs. 20.0%, p<.001) and a Psoriasis Area and Severity Index (PASI) 90 response (71.4 vs. 3.3%, p<.001). At week 24, a significantly higher proportion of guselkumab-treated patients achieved PASI 75 and IGA 0 (clear skin) responses compared to adalimumab-treated patients (PASI 75: 93.7 vs. 66.7%, p<.001; IGA 0: 52.4 vs. 21.2%, p=.004). Through Week 28, guselkumab and adalimumab showed comparable safety profiles. CONCLUSION: The efficacy and safety of guselkumab in Korean psoriasis patients through 28 weeks were consistent with findings for the overall VOYAGE 1 and 2 study population.

Efficacy and safety of brodalumab in the Korean population for the treatment of moderate to severe plaque psoriasis: A randomized, phase III, double-blind, placebo-controlled study.

Psoriasis, a chronic inflammatory skin disease, negatively impacts patients' quality of life (QoL). This randomized, phase III, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of brodalumab, a human anti-interleukin-17 receptor A monoclonal antibody, in Korean patients with moderate to severe plaque psoriasis. Coprimary end-points were the percentage of patients with 75% or more improvement in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment (sPGA) success (score 0/1) at week 12. Secondary end-points included the percentage improvement from baseline in PASI score and proportion of patients with PASI 50/75/90/100 responses. QoL was assessed with the Dermatology Life Quality Index (DLQI). Eligible patients were randomized to receive brodalumab 210 mg (N = 40) or placebo (N = 22) every 2 weeks (Q2W) at a 2:1 ratio for 12 weeks. Subsequently, all patients entered an open-label extension phase and received brodalumab 210 mg Q2W until week 62. At week 12, the proportion of patients who achieved the coprimary end-points, PASI 75 and sPGA success, was significantly higher in the brodalumab 210 mg Q2W group compared with the placebo group (92.5% vs 0%). At week 12, the mean ± SD percentage improvement in the PASI score was 96.87 ± 6.01% in the brodalumab 210 mg Q2W group, which was maintained until study end (week 64). PASI 50/75/90 responses were achieved by 100% of patients receiving brodalumab 210 mg Q2W at weeks 6, 13, and 24, respectively; PASI 100 was achieved by 82.8% of patients at week 64. Brodalumab treatment rapidly improved DLQI scores. The most common treatment-emergent adverse events were nasopharyngitis, upper respiratory tract infections, tinea pedis, and urticaria. Overall, treatment with brodalumab 210 mg Q2W resulted in a rapid and significant clinical benefit and was well tolerated in patients with moderate to severe plaque psoriasis in Korea.

Duration of Oral Antibiotics Administration for Cetuximab-Induced Acneiform Eruption.

BACKGROUND: Acneiform eruption is the most common cutaneous adverse event associated with cetuximab. As it can affect quality of life and adversely affect chemotherapy schedule, additional medical care is required. OBJECTIVES: To investigate the adherence to and the duration of antibiotic administration to treat cetuximab-induced acneiform eruption. METHODS: Medical data of patients who were referred to the Department of Dermatology were reviewed from January 2013 to June 2018. Dermatologists assessed the severity of acneiform eruption and prescribed tetracycline-class antibiotics according to the severity every 2 or 4 weeks. We investigated the duration and amount of oral antibiotic administration and analyzed the factors that may affect the control of acneiform eruption statistically. RESULTS: A total of 207 of 267 patients referred to the Department of Dermatology showed acneiform eruption; 124 patients were treated with minocycline, 34 patients with doxycycline, 27 patients with both, and 22 patients with topical agents. The mean duration of oral antibiotic medication was 82.7 days. A statistical analysis of the factors that prolonged the use of antibiotics for more than 90 days showed that male and younger age were risk factors. Shorter time interval from starting cetuximab to starting antibiotics was associated with longer duration of antibiotic use, statistically. CONCLUSIONS: Cetuximab-induced acneiform eruption can be well controlled with tetracycline-class antibiotics in about 3 months. It can last longer in male and younger patients. The sooner and the more severe it appears, the longer it can last.

Secukinumab demonstrates superior efficacy and a faster response in clearing skin in Asian subjects with moderate to severe plaque psoriasis compared with ustekinumab: Subgroup analysis from the CLEAR study.

The 52-week results from the CLEAR (NCT02074982) study showed high and superior efficacy of secukinumab versus ustekinumab in clearing skin and improving patient-reported outcomes, with comparable safety profile in subjects with moderate to severe psoriasis. Here, we analyzed the efficacy and safety of secukinumab in Asian subjects from the CLEAR study. In this double-blind, phase IIIb study, eligible subjects with moderate to severe plaque psoriasis were randomized (1:1) to receive s.c. injection of secukinumab 300 mg or ustekinumab as per label. Of 62 subjects included in Asian subanalyses, 23 were randomized to secukinumab and 39 to ustekinumab. A significantly higher proportion of subjects achieved 90% or more improvement in Psoriasis Area and Severity Index (PASI 90) with secukinumab versus ustekinumab at week 16 (78.3% vs 35.9%, P = 0.0010) and at week 52 (60.9% vs 33.3%, P = 0.0196). Similarly, a higher proportion of subjects achieved PASI 100 with secukinumab versus ustekinumab at week 16 (43.5% vs 10.3%, P = 0.0029) and at week 52 (30.4% vs 12.8%, P = 0.0704). The median time to achieve 50% improvement in baseline PASI was 2.8 weeks in the secukinumab group versus 6.3 weeks in the ustekinumab group. The safety profile of secukinumab was in line with the known profile and no deaths occurred. Overall, 95.7% and 84.6% of subjects remained on secukinumab and ustekinumab, respectively. Similar to the core study, secukinumab showed sustained and superior efficacy with faster response versus ustekinumab, and no new or unexpected safety concerns were identified, in Asian subjects with moderate to severe plaque psoriasis.

Usefulness of the Psoriatic Arthritis Screening and Evaluation Questionnaire to Monitor Disease Activity in Management of Patients with Psoriasis: Findings from the EPI-PSODE Study.

BACKGROUND: Psoriasis and psoriatic arthritis (PsA) are included in the group of immune-mediated inflammatory diseases (IMIDs) caused by systemic inflammation; however, indicators for monitoring inflammatory activity in patients with psoriasis, such as the Psoriasis Area and Severity Index (PASI), are limited. OBJECTIVE: To determine whether the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire can be used to monitor disease activity in patients with psoriasis. METHODS: This was a multicenter, noninterventional, cross-sectional study. Demographic factors and PASI and PASE scores were collected to investigate associations between each. RESULTS: PASE data were available for 1,255 patients, of whom 498 (39.7%) had a score of ≥37. Compared with the group with PASE score <37, the group with score ≥37 had a higher proportion of women (34.9% vs. 48.8%, p<0.0001), older mean age at diagnosis (36.4 vs. 41.7 years, p<0.0001), more severe disease activity using PASI and body surface area measures (p=0.0021 and p=0.0008, respectively), and higher mean body mass index (23.7 vs. 24.1, p=0.0411). In a multiple linear regression model, PASE score was positively associated with cutaneous disease activity (p<0.0001). CONCLUSION: After risk-adjustment, PASE was positively associated with PASI, which suggests that PASE can be sensitive to disease activity. Since psoriasis is regarded as one of the IMIDs, PASE may be utilized as a tool not only to screen PsA but also to monitor disease activity.

Olmutinib Induced Lichen Planus Like Eruption.

Drug induced lichen planus like eruption is an uncommon cutaneous adverse effect of several drugs. This appears symmetric eruption of erythematous or violaceous plaques resembling lichen planus on the trunk and extremities. A 50-year-old male presented with scaly, violaceous plaques and dusky brown macules on whole body. For four months, the patient was treated with olmutinib, an oral, third-generation epidermal growth factor receptor-tyrosine kinase inhibitor. In May 2016, olmutinib received its first global approval in South Korea for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer. The biopsy specimen from the patient showed features of lichen planus. We diagnosed him with olmutinib-induced lichen planus like eruption. He was treated with oral methylprednisolone and topical desoxymethasone 0.25% ointment. At the same time, olmutinib dose was decreased to three-fourths of this patient's starting dose. After that, the cutaneous lesions improved.

The Clinical Profile of Patients with Psoriasis in Korea: A Nationwide Cross-Sectional Study (EPI-PSODE).

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE: To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS: This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS: A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2 months; mean body mass index was 23.9 kg/m2; and 12.7% of patients had a family history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8% and 8.4%, respectively. Patients with PASI ≥10 accounted for 24.9%; patients with body surface area ≥10 were 45.9%. Patients with DLQI ≥6 accounted for 78.8%. Between PASI <10 and PASI ≥10 groups, significant difference was noted in age at diagnosis, disease duration, blood pressure, waist circumference of female, and treatment experiences with phototherapy, systemic agents, and biologics. CONCLUSION: This was the first nationwide epidemiologic study of patients with psoriasis in Korea and provides an overview of the epidemiologic characteristics and clinical profiles of this patient population.

Efficacy of Punch Reduction Prior to Cryotherapy in Patients with Viral Warts: A Case-Control Study in a Single Tertiary Center.

BACKGROUND: Cutaneous warts are a common complaint to visit dermatologic clinic and its course is variable, ranging from spontaneous resolution to a chronic condition refractory to treatment. OBJECTIVE: To evaluate the efficacy and safety of punch biopsy for cutaneous warts. METHODS: Thirty-nine patients who received punch biopsy for warts were reviewed through charts and photos. Among them, 15 were matched with cryotherapy-only controls in terms of size and location of the wart. We compared the number and cost of treatments between the two groups. RESULTS: Eleven of the total 39 patients were treated with cryotherapy in addition to punch biopsy and the average number of treatments was 4.1±3.3 (mean±standard deviation). In a case-control study, the ratio value of cost was 2.9±3.6 in the experimental group and was 5.9±4.1 in controls (p<0.05). CONCLUSION: Punch biopsies can decrease the number and cost of treatment by reducing the size of warts and inducing local inflammation to accelerate resolution. Therefore, punch reduction should be considered as a viable measure to treat warts.

A multicenter, randomized, open-label pilot trial assessing the efficacy and safety of etanercept 50 mg twice weekly followed by etanercept 25 mg twice weekly, the combination of etanercept 25 mg twice weekly and acitretin, and acitretin alone in patients with moderate to severe psoriasis.

BACKGROUND: Etanercept, a soluble tumor necrosis factor receptor, and acitretin have been shown to be effective in treating psoriasis. Acitretin is widely used in Korea. However, the combination of etanercept plus acitretin has not been evaluated among Korean patients with psoriasis. The objective of this study was to investigate the efficacy and safety of combination therapy with etanercept and acitretin in patients with moderate to severe plaque psoriasis. METHODS: Sixty patients with psoriasis were randomized to receive etanercept 50 mg twice weekly (BIW) for 12 weeks followed by etanercept 25 mg BIW for 12 weeks (ETN-ETN); etanercept 25 mg BIW plus acitretin 10 mg twice daily (BID) for 24 weeks (ETN-ACT); or acitretin 10 mg BID for 24 weeks (ACT). The primary efficacy measurement was the proportion of patients achieving 75 % improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Secondary end points included 50 % improvement in PASI (PASI 50) at week 24 and clear/almost-clear by Physician Global Assessment (PGA) at each visit through week 24. RESULTS: The proportions of patients achieving PASI 75, PASI 50, and PGA clear/almost-clear at week 24 in the ETN-ETN (52.4, 71.4, and 52.4 %, respectively) and ETN-ACT groups (57.9, 84.2, and 52.6 %, respectively) were higher than in the ACT group (22.2, 44.4, and 16.7 %, respectively). The incidence of adverse events was similar across all arms. This was an open-label study with a small number of patients. CONCLUSION: In Korean patients with moderate to severe plaque psoriasis, etanercept alone or in combination with acitretin was more effective than acitretin. All treatments were well tolerated throughout the study. TRIAL REGISTRATION: This study was registered on July 7, 2009 at ClinicalTrials.gov, NCT00936065 .

Topical tranexamic acid as an adjuvant treatment in melasma: Side-by-side comparison clinical study.

BACKGROUND: Tranexamic acid (TNA) is a novel therapeutic agent for hyperpigmented skin disorders. The efficacy and safety of topical TNA in patients with melasma has not been heretofore studied. The main objective of this study is to evaluate the efficacy and safety of topical TNA combined with intense pulsed light (IPL) treatment in Asians with melasma. METHODS: A randomized, split-face (internally controlled) study was conducted in 15 women who received four monthly sessions of IPL to both sides of the face. Topical TNA or vehicle was applied to a randomly assigned side during and after IPL treatment. Patients were followed up for 12 weeks after completing the IPL treatments. Baseline and follow-up melanin index (MI; measured by Mexameter®, Courage and Khazaka, Cologne, Germany) and modified melasma area and severity index (mMASI) scores were determined. RESULTS: Thirteen subjects completed the study without serious adverse events. MI and mMASI decreased significantly from baseline to 12 weeks after the last IPL treatment on the topical TNA side but not on the vehicle side. The efficacy of topical TNA in preventing rebound pigmentation after IPL treatment was also statistically significant. CONCLUSION: Topical TNA can be considered an effective and safe adjuvant to conventional treatment for melasma.

Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial.

BACKGROUND: New therapeutic options are needed for patients with psoriasis. Tofacitinib, an oral Janus kinase inhibitor, is being investigated as a treatment for moderate-to-severe chronic plaque psoriasis. In this study, we aimed to compare two tofacitinib doses with high-dose etanercept or placebo in this patient population. METHODS: In this phase 3, randomised, multicentre, double-dummy, placebo-controlled, 12-week, non-inferiority trial, adult patients with chronic stable plaque psoriasis (for ≥12 months) who were candidates for systemic or phototherapy and had a Psoriasis Area and Severity Index (PASI) score of 12 or higher and a Physician's Global Assessment (PGA) of moderate or severe, and had failed to respond to, had a contraindication to, or were intolerant to at least one conventional systemic therapy, were enrolled from 122 investigational dermatology centres worldwide. Eligible patients were randomly assigned in a 3:3:3:1 ratio to receive tofacitinib 5 mg or 10 mg twice daily at about 12 h intervals, etanercept 50 mg subcutaneously twice weekly at about 3-4 day intervals, or placebo. Randomisation was done by a computer-generated randomisation schedule, and all patients and study personnel were masked to treatment assignment. The co-primary endpoints were the proportion of patients at week 12 with at least a 75% reduction in the PASI score from baseline (PASI75 response) and the proportion of patients achieving a PGA score of "clear" or "almost clear" (PGA response), analysed in the full analysis set (all patients who were randomised and received at least one dose of study drug). This study is registered with ClinicalTrials.gov, number NCT01241591. FINDINGS: Between Nov 29, 2010, and Sept 13, 2012, we enrolled 1106 eligible adult patients with chronic plaque psoriasis and randomly assigned them to the four treatment groups (330 to tofacitinib 5 mg twice daily, 332 to tofacitinib 10 mg twice daily, 336 to etanercept 50 mg twice weekly, and 108 to placebo). Of these patients, 1101 actually received their assigned study medication (329 in the tofactinib 5 mg group, 330 in the tofacitinib 10 mg group, 335 in the etanercept group, and 107 in the placebo group). At week 12, PASI75 responses were recorded in 130 (39·5%) of 329 patients in the tofacitinib 5 mg group, 210 (63·6%) of 330 in the tofacitinib 10 mg group, 197 (58·8%) of 335 in the etanercept group, and six (5·6%) of 107 in the placebo group. A PGA response was achieved by 155 (47·1%) of 329 patients in the tofacitinib 5 mg group, 225 (68·2%) of 330 in the tofacitinib 10 mg group, 222 (66·3%) of 335 in the etanercept group, and 16 (15·0%) of 107 in the placebo group. The rate of adverse events was similar across the four groups, with serious adverse events occurring in seven (2%) of 329 patients in the tofacitinib 5 mg group, five (2%) of 330 in the tofacitinib 10 mg group, seven (2%) of 335 in the etanercept group, and two (2%) of 107 in the placebo group. Three (1%) of 329 patients in the tofacitinib 5 mg group, ten (3%) of 330 in the tofacitinib 10 mg group, 11 (3%) of 335 in the etanercept group, and four (4%) of 107 patients in the placebo group discontinued their assigned treatment because of adverse events. INTERPRETATION: In patients with moderate-to-severe plaque psoriasis, the 10 mg twice daily dose of tofacitinib was non-inferior to etanercept 50 mg twice weekly and was superior to placebo, but the 5 mg twice daily dose did not show non-inferiority to etanercept 50 mg twice weekly. The adverse event rates over 12 weeks were similar for tofacitinib and etanercept. This study indicates that in the future tofacitinib could provide a convenient and well-tolerated therapeutic option for patients with moderate-to-severe plaque psoriasis. FUNDING: Pfizer Inc.

Comparison of Treatment Goals for Moderate-to-Severe Psoriasis between Korean Dermatologists and the European Consensus Report.

BACKGROUND: The development of therapies for psoriasis has led to the need for a new strategy to the treatment of patients with moderate-to-severe psoriasis. New consensus guidelines for psoriasis treatment have been developed in some countries, some of which have introduced treatment goals to determine the timing of therapeutic regimens for psoriasis. OBJECTIVE: To investigate the opinions held by Korean dermatologists who specialize in psoriasis about treatment goals, and to compare these with the European consensus. METHODS: Korean dermatologists who specialize in psoriasis were asked 11 questions about defining the treatment goals for psoriasis. The questionnaire included questions about the factors used to classify the severity of psoriasis, defining the induction and maintenance phases of psoriasis treatment, defining treatment responses during the induction phase, and defining treatment responses during the maintenance phase. RESULTS: The Korean consensus showed responses that were almost similar to the European consensus, even without using the Delphi technique, which uses repeated rounds of questions to reach a consensus. Only one response that related to psoriasis severity in the context of the quality of patients' lives differed from the European consensus. CONCLUSION: The concept of using treatment goals in the treatment of moderate-to-severe psoriasis can be applied to Korean psoriasis patients. Since a tool for assessing the quality of patients' lives is not commonly used in Korea, the development of a simple, rapidly completed, and region-specific health-related quality of life assessment tool would enable treatment goals to be used in routine clinical practice.