Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial.

BACKGROUND: Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of tralokinumab in combination with topical corticosteroids (TCS) in patients with moderate-to-severe AD who were candidates for systemic therapy. METHODS: This was a double-blind, placebo plus TCS controlled phase III trial. Patients were randomized 2 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed over 16 weeks. Patients who achieved an Investigator's Global Assessment (IGA) score of 0/1 and/or 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab were rerandomized 1 : 1 to tralokinumab Q2W or every 4 weeks (Q4W), with TCS as needed, for another 16 weeks. RESULTS: At week 16, more patients treated with tralokinumab than with placebo achieved IGA 0/1: 38·9% vs. 26·2% [difference (95% confidence interval): 12·4% (2·9-21·9); P = 0·015] and EASI 75: 56·0% vs. 35·7% [20·2% (9·8-30·6); P < 0·001]. Of the patients who were tralokinumab responders at week 16, 89·6% and 92·5% of those treated with tralokinumab Q2W and 77·6% and 90·8% treated with tralokinumab Q4W maintained an IGA 0/1 and EASI 75 response at week 32, respectively. Among patients who did not achieve IGA 0/1 and EASI 75 with tralokinumab Q2W at 16 weeks, 30·5% and 55·8% achieved these endpoints, respectively, at week 32. The overall incidence of adverse events was similar across treatment groups. CONCLUSIONS: Tralokinumab 300 mg in combination with TCS as needed was effective and well tolerated in patients with moderate-to-severe AD.

Adalimumab for nail psoriasis: efficacy and safety over 52 weeks from a phase-3, randomized, placebo-controlled trial.

BACKGROUND: Few clinical trials have evaluated long-term treatment of nail psoriasis with biologics. OBJECTIVE: Safety and efficacy of adalimumab [ADA; Humira AbbVie Inc, North Chicago, IL, USA)] long-term treatment (52 weeks) was evaluated in a phase-3, randomized trial in patients with moderate-to-severe plaque psoriasis and concomitant moderate-to-severe fingernail psoriasis. Results from the first 26 weeks (Period A) have been reported. METHODS: Patients receiving 40 mg ADA every other week or placebo in Period A, continued with or switched to 40 mg ADA every-other-week treatment in the subsequent 26-week open-label extension (OLE) period. Main efficacy evaluations were ≥75% improvement in total-fingernail modified Nail Psoriasis Severity Index (mNAPSI 75) and achievement of Physician's Global Assessment for Fingernail Psoriasis of clear or minimal disease (PGA-F 0/1) with a ≥2-grade improvement from baseline, across the trial for patients who continued ADA from Period A through the OLE (Continuous-ADA Population). Safety was evaluated during the OLE and for patients receiving ADA at any time during the study (All-ADA Population). RESULTS: Of the 217 patients initially randomized in Period A, 188 (86.6%; 94 in each treatment group) entered the OLE after completion of or early escape from Period A. For the Continuous-ADA Population (N = 109), endpoint achievement rates improved from OLE entry (Week 26) to Week 52, including total-fingernail mNAPSI 75 (47.4-54.5%); PGA-F 0/1 (51.1-55.6%) and total-fingernail mNAPSI = 0 (6.6-17.9%). Serious adverse event and serious infection rates for the All-ADA Population (N = 203) were 6.9% and 3.4%, respectively. CONCLUSIONS: In this population of psoriasis patients with concomitant, moderate-to-severe nail psoriasis, long-term efficacy and improvement in signs and symptoms of nail disease were demonstrated after every-other-week ADA treatment, including incremental improvements in rate of total clearance of nail disease. No new safety risks were identified for patients receiving at least one ADA dose across 52 weeks.

Human polyomavirus-7-associated eruption successfully treated with acitretin.

Advances in molecular technologies have led to the discovery of several novel human polyomaviruses (HPyVs), including human polyomavirus-7 (HPyV-7). Although low levels of HPyV-7 are shed from apparently normal skin, recent reports have described clinically significant cutaneous infection in immunocompromised patients that manifests as generalized pruritic plaques. The pruritus can be severe, and treatment options have not been described. Herein we report HPyV-7 cutaneous infection in a heart transplant patient who experienced temporary improvement with intravenous cidofovir, and complete remission with acitretin. We report a case of HPyV-7 cutaneous infection demonstrating a good response to treatment.

Efficacy, safety and tolerability of topical terbinafine nail solution in patients with mild-to-moderate toenail onychomycosis: results from three randomized studies using double-blind vehicle-controlled and open-label active-controlled designs.

BACKGROUND: Terbinafine nail solution (TNS) was developed for the treatment of onychomycosis. OBJECTIVE: To assess the efficacy of TNS vs. vehicle and amorolfine 5% nail lacquer. METHODS: Subjects with mild-to-moderate toe onychomycosis (25% to ≤75% nail-involvement, matrix uninvolved) were randomized to receive either TNS or vehicle in two double-blind studies, and to TNS or amorolfine in an active-controlled, open-label study. Primary endpoint was complete cure (no residual clinical involvement and negative mycology) at week 52. Secondary endpoints were mycological cure (negative mycology defined as negative KOH microscopy and negative culture) and clinical effectiveness (≤10% residual-involvement and negative mycology) at week 52. RESULTS: Complete cure was not different between TNS vs. vehicle and amorolfine. Mycological cure was higher with TNS vs. vehicle, as was clinical effectiveness with TNS vs. vehicle, and TNS and amorolfine were not different for secondary efficacy endpoints. Patients achieving mycological cure had a better clinical outcome, and efficacy was improved in subjects with milder disease. Post hoc analysis suggests that nail thickness is an important prognostic factor. Moreover, mycological cure may require 6 months of treatment regimen while complete cure and clinical effectiveness may be achievable only after 10 months. A simulation study suggests that longer treatment duration would have resulted in higher complete cure with TNS vs. vehicle. Study treatments were well-tolerated. CONCLUSION: Primary efficacy objectives were not met in the studies reported herein. Possible reasons for failure to achieve significant outcomes include insufficient length of treatment; stringency of primary endpoint and severity of nail involvement of study population.

Rosacea - global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group.

BACKGROUND: The absence of specific histological or serological markers, the gaps in understanding the aetiology and pathophysiology of rosacea, and the broad diversity in its clinical manifestations has made it difficult to reach international consensus on therapy guidelines. OBJECTIVES: The main objective was to highlight the global diversity in current thinking about rosacea pathophysiology, classification and medical features, under particular consideration of the relevance of the findings to optimization of therapy. METHODS: The article presents findings, proposals and conclusions reached by the ROSacea International Expert group (ROSIE), comprising European and US rosacea experts. RESULTS: New findings on pathogenesis provide a rationale for the development of novel therapies. Thus, recent findings suggest a central role of the antimicrobial peptide cathelicidin and its activator kallikrein-5 by eliciting an exacerbated response of the innate immune system. Cathelicidin/kallikrein-5 also provide a rationale for the effect of tetracyclines and azelaic acid against rosacea. Clinically, the ROSIE group emphasized the need for a comprehensive therapy strategy - the triad of rosacea care - that integrates patient education including psychological and social aspects, skin care with dermo-cosmetics as well as drug- and physical therapies. Classification of rosacea into stages or subgroups, with or without progression, remained controversial. However, the ROSIE group proposed that therapy decision making should be in accordance with a treatment algorithm based on the signs and symptoms of rosacea rather than on a prior classification. CONCLUSION: The ROSIE group reviewed rosacea pathophysiology and medical features and the impact on patients and treatment options. The group suggested a rational, evidence-based approach to treatment for the various symptoms of the condition. In daily practice this approach might be more easily handled than prior subtype classification, in particular since patients often may show clinical features of more than one subtype at the same time.

Rosacea: a review of current topical, systemic and light-based therapies.

Rosacea is a common chronic inflammatory disorder of the facial skin characterized by periods of exacerbation, remission and possible progression. The principle subtypes include erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea and ocular rosacea. Although the pathogenesis is unknown, rosacea is largely recognized as an inflammatory disorder. Individual subtypes are likely a result of different pathogenic factors and respond best to different therapeutic regimens. The non-pharmacologic approach to therapy is adequate skin care, trigger avoidance and photoprotection; in addition, there are several topical, herbal, systemic and light based therapies available. Standard Food and Drug Administration (FDA) approved treatments include topical sodium sulfacetamide, metronidazole, and azelaic acid. Anti-inflammatory dose doxycycline, a controlled-release 40 mg formulation offers a non-antibiotic, anti-inflammatory treatment option. Combination of azelaic acid or topical metronidazole with anti-inflammatory doxycycline appears to have a synergistic effect. Oral isotretinoin may be effective for phymatous rosacea and treatment resistant rosacea. Light based therapies with pulsed dye laser and intense pulsed light are effective in treatment of erythema and telangiectasias. As our knowledge of rosacea and its therapeutic options expand, a multifaceted approach to treatment is warranted.

Onychomycosis and diabetes.

OBJECTIVE: This study aims to discuss factors specific to diabetics in the diagnosis and treatment of onychomycosis. DISCUSSION: Onychomycosis has the potential to cause severe complications in diabetics and should be treated promptly. The existence of comorbid conditions and potential for drug-drug interactions complicates the selection of an appropriate treatment regimen. The role of Candida in onychomycosis is controversial but may be of increased significance in the diabetic population due to an underlying vulnerability to this organism. CONCLUSIONS: Terbinafine is an excellent choice in diabetics due to its low risk of drug-drug interaction and proven efficacy against the typical pathogens that cause onychomycosis. Itraconazole, while an effective treatment for onychomycosis, is not a first-choice therapy due to its black-box cardiac warning and numerous drug interactions. Larger studies are needed in diabetics to determine the frequency of candidal nail infections.

Onychomycosis. Treatment, quality of life, and economic issues.

Onychomycosis is a public health concern because of its high worldwide incidence and prevalence, and its potential for spread of fungal elements to others, as well as complications such as cellulitis, bacterial infection, pain, and extensive dermatophytic infections. The incidence of onychomycosis has been increasing, particularly in individuals over 60 years of age, patients with HIV infection, and patients with diabetes mellitus. Onychomycosis may impact upon physical, functional, psychosocial, and emotional aspects of life. Difficulty walking, wearing shoes, and embarrassment are common complaints. Quantification of such quality-of-life changes are significant to clinical practice in that many factors can affect overall patient health. In light of the potential clinical implications on physical and mental health, onychomycosis should be considered a medical condition that deserves rigorous clinical management. Onychomycosis can be treated effectively and with comparative safety with the new generation of oral antifungal agents (itraconazole, fluconazole and terbinafine). Significantly improved pharmacokinetic and pharmacodynamic profiles permit markedly reduced duration of administration, individual drug exposure, and ultimately enhanced patient compliance and satisfaction with therapy. In addition, a number of pharmacoeconomic studies have documented the cost effectiveness of these newer agents compared with both traditional pharmacologic treatment and topical therapies. The currency figures quoted are 1997 values. With regard to continuous oral antifungal regimens, terbinafine therapy has been found to be most cost effective in the treatment of toenail onychomycosis, with a drug acquisition cost of $US522.50. However, improved safety, tolerability, efficacy and cost effectiveness have been documented with itraconazole intermittent, pulse regimens. With itraconazole pulse therapy, the drug acquisition cost decreases to $US488.90. Additionally, the total cost of medical management is less for itraconazole therapy compared with that of terbinafine ($US261.00 vs $US306.00). Because sensitivity analyses for itraconazole and terbinafine have been found to be somewhat comparable in terms of mycological cure, clinical response, and relapse rates, other variables such as safety and efficacy profiles, and patient attitudes and expectations toward therapy need to be considered when formulating an onychomycosis pharmacologic treatment plan. The drug aquisition cost of fluconazole given as a 300 mg dose once weekly for 6 months is $US562.76 and given as a 150 mg dose once weekly (for 6 months) $US281.38.

Tinea capitis: a current perspective.

UNLABELLED: During the past 50 years, the predominant etiologic agent of tinea capitis in the United States and in Western Europe has changed from Microsporum audouinii to Trichophyton tonsurans. This is thought to be due in part to the sensitivity of M audouinii to griseofulvin treatment and, in part, due to the importing of T tonsurans by people emigrating from geographic areas where that vector had been the prominent cause of tinea capitis. With these changes, prospects for newer therapies with the novel antimycotic agents itraconazole, fluconazole, and terbinafine are reviewed. (J Am Acad Dermatol 2000;42:1-20.) LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the history, epidemiology, and current knowledge of tinea capitis, as well as the newer antifungal agents (ie, itraconazole, fluconazole, and terbinafine) to treat this infection.