A randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40-mg modified-release capsules, versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea.

BACKGROUND: Randomized controlled studies of combination therapies in rosacea are limited. OBJECTIVE: Evaluate the efficacy and safety of combining ivermectin 1% cream (IVM) and doxycycline 40-mg modified-release capsules (ie, 30-mg immediate-release and 10-mg delayed-release beads) (DMR) versus IVM and placebo for treatment of severe rosacea. METHODS: This 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study randomized adult subjects with severe rosacea (Investigator's Global Assessment [IGA] score, 4) to receive either IVM and DMR (combination arm) or IVM and placebo (monotherapy). RESULTS: A total of 273 subjects participated. IVM and DMR displayed superior efficacy in reduction of inflammatory lesions (-80.3% vs -73.6% for monotherapy [P = .032]) and IGA score (P = .032). Combination therapy had a faster onset of action as of week 4; it significantly increased the number of subjects achieving an IGA score of 0 (11.9% vs 5.1% [P = .043]) and 100% lesion reduction (17.8% vs 7.2% [P = .006]) at week 12. Both treatments reduced the Clinician's Erythema Assessment score, stinging/burning, flushing episodes, Dermatology Life Quality Index score, and ocular signs/symptoms and were well tolerated. LIMITATIONS: The duration of the study prevented evaluation of potential recurrences or further improvements. CONCLUSION: Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in cases of severe rosacea.

Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT).

BACKGROUND: Phase 2 psoriasis studies with the Fc-free, PEGylated, anti-tumor necrosis factor biologic certolizumab pegol demonstrated meaningful clinical activity. OBJECTIVE: Assess safety and efficacy of certolizumab in adults with moderate-to-severe chronic plaque psoriasis. METHODS: Patients were randomized 3:3:1:3 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks for 16 weeks or etanercept 50 mg twice weekly for 12 weeks. Certolizumab-treated patients achieving a ≥75% reduction in Psoriasis Area and Severity Index (PASI) at week 16 from baseline PASI were rerandomized to certolizumab or placebo for 32 weeks. The primary endpoint was responder rate (≥75% reduction in PASI from baseline PASI) versus placebo (primary analysis) and etanercept (secondary analysis) at week 12; secondary endpoints included responder rates on various measures versus placebo at weeks 12, 16, and 48. Safety was assessed by treatment-emergent adverse events. RESULTS: All endpoints were significantly greater for certolizumab versus placebo with the greatest response seen with 400 mg. Certolizumab 400 mg was superior to and 200 mg was noninferior to etanercept. Adverse events were consistent with the anti-tumor necrosis factor class of drugs. LIMITATIONS: Etanercept was administered by unblinded study staff or self-administered, but efficacy assessments were performed by a blinded assessor. CONCLUSION: Both certolizumab regimens improved psoriasis symptoms, with a greater response seen with the higher dose. No new safety signals were observed.

Clinical similarity of biosimilar ABP 501 to adalimumab in the treatment of patients with moderate to severe plaque psoriasis: A randomized, double-blind, multicenter, phase III study.

BACKGROUND: ABP 501 is a biosimilar of adalimumab. OBJECTIVE: We sought to compare the efficacy and safety of ABP 501 with adalimumab. METHODS: This 52-week, double-blind study randomized patients with moderate to severe psoriasis to ABP 501 or adalimumab. At week 16, those with 50% or more improvement in Psoriasis Area and Severity Index score from baseline on ABP 501 continued the same treatment, whereas adalimumab-treated patients were rerandomized to adalimumab or ABP 501. Clinical similarity in Psoriasis Area and Severity Index percent improvement from baseline to week 16 (primary end point) was established if the point estimate of treatment difference and its 2-sided 95% confidence interval between groups was within equivalence margin of ±15. Patients, including those undergoing a single transition at week 16, were evaluated for safety and immunogenicity. RESULTS: Psoriasis Area and Severity Index percent improvement at week 16 was 80.9 for ABP 501 and 83.1 for adalimumab (least-square mean difference -2.18 [95% confidence interval -7.39 to 3.02]). Adverse events (67.2% [117/174] vs 63.6% [110/173]) and antidrug antibody incidence (55.2% [96/174] vs 63.6% [110/173]) for ABP 501 vs adalimumab were similar. Safety, including immunogenicity, was similar among groups after single transition (week 20). LIMITATIONS: The 52-week data are not reported here. CONCLUSIONS: ABP 501 was shown to be clinically similar to adalimumab. Safety and immunogenicity were not impacted immediately after single transition (adalimumab to ABP 501).

Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis.

BACKGROUND: Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis. METHODS: In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100). RESULTS: At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab. CONCLUSIONS: Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).

Hypercalciuria in a child with acral peeling skin syndrome: a case report.

We present a case of 3-year-old Caucasian boy who developed monthly cyclic attacks of skin peeling of the palms and soles over 1.5 years. The skin peeling was associated with hypercalciuria. No mutation was present in TGM5 and CSTA genes, but the typical clinical picture and the biopsy from flaccid blisters on the feet confirmed the acral peeling skin syndrome (APSS). The possible associations of rare genetic disorders and metabolic conditions in the course of APSS need to be investigated.

Enhanced Enzymatic Activity of Yeast-like Fungi Responsible for Onychomycosis in Renal Transplant Recipients.

BACKGROUND: Renal transplant recipients (RTR) are regarded as a group especially predisposed to onychomycosis. The exact mechanism of increased frequency of onychomycosis in RTR is however not fully understood. OBJECTIVES: This study was undertaken to evaluate activity of hydrolitic enzymes of fungi most commonly causing fungal nail infections in RTR and to compare it with enzymatic activity of the same fungi isolated from lesional nails in immunocompetent patients. MATERIAL AND METHODS: 28 strains of yeast-like fungi cultured from lesional nails in RTR and 25 strains of yeasts isolated from changed nails in immunocompetent patients were included into the study. All fungi were identified on the basis of routine mycological procedures. Activity of 19 hydrolytic enzymes was assessed by API ZYMÒ test (bioMerieux). RESULTS: Fungi cultured from RTR showed activity of 16 out of 19 enzymes, whereas fungi isolated from immunocompetent patients only 11 out of 19 enzymes. Moreover, yeast-like fungi isolated from RTR showed higher generally higher activity of detected enzymes compared to yeast strains obtained from the lesional nails of immunocompetent patients. CONCLUSIONS: This study shows for the first time enhanced enzymatic activity of yeast-like fungi isolated from lesional nails in RTR in comparison to fungi cultured from changed nails in immunocompetent patients. It is hypothesized that this enhanced enzymatic activity may be responsible for higher incidence of onychomycosis in RTR.

Sun protection in renal transplant recipients: urgent need for education.

BACKGROUND: Renal transplant recipients (RTR) are considered as a high-risk group of skin cancer development. OBJECTIVE: The aim of the present studywas to find out the knowledge about the harmfulness of sunlight and the methods of sun protection among RTR. MATERIAL AND METHODS: 151 RTR (91 males and 60 females) were surveyed using a specially designed questionnaire. RESULTS: The knowledge about the danger of sunlight exposure among RTR appeared to be very unsatisfactory. Only 40.4% of patients knew that the development of skin cancer is connected with the exposure to sunlight. Moreover, only 68.2% of investigated individuals considered RTR as a high-risk group of skin cancer development. Although 74.8% of patients were informed about the necessity of sun protection, only 11.3% could explain what the number of the SPF (sun protection factor) means. Females significantly more often knew that RTR are especially predisposed to the development of skin cancers (p = 0.0001) and significantly more frequently could explain what the SPF number means (p = 0.006). 72.8% of RTR (females significantly more often, p = 0.02) made efforts to avoid sunlight irradiation. However, only 5.3% of the examined patients routinely used creams with SPF (females significantly more often, p < 0.0001). More than a half of the patients (62.3%) did not apply any sun protection. CONCLUSIONS: The present study revealed the urgent necessity of education concerning the harmfulness of sunlight and the methods of sun protection among RTR. Moreover, it is postulated that every patient should be routinely examined by a dermatologist in a dedicated transplant patient clinic.