Efficacy and safety of topical WBI‐1001 in patients with mild to moderate psoriasis: results from a randomized double‐blind placebo‐controlled,phase II trial

Background There is a need for the development of novel non‐steroidal topical drugs for the treatment of psoriasis. Objective To assess the efficacy and safety of topical 1.0% WBI‐1001 in patients with mild to moderate plaque psoriasis. Methods A total of 61 patients with 1–10% body surface area (BSA) covered with plaque psoriasis and a physician’s global assessment score (PGA) of 2–4 were randomized (2 : 1) to receive either 1% WBI‐1001 in a cream formulation or placebo, applied twice daily for 12 weeks. Efficacy was evaluated using PGA, BSA and Psoriasis Area and Severity Index (PASI). The primary endpoint was the change from baseline (Day 0) in PGA at week 12. Results The improvement in PGA at week 12 was 62.8% for patients randomized to WBI‐1001 when compared with 13.0% for patients randomized to placebo (P < 0.0001). At week 12, the proportion of patients who achieved a PGA of clear or almost clear and the mean improvement in BSA were 67.5% and 79.1%, respectively, for patients randomized to WBI‐1001, when compared with 4.8% (P < 0.0001) and an increase of 9.4% (P < 0.0001), respectively, for patients randomized to placebo. More application site adverse drug reactions were observed in patients randomized to WBI‐1001 than in those randomized to placebo. These adverse drug reactions were all mild or moderate in intensity. Conclusion Topical WBI‐1001 induces rapid and significant improvement in patients with plaque psoriasis.     

Topical 2% ketoconazole cream monotherapy significantly improves adult female acne: A double‐blind,randomized placebo‐controlled trial

The emergence of bacterial resistance is a global crisis. Prolonged use of antibiotics especially in acne is one issue of concern among dermatologists. Ketoconazole (KTZ) cream, a topical antifungal with anti‐inflammatory and antiandrogenic actions, can decrease lipase activity of Cutibacterium acnes in vitro. We evaluated the efficacy and safety of KTZ cream in mild adult female acne (AFA) by conducting a randomized, double‐blind, placebo‐controlled trial using KTZ 2% and placebo cream twice daily for 10 weeks. We assessed the improvement of clinical severity, measured by AFA score graded by investigators and participants, and the change of acne count. Forty‐one participants enrolled in our study. The proportion of participants with acne improvement from baseline (42.9% vs 9.5%, P = 0.015) and the success rate (45.0% vs 14.3%, P = 0.043) in the KTZ group were significantly higher than that of the placebo group. The most common adverse events were dryness and itching. The percentage change of acne count decreased significantly compared with baseline but did not differ statistically between the two groups (P = 0.268). We concluded that the KTZ monotherapy showed a plausible effect in improving AFA with excellent safety profile. It should be considered as a viable option for mild AFA treatment.     

Treatment of primary perniosis with oral pentoxifylline (a double‐blind placebo‐controlled randomized therapeutic trial)

Primary perniosis is an annoying cold‐induced dermatosis. Many therapeutic agents have been tried with either unsatisfactory or controversial results. The aim of this study was to assess the efficacy of oral pentoxyfylline in the treatment of primary perniosis. A double‐blind placebo‐controlled randomized therapeutic study conducted in dermatology department of Al‐Yarmouk Teaching Hospital, Baghdad, Iraq during four winter seasons between 2010 and 2014. The patients were randomly allocated into two equal groups: group A patients were given oral pentoxyfylline 400 mg thrice daily whereas patients in group B were given an identical placebo tablet thrice daily for 3 weeks. Therapeutic response of both groups was clinically assessed weekly for 3 weeks and side‐effects were recorded. A total of 110 patients with chilblains completed this therapeutic trial. The mean age was 24.98 ± 9.17 year. Male to female ratio was 1:2.4. All patients presented with erythematous papules, plaques or nodules. Very good therapeutic response was significantly better for group A than that of group B at 7th, 4th, and 21st days of the trial (p‐value: 0.0148, 0.0000004, and 0.0000000, respectively). No side effects were encountered in both groups. Pentoxyfylline is an effective and safe drug for treatment of primary perniosis.     

Methotrexate versus traditional Chinese medicine in psoriasis: a randomized,placebo‐controlled trial to determine efficacy,safety and quality of life

Background. Psoriasis is a common and chronic immune‐mediated skin disorder, for which there is currently no cure. To our knowledge, this is the first randomized placebo‐controlled trial comparing methotrexate and traditional Chinese medicine (TCM) in terms of efficacy, safety, and quality of life for the treatment of psoriasis. Methods. In total, 61 patients with moderate to severe plaque psoriasis were randomized to receive treatment with methotrexate, TCM or placebo for 6 months. The primary outcome measure was the Psoriasis Area and Severity Index (PASI), and secondary outcome measures were the Physician’s Global Assessment (PGA) and the Psoriasis Disability Index (PDI). Results. In all, 50 patients completed the study and were included in the analysis. Dropout rates were highest in the TCM group. Mean PASI change from baseline at 6 months revealed an improvement of 73.9% of the methotrexate group, 15.1% of the TCM group and 32.0% of the placebo group. There was a significant difference between the three groups, with methotrexate showing greater effectiveness than the other two groups. No significant difference was found between the TCM and placebo groups. The methotrexate group also had greater improvement when assessed using the PGA and PDI. Conclusions. Our results verify the therapeutic effect of methotrexate for the management of psoriasis. Despite widespread belief and use of TCM in Asia for the treatment of psoriasis, we were unable to confirm the efficacy of TCM in this study.     

Treatment of palmoplantar psoriasis with infliximab: a randomized,double‐blind placebo‐controlled study

Background Palmoplantar psoriasis is a difficult to treat variant of plaque psoriasis. Objective To study the safety and efficacy of infliximab in non‐pustular palmoplantar psoriasis. Methods Patients with non‐pustular palmoplantar psoriasis affecting at least 10% of their palms and soles and with a modified palmoplantar psoriasis area and severity index (m‐PPPASI) of at least eight were recruited. Patients were randomized (1:1) to receive infliximab 5 mg/kg or placebo at weeks 0, 2 and 6. Patients initially randomized to placebo received infliximab at weeks 14, 16 and 20 whereas patients randomized to infliximab received additional infliximab infusions every 8 weeks until week 22. Results Twenty four (24) patients were randomized in this study. At week 14, 33.3% and 66.7% of patients treated with infliximab achieved m‐PPPASI 75 and m‐PPPASI 50 respectively compared to 8.3% for both m‐PPPASI 75 (P = 0.317) and m‐PPPASI 50 (P = 0.009) for patients randomized to placebo. A reduction of 50.3% in the mean surface area of palms and soles affected with psoriasis was seen at week 14 in patients randomized to infliximab as compared to an increase of 14.9% in patients randomized to placebo (P = 0.009). Conclusions This pilot study did not reach its primary endpoint of m‐PPPASI 75 at week 14. However, infliximab was observed to be more efficacious than placebo in improving PPSA and with respect to the percentage of patients reaching m‐PPPASI 50 at week 14. Larger and longer term studies are needed for severe patients to better assess the efficacy of infliximab in palmoplantar psoriasis.     

Randomized,double‐blind,placebo‐controlled study of safety and efficacy of miltefosine in antihistamine‐resistant chronic spontaneous urticaria

Background Chronic spontaneous urticaria (CSU), a mast cell‐driven condition, is debilitating, common, and hard to treat. Miltefosine, a lipid raft modulator, can inhibit mast cell responses in vivo. Objective To study the safety and efficacy of systemic miltefosine treatment in CSU patients resistant to standard‐dosed antihistamines. Methods In this investigator‐initiated multicentre, randomized, double‐blind, placebo‐controlled study, CSU patients were treated for 4 weeks with daily doses of up to 150‐mg miltefosine (n = 47) or placebo (n = 26). Disease activity was assessed using the urticaria activity score. Safety and tolerability of miltefosine were also assessed. Results After 4 weeks of treatment, Urticaria Activity Score (UAS7) levels were substantially more reduced in miltefosine‐treated patients (?6.3 vs. ?3.5 in placebo‐treated patients; P = 0.05). Also, the number of weals, but not the intensity of pruritus, was significantly reduced in miltefosine‐treated patients vs. placebo‐treated patients (P = 0.02). In general, adverse events were frequent in both groups (miltefosine: 88%, placebo: 65% of patients) but mostly mild to moderate in severity. We did not observe any serious adverse events. Conclusions The results of this study indicate that miltefosine is an effective and safe treatment option for CSU patients who do not respond to standard‐dosed antihistamines.     

The clinical and histological effect of home‐use,combination blue–red LED phototherapy for mild‐to‐moderate acne vulgaris in Korean patients: a double‐blind,randomized controlled trial

Background Blue and red light have been reported to have beneficial effects on acne. However, there has been no double‐blind, randomized study of acne treatment for combined blue and red light‐emitting diode (LED) devices, and the associated molecular mechanisms have rarely been investigated. Objectives To evaluate the efficacy, safety and histological changes of combined blue and red LED phototherapy for acne vulgaris. Methods Thirty‐five patients with mild‐to‐moderate acne were randomly assigned to either a home‐use irradiation group using an LED device, or a control group using a sham device. The treatment group was instructed to serially irradiate their forehead and cheeks with 420‐nm blue light and 660‐nm red light for 2·5 min twice daily for 4 weeks. Results At the final visit at 12 weeks, both inflammatory and noninflammatory acne lesions had decreased significantly, by 77% and 54%, respectively, in the treatment group. No significant difference was observed in the control group. In the treatment group, sebum output reduction, attenuated inflammatory cell infiltrations and a decreased size of the sebaceous gland were found. The immunostaining intensities for interleukin (IL)‐8, IL‐1α, matrix metalloproteinase‐9, toll‐like receptor‐2, nuclear factor‐κB, insulin‐like growth factor‐1 receptor and sterol response element binding protein (SREBP)‐1 were reduced concomitantly. Messenger RNA expression of SREBP‐1c was also decreased. No severe adverse reactions were reported. Conclusions This LED phototherapy was safe and effective for treating not only inflammatory but also noninflammatory acne lesions, with good compliance. The experimental results correlated well with clinical results, partly elucidating the related molecular mechanisms.     

Safety and efficacy of topical cantharidin for the treatment of pediatric molluscum contagiosum: a prospective,randomized, double‐blind,placebo‐controlled pilot trial

Topical cantharidin is a commonly used treatment for molluscum contagiosum (MC). However, studies validating its safety and efficacy are limited. We conducted a 6‐week, randomized, double‐blind, placebo‐controlled trial with subsequent open‐label extension to assess the safety and effectiveness of cantharidin in treating pediatric MC. Ninety‐four participants with MC were randomized to receive cantharidin or placebo, with or without occlusion. The primary outcome was complete lesion clearance. Secondary outcomes included post‐treatment lesion count, adverse events, and side effects. No significant differences between the study arms, including baseline lesion count, were observed. The overall mean (SD) baseline lesion count was 22.2 (12.9). The number of participants achieving total clearance is as follows: 7/23 (30.4%) in the cantharidin only arm, 10/24 (41.7%) in the cantharidin with occlusion arm, 2/25 (8.0%) in the placebo with occlusion arm, and 3/22 (13.6%) in the placebo only arm. Post hoc analysis demonstrated that 17/47 (36.2%) participants in the combined cantharidin arms achieved clearance compared to 5/47 (10.6%) in the placebo arms (P = 0.0065). The mean (SD) lesion count change from baseline was ?5.1 (12.2) in the placebo only arm; the mean change (SD) was ?17.4 (12.8) in the cantharidin only arm (P = 0.0033) and ?15.9 (11.6) in the cantharidin with occlusion arm (P = 0.0101). No serious adverse events or side effects were observed. Topical cantharidin was well‐tolerated and associated with the resolution of MC.     

Topical epidermal growth factor for the improvement of acne lesions: a randomized,double‐blinded,placebo‐controlled,split‐face trial

Acne is one of the most common adverse events associated with the use of anticancer agents, such as epidermal growth factor receptor (EGFR) inhibitors. Based on data from several previous reports, we predicted that topical application of EGF could improve acne vulgaris. To evaluate the clinical efficacy and safety of topical recombinant human EGF (rhEGF) cream for the treatment of facial acne vulgaris. Twenty Korean adults with mild to moderate acne vulgaris applied topical rhEGF cream on one half of the face and a vehicle cream on the other half twice daily for six weeks. Clinical assessments were conducted at baseline, two, four, and six weeks. Two assessment methods were applied: inflammatory and non‐inflammatory acne lesion counts and acne severity score by investigator's global assessment. Skin sebum output level and hydration level were also measured at each visit. All volunteers completed the study. At the final visit, inflammatory acne lesions were reduced by 33.5% on the rhEGF‐applied side. Non‐inflammatory acne lesions also decreased by 25.4%, whereas the lesions on the control side increased. The majority of patients demonstrated improvement on the side of the face where rhEGF cream was applied. Sebum output decreased on the rhEGF side, and skin hydration level increased on both sides. No severe side effects were observed during the study. Topical rhEGF seems to be an effective and safe adjuvant treatment option for mild to moderate acne vulgaris.     

A prospective split‐face double‐blind randomized placebo‐controlled trial to assess the efficacy of methyl aminolevulinate + red‐light in patients with facial photodamage

Background To date, there is no gold standard therapy for skin photoageing. In the last decade, laser technologies have offered great promise among skin‐rejuvenation therapies; however, both non‐ablative and ablative fractional resurfacing modalities have their own benefits and drawbacks. More recently, open‐label studies and few controlled trials have suggested that photodynamic therapy may have therapeutic potential in photodamage. Objective To assess the efficacy of methyl aminolevulinate + red‐light on facial photodamage in a double‐blind split‐face randomized placebo‐controlled trial. Methods Subjects had initially two split‐face treatments 2–3 weeks apart in which half of the face was treated with MAL + red‐light compared with placebo + red‐light. Primary outcome was the assessment of global photodamage 1 month after session 2. Secondary outcomes included the assessment of fine lines, mottled pigmentation, tactile roughness, sallowness, erythema and telangiectasia 1 month after session 2, according to severity scores rated as failure, improvement or success. Results Based on the intention‐to‐treat analysis, a total of 48 patients (96 split‐faces) were included. Facial global photodamage success or improvement had occurred in 94 split‐faces and in no split‐faces receiving placebo (RR: 0.02; 95% confidence interval, 0.0–0.14; P = 0.0000). One patient had an adverse event that led to the discontinuation of the therapy after session 1. Conclusions Methyl aminolevulinate + red‐light demonstrated significantly superior efficacy in global facial photodamage compared with placebo. This therapy was also useful for all other specific secondary outcomes, except for telangiectasia. Overall, MAL + red‐light sessions were well tolerated and resulted in high/total patient satisfaction in the majority of subjects (80.4%).