Dane Hill

Impact and management of depression in psoriasis patients

Psoriasis causes emotional and social burdens [1,2]. Psoriasis patients are 1.5 times more likely to experience depression compared to thosewithout psoriasis (odds ratio 1.57; 95% confidence interval 1.40–1.76) [3]. The proportion of psoriasis patients who have depressive symptoms ranges from 9% to 55%, likely due to differences in screening methods and study populations (Table 1). Estimated adherence to therapies is 40–50% [4,5]. Psychiatric comorbidity is a strong predictor of poor adherence [6,7]. Depression in psoriasis patients may reduce adherence to treatment, resulting in worse psoriasis and more depression [7]. Managing depression may improve adherence and outcomes. To treat depression, it must be detected. Dermatologists’ clinical judgment has a sensitivity and specificity of 60% and 21% for detecting depression [8]. Clinical judgment of depression in psoriasis patients, unaided by formal measures, is poor. This study reviews factors relating to depression in psoriasis patients, estimates the proportion of psoriasis patients with depression and the effect depression has on adherence in psoriasis patients, and discusses management of depression in psoriasis patients. The study also proposes an algorithm for detecting and managing depression in psoriasis patients using two easy-to-use, validated questionnaires.

Current challenges and emerging drug delivery strategies for the treatment of psoriasis

ABSTRACT Introduction: Psoriasis is a common skin disorder associated with physical, social, psychological and financial burden. Over the past two decades, advances in our understanding of pathogenesis and increased appreciation for the multifaceted burden of psoriasis has led to new treatment development and better patient outcomes. Yet, surveys demonstrate that many psoriasis patients are either undertreated or are dissatisfied with treatment. There are many barriers that need be overcome to optimize patient outcomes and satisfaction. Areas covered: This review covers the current challenges associated with each major psoriasis treatment strategy (topical, phototherapy, oral medications and biologics). It also reviews the challenges associated with the psychosocial aspects of the disease and how they affect treatment outcomes. Patient adherence, inconvenience, high costs, and drug toxicities are all discussed. Then, we review the emerging drug delivery strategies in topical, oral, and biologic therapy. Expert opinion: By outlining current treatment challenges and emerging drug delivery strategies, we hope to highlight the deficits in psoriasis treatment and strategies for how to overcome them. Regardless of disease severity, clinicians should use a patient-centered approach. In all cases, we need to balance patients’ psychosocial needs, treatment costs, convenience, and effectiveness with patients’ preferences in order to optimize treatment outcomes.

Current status and future prospects for biologic treatments of psoriasis.

ABSTRACT Introduction: Biological agents have transformed psoriasis treatment by selectively targeting immune signaling molecules involved in psoriasis pathogenesis. While biologics offer the most effective treatment of moderate to severe psoriasis, they are not without complications. Some patients treated with biologics have poor clinical responses, form anti-drug antibodies, or develop adverse events. Additionally, there is growing need for head-to-head studies comparing biologic treatment regimens, efficacy, and safety. Areas covered: Here we review the literature surrounding biologics already in clinical use and those undergoing development and clinical trials. We also investigate the development and approval of small molecules inhibitors and biosimilars used to treat psoriasis. Expert commentary: As the psoriasis treatment armamentarium continues to expand, it is important to follow the safety profile of these drugs both in clinical trials and in post-marketing registries to ensure their long-term safety. Physicians must be aware of the limitations of existing safety data of a drug and the potential risk for rare adverse events when selecting appropriate treatments and monitoring patient outcomes.

Pharmacoeconomic Considerations in Treating Actinic Keratosis: An Update

Actinic keratosis is one of the most common dermatological diagnoses worldwide, especially among the elderly, fair-skinned, and immunocompromised, and is associated with a risk of transformation to skin cancer. With actinic keratosis and skin cancer prevalence increasing as the aged population expands in the US, optimizing treatment strategies may produce cost savings for the healthcare system. Since the time of our last review in 2008, investigation of the economic considerations in treating actinic keratosis has advanced. To provide an update of treatment cost effectiveness and to review factors relating to the costs of care, we conducted a systematic review of pharmacoeconomic publications since December 2008. We identified 11 pharmacoeconomic studies, with one cost-of-treatment, five cost-effectiveness, and five cost-utility analyses. Photodynamic therapy (PDT) was well tolerated and produced a favorable cosmetic outcome in most studies. Ingenol mebutate, the newest but most expensive topical field therapy, 5-fluorouracil, and PDT were the most cost-effective treatments in our review. Patient adherence to therapy and the management of adverse effects were significant contributors to treatment costs. In the US, treatment guidelines and formalized cost-effectiveness analyses for actinic keratosis are absent from the recent literature. Future pharmacoeconomic investigation will depend on up-to-date comparative efficacy data, as well as clarification of rates of, and management strategies for, adverse effects, therapeutic non-adherence, and lesion recurrence.

Review of maintenance of response to psoriasis treatments

Abstract Background: Biologics are highly effective treatments for moderate-severe psoriasis with a high percentage of patients achieving 75% improvement in Psoriasis Area Severity Index (PASI75) at 12 weeks. However, psoriasis is a chronic disease, and long-term efficacy is critical. Objective: Long-term responses of systemic psoriasis treatments and how this effect is reported. Methods: A PubMed literature was performed to identify studies describing long-term response rates to available systemic psoriasis treatments. Within these studies, we examined how maintenance rates were reported. All studies with long-term efficacy data ranging from 24 to 244 weeks were considered. Results: Thirteen studies met the inclusion criteria. When comparing medications at 1 year, response rates among the initial treatment groups were best with secukinumab (65.2%) and worst with apremilast (18.7%). Among only initial responders at 10–16 weeks who received 1 year of continuous treatment, maintenance was best with adalimumab (95.2%) and worst with apremilast (61%). Limitations: The different methodologies used to report maintenance of response over time make it difficult to compare response rates across drugs studied in different trials. Conclusion: Long-term response rates of systemic treatment of psoriasis are high. Effect may be influenced by many factors and can be analyzed in different ways, making comparisons across different trials difficult.

Oral tofacitinib for the treatment of adults with moderate to severe chronic plaque psoriasis

ABSTRACT New treatments for psoriasis have been developed based on increasing knowledge of the underlying pathogenesis of the disease. The development of very safe and highly effective biologics has revolutionized the treatment of moderate-to-severe psoriasis. Biologics are not perfect, however, as they are delivered parenterally, immunogenic, and costly. Small molecule agents, with molecular weights of less than 1 kDa, are being developed and hold the advantage of being administered orally. Tofacitinib is an oral Janus kinase inhibitor that has been developed to disrupt the aberrant JAK-STAT pathway that contributes to the pathogenesis of psoriasis. Phase II and Phase III clinical trial results for tofacitinib are encouraging, demonstrating substantial efficacy and satisfactory safety in the treatment of patients with moderate-to-severe chronic plaque psoriasis. An effective oral treatment without the organ toxicities of methotrexate and cyclosporine, tofacitinib is a promising alternative to biologics in the treatment of moderate-to-severe psoriasis.

Reply to: “Comment on ‘Review of patient registries in dermatology’”

To the Editor: We thank Zweegers et al for suggesting additional helpful, important registries. The psoriasis registries they described provide important complements to randomized control trial (RCT) data. Registries provide information about real-world effectiveness, about how well drugs work over the courseof long-term, chronicdiseases, andperhaps most importantly, about drug safety, as clinical trials tend not to be large enough or long enough to fully elucidate rare risks. A limitation of patient registries is that patients are generally not randomized to different treatment groups, making it essential to address potential biases in treatment assignment when making comparisons between different treatment groups. Registries can provide information that reflects how patients experience diseases and treatments in the real-world and may offer information that is more generalizable than the information obtained from RCTs. Registries and RCTs are complementary, and the data gleaned from these resources together help physicians and patients to make more informed decisions about the management of dermatologic diseases.

A Review of Localized Office and Home Devices in the Treatment of Psoriasis

Importance Targeted phototherapy for treatment of localized psoriasis has advantages over non-targeted phototherapy. It delivers high ultraviolet doses to only the diseased skin, sparing irradiation to normal skin. Objective This study aims to review the devices that are available for targeted treatment of psoriasis. Evidence Review A PubMed literature review was conducted to identify devices for localized psoriasis phototherapy. Device manufacturer websites were searched for specific information. Findings Eighty-four papers were identified that met the inclusion criteria. We identified and described seven laser/light therapies and 22 devices for localized psoriasis treatment. Limitations There is potential bias for each device since the products’ information was provided by their manufacturer. Some devices were excluded due to lack of relevant information. Conclusions and Relevance Excimer laser and narrow band ultraviolet B devices are valuable treatment modalities for localized psoriasis. Handheld, narrow band ultraviolet B devices are efficacious and available for home treatment.

Online Reviews of Physicians Valuable Feedback, Valuable Advertising

This is the best time to be alive in human history. Technology has objectively improved our lives in countless ways. In dermatology, this is perhaps best exemplified by the treatments we now have for psoriasis. Just a few years ago, we would have been ecstatic for a cyclosporine-like drug that did not cause renal adverse effects, but now we have biologic drugs that are far safer and more effective than we would have dreamed of. Electronics have revolutionized our lives. Smart phones give us entire libraries at our fingertips, searchable by voice command; the ability to communicate on the spot with our family, friends, and medical colleagues; and countless other ways to spend our time, productively or otherwise. We have medical technologies that can peer inside the body completely unobtrusively, and we have medical record systems that remind us of needed screenings, warn us of potential harmful interactions, and, for better and worse, put the entire medical record of a patient’s care at our disposal. Despite this, it seems we are no happier, a paradox of how the human psyche is wired. In part, we are no happier because, when it comes to happiness, technology pales in importance to human interaction. Patients’ satisfaction with us, their physicians, and the care we provide is derived largely from our relationship with them and their perceptions of how much we care about them.1 We may be great at making the right diagnosis and prescribing the right therapy very efficiently (perhaps too efficiently from the patients’ perspective), but if a patient does not feel connected to the physician in a strong patient-physician relationship, it can greatly affect their perception of the care they have received. In this issue of JAMA Dermatology, Smith and Lipoff2 present an enlightening qualitative analysis of online reviews of dermatologists, revealing the extent to which patient satisfaction is related to feeling cared for. In a high-tech, fast-paced world, patients prefer a slower, more elaborate, and thorough evaluation of their health by courteous doctors and office staff members in a clean, well-run environment. In addition, higher satisfactionscoreswereassociatedwithcostcognizance,competence, empathy, and respect. This is consistent with previous patient surveys1,3 andshouldnotbesurprisingtopractitioners,evenwith the far greater emphasis paid to biochemistry, physiology, and pharmacology in medical school. What is more surprising is the striking statistic that nearly 2 out of 3 of patients felt that online reviews of physicians and/or practices were, at minimum, “somewhat” important when choosing a physician.2 This highlights the increasingly large role that online reviewing now plays and the expanding role it will play in the future as Internet-based communications continue to become more widely used. Patients now have an expanding database of reviews that can steer them toward a physician, or away from one. Because unhappy patients are more likely to make the effort to write an online comment, some practitioners may view online reviews as a negative trend, but patient-written reviews can provide excellent, personalized feedback for physicians and practices. Patient surveys used to be slow and tedious, lacking benchmarks for comparison. With constant changes in the health care system, online surveys can provide a ready source of up-to-the-minute feedback that is unique to each area and specialty. Physicians have the opportunity to regularly collect and examine online reviews to strengthen potential weaknesses in anything from perceived skill and/or knowledge to patient interactions or office flow. Each negative comment can be a gift, helping guide the physician toward providing better care. Though every critical review may not merit a change in practice, trends of similar critiques may warrant a change that can then potentially increase patient satisfaction and clinical outcomes (since outcomes depend on adherence to treatment, and adherence depends on patients’ perception of their physicians4,5). Making adjustments in the medical practice in response to feedback can also make the physician a more sought-out practitioner, increasing patient referrals in a competitive market. While online reviews are a very fast, low-cost, and efficient way to get actionable feedback from patients, those reviews expose us and the care we provide to public scrutiny, which is a very good thing. Without transparency, all patients have is personal experience and the experience of a few friends to help them decide whether a physician might be a good fit. They also have the news. Using the news can be particularly misleading because the news nearly always reports what is new and different, not what is ordinary, normal, or relevant to the person. If we relied on the media for all our information, we would think that in order to see a physician, we would be likely to have a serious medical misadventure.6 The apocryphal Mark Twain quote seems apt: “If you don’t read the newspaper, you are uninformed. And if you do read the newspaper, you are misinformed.” Accurate, unrepresentative information can be very misleading.6,7 The Wake Forest University health care system solicits patients’ comments and makes those comments, both good and bad, freely available on the medical center’s website. The comRelated article page 153 Opinion

Calcipotriene and betamethasone dipropionate for the topical treatment of plaque psoriasis

ABSTRACT Introduction: Psoriasis affects an estimated 2% of the worlds population, with higher rates in developed countries. 80% have mild-to-moderate disease and 50 to 80% have scalp involvement. Topical treatments are the mainstay of treatment. Areas covered: Two-compound calcipotriene and betamethasone dipropionate (BD) is a common topical combination therapy consisting of a vitamin D analogue and a corticosteroid. It comes in ointment, gel/suspension, and foam formulations. Phase II and III clinical trials have consistently shown the two-compound formulation to be effective and safe, with no clinically significant skin atrophy, calcium level changes, or adrenal suppression were seen. Topical scalp solution was also safe and effective in treating scalp psoriasis in pediatric populations. Expert commentary: Calcipotriene plus BD is more effective and safer than the individual ingredients in the same vehicle for treating body and scalp psoriasis. It should be considered a first line therapy for mild-to-moderate plaque psoriasis.