A randomized clinical trial in psoriasis: synchronous balneophototherapy with bathing in Dead Sea salt solution plus narrowband UVB vs. narrowband UVB alone (TOMESA‐study group)

Background Synchronous balneophototherapy (sBPT) simulates treatment conditions at the Dead Sea for outpatient use. In the past, sBPT proved to be an effective treatment for psoriasis. However, there is a lack of sufficiently large randomized controlled clinical trials evaluating the additional benefit of sBPT compared with ultraviolet B (UVB) monotherapy. Objectives The purpose of this study was to compare the effectiveness and safety of sBPT with UVB phototherapy (PT) alone in a randomized controlled effectiveness study. Methods In this phase III, multicentre effectiveness study, 367 patients with moderate to severe psoriasis were randomly allocated in a 1 : 1 ratio to receive either sBPT consisting of narrowband UVB PT with 311 nm and synchronous bathing in 10% Dead Sea salt solution or PT with 311 nm alone. Primary endpoint, analysed on an intention‐to‐treat basis (n = 356), was the relative improvement of the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment (35 sessions or clearance). Sample size calculation aimed at the detection of superiority of at least 10%. Results Median PASI values were comparable at baseline (sBPT: 15.1, interquartile range: 10.9–24.3; PT: 15.3, interquartile range: 10.0–23.7). A clinically relevant and statistically significant difference of 49.5% between sBPT and PT could be proven at the end of the therapy phase (P < 0.001; Wilcoxon–Mann–Whitney test). Exploratory testing showed a statistically significant superiority of sBPT after 6 months. Conclusions In routine clinical practice, sBPT is superior to PT alone after 35 treatment sessions and a follow‐up of 6 months. Both treatments demonstrated to be safe.     

A first prospective randomized controlled trial on the efficacy and safety of synchronous balneophototherapy vs. narrow‐band UVB monotherapy for atopic dermatitis

Background Data from an uncontrolled trial suggest synchronous balneophototherapy (sBPT), which simulates treatment conditions at the Dead Sea, to be effective in the management of atopic dermatitis (AD). Objectives The purpose of this prospective randomized controlled study was to compare the efficacy and safety of sBPT with narrow‐band (NB) UVB monotherapy (PT) for AD. Methods In this phase III multicentre trial, 180 patients with moderate‐to‐severe AD were allocated to two groups in a 1 : 1 ratio; group 1 received sBPT consisting of NB UVB treatment and synchronous bathing in 10% Dead Sea salt solution, group 2 monotherapy with UVB 311 nm. The confirmatory study design consisted of up to 35 treatment sessions. Primary endpoint, analysed on an intention‐to‐treat‐basis (n = 169), was the relative improvement of the severity SCORing of the Atopic Dermatitis Index (SCORAD) from baseline to the end of treatment (35 sessions or early cure). Sample‐size calculation aimed at establishing at least 15% superiority. Results SCORing of the Atopic Dermatitis Index at baseline was comparable between sBPT (61.8 ± 14.1) and PT (61.5 ± 12.4) group. At the end of therapy, a clinically relevant and statistically significant difference of 26.2% could be shown (P < 0.001). Exploratory testing showed statistically significant superiority of sBPT after 6 months. Mild adverse events more frequently occurred in the sBPT group (n = 46, PT: n = 31), whereas more patients withdrew early because of adverse events in the PT group (n = 6, sBPT: n = 2). Conclusions A clear advantage of sBPT in comparison to PT was proven. Tolerability was comparable; both treatments showed to be safe.     

Climatotherapy of atopic dermatitis at the Dead Sea: demographic evaluation and cost-effectiveness

BACKGROUND: About 21% of the patients coming yearly to the DMZ Clinic at the Dead Sea for climatotherapy suffer from atopic dermatitis. This is a common, chronic, and relapsing disease which necessitates drug treatment (topical corticosteroids, antimicrobials, antihistamines, or immunomodulators), phototherapy, or climatotherapy. Objective and methods As the improvement in the condition of patients after 4 weeks of climatotherapy at the Dead Sea is remarkable, we undertook to evaluate the demographic factors that have the strongest impact on this beneficial effect, in adults and children. The major factors studied were: gender, previous medical history, previous stays at the Dead Sea, skin type, skin involvement, age, and duration of treatment. Results A retrospective study of 1718 patients revealed that previous treatments at the Dead Sea and stays longer than 4 weeks caused a clearance greater than 95%, the length of sun exposure was no longer than 5 h daily, and there was no impact of the percentage of skin involvement on the clearance of patients staying more than 4 weeks. CONCLUSION: s Climatotherapy of atopic dermatitis at the Dead Sea is a highly effective modality for treating this disease. It is also a highly cost-effective method, as the patients take no medications and experience no side-effects. Successful climatotherapy of atopic dermatitis requires strict medical supervision throughout the whole length of the patient's stay on shore.     

Differences in efficacy between intention-to-treat and per-protocol analyses for patients with psoriasis vulgaris and atopic dermatitis: clinical and pharmacoeconomic implications

BACKGROUND: Pharmacoeconomic outcome research is based on three criteria: (i) evaluation of objective therapeutic effects; (ii) quality of life; and (iii) treatment costs. Evaluation of therapeutic effect is mainly based on the results of clinical trials using objective clinical measures, e.g: Psoriasis Area and Severity Index (PASI) (score for psoriasis vulgaris) and the Severity Scoring of Atopic Dermatitis (SCORAD) (score for atopic dermatitis). In most studies, only results for a treatment-optimized subpopulation (patients treated according to the protocol) are presented in publications. The relevance of such data for daily routine therapy is doubtful. OBJECTIVES: Our purpose was to investigate the expected loss of effectiveness of switching from a clinical trial to daily routine therapy for the synchronous application of narrow-band ultraviolet (UV) B phototherapy (311 nm) and bathing in 10% Dead Sea salt solution (synchronous balneophototherapy) for patients with psoriasis vulgaris and atopic dermatitis. METHODS: We conducted a multicentre, uncontrolled observational study of outpatients. To achieve data for 'clinical trial' and 'daily routine' situations, two populations were compared: (i) all patients strictly treated according to the protocol (ATP) with no protocol deviations (data published in clinical trials), and (ii) all patients participating in the study who received active treatment at least once, despite treatment irregularities, non-compliance, early withdrawal or other protocol violations [intention-to-treat-population (ITT), model for 'daily routine']. RESULTS: A total of 2526 patients were included in the ITT analysis for psoriasis vulgaris (n = 487 for atopic dermatitis), of which 818 patients could be analysed according to protocol (n = 104 for atopic dermatitis). Striking differences in the therapeutic effect between both groups (ITT and ATP) were found using relative PASI and SCORAD score improvement: 11% (57% 'daily routine' vs. 68% in 'clinical trial') for psoriasis vulgaris and 16% (39% 'daily routine' vs. 55% 'clinical trial') for atopic dermatitis. The main reasons for excluding patients from the 'clinical trial' group were early study withdrawal in 29% (atopic dermatitis, 47%) of patients and fewer treatments per week than planned in the protocol in 24% (atopic dermatitis, 52%). CONCLUSIONS: Our data clearly indicate that for the prediction of the therapeutic effect for daily routine therapy the ITT data appear to be more relevant than the ATP results (i.e. those presented in clinical trials). Although these data are only a first step for evaluating the 'real' therapeutic effect of a treatment modality in daily routine, they seem to support the requirements for ITT analyses in efficacy studies and demonstrate the necessity of ITT data for pharmacoeconomic evaluation.     

Dead Sea climatotherapy for vitiligo: a retrospective study of 436 patients

Background Vitiligo is an acquired idiopathic skin disorder characterized by depigmented macules and patches. Despite many therapies available today, treatment of vitiligo remains a challenge. Preliminary reports cite encouraging results for Dead Sea Climatotherapy (DSC) in vitiligo patients. Objective To evaluate the efficacy of DSC in 436 patients suffering from vitiligo. Methods Files of 436 vitiligo patients, who were treated by DSC between the years 1997 and 2005 at the Deutsches Medizinisches Zentrum (DMZ) Medical Center, were retrieved for analysis. Climatotherapy, including gradually increased sun exposure following a sea bath, was administered in accordance with a computer‐designed protocol. Age at vitiligo onset, skin phototype, skin involvement, duration of disease, as well as timing and duration of DSC were recorded. Logistic regression was used to estimate the effect of each one of the parameters analysed on the treatment’s success. Results Following treatment, 3.9% of patients demonstrated total or significant repigmentation (defined by more than 50% repigmentation in more than 50% of the lesions); 81.4% showed good repigmentation; 13.1% showed no repigmentation but their vitiligo spots were pink‐colored and 1.6% appeared not to be affected at all by DSC. Patient response to the treatment was inversely proportional to the size of the affected area. A negative correlation was found between duration of the vitiligo and the clinical short‐term response to DSC. In addition, the longer the stay at the Dead Sea the better was the result. Conclusion Climatotherapy at the Dead Sea is an effective treatment modality for vitiligo. Disease duration and severity, as well as length of treatment, were the main factors found to favourably influence the clinical response.     

Clinical efficacy and safety of oral terbinafine in fungal mycetoma

OBJECTIVES: An open-label study was performed to assess the efficacy and safety of terbinafine in the treatment of eumycetoma. METHODS: Single-center, open-label study, including 27 patients with signs and symptoms of eumycetoma which had developed within 5 years and was confirmed by mycological examination. The intention-to-treat population (n=23) received 500 mg of terbinafine bid for 24-48 weeks. Efficacy evaluations included clinical signs and symptoms (e.g. sinuses open or closed, degree of tumefaction, and emission of grains either present or absent); mycological examinations from Week 24 onwards; and investigators' overall assessment of efficacy (cure, improved since baseline, unchanged since baseline, or deterioration since baseline). Safety evaluations included monitoring of adverse events, laboratory assessments, vital signs and physical examinations. RESULTS: Good clinical improvement was seen in patients who completed the study (n=20). Tumefaction was absent or improved in 80% of patients; sinuses were closed in 50% of patients, and grain emissions were absent in 65% of patients. Of the 16 patients who had repeat mycological assessment, four (25%) were mycologically cured. In the investigators' overall opinion at the end of the study, five (25%) were cured and 11 (55%) were clinically improved. The majority of adverse events reported were mild to moderate, and consistent with the known tolerability profile of terbinafine. CONCLUSION: High-dose terbinafine (1,000 mg/day) is well tolerated and clinically effective in patients with eumycetoma, a difficult-to-treat subcutaneous mycoses.     

Hair Removal Using a New Intense Pulsed Light Source in Chinese Patients

Background: Unwanted hair is a widespread cosmetic problem. Several lasers and intense pulsed light (IPL) have been utilized for this purpose. A new IPL device (Lumenis One^?) with OPT is one of the newer modalities to be studied in Chinese patients. Objective: This study evaluates the short-term efficacy and side effects of the new IPL device for epilation in Chinese patients. Methods: Eighteen Chinese women with Fitzpatrick skin types III–V and black hair, were treated four times at 4 to 6-week intervals using IPL (Lumenis One^?) on the axillae (n=13) and the upper lip (n=5). The energy density for treatment ranged from 14 to 22 J/cm². Parameters utilized were 695-/755-nm filters, triple pulse for patients on the axillae, and 640-/695-nm filters, double pulse for patients on the upper lip (3.5- to 7-ms pulse, 30- to 90-ms pulse delay, 15×35 mm spot size). Hair reduction was assessed at baseline, immediately before each treatment session, and at 4 weeks after the fourth treatment. Patient's satisfaction on a 5-point scale was also evaluated. Results: The average hair reduction for all sites was 49.9% after one session, 58.6% after two sessions, 79.3% after three sessions, and 83.8% after four sessions (p=0.001). The hair reduction of 44.1%, 52.1%, 81.1%, and 86.0% were achieved after each treatment for axillae, with 65.1%, 75.7%, 74.6%, and 78.0% for upper lip. Patients got more satisfaction after four sessions (score 3.1) than that after two sessions (2.0) (p=0.001). In both the assessments, upper lip appeared to show a better response than axillae after two IPL treatments, which reversed after four treatments. No significant complications or adverse events were reported. Conclusion: The new IPL device provides a safe and effective means of hair removal for Chinese patients. Treatment efficacy varies with the anatomic location and number of treatments. However, further study is necessary to determine the long-term clinical efficacy in Chinese patients.     

Pulsed alexandrite laser for treatment of melasma in Asian patients

Background: Melasma is a common acquired facial hypermelanosis with irregular brownish macules and patches. The clinical course is often fluctuated and refractory to treatment. The present study was conducted to evaluate the efficacy and safety of pulsed alexandrite laser for the treatment of melasma. Materials and methods: In the present study, we enrolled Asian patients with melasma. All the patients received four monthly treatments with a pulsed alexandrite laser. The severity of melasma was evaluated by a blinded dermatologist, using the Modified Melasma Area and Severity Index (MMASI), and by patient assessment, using a visual analogue scale, at baseline, before each treatment, and at the 1-month and 3-month follow-up visits after the last treatment. Results: Twenty-three patients completed all treatments and follow-up visits. The MMASI scores decreased significantly from 8.71 ± 5.83 at baseline to 6.07 ± 4.65 after four sessions of treatment (P < 0.05) and 6.91 ± 4.97 at 3 months after the last laser treatment (P < 0.05). After 4 sessions of treatment, 10 patients (43.5%) described their improvement as marked and excellent (>60% improvement). The treatments were well tolerated with only mild skin reaction. Conclusion: In the present study, we demonstrated that the pulsed alexandrite laser is safe and effective to treat melasma in Asian skin.     

Tazarotene gel with narrow-band UVB phototherapy: a synergistic combination in psoriasis

Background: Narrow-band UVB (NB-UVB) has been shown to be one of the most effective treatment modalities for psoriasis. Tazarotene, a known effective anti-psoriatic modality, when combined with NB-UVB may enhance the therapeutic success.Objective: To study clinical efficacy and safety of combination of NB-UVB with topical tazarotene 0.05% gel in psoriasis.Method: Thirty patients with plaque psoriasis having symmetrical lesions were enrolled for 12 weeks. All patients were instructed to apply tazarotene gel on target plaque on left side of body once daily. In addition, the whole body was irradiated with NB-UVB twice weekly. Efficacy was assessed by target plaque scoring and number of treatment sessions for clearance.Result: Our study resulted in 3 key findings: Firstly, therapeutic efficacy of NB-UVB was enhanced by addition of tazarotene. This enhanced efficacy was more apparent in decreasing scaling and thickness as compared to decrease in erythema. Secondly, combination therapy showed faster clearance of target plaques, with reduction in mean number of treatment sessions. Thirdly, mean cumulative NB-UVB dose needed to achieve clearance of target plaques was significantly reduced with combination therapy.Study limitations: The study was not randomized or controlled, but an open-label trial. The study period was relatively short, i.e., 12 weeks, without any follow-up period.Conclusion: Tazarotene gel significantly enhances the therapeutic efficacy of NB-UVB irradiation with faster clearance and without serious side effects.     

Topical methyl aminolaevulinate photodynamic therapy for treatment of facial acne vulgaris: results of a randomized, controlled study

BACKGROUND: There is a need for alternative treatments for moderate to severe acne vulgaris. Preliminary experience suggests that topical methyl aminolaevulinate photodynamic therapy (MAL-PDT) may have potential. OBJECTIVES: To investigate the efficacy and tolerability of MAL-PDT for treatment of moderate inflammatory facial acne. PATIENTS/METHODS: Thirty patients aged 15-28 years with moderate to severe acne were included in a blinded, prospective, randomized, placebo-controlled multicentre study. Each side of each patient's face was randomly assigned to treatment with MAL (160 mg g1) or placebo cream, applied for 3 h prior to illumination. A second treatment was given 2 weeks later. On each occasion, patients assessed the intensity of pain using a 10-cm visual analogue scale. Inflammatory and noninflammatory acne lesions were counted at baseline and 4 and 10 weeks after the last PDT treatment. The investigator assessed the global severity of acne at baseline (seven patients had severe acne on at least one side of the face) and each study visit using a six-point rating scale. Data were analysed on an intention-to-treat basis, including all 30 patients. RESULTS: There was a statistically significant greater reduction in the total inflammatory lesion count with MAL-PDT compared with placebo PDT at week 12; median reduction 54% [95% confidence interval (CI) 35-64%] vs. 20% (95% CI 8-50%), P = 0.0006. MAL-PDT was associated with more pain than placebo PDT, although intensity varied across centres and was reduced with repeated treatment. Local adverse events were consistent with this treatment modality. CONCLUSIONS: MAL-PDT is effective in the treatment of moderate to severe inflammatory facial acne. Further studies are warranted to optimize this promising procedure.     

Photodynamic therapy with 5‐aminolevulinic acid in actinic cheilitis: an 18‐month clinical and histological follow‐up

Background Actinic cheilitis (AC) may bear the initial and superficial changes of actinically induced squamous cell carcinoma (SCC) and may progress into fully developed SCCs. Early and effective treatment is important. Objective To assess the clinical and histological long‐term outcome in AC after two ALA‐PDT sessions. Methods Patients with histologically proven grade 1 and 2 AC received two ALA‐PDT sessions at 2 weeks interval. Subjects with complete clinical response at 3 months were evaluated further clinically and histologically at months 6, 12 and 18. Long‐term study outcome was defined as clinical and histological AC recurrence among patients with complete clinical response 3 months after treatment. Cosmetic outcome was assessed by the investigators at the final follow‐up visit at 18 months. Results Of the 40 patients enrolled, 38 completed the study. Complete clinical response at 3 months was achieved in 26 patients. At 6 months, clinical and histological recurrence occurred in three patients and at 12 months, one more patient showed clinical and histological recurrence. At 18 months, overall clinical recurrence rate was 15.38% (4/26), while overall histological recurrence rate was 34.61% (9/26). Cosmetic outcome was rated as excellent in more than 80% of evaluated cases. Conclusion PDT represents a moderately effective treatment modality in AC. Optimization of treatment procedure and protocols is still needed for higher response rates to be achieved. Moreover, the high treatment cost should be given consideration. Further long‐term follow‐up studies are needed for assessment of clinical and histological very late recurrences that could be expected after PDT.     

Climatotherapy at the Dead Sea for Pediatric-Onset Psoriasis Vulgaris

Abstract:   Climatotherapy at the Dead Sea is highly effective and safe for the treatment of psoriasis vulgaris in adults. We examine the efficacy and safety of climatotherapy at the Dead Sea in children with psoriasis vulgaris. More than 75% improvement in the Psoriasis Area and Severity Index was noted in 35.3% of the patients. None of the patients had side effects.     

Efficacy and safety of adalimumab when added to inadequate therapy for the treatment of psoriasis: results of PRIDE, an open-label, multicentre, phase IIIb study

Background Adalimumab is an effective treatment for chronic plaque psoriasis. Objective To evaluate the safety and efficacy of adalimumab for psoriasis patients who did not adequately respond to prior psoriasis therapy. Methods PRIDE (an Open‐Label Access PR ogram to Evaluate the Safety and Effectiveness of Adalimumab When Added to I naDE quate Therapy for the Treatment of Psoriasis) was a multicentre, Phase IIIb study in Canada. Patients with active moderate‐to‐severe plaque psoriasis who failed to respond to, or were intolerant of, prior therapies received adalimumab 80 mg at Week 0 followed by adalimumab 40 mg every other week Weeks 1 through 23. The primary efficacy measure was PASI (Psoriasis Area Severity Index) 75 response at Week 16. Secondary efficacy measures included PASI 90/100 and percentage change from baseline PASI score. Adverse events (AEs) and serious AEs were recorded. Results A total of 203 patients were enrolled at 26 sites. Baseline characteristics were: male, 61.1%; mean age, 45.5 years; mean PASI score, 20.0; previous exposure to biologics, 38.4%. At Week 16, PASI 75/90/100 responses were achieved by 70.9%/49.3%/24.1% of patients, respectively. Mean percentage PASI score decrease from baseline to Week 16 was 79.5%. Mean percentage PASI improvement and response rates were maintained through Week 24. Nasopharyngitis and upper respiratory tract infection were the only AEs to occur in ≥5% of patients. Nine patients experienced serious AEs; four were considered possibly or probably related to adalimumab. Conclusion Adalimumab was safe, well‐tolerated and effective for treatment of active plaque psoriasis in patients who had not adequately responded to prior therapy.     

Treatment of port-wine stains with a noncoherent pulsed light source: a retrospective study.

OBJECTIVE: We investigated whether a noncoherent intense pulsed light source (IPLS) would be effective in therapy of port-wine stains (PWSs). DESIGN: To evaluate the efficacy in treatment of PWSs with IPLS, a retrospective study was initiated. SETTING: The data were collected by physicians working in private practices and departments of university hospitals and medical centers, respectively. PATIENTS: A total of 37 randomly selected patients with a total of 40 PWSs were included in the study. Clinical PWS characteristics recorded were color and location of the PWS. INTERVENTIONS: All patients were treated with IPLS. MAIN OUTCOME MEASURES: Data collected included treatment parameter (filters, pulse duration, fluence, and pulse sequencing), percentage of clearance, and side effects (purpura, blisters, crusting, altered pigmentation, and scarring). RESULTS: Good and complete (70%-100%) clearance was achieved in 28 of 40 PWSs treated with IPLS. The average number of treatment sessions in PWSs reaching 100% clearance included 4.0 for pink PWSs and 1.5 for red PWSs. The average number of sessions for purple PWSs reaching good clearance (70%-99%) was 4.2 sessions. Parameters used most frequently were 515- and 550-nm cut-off filters, pulse duration of 2.5 to 5.0 milliseconds, and fluences of 24 to 60 J/cm2. Side effects included purpura in 133 (76%), superficial blisters in 14 (8%), and crusting in 35 (20%). Transient pigmentation changes were seen in 10.8% of patients (hypopigmentation in 3 [8.1%], hyperpigmentation in 1 [2.7%]). No scarring was observed. CONCLUSION: Intense pulsed light source presents an effective and safe method for treating PWSs, especially purple PWSs.     

Utilizing fractional resurfacing in the treatment of therapy-resistant melasma.

BACKGROUND: Multiple treatment modalities have been employed for the management of melasma with minimal to no success. OBJECTIVE: We propose fractional resurfacing as a new treatment modality for melasma. METHODS: A 31-year-old Caucasian female with facial epidermal and dermal melasma, resistant to multiple courses of topical therapies, was treated with two sessions of full-face fractional resurfacing (Fraxel(TM) Laser; Reliant technologies, San Diego, CA), separated by a three-week interval. Clinical improvement was assessed by Wood's Lamp examination as well as parallel and cross-polarized comparative photography at baseline and 6 months later. RESULTS: Marked reduction in epidermal and dermal facial pigmentation was observed at the six-month follow-up visit. CONCLUSION: Fractional resurfacing may prove to be an effective and safe treatment modality for lightening of the epidermal and dermal pigmentation of melasma. Further studies with long-term follow-up periods and multiple patients with diverse skin phototypes and different variants of melasma are warranted.     

Evaluation of a multicentre study of synchronous application of narrowband ultraviolet B phototherapy (TL-01) and bathing in Dead Sea salt solution for psoriasis vulgaris

The synchronous application of narrowband UVB phototherapy with 311 nm lamps (Philips TL-01) and bathing in Dead Sea salt solution was evaluated in a multicentre trial (n = 60) in outpatients suffering from psoriasis vulgaris. The study design consisted of an initial therapy phase of up to 35 treatments (three to five times a week) followed by maintenance therapy with up to 35 further applications (once or twice a week). Evaluation was performed separately for patients in according-to-protocol (ATP) (n = 280) and intention-to-treat (ITT) (n = 692) groups. An overall significant improvement of the Psoriasis Area and Severity Index (PASI) score (P < 0.05) could be shown for both groups during initial therapy with 71.4% improvement for ATP and 61% for ITT patients. The mean PASI for ATP (values for ITT in parentheses) was 17.7 (18.6) at baseline, 9.5 (10.7) after 20 applications and 5.2 (7.4) at the end of initial therapy. On average, ATP patients received 3.9 (3.5) applications per week with a cumulative irradiation dose of 19.5 J cm-2 (16.2 J cm-2). The most frequent side-effect was erythema, observed in 8.7% of the patients. Subjective evaluation of the therapy by the patients (n = 168) was excellent. Seventy-nine per cent of patients preferred the new treatment strategy in comparison with other previous therapies and 88% regarded this therapy as pleasant and comfortable. In conclusion, we could demonstrate a significant effect of therapy in both the ATP and the ITT groups for this new treatment system which imitates, as far as possible, the Dead Sea climatic conditions, with no severe side-effects and a high acceptance by the patients.     

Adalimumab in Japanese patients with active ulcers of pyoderma gangrenosum: Twenty-six-week phase 3 open-label study

This phase 3 multicenter study, including 26-week treatment and extension periods, evaluated the efficacy and safety of adalimumab in Japanese patients with active ulcers due to pyoderma gangrenosum. Patients received adalimumab 160 mg at week 0, 80 mg at week 2, and then 40 mg every week starting at week 4. Of the 22 enrolled patients, 12 (54.5%, P < 0.001) achieved the primary efficacy end-point of pyoderma gangrenosum area reduction 100 (PGAR 100, defined as complete skin re-epithelialization) for the target ulcer at week 26 assessed by digital planimetry. PGAR 100 response was observed as early as week 6 (13.6%) and continued to increase over time. The mean percent change from baseline in target ulcer area was −31.8% at week 6 and −63.8% at week 26. A Physician’s Global Assessment score of 0 (PGA 0, all ulcers completely clear) was achieved by two patients (9.1%) at week 6 and eight (36.4%) at week 26, while PGA 0/1 (completely/almost clear) was achieved by five (22.7%) and 12 patients (54.5%) at week 6 and 26, respectively. Mean changes from baseline in pain numeric rating scale (−1.8 at week 6 and −2.5 at week 26) and the Dermatology Life Quality Index (−3.1 at week 6 and −3.6 at week 26) improved over time. Adverse events were reported by 18 patients, most commonly infections (n = 11), and serious adverse events by four. These results suggest that adalimumab is effective and generally well tolerated in Japanese patients with active ulcers of pyoderma gangrenosum.     

Rapid initiation of repigmentation in vitiligo with Dead Sea climatotherapy in combination with pseudocatalase (PC-KUS)

BACKGROUND: Low catalase levels and cellular vacuolation in the epidermis of patients with vitiligo support major oxidative stress in this compartment. There is now in vivo evidence for increased epidermal hydrogen peroxide (H(2)O(2)) accumulation in this patient group by utilizing noninvasive Fourier Transform Raman spectroscopy (FT Raman). Epidermal H(2)O(2) can be removed with a topical application of narrow band UVB activated pseudocatalase cream (PC-KUS). (Mn/EDTA-bicarbonate complex, patent No. EPO 58471 1 A), yielding initiation of repigmentation. Dead Sea climatotherapy is another successful treatment modality for vitiligo, but the mode of action has escaped definition so far. METHODS: Epidermal hydrogen peroxide (H(2)O(2)) was assessed in vivo before and after 21 days treatment at the Dead Sea using noninvasive Fourier-Transform Raman spectroscopy. The effectiveness of repigmentation was followed in 59 patients with vitiligo by comparing Dead Sea climatotherapy alone with the combination of Dead Sea climatotherapy/pseudocatalase cream (PC-KUS) as well as Dead Sea climatotherapy/placebo cream. Clinical repigmentation was documented by standardized black/white photography using non-UV coated bulbs as flashlight and by color photography. RESULTS: This study on 59 patients who had vitiligo for an average time of 17 years (range 3-53 years) confirmed in vivo H(2)O(2) accumulation in mM concentrations in the epidermis of untreated patients. Furthermore, we demonstrated a pseudocatalase activity after 15 min of Dead Sea bathing, but the decrease of epidermal H(2)O(2) levels was significantly less compared to narrowband UVB activated pseudocatalase cream (PC-KUS). Initiation of repigmentation was already observed between day 10 and day 16 after a combination of Dead Sea climatotherapy/pseudocatalase cream compared to conventional pseudocatalase monotherapy (8-14 weeks) and Dead Sea climatotherapy alone (5-6 weeks). CONCLUSION: The results of this study show a significantly faster initiation of repigmentation in vitiligo after a combination of short-term climatotherapy (21 days) at the Dead Sea in combination with a pseudocatalase cream (PC-KUS) compared to either conventional climatotherapy at the Dead Sea alone or with placebo cream in combination with climatotherapy. This combined therapy is significantly faster in repigmentation than narrowband UVB activated pseudocatalase cream (PC-KUS) treatment alone. The results of this study support the necessity of epidermal H2O2 removal as well as the influence of solar UV-light in the successful treatment of vitiligo.     

CLinical Experience Acquired with Raptiva® (CLEAR) trial in patients with moderate‐to‐severe plaque psoriasis: results from extended treatment in an international,Phase III,placebo‐controlled trial

Background: The 12‐week, double‐blind, placebo‐controlled, first‐treatment (FT) CLEAR trial period demonstrated the efficacy/safety of efalizumab in moderate‐to‐severe plaque psoriasis, including refractory or contraindicated patients unsuitable for other systemic treatments. This study assessed the efficacy/safety of open‐label extended treatment (up to 24 weeks' continuous treatment) in patients not achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI‐75) at week 12 of the FT period. Time to relapse after treatment cessation, and efficacy/safety of 12 weeks' open‐label re‐treatment in patients achieving PASI‐75 at week 12 FT were also assessed. Patients and methods: Patients with PASI‐75 at week 12 FT were observed without treatment until relapse, then re‐treated with open‐label efalizumab (1.0 mg/kg/week for 12 weeks). Others received open‐label extended treatment without intervening observation. Results: Among efalizumab‐treated patients (n = 308) who had < 75% PASI improvement at week 12 FT, extended treatment led to PASI‐75 in 26.6%. Among patients with between ≥ 50 and < 75% PASI improvement at week 12 FT (n = 118), 47.5% improved to PASI‐75 with extended treatment. Forpatients achieving PASI‐75 at week 12 FT (n = 164), median time to relapse was 58 days. Re‐treatment after relapse led to mean PASI improvement of 62.3% from study baseline (n = 145). Safety results were consistent with pre‐vious studies, with no new safety concerns. Conclusions: These results demonstrate additional benefit of continuing efali‐zumab. Re‐treatment re‐established disease control in patients with PASI‐75 who relapsed following treatment cessation. The safety profile remained consistent with that seen at 12 weeks.     

Use of a novel combined radiofrequency and ultrasound device for lipolysis,skin tightening and cellulite treatment

Introduction: Skin laxity and excessive subcutaneous fat are growing cosmetic concerns. The objective of this study is to evaluate the efficacy and safety of a novel radiofrequency and ultrasound workstation for lipolysis, circumference reduction, treatment of skin laxity and cellulite. Materials and methods: Two hundred seventy-five (235 women and 40 men) patients were enrolled into the study. Each patient received 3 treatment sessions, each session comprising Ultrasound and Radiofrequency treatments, at two-week intervals. Some received treatment for the abdomen, some for the thighs and some for both. Efficacy was assessed accordingly by measuring changes in abdominal circumference, thigh circumference and appearance of cellulite. Any adverse effect was noted. Result: Paired t-test between measurements at baseline and 4 weeks after 3rd session was significant amongst all the groups, showing that most patients showed improvement in abdominal and/or thigh circumferences. No significant adverse effects were noted during or after the treatment. Conclusion: A combination of alternating hot and cold module Ultrasound and Radiofrequency technologies is a safe and effective modality for lipolysis and to treat skin laxity and cellulite.