Pimecrolimus cream 1% in the long-term management of adult atopic dermatitis: prevention of flare progression. A randomized controlled trial

BACKGROUND: Previous studies suggested that early intervention with pimecrolimus cream 1% at the first signs and/or symptoms of a relapse of atopic dermatitis (AD) following remission may prevent the occurrence of more severe flares and therefore reduce corticosteroid exposure in the long term. However, this possibility was not rigorously evaluated. OBJECTIVES: To evaluate the effectiveness of pimecrolimus cream 1% for the prevention of flare progression in adults with AD. METHODS: A 26-week randomized controlled study was conducted in 543 patients aged>or=18 years, with a history of mild or moderate AD, who were clear/almost clear of disease before randomization to pimecrolimus cream 1% (n=277) or matching vehicle cream (n=266). Twice-daily treatment with study medication was started at the onset of the first signs and/or symptoms of a relapse. If disease worsened, despite the application of study medication for at least 3 days, treatment with a moderately potent topical corticosteroid (TCS) was allowed in both groups. The primary efficacy endpoint was the number of days without TCS use for disease worsening. RESULTS: The mean number of TCS-free days was significantly higher (P<0.001) in the pimecrolimus cream 1% group (152 days) than in the vehicle cream group (138.7 days). In comparison with vehicle cream, pimecrolimus cream 1% reduced the mean number of flares requiring TCS use from 1.39 to 0.97 (P=0.0014). Patients on pimecrolimus cream 1% made 30% fewer unscheduled visits (156) than patients on vehicle cream (223). CONCLUSIONS: In adults with a history of mild or moderate AD but free of active skin lesions, intervention with pimecrolimus cream 1% at the first signs and/or symptoms of a subsequent recurrence reduces the number of flares requiring TCS use and decreases the number of disease-related office visits.     

The effectiveness of integrated care for patients with hand eczema: results of a randomized, controlled trial

Objectives. To evaluate the effectiveness of integrated, multidisciplinary care as compared with usual care for patients with moderate to severe, chronic hand eczema after 26 weeks of follow‐up. Background. This study was designed as a randomized, controlled trial. Methods. Patients who visited one of the participating hospitals were randomized to integrated care or usual care. Integrated care was carried out by a multidisciplinary team, and integrated clinical and occupational care to optimize treatment, and the patient's quality of life and social functioning. Outcome variables were clinical assessment of hand eczema with the Hand Eczema Severity Index (HECSI) (primary outcome), quality of life, patient's global assessment of hand eczema, and sick leave. Results. Average improvement on the HECSI was 22.4 points in the intervention group and 11.7 points in the control group. The mean difference in improvement on the HECSI between both groups after 26 weeks was 10.7 points in favour of the integrated care group (standard error 5.3, 95% confidence interval 0.3–21.1, p = 0.044). No differences in improvement between the groups were found for any of the other outcomes. Conclusions. The integrated care programme significantly improved clinical outcome measures as compared with usual care, and was effective for treating patients with chronic hand eczema.     

Effectiveness of combined conventional treatment with a tailored exercise training program on wound healing in patients with venous leg ulcer: A randomized controlled trial

IntroductionVenous leg ulcer (VLU) is a therapeutic challenge. The mainstay of care is compression therapy and wound care. Exercise is also recommended for facilitating wound healing. This study aimed to determine whether adding tailored exercise training to conventional treatment would be superior on wound healing, ankle mobility, calf muscle function, and functional ability compared to those with the conventional treatment alone.MethodsA randomized controlled trial, single-blinded was conducted. VLU patients were randomized to the conventional treatment plus tailored exercise training (intervention group) and the conventional treatment alone (control group) (12/group). The conventional treatment contained foam dressing and short-stretch bandage, while the tailored exercise training consisted of stretching, resistive, and aerobic exercise sessions (3-day/week, for 12-week). Primary outcomes included healing rate and wound size parameters. Secondary outcomes were ankle range of motion (ROM), calf circumference, calf muscle endurance and strength, and functional ability. All outcomes were assessed at baseline, 6-, and 12-week intervention.ResultsThe intervention group had a higher trend of healing rate after 12-week training than those in the control group, but this trend was not significantly different (92% versus 58%, p = 0.06). After training, the intervention group had significantly decreased wound size. The intervention group had significantly higher ankle ROM and dorsiflexor muscle strength after 6- and 12-week training than those in the control group.ConclusionAdding the tailored exercise training incorporated with the conventional treatment may provide a greater tendency on wound healing and have the potential to improve ankle mobility than the conventional treatment alone.Trial registration numberTCTR20170405002.     

Cost-effectiveness of tacrolimus ointment vs. standard treatment in patients with moderate and severe atopic dermatitis: a health-economic model simulation based on a patient survey and clinical trial data

BACKGROUND: Atopic dermatitis (AD) affects health and quality of life (QoL) and also has great impact on both healthcare costs and costs to society. OBJECTIVES: The aim of the study was to analyse the cost-effectiveness of treatment with tacrolimus ointment vs. standard treatment in patients with moderate to severe AD. METHODS: A Markov simulation model was constructed capturing several key features of AD and its treatment: disease severity, treatment alternatives, and QoL. The model was populated with data from three sources: (i) efficacy data from a randomized controlled trial including patients with moderate to severe AD treated with either tacrolimus ointment or standard treatment (corticosteroids), (ii) resource utilization and QoL data from a patient survey including 161 Swedish patients with AD, and (iii) official price lists. Costs were calculated according to disease severity for the two treatment alternatives using the perspective of the Swedish healthcare sector. Two analyses were performed, one based on the quantity of medication used in the trial and one based on the survey data. The relationship between effectiveness of tacrolimus ointment and the amount of medication used was tested in sensitivity analyses. RESULTS: In the model simulations patients with severe AD treated with tacrolimus ointment experienced on average 4.6 more AD-free weeks per year than patients given standard treatment. The corresponding figure for patients with moderate AD was 6.5 more AD-free weeks per year. The cost-effectiveness ratios [cost per Quality Adjusted Life Year (QALY) gained] for treatment with tacrolimus ointment vs. standard treatment were 2,334 British pound for moderate AD and 3,875 British pound for severe AD when treatment patterns from the survey were assumed, and 8,269 British pound for moderate AD and 12,304 British pound for severe AD when treatment patterns from the clinical trial were assumed. The results of sensitivity analyses were all well within limits to be considered cost-effective. CONCLUSIONS: Estimates of the incremental cost-effectiveness ratio are far below the currently discussed threshold in Sweden, corresponding to approximately 48,700 British pound per QALY gained, and equivalent thresholds in other countries. Treatment with tacrolimus ointment in patients with moderate and severe AD can therefore be considered cost-effective.     

The treatment of facial atopic dermatitis in children who are intolerant of, or dependent on, topical corticosteroids: a randomized, controlled clinical trial

Background  Atopic dermatitis (AD) is most prevalent in areas of reduced skin barrier reserve, like face and neck, especially in children. Treatment with topical corticosteroids (TCS) is limited due to heightened risk of treatment-associated side-effects, thus necessitating alternative AD therapies.
Objectives  The primary study objective was to determine the efficacy of pimecrolimus cream 1% in children with mild–moderate facial AD dependent on/intolerant of TCS. Secondary objectives included effects on overall Eczema Area and Severity Index (EASI), head/neck EASI, pruritus severity and time to clearance of facial AD.
Methods  A multicentre, double-blind (DB) study of ≤ 6 weeks, followed by a 6-week, open-label (OL) phase was conducted. Two hundred patients (aged 2–11 years) were randomized 1 : 1 to pimecrolimus cream 1% ( n  =   99) or vehicle ( n  =   101) twice daily until clearance of facial AD or for a maximum of 6 weeks (DB phase). Sixteen patients receiving vehicle were allowed to switch to the OL phase at day 22.
Results  Significantly more pimecrolimus-treated vs. vehicle-treated patients were cleared/almost cleared of facial AD (Investigators' Global Assessment 0/1): 74·5% vs. 51·0%, P  <   0·001 (day 43) [57·1% vs. 36·0%, P  =   0·004 (day 22)]. Median time to clearance was 22·0 vs. 43·0 days (pimecrolimus vs. vehicle, respectively). Statistically significant differences for pimecrolimus vs. vehicle were also seen on head/neck EASI, overall EASI, and head/neck pruritus scores. Adverse events were mainly mild–moderate, occurring with similar frequency in both treatment groups.
Conclusions  In children with facial dermatitis intolerant of/dependent on TCS, pimecrolimus cream 1% effectively controls eczema and pruritus and is well tolerated.     

Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor,in Japanese adult patients with atopic dermatitis: Results of a randomized,vehicle‐controlled,multicenter clinical trial

The safety and efficacy of topical E6005, a novel phosphodiesterase 4 inhibitor, in Japanese adults with atopic dermatitis were evaluated. A total of 78 patients were randomized to receive either the 0.2% E6005 ointment or vehicle control (without E6005) at an allocation ratio of 2:1. The randomization phase of 4 weeks was followed by an extension phase of 8 weeks. In the extension phase, all 67 subjects who completed the randomization phase were treated with 0.2% E6005 ointment. The 4‐week application of topical E6005 twice daily was safe and well tolerated. The safety profile for up to 12 weeks was similar to that for the first 4 weeks. No deaths or other serious adverse effects were observed during the entire study period of 12 weeks. Plasma E6005 was undetectable in all subjects at all sampling points while very low plasma concentrations of an E6005 metabolite were detected in 47% of subjects receiving E6005 treatment. At the end of week 4, Eczema Area and Severity Index (EASI), Severity Scoring Atopic Dermatitis (SCORAD)‐objective, SCORAD‐C (visual analog scales for pruritus and sleep loss), itch Behavioral Rating Scale, and the severity of the targeted eczematous lesions in the topical E6005 group showed trends toward improvement compared with those in the vehicle group (not statistically significant). However, the group receiving topical E6005 for 12 weeks showed significant score reductions from baselines for EASI (P = 0.030), SCORAD‐objective (P < 0.001) and SCORAD‐C (P = 0.038). These results further support the development of topical E6005 for the treatment of atopic dermatitis.     

A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day-care setting

BACKGROUND: Calcipotriol has become a first-line treatment for psoriasis. Its efficacy and safety have been shown in many comparative clinical trials carried out in outpatients. In a comparative study in patients visiting the outpatient department once every 14 days, it was shown that calcipotriol was more effective and better tolerated compared with dithranol. OBJECTIVES: To compare the clinical efficacy of calcipotriol ointment with that of dithranol cream in a supervised treatment regimen. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. RESULTS: This study failed to prove that calcipotriol is as efficacious as dithranol when used in a day-care setting (noninferiority test). The mean percentage reduction in Psoriasis Area and Severity Index from baseline to end of treatment was 57.0% in the calcipotriol group vs. 63.6% in the dithranol group. However, the two-sided test for superiority indicated no statistically significant difference between the treatment groups (P = 0.39). At the end of treatment, 15% of the patients treated with calcipotriol ointment and 25% of those treated with dithranol cream did not require any further treatment. Although calcipotriol ointment appeared to be more effective during the first 8 weeks, a difference was no longer apparent at 12 weeks. In comparison with the high number of drop-outs due to cutaneous side-effects in the calcipotriol group, the frequency of a tolerable degree of irritation appeared to be higher in patients treated with dithranol. However, concomitant corticosteroid treatment of dithranol irritation in seven patients may have contributed to this difference between both treatments. Moreover, patients receiving therapy with calcipotriol ointment experienced fewer application-related skin and subcutaneous tissue disorders than patients treated with dithranol cream: 21 of 53 (40%) and 37 of 52 (71%), respectively. This difference is statistically significant (P = 0.001). CONCLUSIONS: The hypothesis that calcipotriol ointment might be at least as effective as dithranol cream in the day-care setting could not be proven in the present study. Whereas calcipotriol has become a mainstay in the routine outpatient treatment of psoriasis not requiring a day-care setting, dithranol treatment, being difficult as a routine outpatient therapy, has increased efficacy and improved tolerability if the treatment is carried out in a day-care setting.     

A comparison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: quality-of-life outcomes of a randomized controlled trial of supervised treatment of psoriasis in a day-care setting

BACKGROUND: Calcipotriol ointment and short-contact dithranol cream therapy are well-established topical treatments for psoriasis. Quality of life, i.e. the physical, psychological, and social functioning and well-being of the patient, has become an essential outcome measure in chronic skin disease. OBJECTIVES: To compare the quality-of-life outcomes of calcipotriol ointment with that of short-contact dithranol cream in a supervised treatment regimen, and to determine the degree of improvement in quality of life these topical treatments can accomplish. METHODS: In a multicentre randomized controlled trial in six centres in the Netherlands, 106 patients with chronic plaque psoriasis were included, 54 receiving calcipotriol ointment twice daily and 52 dithranol cream once daily in a 12-week intensive treatment programme. Patients were treated at the day-care centre, using the care instruction principle of daily visits during the first week and twice-weekly visits subsequently for up to 12 weeks. Quality of life was assessed with the Skindex-29 and the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36). RESULTS: At the end of treatment, no statistically significant differences were found between the calcipotriol and the dithranol group in any of the quality-of-life domains or scales of the Skindex-29 and the SF-36. Over time, a significant improvement of quality of life was found on all three scales of the dermatology-specific Skindex-29, predominantly of a moderate magnitude. In the calcipotriol group, a significant change of a small magnitude was found in the Physical Component Summary of the SF-36. No significant changes were found in the Mental Component Summary (or on any of the eight scales composing the questionnaire) of the SF-36. CONCLUSIONS: The hypothesis was confirmed, that no statistically significant differences in improvement of quality of life could be found between calcipotriol ointment and dithranol short-contact cream in a day-care setting. Given this result, both calcipotriol and dithranol can be welcome alternatives for the patient. Calcipotriol, being more practical and patient friendly, can be considered as a first-line approach in clinical practice. However, in patients recalcitrant to calcipotriol and/or other topical treatments, preference should be given to the dithranol regimen. Topical treatment in combination with interventions explicitly focusing on improvement of coping behaviour and psychosocial functioning may further increase the degree of improvement in the psychosocial domains of quality of life. The results of this study are likely to give further evidence to the notion that the generic SF-36 is little or not responsive to small to moderate changes in quality of life in mild to moderate psoriasis.     

Superiority of a vitamin B12‐barrier cream compared with standard glycerol‐petrolatum‐based emollient cream in the treatment of atopic dermatitis: A randomized,left‐to‐right comparative trial

Atopic dermatitis (AD) is a result of complex genetic, epigenetic, environmental, and immunological interactions with an overlapping epidermal barrier defect. The study evaluates the efficacy and tolerability of topical Vitamin B12‐barrier cream (MB12) compared with standard glycerol‐petrolatum‐based emollient cream (GPC) used three times a day for mild AD. The study was conducted as a on one hemi‐body randomized, controlled, single‐blind, intra‐patient left‐to‐right comparative trial by patients with clinical diagnosis of mild AD measured with total SCORAD index over 4 months. MB12 was compared on one hemi‐body treated (GPC). The comparisons of score values were performed primarily by using non‐parametric procedures: Mann–Whitney‐U test (for independent samples) and Wilcoxon test (for dependent samples). All 22 patients were randomized (left or right side treated with MB12 or GPC). At week 12 a reduction from baseline in SCORAD index was assessed in both body sites with 77.6% SCORAD index reduction in the MB12 treated body sites versus 33.5% in the GPC treated body sites. These results suggest that MB12 could represent a new option in the treatment of mild AD.     

The effectiveness of lying surfaces in nursing care beds,a comparison of spring element systems versus conventional systems: A post marketing clinical follow-up pilot study

BackgroundReduced mobility is a strong risk factor for pressure ulcer development in a nursing home setting. Despite this, there is a surprising lack of data regarding suitable nursing care beds in general and the prevention of pressure ulcers provided by lying surface systems in particular. In this context we aimed to assess the mobility of patients using lying surface systems either with spring elements (SES) and to compare these to conventional systems (CS; wooden slats or steel bars).MethodsThis was a prospective, randomized, controlled study in 29 patients with an age range of 54–95 years. Patients were randomly assigned to SES (n = 15) or CS (n = 14). The primary objective was to show a statistically significant difference in the proportion of patients with normal (up to 4 movements per hour) movements as evaluated by the Mobility Monitor^®. Pressure distribution of the lying body weight was measured by a full body pressure mapping system XSensor^®. Comfort, possibility of movement and recovery of sleep as well as pain at rest were self-rated.ResultsWe screened a total of 39 patients of which 29 were eligible to be randomized into the two groups and 27 were finally analysed (SES = 14; CS = 13). The mean age was 81.7 ± 9.5 years, 81.5% were female and the mean Braden Scale Score 22.4 ± 1.3. We observed no statistically significant difference in the primary evaluation criterion (proportion of patients with a normal number of movements across 14 nights) between the SES group (81.4 ± 10.8%) and the CS group (72.9 ± 16.3%; p = 0.0757). There was a consistent trend for more movements in the normal range in the SES group however, which was observed when the number of hours with normal movement was plotted per night (p = 0.0004). Measured pressure values showed overall higher values for the lateral compared to the dorsal position with the SES but not the CS forming a “shoulder” between 35-55 mmHg in the dorsal position and between 35-45 mmHg in the lateral position. Self-rated comfort was significantly higher with the SES after night 14 (p = 0.0192) than with CS.ConclusionsThe study is not aimed at the hard endpoint pressure ulcer, but at the physiological movement profile of patients in bed, which justifies a much smaller number of cases. For elderly nursing home patients it appears that beds with spring elements may be associated with higher normality of body movements and higher self-rated comfort. The presented study could be a contribution to reduce the care dependency of patients regarding mobility.