The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate. The Netherlands Adult Atopic DermatitisStudy Group.

This study was designed to investigate a long-term therapeutic strategy for the management of recurring atopic dermatitis (AD) in adults using fluticasone propionate (FP) ointment (CutivateTM) whereby FP could help to prevent a relapse of AD once symptoms were under control. Adult patients with chronic, moderate to severe AD entered this multicentre study. All patients were initially treated with FP 0.005% (g/g) ointment in two different regimens. Patients whose AD had been completely healed by these treatments then entered a long-term treatment phase applying FP or placebo ointment once daily, two times per week for 16 weeks to 'known' healed lesions. By the end of the initial treatment period, mean SCORAD values had significantly (P < 0.0005) improved from baseline. Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks, demonstrated its superior efficacy (P = 0.018) over placebo, maintaining the improvements achieved after the initial treatment phase, reducing risk of relapse and delaying time to relapse (P = 0.013). No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements. Intermittent FP applied two times per week maintained a significant level of control, and delayed relapse of AD by comparison with placebo.     

Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients

BACKGROUND: One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease. OBJECTIVE: To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD. METHODS: Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved 'treatment success' (Global Assessment Score 相似文献   

Treatment with a barrier-strengthening moisturizing cream delays relapse of atopic dermatitis: a prospective and randomized controlled clinical trial

Background  Standard treatment of atopic dermatitis (AD) is based on topical glucocorticosteroids or calcineurin inhibitors to treat flares combined with moisturizer treatment to alleviate dry skin symptoms. Patients with AD have an abnormal skin barrier function, and strategies for reducing the risks for eczema would be to repair the barrier or prevent barrier dysfunction.
Objectives  The objective of this study was to explore the time to relapse of eczema during a 26-week maintenance treatment with a urea containing moisturizer compared to no treatment (neither medical nor non-medicated preparations) after successful clearing of atopic lesions. The moisturizer has previously been shown to improve skin barrier function.
Methods  Patients applied betamethasone valerate (0.1%) on eczematous lesions during a 3-week period. Those with cleared eczema entered a 26-week maintenance phase, applying the moisturizer or left the previously affected area untreated. Upon eczema relapse, patients were instructed to contact the clinic and to have the relapse confirmed by the investigator.
Results  Fifty-five patients entered the study and 44 patients were included in the maintenance phase (22 using moisturizer twice daily and 22 using no treatment). Median time to relapse for patients treated with moisturizer was > 180 days (duration of the study) compared with 30 days for the no-treatment group. Sixty-eight per cent of the patients treated with the moisturizer and 32% of the untreated patients remained free from eczema during the observation period.
Conclusions  Maintenance treatment with a barrier-improving urea moisturizer on previous eczematous areas reduced the risk of relapse to approximately one third of that of no treatment.     

Efficacy and safety of topical WBI-1001 in patients with mild to severe atopic dermatitis: results from a 12-week, multicentre, randomized, placebo-controlled double-blind trial

Background There is a need for the development of novel nonsteroidal topical drugs for the treatment of atopic dermatitis (AD). Objectives The primary objective was to evaluate the efficacy of WBI‐1001 over 6 weeks of treatment of mild to severe AD. Methods Patients with AD affecting 3–20% of their body surface area and with an Investigator’s Global Assessment (IGA) of 2–4 were randomized (1 : 1 : 1) to receive placebo, WBI‐1001 0·5% or WBI‐1001 1·0% in a cream formulation applied twice daily for 6 weeks. At the end of this phase, patients receiving WBI‐1001 continued the same treatment for an additional 6 weeks. Patients receiving placebo entered into a 6‐week double‐blind phase with re‐randomization (1 : 1) to WBI‐1001 0·5% or 1·0% cream. The primary objective was to evaluate the efficacy of WBI‐1001 over 6 weeks of treatment of mild to severe AD. The primary endpoint was the mean change from baseline in IGA at day 42 (week 6). Results In total, 148 patients were randomized and analysed in the placebo (51), WBI‐1001 0·5% (50) and WBI‐1001 1·0% (47) groups. There was a decrease of 1·3 [43%; P < 0·001; 95% confidence interval (CI) ?1·2 to ?0·5] and 1·8 (56·3%; P < 0·001; 95% CI ?1·6 to ?0·9) in IGA at day 42 in the WBI‐1001 0·5% and 1·0% groups, respectively, as compared with a decrease of 0·5 (14·7%) in the placebo group. Adverse drug reactions included a few cases of folliculitis and contact dermatitis. Conclusions WBI‐1001 is an efficacious novel topical anti‐inflammatory molecule for the treatment of AD.     

0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial

BACKGROUND: Topical corticosteroids are the usual treatment for atopic dermatitis (AD) in children but can have side-effects. OBJECTIVES: This study compared the efficacy and safety of 0.03% tacrolimus ointment applied once or twice daily over a 3-week period with the twice daily application of 1% hydrocortisone acetate (HA) ointment in children with moderate to severe AD. PATIENTS AND METHODS: Patients applied ointment daily to all affected body surface areas. The primary study endpoint was the percentage change in the modified Eczema Area and Severity Index (mEASI) between baseline and treatment end. RESULTS: Six hundred and twenty-four patients, aged 2-15 years, applied 0.03% tacrolimus ointment once daily (n = 207), twice daily (n = 210) or 1% HA twice daily (n = 207). By the end of treatment, application of 0.03% tacrolimus ointment both once or twice daily resulted in significantly greater median percentage decreases in mEASI (66.7% and 76.7%, respectively) compared with 1% HA (47.6%; P < 0.001). Furthermore, the median percentage decrease in mEASI was significantly greater for patients applying 0.03% tacrolimus twice daily compared with once daily (P = 0.007). Patients with severe AD benefited especially from twice daily application of 0.03% tacrolimus ointment compared with once daily application (P = 0.001). Transient mild to moderate skin burning occurred significantly more often in the 0.03% tacrolimus groups (P = 0.028) but resolved in most cases within 3-4 days. Laboratory parameters showed no clinically relevant changes. CONCLUSIONS: 0.03% tacrolimus ointment applied once or twice daily is significantly more efficacious than 1% HA in treating moderate-severe AD in children. Twice daily application of 0.03% tacrolimus ointment results in the greatest improvement in mEASI, and is especially effective in patients with severe baseline disease.     

Efficacy and safety of topical tacrolimus for the treatment of face and neck vitiligo

Vitiligo is a common acquired idiopathic hypomelanotic disorder characterized by circumscribed depigmented maculae. The conventional treatments are limited by their inconsistent and incomplete responses, relapse rate, inconvenience to apply, side-effects and especially long-term effects. The aim of the present study was to determine the efficacy and safety of topical tacrolimus as monotherapy for the treatment of face/neck vitiligo in Taiwan. This was a multicenter, open-label, non-comparative study. Patients were at least 16 years old and had vitiligo lesions with Vitiligo Index of Disease Activity score +1 or more on face or neck. Patients received a monotherapy with 0.1% of tacrolimus ointment twice daily for 12 weeks. The efficacy was measured by the percentage of repigmentation of target lesion, which was graded as minimal (1–25%), mild (26–50%), moderate (51–75%) or excellent (76–100%). Patients who had at least mild repigmentation were defined as responders. A total of 61 patients were enrolled in this investigation. Most of the patients showed repigmentation at week 4. At the end of treatment, all patients showed repigmentation and 45.9% of patients were responders. During the study, 15 adverse events related to the ointment were reported. All the reported adverse events were mild and similar to the well-known adverse effect of tacrolimus in the treatment of atopic dermatitis. Tacrolimus ointment is effective and well tolerated for the treatment of patients with vitiligo in Taiwan. It will be another drug of choice for persons with vitiligo who are unable to receive regular phototherapy and fear the side-effects of topical steroid in long-term use.     

Reduction of relapses of atopic dermatitis with methylprednisolone aceponate cream twice weekly in addition to maintenance treatment with emollient: a multicentre, randomized, double-blind, controlled study

Background The relapsing nature of atopic dermatitis (AD) presents a challenge for its long‐term treatment. Efficacy and safety of corticosteroids have been proven in the acute treatment of active AD, but their long‐term efficacy and potential to reduce or prevent relapses have only partially been addressed. Objectives To investigate long‐term management (16 weeks) of AD with methylprednisolone aceponate (MPA) 0·1% cream twice weekly in addition to an emollient (Advabase^®) after stabilization of an acute severe or very severe flare of AD with MPA cream. Methods Patients ≥ 12 years of age with a ≥ 2‐year history of moderate to severe AD were eligible for this multicentre, randomized, double‐blind, controlled study if they presented with an acute flare of severe or very severe AD [Investigator’s Global Assessment (IGA) score ≥ 4]. After successful treatment of the flare in an acute phase (AP), patients received either MPA twice weekly plus emollient or emollient alone over a 16‐week maintenance phase (MP). The primary study endpoint was time to relapse of AD. Secondary endpoints included relapse rate and disease status, the patient’s assessment of intensity of itch, the Eczema Area and Severity Index, the IGA score, affected body surface area, Dermatology Life Quality Index (DLQI) and children’s DLQI (CDLQI), patient’s and investigator’s global assessment of response and patient’s assessment of quality of sleep. Results Two hundred and forty‐nine patients entered the AP and 221 continued into the MP. Time to relapse was longer in the MPA group than in the emollient group. The probability of remaining free from relapse after 16 weeks was 87·1% in the MPA group compared with 65·8% for the emollient. Patients treated with MPA twice weekly had a 3·5‐fold lower risk of experiencing a relapse than patients treated with emollient alone (hazard ratio 3·5, 95% confidence interval 1·9–6·4; P < 0·0001). MPA was also superior to emollient for all other efficacy endpoints. Therapy with both treatments was well tolerated. Conclusions MPA twice weekly plus an emollient provides an effective maintenance treatment regimen to control AD. Once stabilized, treatment with MPA significantly reduces the risk of relapse and the intensity of itching, and improves the overall patient status.     

Wet-wrap treatment using dilutions of tacrolimus ointment and fluticasone propionate cream in human APOC1 (+/+) mice with atopic dermatitis

Background  Wet-wrap treatment (WWT) with diluted topical steroids is widely used in atopic dermatitis (AD). Mice with transgenic overexpression of human apolipoprotein C1 (APOC1) in the liver and the skin are not only characterized by hyperlipidaemia and raised IgE levels, but also by pruritic dermatitis and a disturbed skin barrier function, providing a novel in vivo mouse model for AD.
Objectives  We investigated an adapted WWT method in the AD model in APOC1 mice in order to establish its efficacy.
Methods  The effect of topical 0·1% and 0·03% tacrolimus ointment, tacrolimus base ointment, different dilutions of 0·05% fluticasone propionate (FP) cream and emollient on the development of dermatitis in APOC1 mice was investigated. WWT was performed with 0·03% tacrolimus ointment or 0·017% FP cream.
Results  AD in APOC1 mice responded to topical treatment with tacrolimus or FP. In contrast to tacrolimus treatment, FP treatment was associated with loss of body weight. WWT reinforced several therapeutic aspects, notably improvements in transepidermal water loss and in epidermal thickness. WWT using tacrolimus 0·03% ointment was more effective than WWT using FP 0·017% cream.
Conclusions  AD in APOC1 mice responds to treatment with (diluted) tacrolimus or FP; treatment with FP cream, but not tacrolimus ointment, was associated with weight loss. In this study, the adapted WWT using tacrolimus or FP in mice had a limited improving effect as compared with open application of tacrolimus or FP.     

Maintenance Therapy of Facial Seborrheic Dermatitis with 0.1% Tacrolimus Ointment

Background

Topical calcineurin inhibitors (TCIs) have been successfully used to treat seborrheic dermatitis (SD) patients. Meanwhile, treatment of atopic dermatitis (AD) with low-dose, intermittent TCI has been proved to reduce disease flare-ups. This regimen is known as a maintenance treatment.

Objective

The aim of this trial was to investigate the efficacy and tolerability of a maintenance treatment with tacrolimus ointment in patients with facial SD.

Methods

During the initial stabilization period, patients with facial SD or AD applied 0.1% tacrolimus ointment twice daily for up to 4 weeks. Clinical measurements were evaluated on either in the whole face or on separate facial regions. When an investigator global assessment score 1 was achieved, the patient applied tacrolimus twice weekly for 20 weeks. We also compared our results with recent published data of placebo controlled study to allow an estimation of the placebo effect.

Results

The time to the first relapse during phase II was similar in both groups otherwise significantly longer than the placebo group. The recurrence-free curves of two groups were not significantly different from each other; otherwise the curve of the placebo group was significantly different. There were no significant differences between the 2 groups in the number of DEs, and treatment days for disease exacerbations (DEs). The adverse event profile was also similar between the 2 groups. During the 20 weeks of treatment, the study population tolerated tacrolimus ointment well.

Conclusion

The results of this study suggest that maintenance treatment with tacrolimus may be effective in preventing the occurrence of facial SD exacerbations.     

Superiority of tacrolimus 0·1% ointment compared with fluticasone 0·005% in adults with moderate to severe atopic dermatitis of the face: results from a randomized, double-blind trial

Summary Background No specific data are available on tacrolimus ointment as a second‐line treatment in adults with facial eczema. Objectives To compare tacrolimus 0·1% and fluticasone 0·005% ointments in adults with moderate to severe atopic dermatitis (AD) of the face in whom conventional treatment was ineffective or poorly tolerated. Methods Patients were randomized to double‐blind treatment of facial AD with twice‐daily tacrolimus ointment (n = 288) or fluticasone ointment (n = 280) for 3 weeks or until clearance. After day 21, patients could continue without the study treatment, apply the same ointment once daily, or switch to the other medication twice daily, depending on lesion clearance and patient/physician satisfaction. The primary endpoint was the day‐21 response [≥ 60% reduction in the modified Local Eczema and Severity Index (mLEASI) score]. Secondary endpoints included facial erythema and pruritus, global clinical response, treatment switching at day 21 and safety. Results Response with tacrolimus ointment (93%) was superior to that with fluticasone (88%; P = 0·026). Improvements in mLEASI components were also greater with tacrolimus ointment. Facial erythema and pruritus improved in both groups. Global clinical response was rated ‘marked improvement’ or better in 88% and 79% of patients in the tacrolimus ointment and fluticasone groups, respectively. At day 21, 9% of patients switched from fluticasone to tacrolimus ointment, while 4·5% switched from tacrolimus ointment to fluticasone. Adverse events were more frequent with tacrolimus ointment as a result of the higher incidence of application‐site skin burning sensation. Safety of both drugs was in line with their respective summary of product characteristics. Conclusions Tacrolimus 0·1% ointment has superior efficacy to fluticasone 0·005% ointment for twice‐daily treatment of adults with moderate to severe facial AD in whom conventional therapy was inadequately effective or not tolerated. Tacrolimus 0·1% ointment is a safe and effective second‐line treatment for the control of moderate to severe AD of the face.     

Efficacy of oral naltrexone on pruritus in atopic eczema: a double-blind, placebo-controlled study

Aim  The intent of our study was to determine the efficacy of oral naltrexone, an opiod antagonist, in the treatment of pruritus in patients with chronic eczema.
Methods  This double-blind, placebo-controlled study recruited 38 patients with eczema complaining from pruritus. Pruritus scores were evaluated. Patients were given placebo ( n  = 20) or naltrexone 50 mg ( n  = 18) for 2 weeks period. During the study, pruritus scores based on visual analogue scale system (VAS) were assessed three times: at the start of study, after 1 week, and after 2 weeks.
Results  In both groups, decreased VAS scores were observed, but naltrexone showed to be significantly more effective than placebo in decreasing VAS score after 1 week ( P <  0.005) and 2 weeks ( P <  0.001).
Conclusion  Naltrexone is more effective than placebo in the treatment of pruritus in patient with eczema. Naltrexone might be considered as an adjunct treatment in the treatment of pruritus. However, further studies in this aspect are highly fostered.

Conflicts of interest

This study and the authors were not supported by any company with a vested interest in the product being studied and the project was funded by Skin Research Center.     

Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study

Background Long‐term treatment for atopic dermatitis (AD) using low‐dose, intermittent, topical anti‐inflammatory agents may control acute disease and prevent exacerbations. Objectives This 12‐month, European, multicentre, randomized study investigated if proactive, twice‐weekly application of 0·03% tacrolimus ointment can keep AD in remission and reduce the incidence of disease exacerbation (DE) in children. Patients and methods During the initial open‐label period, 267 children with AD applied 0·03% tacrolimus ointment twice daily for up to 6 weeks to all affected areas. When an Investigator Global Assessment (IGA) score of ≤ 2 was achieved, the patient entered the disease control period (DCP) and was randomized to receive tacrolimus (n = 125) or vehicle ointment (n = 125) twice weekly for 12 months. Exacerbations were treated with 0·03% tacrolimus ointment twice daily until an IGA ≤ 2 was regained, then randomized treatment was restarted. Results The outcome measure was the number of DEs during the DCP that required substantial therapeutic intervention. Proactive application of 0·03% tacrolimus ointment significantly reduced the number of DEs during the DCP that required substantial therapeutic intervention (median difference: 1·0; P < 0·001; Wilcoxon rank‐sum test), the percentage of DE treatment days (median difference: 6·2; P < 0·001; Wilcoxon rank‐sum test), and increased the time to first DE requiring intervention (median: 173 vs. 38 days; P < 0·001; stratified log‐rank test). Differences in quality of life scores were not significant between groups. The adverse event profile was similar for both treatment approaches. Conclusions Twice‐weekly proactive application of 0·03% tacrolimus ointment over 12 months was effective for most paediatric study patients in preventing, delaying and reducing the occurrence of AD exacerbations.     

A multicentre, randomized, double-blind, controlled study of long-term treatment with 0.1% tacrolimus ointment in adults with moderate to severe atopic dermatitis

BACKGROUND: Atopic dermatis (AD) is a chronic disease that often requires long-term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side-effects. OBJECTIVES: In a randomized, double-blind, comparative study, to compare the efficacy and safety of a 6-month treatment period with 0.1% tacrolimus ointment vs. a corticosteroid ointment regimen in adults with moderate to severe AD. METHODS: Treatment was applied twice daily for a maximum of 6 months. Patients in the tacrolimus treatment group (n = 487) applied 0.1% tacrolimus ointment to all affected areas over the whole body. The patients treated with the corticosteroid regimen (n = 485) applied 0.1% hydrocortisone butyrate ointment to affected areas on the trunk and extremities and 1% hydrocortisone acetate ointment to affected areas on the face and neck. The study primary endpoint was the response rate, i.e. the proportion of patients with at least 60% improvement in the modified Eczema Area and Severity Index (mEASI) between baseline and month 3. RESULTS: By month 3, more patients in the 0.1% tacrolimus group responded to treatment (72.6% vs. 52.3% in the corticosteroid group, P < 0.001). The patients treated with 0.1% tacrolimus also showed greater improvement in mEASI, EASI, affected body surface area and physician and patient assessments of global response. Patients applying 0.1% tacrolimus ointment experienced more skin burning (52.4% vs. 13.8% in the corticosteroid group; P < 0.001). In most patients, skin burning was mild to moderate in severity and decreased rapidly after the first week of treatment. There was no increase in the incidence of infections or malignancies over time in either treatment group. CONCLUSIONS: Long-term treatment with 0.1% tacrolimus ointment is significantly more efficacious than a corticosteroid ointment regimen in adults with moderate to severe AD.     

Secukinumab induction and maintenance therapy in moderate‐to‐severe plaque psoriasis: a randomized,double‐blind,placebo‐controlled,phase II regimen‐finding study

Background Interleukin (IL)‐17A has major proinflammatory activity in psoriatic lesional skin. Objectives To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti‐IL‐17A antibody, in moderate‐to‐severe plaque psoriasis in a phase II regimen‐finding study. Methods A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed‐interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment‐at‐start‐of‐relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67). Results At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5% and 42·0% vs. 1·5%; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed‐interval regimen [85% (n = 55) and 58% (n = 38), respectively] vs. the start‐of‐relapse regimen [67% (n = 45), P = 0·020, and 21% (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10% of patients in the fixed‐interval and start‐of‐relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection‐site reactions were reported. Reported cases of neutropenia were mild‐to‐moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long‐term safety. Conclusions Secukinumab shows efficacy for induction and maintenance treatment of moderate‐to‐severe plaque psoriasis.     

莫匹罗星局部抗菌治疗特应性皮炎的临床研究

目的探讨莫匹罗星局部抗菌治疗在特应性皮炎(AD)中的作用。方法采用随机双盲对照试验将48例AD患者分为2组,前2周分别给予莫匹罗星+来可得与莫匹罗星基质+来可得外用对比治疗;后2周改为开放试验,所有患者均给予莫匹罗星+来可得治疗。结果治疗后第1周、第2周2组患者总有效率分别为:研究组74.07％、88.88％,对照组25％、60％,经统计学检验研究组总有效率优于对照组(P<0.01,P<0.05);治疗后第4周2组总有效率分别为:研究组92.59％,对照组95％,经统计学检验2组总有效率无差异(P>0.05)。治疗后第1、2、4周时细菌学清除率2组相比统计学无差异(P>0.05)。结论局部抗菌药物与皮质类固醇联合应用治疗AD疗效优于单用皮质类固醇。     

Short term treatment of pityrosporum folliculitis with itraconazole

We compared the efficacy and safely of short-term itraconazole with that of placebo in 26 patients of pityrosporum folliculitis. Twenty-six patients of mycologically proven pityrosporum folliculitis entered a double-blind placebo-controlled trial. Patients were randomly assigned to 7 days of treatment with either itraconazole, 200 mg once daily, or placebo. A global clinical assessment and mycological examination (KOH and smear examination) were performed at baseline and at 4 weeks after treatment. In this study, itraconazole in a dose of 200 mg for 7 days produced a distinct and statistically significant improvement over placebo (p<0.01). 84.6% of itraconazole treated patients were considered to be healed or markedly improved at the study's end point compared with 8.3% of placebo treated group (p<0.01). Eighty-four percent of patients receiving active treatment showed negative mycological examination as compared to 8.3% of placebo-treated group (p<0.01). Short-term treatment with itraconazole is effective and well tolerated in the management of pityrosporum folliculitis.     

Safe and effective treatment of refractory facial lesions in atopic dermatitis using topical tacrolimus following corticosteroid discontinuation

BACKGROUND: Topical corticosteroids are commonly applied in atopic dermatitis (AD) treatment. However, their chronic use may be associated with significant side effects at the application site. Skin atrophy and other undesirable effects are frequently seen after long-term corticosteroid treatment. In addition, when application of corticosteroids is discontinued, a rebound phenomenon in the facial lesions can occur within several days. Topical tacrolimus, an immunosuppressant currently used to prevent rejection after solid-organ transplantation, presents a potential alternative therapeutic agent for AD. OBJECTIVE: The present study is the first trial designed to evaluate the efficacy and safety of topically applied tacrolimus ointment after corticosteroid discontinuation without a washout phase in severe, long-term facial AD. PATIENTS/METHODS: Forty-seven patients with facial refractory AD were recruited, of whom 38 had undergone topical corticosteroid treatment for at least 4 weeks before enrollment (group 1) and the other 9 had not received steroid treatment (group 2). All 47 patients received 0.1% tacrolimus ointment, and the severity index and pruritus score were assessed as an AD clinical activity index every week and compared with baseline data. RESULTS: Both the severity index and pruritus score improved significantly in group 1 after 1 and 2 weeks of application (p < 0.01, respectively). Group 2 showed the greatest improvement at 4 weeks (p < 0.05). In this trial, none of the patients experienced a rebound phenomenon associated with tacrolimus treatment. A transient sensation of burning at the application site was the only adverse event in 31 of the 47 (66%) enrolled patients, but this condition improved after several days. Spectrophotometric assessment of the facial lesion following treatment revealed significant improvement in group 1 (p < 0.05). CONCLUSION: The present results indicate that topical tacrolimus treatment following corticosteroid discontinuation is safe and effective in refractory facial AD.     

A randomized, double-blind study to assess the efficacy of addition of tetracycline to triamcinolone acetonide in the treatment of moderate to severe atopic dermatitis

Objective To assess the efficacy of tetracycline in triamcinolone acetonide ointment compared with triamcinolone acetonide ointment in patients with moderate to severe atopic dermatitis. Design Randomised, double‐blind parallel group study of 8 weeks’ duration. Setting Outpatient clinic in a university hospital. Participants Forty‐four adult patients with moderate to severe atopic dermatitis (objective SCORAD > 25). Interventions Initial phase (2 weeks): 3% tetracycline 0.1% triamcinolone acetonide vs. 0.1% triamcinolone acetonide twice daily all over the body. Maintenance phase (6 weeks) 0.1% triamcinolone acetonide once daily for 2 weeks, followed by every other day for 2 weeks. In the last 2 weeks, two applications a week were done. An emollient was used additionally once daily. Main outcome measures Primary outcomes were the disease severity scores assessed by objective SCORAD and SASSAD at week 2. Secondary outcomes were the objective SCORAD and SASSAD at weeks 4 and 8, and Staphylococcus aureus colonization at weeks 0 and 2. Results No significant differences in disease severity outcomes were found between the two groups. Both groups showed clinically relevant improvements in disease severity compared with baseline at weeks 2 and 4. At week 8, there was some worsening in disease severity in both groups, but the disease severity was still significantly lower than at the beginning of the study. Improvement of bacterial colonization was seen in 14 (63.6%) out of the 22 patients in the 3% tetracycline 0.1% triamcinolone acetonide group and in 5 (22.7%) out of the 22 patients in the 0.1% triamcinolone acetonide group. Conclusion The addition of tetracycline was effective on skin colonization by S. aureus but did in our patients with atopic dermatitis not result in a significantly different improvement compared with the group treated without tetracycline.     

Phase 2a,randomized, double‐blind,placebo‐controlled,multicenter, parallel‐group study of a H4R‐antagonist (JNJ‐39758979) in Japanese adults with moderate atopic dermatitis

This trial was conducted to evaluate the safety and efficacy of the H₄R‐antagonist JNJ‐39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ‐39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double‐blind, multicenter, placebo‐controlled study. Primary efficacy was assessed via week‐6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient‐reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty‐eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end‐point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ‐39758979 100 mg (?3.7) and 300 mg (?3.0) versus placebo (?1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ‐39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ‐39758979 and placebo with the exception of two patients (both receiving JNJ‐39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H₄R‐antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ‐39758979 appears to be associated with drug‐induced agranulocytosis, likely an off‐target effect.