Lyn Guenther

Topical treatment of actinic keratoses with 3·0% diclofenac in 2·5% hyaluronan gel

Summary Background  Actinic keratoses (AKs) are premalignant skin lesions, which, if left untreated, can develop into squamous cell carcinoma. Current treatments for AKs are destructive and are often associated with significant adverse events. The development of an effective and well‐tolerated topical treatment for AK is desirable.

Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial

Summary  Background Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 µg g−1) and betamethasone dipropionate (0·5 mg g−1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone.

Socioeconomic Burden of Immune-Mediated Inflammatory Diseases — Focusing on Work Productivity and Disability

Chronic disabling conditions, such as immune-mediated inflammatory diseases (IMID), adversely affect patients in terms of physical suffering and pain, impaired function, and diminished quality of life. These persistent relapsing diseases have a significant influence on individual employment status and work-related productivity. In addition to the significant burden on patients and their families, IMID represent a sizable burden to society due to high healthcare and non-healthcare related costs. Non-healthcare related, or indirect, costs — primarily associated with decreased work productivity, disability payments, and early retirements — are typically greater contributors than direct healthcare costs to the total costs associated with IMID. This article discusses the socioeconomic impact of several IMID, including rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, and psoriasis.

Optimizing Treatment with Topical Tazarotene

Tazarotene is a receptor-selective retinoid, which is efficacious in the treatment of patients with psoriasis, acne vulgaris, and photoaging. It normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation, and has anti-inflammatory effects. Clinical studies have shown that tazarotene 0.1% gel has greater comedolytic activity than tretinoin (Retin-A®1 0.025% gel, Retin-A Micro® 0.1%) and adapalene (Differin®) 0.1% gel. Although it is efficacious as monotherapy, tazarotene is more commonly used as part of combination therapy with a topical antibacterial in patients with acne vulgaris, and with a mid- or high-potency topical corticosteroid or with phototherapy in patients with psoriasis. Combination therapy enhances efficacy and tolerability. Tazarotene 0.1% gel, used in combination with mometasone furoate 0.1% cream, was shown in psoriasis clinical trials to be more efficacious than calcipotriene (calcipotriol) ointment used twice daily, or mometasone furoate 0.1% cream used twice daily. Use of tazarotene in conjunction with broad band UVB, narrow band UVB or bath psoralens + UVA (PUVA) results in greater efficacy than with phototherapy alone. Tazarotene should not be administered during pregnancy or in women who are not practicing adequate contraception. Adverse events consist primarily of irritation, peeling, erythema, dryness, burning, and itching. They are most common during the first 1–2 weeks of therapy and can be minimized with use of the cream formulation, alternate day application, short contact therapy, mild cleansers, and combination therapy.

Epidemiology of immune-mediated inflammatory diseases: incidence, prevalence, natural history, and comorbidities.

Immune-mediated inflammatory diseases (IMID) present a group of common and highly disabling chronic conditions that share inflammatory pathways. Several incidence and prevalence studies of IMID during the past decades have reported a considerable variation of the disease occurrence among different populations. Overall, the estimated prevalence of IMID in Western society is 5%–7%. This article provides an overview of studies of the incidence, prevalence, natural history, and comorbidities of IMID.

The Role of Inflammation in the Pathophysiology of Depression: Different Treatments and Their Effects

Compelling evidence suggests that inflammation contributes to the development of depression. Many depressed individuals have higher levels of proinflammatory mediators, which appear to interact with many of the pathophysiological domains of depression, including neuroendocrine function, neurotransmitter metabolism, and synaptic plasticity. This is further supported by observation that therapeutic administration of interferon-α (IFN-α) leads to depression in a significant proportion of patients. These findings suggest that targeting proinflammatory cytokines and their signaling pathways may represent a unique therapeutic opportunity to treat depression and related conditions, such as labile anger, irritability, and fatigue.

Impact of ustekinumab on health-related quality of life and sexual difficulties associated with psoriasis: results from two phase III clinical trials

Background  Ustekinumab, a human anti‐interleukin‐12/23 monoclonal antibody, has been shown to effectively treat moderate‐to‐severe psoriasis which significantly affects health‐related quality of life (HRQoL), including patients’ sexual lives.

Efficacy and safety of adalimumab in patients with plaque psoriasis who have shown an unsatisfactory response to etanercept

BACKGROUND The safety and efficacy of adalimumab in patients who have shown an unsatisfactory response to etanercept are unknown. OBJECTIVE We sought to evaluate the safety and efficacy of adalimumab in patients who failed to show a satisfactory response or lost their satisfactory response to etanercept. METHODS This multicenter study enrolled patients who either failed to reach a physician global assessment (PGA) score of 0 or 1 after 12 weeks of etanercept (group A; 50 patients) or who lost their PGA score of 0 or 1 at any time after etanercept dose decrease from 50 mg twice a week to 50 mg every week (group B; 35 patients). Patients received adalimumab 40 mg every other week without loading dose for 12 weeks followed by 40 mg every week for an additional 12 weeks if they did not reach a PGA score of 0 or 1. RESULTS After 12 weeks of adalimumab, 34.0% (n = 17; 95% confidence interval [CI] 20.4-47.6) and 31.4% (n = 11; 95% CI 15.2-47.6) of patients from groups A and B, respectively, reached a PGA score of 0 or 1. A total of 46.0% (n = 23; 95% CI 31.7-60.3) and 45.7% (n = 16; 95% CI 28.4-63.1) of patients from group A and B, respectively, achieved a PGA score of 0 or 1 after 24 weeks of adalimumab. Adalimumab was well tolerated and no serious adverse events were reported. LIMITATIONS This was an open-label uncontrolled study. CONCLUSIONS Adalimumab should be considered as an alternative in patients with psoriasis who have not shown an adequate response or who lost their response to etanercept after a dose decrease.

Neutropenia and pancytopenia associated with oral terbinafine

A 53-year-old woman had chronic tinea pedis and onychomycosis caused by Trichophyton rubrum. In 1987 she was treated with ketoconazole for 1 month with temporary improvement of the tinea pedis. Subsequently, she was treated intermittently with econazole and chlorphenesin powder. The patient was given oral terbinafine, 250 mg daily. A complete blood cell count (CBC), ordered 5 months later because of fatigue, was normal except for a low white blood cell (WBC) count (1.9 X 109/L) and neutropenia (0.01 X 109/ L). A CBC 2 months earlier had been normal. Bone marrow aspirate and a biopsy specimen showed a relative and absolute decrease in the granulocytic line with a left shift. Terbinafine treatment was discontinued, and the patient was treated with granulocyte colony-stimulating factor twice daily for 5 days. Seven days after her last dose of terbinafine, her neutrophil count normalized (4.2 X 109/L) and remained normal for 3 months.

Ustekinumab decreases work limitations, improves work productivity, and reduces work days missed in patients with moderate-to-severe psoriasis: Results from PHOENIX 2

Abstract Objective: To assess the effect of ustekinumab on productivity and work limitations among 1230 psoriasis patients treated with ustekinumab 45 mg or 90 mg or placebo during the Phase III PHOENIX 2 trial. Methods: The self-administered Work Limitations Questionnaire (WLQ) was used to determine the on-the-job limitations at baseline and weeks 12 and 24. Productivity was assessed using a Visual Analog Scale (VAS), and the number of work days missed due to psoriasis was recorded. Results: At baseline, work limitations and productivity were similar across treatment groups. At week 12, improvement in productivity VAS scores was significantly (p < 0.001) higher in the 45 mg (72.6%) and 90 mg (71.4%) ustekinumab groups versus placebo (no change), and the proportion of patients who missed work days was significantly lower (2.0% for each ustekinumab group vs 8.3% for placebo; p < 0.001). Mean improvements from baseline to week 12 were greater with ustekinumab than with placebo for WLQ domains, including time management (6.6/9.1 vs –0.7), mental-interpersonal (7.8/7.5 vs –1.1), and output demands (6.8/7.0 vs –1.1) (p < 0.001 for ustekinumab 45 mg/90 mg vs placebo). Improvements were maintained through week 24. Conclusions: Ustekinumab 45 mg or 90 mg significantly increased productivity, reduced work days missed, and improved work limitations compared with placebo in patients with moderate-to-severe psoriasis.