Secukinumab demonstrates high efficacy and a favourable safety profile in paediatric patients with severe chronic plaque psoriasis: 52-week results from a Phase 3 double-blind randomized, controlled trial.

BACKGROUND: Secukinumab has demonstrated sustained long-term efficacy with a favourable safety profile in various psoriatic disease manifestations in adults. OBJECTIVES: Here, the efficacy and safety of two secukinumab dosing regimens [low dose (LD) and high dose (HD)] in paediatric patients with severe chronic plaque psoriasis over one year are reported. METHODS: In this multicentre, double-blind study (NCT02471144), patients aged 6 to <18 years with severe chronic plaque psoriasis were stratified and randomized by weight (<25 kg, 25 to <50 kg, ≥50 kg) and age (6 to <12 years, 12 to <18 years) to receive low-dose (LD: 75/75/150 mg) or high-dose (HD: 75/150/300 mg) subcutaneous secukinumab or placebo or etanercept 0.8 mg/kg (up to a max of 50 mg). RESULTS: Overall, 162 patients were randomized to receive secukinumab LD (n = 40) or HD (n = 40), etanercept (n = 41) or placebo (n = 41). The co-primary objectives of the study were met with both secukinumab doses (LD and HD) showing superior efficacy compared to placebo (P < 0.0001) with respect to PASI 75 response (80.0%, 77.5% vs. 14.6%) and IGA mod 2011, 0 or 1 response (70%, 60% vs. 4.9%) at Week 12. Both secukinumab doses were superior to placebo (P < 0.0001) with respect to PASI 90 response at Week 12 (72.5%, 67.5% vs. 2.4%). The efficacy of both doses was sustained to Week 52 with secukinumab achieving higher responses vs. etanercept (PASI 75/90/100: LD, 87.5%/75.0%/40.0% and HD, 87.5%/80.0%/47.5.% vs. etanercept, 68.3%/51.2%/22.0% and IGA 0 or 1: LD, 72.5% and HD, 75.0% vs. etanercept, 56.1%). The safety profile of secukinumab was consistent with the adult Phase 3 studies, with no new safety signals identified. CONCLUSIONS: Both doses of secukinumab demonstrated high and sustained efficacy up to Week 52 with a favourable safety profile in paediatric patients with severe chronic plaque psoriasis.

The regular use of an emollient improves symptoms of atopic dermatitis in children: a randomized controlled study.

BACKGROUND: Emollients are considered as a first-line therapy for the treatment of atopic dermatitis (AD). However, evidence-based proof that the regular use of emollients reduces AD severity is lacking. OBJECTIVE: To assess whether the regular use of emollients results in a reduction in AD severity in children with AD. METHODS: In this multicentre randomized, parallel group, open-label study, children with mild-to-moderate AD were recruited during a flare. After flare resolution with a topical corticosteroid, patients were randomized to V0034CR emollient, reference emollient or no emollient (1:1:1 ratio), for 12 weeks. AD severity was assessed regularly by physicians [Scoring for Atopic Dermatitis (SCORAD) and subcomponents, IGA] and by parents (PO-SCORAD and POEM). RESULTS: A total of 335 patients were randomized to V0034CR (n = 111), reference emollient (n = 116) or no emollient (n = 108). After 12 weeks of treatment, SCORAD score was reduced by 5.28 points in the V0034CR group and by 3.36 points in the reference emollient group compared with the no emollient group (+4 points; P < 0.001 in both emollient groups vs. no emollient group). In a similar manner, PO-SCORAD score was reduced by 4.88 and 2.67 points in the V0034CR and reference emollient groups, respectively, but increased by 2.90 points in the no emollient group (P < 0.001). Similar results were observed for POEM. A continuous decrease in all scores was observed over the 12-week treatment period. At the end of the study, the percentage of patients in complete remission (i.e. without a new flare over the treatment period) was higher in the V0034CR (59.5%) and reference emollient (44.3%) groups than in the no emollient group (29.8%; P < 0.001). CONCLUSION: These results demonstrate that the regular use of emollients in children with mild-to-moderate AD reduces the severity of symptoms and, therefore, support their use as a first-line treatment for these patients.

Genetic and environmental predictors of chronic kidney disease in patients with type 2 diabetes and diabetic foot ulcer: a pilot study.

Chronic kidney disease (CKD) is often observed among patients with type 2 diabetes mellitus (T2DM) and diabetic foot (DF) leading to end stage renal disease. The aim of this pilot study was to determine genetic and environmental factors involved in the etiology of CKD among patients with DF. The following polymorphisms were studied: rs1800469, rs759853, rs1553005, rs1799983, rs1801133, rs3134069, rs2073618, rs8192678, rs6330, rs11466112, rs121917832 in terms of alleles distribution in patients with DF and T2DM, with or without CKD. The study includes 101 patients with T2DM and DF. Studied groups were divided into 39 individuals with CKD (cases) and 62 controls, depending on the presence of kidney failure defined as eGFR < 60ml/min/1.73m(2) and coexistence of microalbuminuria > 30 mg/dl in at least 3 urine samples. Cases and controls were matched according to mean age, gender, mean duration of T2DM, mean duration of insulin therapy, mean duration of DF cholesterol levels and smoking frequencies. The study showed that CKD risk factors were the following variables: creatinine level, body weight, hips circumference, ischemic heart disease, hypertension and diabetic retinopathy. Moreover, the results suggest the protective role of the allele C of rs3134069 polymorphism in CKD development in patients with T2DM and DF in the following allelic variants: [AA] vs. [AC] and [AA] vs. [AC + CC]. The allele C was observed to be less frequent than the allele A in patients with T2DM and DF. None of the other following polymorphisms was observed to be a potential risk factor of CKD in T2DM and DF population: rs6330, rs759853, rs1553005, rs1799983, rs1801133, rs1800469, rs8192678, rs11466112, rs121917832. We concluded that the rs3134069 polymorphism seems to be the most likely protective genetic factor in CKD development in patients with T2DM and DF.

Impact of psoriasis severity on family income and quality of life.

BACKGROUND: Psoriasis is a common disease and the costs of its therapy, medical care and loss of productivity are a major financial burden for patients and society. The financial status of psoriasis patients and its relationship with disease severity and quality of life (QoL) remains ill characterized. OBJECTIVE: The aim of this study was to assess the economic status of psoriasis patients and to investigate its correlation with disease severity and its impact on QoL. METHODS: A total of 83 (45 male) psoriasis patients, treated at a Polish specialty clinic, were assessed for their financial and employment status. QoL was measured with a generic (WHOQOL-BREF) and a skin disease-related QoL instrument (dermatology life quality index--DLQI). The effects of demographic and clinical variables, including disease severity measured by Psoriasis Area and Severity Index (PASI), on the family income of patients were analyzed by multiple logistic regression. The mediating effect of family income between PASI and QoL was assessed by using the Baron and Kenny's procedure. RESULTS: Patients' family income correlate negatively with psoriasis severity (Spearman's rho = -0.356; P < 0.01). Disease severity in patients with a family income below the social minimum was significantly higher (PASI: 20.5 ± 12.2) than in patients with a higher family income (PASI: 11.7 ± 7.7, P < 0.001). We found that education, disease severity and age predict 50% of the variability in family income (P < 0.001). Disease severity showed the second strongest impact on income after education (P < 0.01). Family income was found to link disease severity to global QoL impairment (P < 0.05). CONCLUSION: Disease severity negatively affects the financial status of psoriasis patients, which in turn, is a mediator of global QoL impairment. Our findings are alarming and call for long-term solutions that equalize employment opportunities for patients with psoriasis.

Long-term emollient therapy improves xerosis in children with atopic dermatitis.

BACKGROUND: Hydration with topical emollients forms the backbone of treatment for mild atopic dermatitis (AD), but few randomized controlled trials have assessed their efficacy in young children. OBJECTIVES: Assess the efficacy and tolerability of long-term emollient therapy in the treatment of moderate to severe xerosis in young children with AD. METHODS: This was a phase III, multicentre, double-blind, randomized, vehicle-controlled trial. Children (n = 251) aged 2-6 years with AD-associated xerosis were randomized 1 : 1 to a 28-day treatment with an emollient combining glycerol and paraffin or its vehicle. Non-responders at the end of the double-blind period were treated open label with emollient until day 84. Responders stopped treatment until reassessment on day 56. Those who relapsed after stopping treatment were treated open label with emollient until day 84. RESULTS: During the double-blind period, xerosis score (XS) of the scoring atopic dermatitis (SCORAD) index, objective SCORAD and visual analogue score decreased and skin hydration increased more in the emollient group than in the vehicle group (P < 0.001 for all measures). More patients were responders with emollient than with vehicle (66.1% vs. 45.6%, P < 0.001). During the open-label period, stopping emollient treatment led to relapse but improvement returned if treatment was restarted with emollient. Regular use of the emollient also yielded improvement in children who did not initially respond. Adverse events were similar in the two groups, and no treatment-related severe adverse events were reported. CONCLUSIONS: Long-term therapy with emollient is effective and well tolerated for the treatment of xerosis in children with atopic dermatitis.

Adapalene-benzoyl peroxide, a unique fixed-dose combination topical gel for the treatment of acne vulgaris: a transatlantic, randomized, double-blind, controlled study in 1670 patients.

BACKGROUND: Combination therapy utilizing agents with complementary mechanisms of action is recommended by acne guidelines to help simultaneously target multiple pathogenic factors. A unique, topical, fixed-dose combination gel with adapalene 0.1% and benzoyl peroxide (BPO) 2.5% has recently been developed for the once-daily treatment of acne. OBJECTIVES: To evaluate the efficacy and safety of adapalene 0.1%-BPO 2.5% fixed-dose combination gel (adapalene-BPO) relative to adapalene 0.1% monotherapy (adapalene), BPO 2.5% monotherapy (BPO), and the gel vehicle (vehicle) in a large population for the treatment of acne vulgaris. METHODS: In total, 1670 subjects were randomized in a double-blind controlled trial to receive adapalene-BPO, adapalene, BPO or vehicle for 12 weeks (1 : 1 : 1 : 1 randomization). Evaluations included success rate (subjects 'clear' or 'almost clear'), percentage change in lesion count from baseline, cutaneous tolerability and adverse events. RESULTS: Adapalene-BPO was significantly more effective than corresponding monotherapies, with significant differences in percentage lesion count change observed as early as 1 week. Cutaneous tolerability profile was similar to adapalene. Adverse events were more frequent with the combination therapy (mainly due to an increase in mild-to-moderate dry skin), occurred early in the study, and were transient. CONCLUSIONS: Adapalene-BPO provides significantly greater and synergistic efficacy and a faster onset of action with an acceptable safety profile in the treatment of acne vulgaris when compared with the corresponding vehicle and the adapalene and BPO monotherapies.

Once weekly administration of etanercept 50 mg is efficacious and well tolerated in patients with moderate-to-severe plaque psoriasis: a randomized controlled trial with open-label extension.

BACKGROUND: In previous studies, etanercept 25 mg twice weekly (BIW) or 50 mg BIW significantly reduced disease severity in patients with plaque psoriasis and demonstrated a favourable safety profile. OBJECTIVES: To assess the efficacy and safety of etanercept 50 mg administered once weekly (QW) compared with placebo in patients with moderate-to-severe plaque psoriasis over 24 weeks. METHODS: This study was conducted in two parts: (i) a 12-week, double-blind, placebo-controlled phase, in which patients received etanercept 50 mg QW or placebo QW; and (ii) a 12-week, open-label extension phase, in which all patients received etanercept 50 mg QW. Primary endpoint was a 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 12. Secondary endpoints included percentage PASI improvement and Physician's Global Assessment (PGA). RESULTS: One hundred and forty-two patients were analysed in the double-blind phase; 126 patients entered the open-label phase. At week 12, significantly more patients receiving etanercept 50 mg QW (37.5%) achieved PASI 75 response than patients receiving placebo (2.2%; P < 0.0001). At week 24, 71.1% in the etanercept-etanercept group and 44.4% in the placebo-etanercept group achieved PASI 75. Mean percentage of PASI improvement from baseline was 55.4% with etanercept vs. 9.4% worsening with placebo at week 12 (P < 0.0001), with 77.4% and 57.7% improvement in the etanercept-etanercept and placebo-etanercept groups at week 24. A PGA score of 0-1 (clear-almost clear) was achieved by 64% and 42% in the etanercept-etanercept and placebo-etanercept groups at week 24, respectively. Etanercept 50 mg QW was well tolerated. No deaths, serious infections, opportunistic infections (including tuberculosis), demyelinating disorders, malignancies or new safety signals were reported. CONCLUSIONS: Nearly three-quarters of patients with moderate-to-severe psoriasis receiving etanercept 50 mg QW achieved significant improvement in disease severity over 24 weeks. This study also showed a favourable tolerability and safety profile with etanercept 50 mg QW.

Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Patients with severe chronic hand eczema (CHE) refractory to topical corticosteroids currently have limited treatment options suited for chronic use, and few controlled clinical studies have investigated new therapies in this setting. OBJECTIVES: To assess the efficacy and safety of oral alitretinoin (9-cis retinoic acid) taken at 10 mg or 30 mg once daily for up to 24 weeks, compared with placebo control, in the treatment of severe CHE refractory to topical corticosteroids. METHODS: A randomized, double-blind, placebo-controlled, prospective, multicentre trial was conducted in 111 dermatology outpatient clinics in Europe and Canada. A total of 1032 patients with severe refractory CHE were randomized in a 1 : 2 : 2 ratio to placebo, or 10 mg or 30 mg of oral alitretinoin once daily for up to 24 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for relapse for 24 weeks after the end of therapy. The primary efficacy parameter was Physician Global Assessment of overall CHE severity, with response defined as clear or almost clear hands. RESULTS: Responses, defined as clear or almost clear hands, were achieved in up to 48% of patients treated with alitretinoin, compared with 17% for placebo (P < 0.001), with up to 75% median reduction in disease signs and symptoms. Treatment was well tolerated, with dose-dependent adverse effects comprising headache, mucocutaneous events, hyperlipidaemia, and decreased free thyroxine and thyroid-stimulating hormone. The median time to relapse, defined as recurrence of 75% of initial signs and symptoms, was 5.5-6.2 months in the absence of anti-eczema medication. CONCLUSIONS: Alitretinoin given at well-tolerated doses induced clearing of CHE in a substantial proportion of patients with severe disease refractory to standard therapy.

Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled multicentre study.

BACKGROUND: Chronic urticaria is one of the most common and disturbing cutaneous condition. The treatment of chronic idiopathic urticaria (CIU) is still a challenge. Antihistamines are recommended as first-line treatment. Rupatadine is a new potent nonsedative anti-H1. OBJECTIVE: To study rupatadine efficacy and safety for moderate to severe CIU treatment. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, multicentre, study was designed to assess primarily mean pruritus score (MPS) reduction with rupatadine, 10 and 20 mg, administered once daily for 4 weeks. Three hundred and thirty-three patients with active episodes of moderate-to-severe CIU were included. RESULTS: A 57.5% (P < 0.005) and 63.3% (P = 0.0001) significative MPS reduction from baseline, was observed at week 4 with 10 and 20 mg rupatadine, respectively, compared with placebo (44.9%). Both doses of rupatadine were not significantly different at any time point, with respect to their effects on pruritus severity, number of wheals and total symptoms scores. Rupatadine 10 mg had an overall better adverse event profile. CONCLUSION: Rupatadine 10 mg is a fast, long-acting, efficacious and safe treatment option for the management of patients with moderate-to-severe CIU.

[Effectiveness of a micronized purified flavonoid fraction (MPFF) in the healing process of lower limb ulcers. An open multicentre study, controlled and randomized]. / Efficacia della frazione flavonoica purificata micronizzata (FFPM) nell'aumentare la guarigione della ulcere agli arti inferiori. Studio multicentrico in aperto, controllato e randomizato.

OBJECTIVE: To determine the increase in healing rate of venous ulcer in patients receiving a micronised purified flavonoid fraction (MPFF) as supplementation to standard local care. DESIGN: A randomised, open, controlled, multicentre study. SETTING: Departments of Dermatology and University Outpatients Clinics. PATIENTS: One hundred and forty patients with chronic venous insufficiency and venous ulcers. INTERVENTION: PATIENTS received standard compressive therapy plus external treatment alone or 2 tablets of MPFF daily in addition to the above treatment for 24 weeks. MAIN OUTCOME MEASURE: Healing of ulcers and their reduction in size after 24 weeks of treatment. RESULTS: The percentage of patients whose ulcers healed completely was found to be markedly higher in those receiving MPFF in addition to standard external and compressive treatment than in those treated with conventional therapy alone (46.5% vs 27.5%; p<0.05. OR=2.3, 95% CI 1.1-4.6). Ulcers with diameters <3 cm were cured in 71% of patients in the MPFF group and in 50% of patients in the control group, whereas ulcers between 3 and 6 cm in diameter were cured in 60% and 32% of patients (p<0.05), respectively. The mean reduction in ulcer size was also found to be greater in patients treated with MPFF (80%) than in the control group (65%) (p<0.05). The cost-effectiveness ratio (cost per healed ulcer) in the MPFF group was 1026.2 compared with 1871.8 in the control group. CONCLUSIONS: These results indicate that MPFF significantly improves the cure rate in patients with chronic venous insufficiency.

Fungal flora in human skin and skin appendages infections in the region of Lódz, Poland.

In the years 1987-95, 3550 patients with mycotic skin infections were divided into two groups: a group of 2282 (64.3%) subjects with dermatophytosis and a group of 1268 (35.7%) subjects with other fungal infections. Among dermatophytes the most common infectious agent was Trichophyton mentagrophytes (33%), followed by T. rubrum (30%) and Microsporum canis (11%). A total of 17% of all infections were caused by Candida sp.

[White blood cell picture of the peripheral blood of psoriatic patients treated with PUVA and cignoline]. / Obraz bialokrwinkowy krwi obwodowej chorych na luszczyce leczonych metoda PUVA i cygnolina.

White blood cell picture of the peripheral blood was determined in 37 patients with psoriasis vulgaris treated with PUVA and cignoline. The studies were performed during active period of the disease, during its treatment and in the initial period of the remission. The results were compared with those obtained in 20 healthy age-matched persons and they were correlated with the skin surface area involved, duration of the diseases and duration of its latest relapse. In the active period of the disease per cent of peripheral blood neutrophils and basophils is significantly increased, while per cent of lymphocytes is lowered. Increased per cent of neutrophils positively correlates with the skin surface area involvement.

[Selective phototherapy (SUP) in the treatment of psoriasis]. / Selektywna fototerapia (SUP) w leczeniu luszczycy.

113 psoriatic patients were treated with SUP combined with 0.1-0.3 per cent cignoline. The lamps produced by Heraeus were used, in 48 patients--Psorilux 3060 and in 65--Psorilux 5050. The first symptoms of improvement were visible after 7-10 days. The mean duration of the treatment was 4 weeks. In 46 per cent of the patients psoriatic eruptions disappeared completely and in the further 44 per cent ones a considerable improvement was observed. The better results were obtained in patients irradiated with lamp of greater power and in those, who received a greater number of irradiations. Severe side effects were observed only in 2 cases. Selective ultraviolet phototherapy was found to be a useful method in the treatment of psoriasis.

[Evaluation of metabolic efficiency of the liver in patients with psoriasis by the antipyrine test]. / Ocena sprawnosci metabolicznej watroby u chorych na luszczyce na podstawie próby antypirynowej.

In 47 patients with generalized psoriasis vulgaris and 23 healthy subjects the effectiveness of the hepatic metabolism reflected by drug biotransformation was assessed with the antipyrine elimination test. In the group of psoriatic patients there were 25 men and 22 women and in the control group--age-matched 12 men and 11 women. The half-time of antipyrine was longer and the clearance index was lower in the patients than those in the control group. The differences were statistically significant. After 2 weeks of PUVA or SUP-therapy the differences were more significant. The findings indicate an impairment of the liver metabolic effectiveness reflected by drug biotransformation in psoriatic patients.

[Production of superoxide free radicals by peripheral blood leukocytes in patients with psoriasis treated by the Re-PUVA-C method]. / Generowanie wolnych rodników ponadtlenkowych przez leukocyty krwi obwodowej u chorych na luszczyce leczonych metoda Re-PUVA-C.

The investigations were carried out in 20 patients with severe forms of psoriasis, and in 18 healthy subjects. The generation of free superoxide radicals by polymorphonuclear leukocytes of peripheral blood was evaluated by Bellavite et al. (1983) method by use superoxide dismutase of Sigma firm. The obtained results may confirm alterations in PMNL functions in patients with psoriasis observed by many authors. It may confirm the probability of damage of membrane structures and alterations in their bactericidal functions.

[Retinoids in the treatment of skin diseases in the light of the data of the Dermatology Clinic, Medical Academy, in Lódz]. / Retinoidy w leczeniu chorób skóry w swietle materialu Kliniki Dermatologicznej WAM w Lodzi.

Tigason was applied in 51 patients with psoriasis and 19 with other skin diseases. In 18 patients was applied alone, in 42 combined with PUVA and in 10 with SUP. Roaccutan was applied in 18 patients with acne conglobata et phlegmonous resistant to other methods of treatment. Tigason was found to be a useful drug in psoriasis and some other skin diseases. The combination with PUVA or SUP allowed to reduce the doses of drugs and the dose of radiation. Roaccutan was found to be a useful drug in severe forms of acne vulgaris. The side effects of the treatment with retinoids were transient and they did not create danger to the patients.

[Lysozyme activity in the blood serum and lysosomes and lysosomal supernatant of neutrophils in patients with psoriasis treated by the PUVA method]. / Aktywnosc lizozymu w surowicy krwi, w lizosomach i w nadsaczu lizosomalnym granulocytów obojetnochlonnych u chorych na luszczyce leczonych metoda PUVA.

The determinations of the activity of lysozyme in the serum, lysosomes and lysosomal supernatant of neutrophil granulocytes were done in 33 patients with generalized psoriasis and in 19 healthy controls. A decrease of lysozyme activity was demonstrated in the serum, lysosomes and lysosomal supernatant in the patients. During treatment by the PUVA method this activity rose gradually above the values in the control group. Systematic determination of lysozyme activity may help in monitoring of treatment progress.

[Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients]. / Lymphozytentransformationstest nach Stimulation mit Proteinfaktor aus neutrophilen Granulozyten (PMNL) bei Psoriasiskranken.

The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.