Part 3 of a webcast on the management of patients
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Dr. Stein Gold discusses innovations in topical therapy for patients with psoriasis at the 2020 Maui Derm for Dermatologists Meeting.
Psychological Burden of Psoriasis—Prof. Dimitrios Ioannides (EADV Virtual Congress 2020)
Prof. Dimitrios Ioannides of the Hospital for Skin and Venereal Diseases and the Medical School of Thessaloniki, Greece, presented on the psychological burden of psoriasis. Prof. Ioannides began by acknowledging the significant socioeconomic burden on people with psoriasis, characterized by functional impairment, loss of professional opportunities, and costs of psoriasis treatment. Prof. Ioannides also discussed a 2016 report from the World Health Organization (WHO) that emphasized the immense impact on the lives of patients with psoriasis, citing such difficulties as the unpredictable disease course and association with significant comorbidities, such as cardiovascular disease, metabolic syndrome, inflammatory bowel disease, and depression. According to Prof. Ioannides, the WHO report also indicated that many patients with psoriasis experience incorrect or delayed diagnoses, emphasizing the opportunity for improvement in psoriasis treatment. Prof. Ioannides also discussed research that investigated specific social and emotional obstacles faced by patients with psoriasis. In addition, he discussed the mechanistic explanation of the association between psoriasis and depression, citing the impact of systemic inflammation and the overlapping cytokines indicated in the pathogenesis of both depression and psoriasis. Prof. Ioannides concluded his talk by outlining the ultimate goal in psoriasis treatment—timely, sustained control of the multiple manifestations of the disease while also addressing other dimensions of patients’ lives through collaboration with psychologists.
Choosing highly effective drugs (ixekizumab and other FDA-approved drugs including IL-17 and IL-23) for moderate-to-severe psoriasis: comparative evidence from network meta-analyses (Abstract presented at Maui Derm Virtual Congress 2020)
There are currently 11 FDA-approved biologics for the treatment of moderate-to-severe psoriasis: brodalumab, ixekizumab, and secukinumab (IL-17 inhibitors), ustekinumab (IL-12/-23 inhibitor), guselkumab, risankizumab, and tildrakizumab (IL-23 inhibitors), and adalimumab, certolizumab pegol, etanercept, and infliximab (TNF-inhibitors). Here, Leonardi et al analyzed the effectiveness of the 11 available biologics (in terms of number needed to treat) in order to assist health care providers and patients create the optimal treatment plan in pursuit of achieving psoriasis area and severity index PASI 90 and PASI 100. The authors noted that estimates of number needed to treat make comparing treatment options easier for providers and patients. They collected data from 41 Phase III studies that reported Week 12, 16, 48, and 52 PASI 90 and 100 response rates. According to previously published data, ixekizumab demonstrated the highest success rate at Week 12 and 16. At Week 12, brodalumab had the highest efficacy for PASI 100 response. However, the numbers needed to treat did not vary between ixekizumab, guselkumab, risankizumab, and tildrakizumab by Week 48/52. Number needed to treat was lowest for guselkumab, risankizumab, brodalumab, and ixekizumab at Week 48/52 for both PASI 90 and PASI 100. According to Leonardi et al, ixekizumab and brodalumab appeared to provide the most patients clear or almost clear skin within the first three months, while risankizumab, brodalumab, ixekizumab, and guselkumab appeared to provide the most patients clear or almost clear skin out to one year of treatment.
Thaci D, Blauvelt A, Reich K, et al. Long-Term Efficacy of Certolizumab Pegol Dosed at 400mg Every Two Weeks in Patients with Plaque Psoriasis: Pooled 128-Week Data from Two Phase 3 Trials (CIMPASI-1 and CIMPASI-2) (Abstract presented at Maui Derm for Dermatologists 2020)
Certolizumab pegol has been approved by the United States Food and Drug Administration and European Medicines Agency to treat cases of moderate to severe plaque psoriasis. Here, researchers shared Phase III data from a study of participants with moderate to severe plaque psoriasis after they were given 200mg to 400mg of certolizumab pegol every two weeks for about 128 weeks. Participants with plaque psoriasis persisting for six months or longer, and with Psoriasis Area and Severity Index (PASI) ≥12, ≥10% body surface area affected, and Physician’s Global Assessment (PGA) ≥3 on a 5-point scale, qualified for the study. By Week 16, 77.2 percent of patients achieved PASI 75, while 50.2 percent achieved PASI 90. From that point until Week 128, psoriasis improvements were maintained, indicating the long-term effectiveness and longevity of certolizumab pegol.
Dermatology Update 2020 (Maui Derm Connect 2020 Coverage)
In this session, featuring Ted Rosen, MD, Matthew Zirwas, MD, Lucia Diaz, MD, and Seemal Desai, MD, top articles from the literature in 2019 and 2020 that affect the way we practice dermatology were discussed. Dr. Rosen began the lecture with an update from the literature on patient care, surgery, and cutaneous oncology. Additional topics discussed throughout the presentation were the use of vibrational anesthesia to prevent the pain of local injections, the importance of hedgehog inhibitors for the improved quality of life of patients with prominent lesions related to end-stage cancer, and the increased prevalence of thyroid dysfunction in people with psoriasis. The segment ended with studies that evaluated the link between atopic dermatitis and cancer.
Next, Dr. Zirwas presented articles that covered topics such as dietary modifications for patients with psoriasis to improve their symptoms and optimizing the way physicians speak to patients to promote better adherence and agreement. Dr. Zirwas also discussed literature that examined the relationship between atopic dermatitis and statin use and articles that reported on the effectiveness of hypnosis when treating atopic dermatitis.
Following this, Dr. Diaz provided updates in pediatric dermatology practices, including new practice and treatment guidelines from pediatric dermatology specialists. Dr. Diaz shared data on the use of dupilumab for children and the methods for use depending on age. Lastly, Dr. Desai reviewed more notable additions to the dermatology literature, beginning with a study of global epidemiology and clinical spectrum of rosacea in skin of color. The differential diagnosis for various skin conditions in patients with skin of color were also discussed.
Psoriasis and Psoriatic Arthritis (Maui Derm Connect 2020 Coverage)
This session, featuring Bruce Strober, MD, PhD, Arthur Kavanaugh, MD, and Melodie Young, MSN, ANP-c, was designed as a series of case-based studies covering a wide range of diseased states in psoriasis that challenged even the most experienced clinician. The featured physicians began by advocating for the safe continuation of biologic therapies during the era of COVID-19, using cases of patients with psoriasis who wanted to discontinue their treatment as a precautionary measure. After reviewing a few biologic options, each physician discussed the importance of monitoring patients being treated with biologics, infection risks, the biologic response to vaccines, and how patients can effectively be vaccinated in conjunction with treatment.
Next, using published data, Dr. Strober compared the 24-week clinical trial responses and changes in joint structural damage effects of treatment options for psoriatic arthritis. Based on this data, Dr. Kavanaugh explored whether different inhibitors should be used interchangeably for psoriatic arthritics; moreover, questions regarding drug efficacy in axial spondyloarthritis were thoroughly examined. Dr. Young discussed treatment plans for patients with guttate psoriasis or palmoplantar psoriasis, analyzing cases of patients with the these conditions that featured photos depicting clearance progression. This led to the exploration of biologic treatments for pediatric patients with psoriasis or psoriatic arthritis.
The presenters concluded their lecture by examining how weight affects and potentially dictates psoriasis and psoriatic arthritis treatment (and vice versa). Each physician outlined their treatment choice logic based on patients with psoriasis and obesity, then examined various weight quartiles for dosing and PASI scores from related studies.
Psoriasis: A Systemic Disease—Prof. Paolo Gisondi (EADV 2020 Virtual Congress)
Prof. Paolo Gisondi of the University of Verona and Borgo Trento Hospital discussed the frequent association between moderate to severe psoriasis and metabolic and inflammatory comorbidities, possible reasons for this association, and the expression of psoriasis-related inflammation that manifests beyond the skin. Prof. Gisondi discussed the common genetic background linking psoriasis and its comorbidities and reviewed specific overlapping genes between psoriasis and these comorbidities, including obesity, diabetes, and myocardial infarction. He also noted how inflammatory mediators released from psoriatic lesions can have systemic effects, including effects on the liver, adipose tissue, and skeletal muscle that contribute to endothelial dysfunction and atherosclerosis. Prof. Gisondi also discussed the similar metabolic and immunologic pathways shared between psoriasis and obesity. Prof. Gisondi closed his talk by discussing whether systemic treatment of psoriasis could prevent the development of comorbidities and identified this as an area for future investigation.
Aldredge L, Stein Gold L, Elewski B, Draelos Z, Chao TJ, Jacobson A. Efficacy of a Fixed Combination Halobetasol Propionate 0.01% and Tazarotene 0.045% Lotion in Females with Psoriasis and Perception of Vehicle Properties (Abstract Presented at Maui Derm Virtual Congress 2020)
Treating psoriasis by combining the topical corticosteroid halobetasol propionate (HP), with the retinoid tazarotene (TAZ) may enhance efficacy, reduce side effects of both HP and TAZ, and sustain treatment response posttreatment. A fixed combination HP 0.01%/TAZ 0.045% lotion has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis. However, according to Aldredge et al, disease characteristics and optimal treatment strategies for psoriasis may differ between male and female patients. In this post-hoc analysis of data from two pooled Phase 3 studies, the authors of this abstract, presented at the Maui Derm 2020 Virtual Congress, evaluated the efficacy of HP/TAZ lotion in female participants with moderate-to-severe psoriasis and assessed the perception of the vehicle lotion properties through a questionnaire. A total of 146 female participants were included in the pooled Phase 3 studies. At Week 8, 44.5 percent of the female participants treated with HP/TAZ achieved treatment success (defined as a ≥2‑grade improvement from baseline in the Investigator’s Global Assessment score and score of “clear” or “almost clear”). This was significantly greater than female participants treated with the vehicle (9.9%; P<0.001). Additionally, 93 to 100 percent of the health female controls who were given the vehicle lotion agreed that it was hydrating, moisturizing, and was easily absorbed into the skin. The researchers highlighted that the female patients with psoriasis experienced rapid and notable disease reductions, and the healthy controls were in favor of the bene¬fits of the vehicle lotion.
Psoriasis and Psoriatic Arthritis in the COVID-19 Era (Maui Derm Connect)
New drugs, new data, new approaches to psoriasis and psoriatic arthritis were discussed in this series of lectures from Joel Gelfand, MD, Bruce Strober, MD, PhD, and Arthur Kavanaugh, MD. The talks were followed by a discussion of a series of challenging case scenarios. Dr. Gelfand provided a brief overview of the National Psoriasis Foundation and the COVID-19 taskforce, addressing COVID-19-related questions and concerns, especially within the psoriasis and psoriatic arthritis community. The methods of protection, continuation of treatment, and effects on psoriatic disease were covered. Dr. Gelfand concluded this part of the presentation by offering management instructions for those with psoriatic disease who have contracted COVID-19, as well as an in-depth look at the scientific progressive of COVID-19. Next, Dr. Strober provided updates of modern psoriasis therapies and current data on the skin disease. To begin, Dr. Strober compared the cytokine-regulation abilities of tyrosine-protein kinase- and Janus kinase 1 inhibitors. Then, the efficacy, safety, and changes in PASI scores of the IL-17 and IL-17f inhibitor, bimekizumab, was examined through solid findings from Phase III studies. Following this, Dr. Strober switched focus to IL-23 inhibitors, specifically guselkumab, sharing current findings and tolerability and safety data. Dr. Strober later compared changes in PASI scores and above data between IL-17 inhibitors and IL-23 inhibitors. The segment ended with the exploration of current topical treatments and severity guidelines for the treatment of psoriasis.
New Therapeutic Targets Based on Pathophysiology(EADV 2020 Virtual Congress)
Dr. Luís Puig, of the Department of Dermatology at the Hospital de la Santa Creu I Sant Pau in Barcelona, Spain, presented on new therapeutic targets based on psoriasis pathophysiology. Dr. Puig provided a review of the current concept of the pathogenesis of psoriasis and acknowledged a more recent focus on keratinocytes as key drivers of inflammation in psoriasis through the production of several cytokines, including interleukin (IL)-36, which Dr. Puig payed special attention to during his talk. Patients with severe autoinflammatory types of generalized pustular psoriasis, says Dr. Puig, are thought to have mutations of the antagonist of the receptor of IL-36. Dr. Puig also discussed specific genes implicated in the pathogenesis of pustular psoriasis and reviewed the IL-1 cytokines superfamily, of which IL-36 is a part. Dr. Puig then discussed IL-36 receptor binding kinetics in connection to psoriasis, which leads to the production of IL-17A by CD4+ T cells in generalized pustular psoriasis and other conditions characterized by pustulosis. Dr. Puig then discussed therapies in development that block the activation of the IL-36 receptor, including spesolimab and imsidolimab.
Blauvelt A, Mabuchi T, Leung A, et al. Ixekizumab Demonstrates Sustained High Efficacy and Consistent Safety in Patients with Moderate-to-Severe Psoriasis: 5 Years of Follow-up from UNCOVER-3 (Abstract Presented at Maui Derm Virtual Congress 2020)
During clinical trials, interleukin (IL)-17a inhibitor ixekizumab demonstrated safety and efficacy as a therapeutic option for patients with moderate-to-severe plaque psoriasis. Here, Blauvelt et al assessed the safety and effectiveness data of approved ixekizumab dosing from the UNCOVER-3 study after ¬five years of treatment. In the study, participants 18 years of age or older with moderate-to-severe plaque psoriasis and a Psoriasis Area and Severity Index (PASI) score of at least 12 at baseline were randomized to either receive 80mg of ixekizumab every two weeks (or four weeks following a 160mg dose at baseline), 50mg of etanercept twice a week, or a placebo during the 12-week induction. By Week 12, all participants were being dosed every four weeks, while safety, efficiency, and adverse effects were being monitored and evaluated throughout, condensed by the modi¬fied nonresponder imputation method. At Week 264, 97.4 percent of participant achieved PASI75, 90.2 percent achieved PASI90, and 66.5 percent achieved PASI 100. Typical adverse effects included infection (in 72.7% of participants), and there were two cases of Crohn’s disease, one case of ulcerative colitis, and three deaths. Researchers were able to conclude participants maintained high rates of improvement and that the safety of ixekizumab was consistent with prior findings.
Gordon K, Warren B, Gottlieb AB, et al. Long-term improvements in health-related quality of life of patients with moderate to severe plaque psoriasis treated with certolizumab pegol: Results from the CIMPASI-1 and CIMPASI-2 Phase III trials (Abstract presented at EADV 2020 Virtual Congress)
Using Phase III data collected from CIMPASI-1 and CIMPASI-2 trials, Gordon et al sought to determine how treatment with 200mg to 400mg of certolizumab pegol impacted health-related quality of life, as plaque psoriasis has been typically correlated with discomfort, pain, social stigmatization, and psychological distress in those with the skin condition. Changes in health-related quality of life over the course of both trials (around 144 weeks) were tracked via the Dermatology Life Quality Index. After collecting and observing the data, Gordon et al reported both mental and physical improvements in the participants, as early as Week 8, throughout the 144 weeks. Researchers noted that bodily pain and social functioning were most positively affected by treatment with certolizumab pegol.
