Leah A. Cardwell

Interleukin-17 inhibition: role in psoriasis and inflammatory bowel disease

Abstract Introduction: Interleukin 17 (IL-17) antagonism provides a highly effective approach for treating psoriasis. Exacerbations of inflammatory bowel disease have been reported in anti-IL-17 psoriasis trials. Aim: To characterize the relationship between IL-17 inhibition and inflammatory bowel disease. Methods: A review of English-language articles was performed. Search terms included IL-17, psoriasis, inflammatory bowel disease, secukinumab, ixekizumab and brodalumab. Results: IL-17 A inhibition, IL-17RA inhibition and IL-17 knockout led to induction or exacerbation of colitis in mouse models. The placebo groups fared better than the treatment group in controlled trials of anti-IL-17 antibody and anti-IL-17 receptor for Crohn’s disease (CD). A brodalumab study (N = 1576) revealed one reported CD case. An ixekizumab study (N = 3736) evaluating moderate-to-severe psoriasis, four patients reported CD and seven reported UC while ixekizumab every 2 weeks led to a moderate exacerbation of UC in one patient and new-onset CD in one patient. A secukinumab study (N = 3430) revealed exposure adjusted incidence rates of 0.11 and 0.15 per 100 patient-years for CD and UC, respectively. Discussion: Anti-IL-17 medications are associated with IBD exacerbation. Caution should be used in prescribing these medications in patients with diagnosed IBD or personal history suggestive of IBD.

An Anchoring-Based Intervention to Increase Patient Willingness to Use Injectable Medication in Psoriasis

This study examines the association of anchoring with patient willingness to use a monthly injectible medication for psoriasis.

New developments in the treatment of rosacea – role of once-daily ivermectin cream

Rosacea is a chronic dermatological disorder with a variety of clinical manifestations localized largely to the central face. The unclear etiology of rosacea fosters therapeutic difficulty; however, subtle clinical improvement with pharmacologic treatments of various drug categories suggests a multifactorial etiology of the disease. Factors that may contribute to disease pathogenesis include immune abnormality, vascular abnormality, neurogenic dysregulation, presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction. The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin and metronidazole, ivermectin was more effective; this treatment modality boasted more improved quality of life, reduced lesion counts, and more favorable participant and physician assessment of disease severity. Patients who received ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious in decreasing inflammatory lesion counts and erythema.

Chemical pharmacotherapy options for managing adult acne.

ABSTRACT Introduction: The incidence of adult acne is increasing worldwide. Despite clinical overlap with conventional acne, it has distinct features. Areas covered: A literature search of English-language review articles, randomized control studies and retrospective studies conducted over the past 30 years was performed using PubMed and Google Scholar. Search terms included acne, adult, topical medication, oral medication and skin of color. We highlight important clinical features and treatment modalities pertinent to the evaluation and management of adult acne. Given the relative dearth of literature detailing treatment options specific to adult acne, we offer expert opinion regarding management of the condition especially in special populations such as skin of color and pregnancy. Expert Opinion: It is unclear whether adult acne represents a distinct entity or a continuum of adolescent disease. Providers may opt to use topical medication as first-line, but should have a low threshold for switching to systemic therapy given the magnitude of psychosocial and emotional burden associated with the condition.

Psoriasis, Depression, and Inflammatory Overlap: A Review

Psoriasis has an enormous impact on patients’ lives and is frequently associated with depression. Depression in psoriasis may be attributed, at least in part, to elevated proinflammatory cytokines rather than the psychosocial impact of psoriasis itself. Biologics that target inflammatory cytokines treat the clinical manifestations of psoriasis, but may also play a role in reducing associated depression. Multiple biologics have decreased symptoms of depression during clinical trials in psoriasis; however, these studies used a variety of depression screening tools, which limits comparison. Furthermore, it is difficult to distinguish whether improved depression is the result of the direct anti-inflammatory effect of the biologic, or the indirect effect of improved psoriasis leading to better psychological status. Future studies evaluating depression in patients with psoriasis could benefit from a standardized depression screening tool to mitigate discrepancies and facilitate comparison across treatment types. Here, we highlight the inflammatory overlap between psoriasis and depression by examining the pathophysiology of depression, and reviewing psoriasis clinical studies that assessed depression as an outcome measure.

Recent Advances in Small Molecule and Biological Therapeutic Approaches in the Treatment of Psoriasis

New treatments continue to be developed for psoriasis. In this review, we aim to summarize the results of the major published studies on biologic and small molecule drugs for the treatment of psoriasis. We emphasize the safety, efficacy, and tolerability of these treatment options. A review of the MEDLINE database was conducted for each class of medication. Randomized controlled trials were identified for each medication; data on efficacy, safety, and tolerability were reviewed. Biologic and small molecule treatment options are more effective than placebo, although there were few head‐to‐head trials to assess relative efficacy between biologics and small molecule treatments. These drugs offer favorable safety profiles with only rare serious adverse events reported. Biologic and small molecule drugs offer diverse therapeutic regimens, particularly in patients with recalcitrant disease.

Adherence to biologics in patients with psoriasis

ABSTRACT Introduction: Psoriasis has a profound impact on patients’ lives, but adherence to topical treatment of psoriasis is still poor. Biologic treatment has revolutionized the management of psoriasis, but adherence to treatment may still be a barrier for some patients. Areas covered: A PubMed search was conducted in August 2017 using the terms ‘biologics psoriasis adherence’ and ‘biologics psoriasis survival.’ Additional articles were obtained by perusing the references of articles identified in the original PubMed search. Articles that did not specifically mention ‘survival,’ ‘adherence,’ or ‘persistence’ were not included. We review the measures used to assess adherence to biologics for psoriasis and the factors impacting drug survival and adherence rates for biologics in psoriasis. Expert commentary: Drug survival and adherence rates for biologic therapy is less than ideal but may be modifiable. Means that may improve adherence and drug survival include individualized choice of biologic and providing additional support for patients who are at increased risk for prematurely stopping treatment.

Spotlight on brimonidine topical gel 0.33% for facial erythema of rosacea: safety, efficacy, and patient acceptability

Background Brimonidine tartrate is a highly selective alpha 2 agonist that induces direct vasoconstriction of small arteries and veins, thereby reducing vasodilation and edema. Objective To review the current literature regarding the safety, efficacy, and patient acceptability of brimonidine 0.33% gel. Methods A PubMed search was performed using the terms brimonidine 0.33% gel, rosacea, safety, efficacy, and acceptability. Peer-reviewed clinical trials and case reports from 2012 to 2016 were screened for inclusion of safety, efficacy, and/or patient acceptability data. Results Brimonidine topical gel 0.33% is associated with mild, transient skin-related adverse reactions. Efficacy may be achieved within 30 minutes of administration with maximal reductions in erythema 3–6 hours after administration. Patient satisfaction with use of brimonidine topical gel is superior to vehicle gel for facial appearance, treatment effect, facial redness, and daily control of facial redness. Limitations Studies were typically limited to 1-year follow-up. Only one study has examined the use of brimonidine topical gel in combination with other rosacea and acne medications. Discussion Brimonidine topical gel 0.33% is a safe, effective, and patient-accepted treatment for facial erythema of rosacea.

Advances in treating psoriasis in the elderly with small molecule inhibitors

ABSTRACT Introduction: Due to the chronic nature of psoriasis, the population of elderly psoriasis patients is increasing. However, many elderly psoriatic patients are not adequately treated because management is challenging as a result of comorbidities, polypharmacy, and progressive impairment of organ systems. Physicians may hesitate to use systemic or biologic agents in elderly psoriasis patients because of an increased risk of adverse events in this patient population. Small molecule medications are emerging as promising options for elderly patients with psoriasis and other inflammatory conditions. Areas covered: Here we review the efficacy, safety and tolerability of small molecule inhibitors apremilast, tofacitinib, ruxolitinib, baricitinib, and peficitinib in the treatment of psoriasis, with focus on their use in the elderly population. Expert opinion: Although small molecule inhibitors demonstrate efficacy in elderly patients with psoriasis, they will require larger head-to-head studies and post-marketing registries to evaluate their effectiveness and safety in specific patient populations. Apremilast, ruxolitinib, and peficitinib are effective agents with favorable side effect profiles; however, physicians should exercise caution when prescribing tofacitinib or baricitinib in elderly populations due to adverse events. The high cost of these drugs in the U.S. is likely to limit their use.

Pilot study of the feasibility of a double-blind, randomized, placebo-controlled localized area ultraviolet phototherapy trial methodology

Localized ultraviolet (UV) phototherapy is an effective treatment for many inflammatory dermatoses.1 Localized UV treatment modalities include excimer lasers, excimer nonlaser devices, and nonexcimer devices.2 In order to delineate the efficacy of the different options, wellcontrolled clinical trials are critical. However, trials comparing the efficacy of phototherapy devices are often not blinded, leading to participation and expectancy biases. The purpose of this study is to test a methodology suitable for robust doubleblind, randomized, placebocontrolled, localized area UV phototherapy intervention trials.