Focus on Psoriasis

A report from the 2019 EADV Congress

By Deepak Balak, MD PhD MSc

More than 12,000 participants attended the 28th Congress of the European Academy of Dermatology and Venereology (EADV), which took place Oct. 9-13, 2019, in Madrid, Spain, and featured more than 750 speakers presenting more than 150 lectures. The well-attended meeting included the latest information on innovations in skin research and provided up-to-date clinical reviews of several dermatological conditions, including psoriasis, which was a popular discussion topic. The following report presents summaries of the congress’s psoriasis- focused sessions.

CONTENTS AND QUICK LINKS

• Long-term risankizumab treatment
• Long-term effectiveness and safety of adalimumab
• Global Psoriasis Atlas update
• Guselkumab vs secukinumab phase 3 study
• Long-term effects of apremilast
• Indirect comparisons of psoriasis treatments
• Therapeutic inertia in psoriasis management
• Secukinumab/etanercept in patients with psoriasis and comorbidities
• Adalimumab vs adalimumab with methotrexate
• Impact of IL-17A genetic variants on IL-17 blockade
• Psoriasis pathogenesis update
• Challenges in diagnosing psoriasis
• Topicals and phototherapy in disease management
• Therapeutic advances in psoriasis
• Poster presentations

Long-term risankizumab treatment

Dr. Kim Papp, K. Papp Clinical Research, Waterloo, Canada, presented data from the LIMMitless study, which assessed the long-term efficacy and safety profile of risankizumab, a novel interleukin (IL)-23 inhibitor that was granted market authorization for psoriasis treatment in 2019. LIMMitless is an ongoing open-label extension study that enrolled patients who had participated in one of 3 earlier risankizumab phase 3 trials. Patients in this study continued risankizumab in a dose schedule of 150 mg every 12 weeks. At week 136, 87% of 787 patients achieved a Psoriasis Area and Severity Index (PASI) 90 response and 61% achieved a PASI 100 response. In terms of safety, the incidence of treatment-emergent adverse events did not increase with continuous risankizumab use up to week 160. Of note, no cases of systemic candida infections, inflammatory bowel disease, or active tuberculosis were reported. Dr. Papp concluded that long-term risankizumab treatment provides durable maintenance of clinical response and that the use of risankizumab is well tolerated with no new safety signals noted throughout nearly 3 years of continuous treatment.  

Long-term effectiveness and safety of adalimumab

The long-term effects of the tumor necrosis factor (TNF)-alpha inhibitor adalimumab in daily clinical practice were presented by IPC Councilor Professor Diamond Thaçi, University of Luebeck, Germany. He discussed an interim analysis from the ESPRIT registry, a multicenter prospective observational study evaluating the safety and effectiveness of adalimumab treatment for psoriasis as prescribed in routine practice over a 10-year period. The inclusion period ran from September 2008 to November 2012 in 13 countries in North America and Europe. The ESPRIT registry includes a total of 6,014 patients and currently encompasses 28,161 persons years of adalimumab exposure. The effectiveness of adalimumab – as measured by the proportion of patients achieving a Physician Global Assessment (PGA) of clear or minimal – was fairly consistent across the 10-year period, ranging from 57% to 71%. The incidence rates of treatment-emergent adverse events, in particular cardiovascular events, serious infections, and malignancies did not increase with up to 10 years of adalimumab exposure. Interestingly, the number of deaths observed in the ESPRIT registry (n = 60) was lower than would be expected in an age-, sex- and country-matched population (n = 144). Professor Thaçi concluded that the effectiveness of adalimumab is maintained through 120 months of treatment and that the safety profile of adalimumab is consistent with the known safety profile from clinical trials, with no emergence of new safety signals.

Global Psoriasis Atlas update

Dr. Rosa Parisi, University of Manchester, United Kingdom, shared new results from the Global Psoriasis Atlas (GPA) project. This initiative – which is supported by the IPC, along with the International Federation of Psoriasis Associations (IFPA) and the International League of Dermatological Societies (ILDS) – aims to identify and report on the global burden of psoriasis. The first step of the GPA was to conduct a systematic review to obtain existing worldwide data on the epidemiology of psoriasis. The literature search yielded 131 studies on the prevalence of psoriasis, with most (67%) of the studies reporting from high-income countries. After a filtering process, the data were statistically analyzed by using a Bayesian hierarchical mixed model. Geographical clustering was used to generate estimates for countries with missing information. The global prevalence of physician-diagnosed psoriasis in adults in 2017 was 0.59% (0.14-2.21%), corresponding to 29.4 million adults affected. If self-reported data are considered, the global prevalence increases to 0.96% (0.26-3.26%), which totals to almost 48 million adults. Differences between continental regions were observed: The prevalence of psoriasis in Western Europe was estimated at 2.5%, whereas in East Asia the prevalence was as low as 0.17%. Country-specific prevalences are now available for 189 countries and accessible via the GPA website at https://globalpsoriasisatlas.org/. One limitation is that the majority of data identified came from high-income countries – therefore, the prevalence in low-income countries may be underestimated. To address this limitation, the GPA initiative is undertaking new studies in countries for which epidemiological data on psoriasis are lacking.

Guselkumab vs secukinumab phase 3 study

The ECLIPSE study was the first phase 3 trial to directly compare an anti-IL23 biologic (guselkumab) with an anti-IL17A biologic (secukinumab) in patients with moderate to severe plaque psoriasis. In this trial, 1,048 patients with moderate to severe plaque psoriasis were enrolled. IPC Councilor Professor Richard Langley, Dalhousie University, Halifax, Canada, highlighted week 48 data from the study, focusing on PASI 90 improvement by body region (ie, head, trunk, upper and lower extremities). At week 48, greater proportions of patients achieved ≥ 90% improvement in PASI body region component scores when comparing guselkumab with secukinumab. For instance, ≥ 90% improvement for the PASI trunk scores was achieved by 88% of patients taking guselkumab, compared to 80% of patients on secukinumab. The largest treatment differences between guselkumab and secukinumab were seen for the upper extremities (82% vs 67%, respectively) and lower extremities (82% vs 67%). Similar outcomes were observed for 100% improvement in PASI body region scores. Professor Langley concluded that guselkumab more than secukinumab showed consistently greater improvement across the different PASI body region components.

Long-term effects of apremilast

IPC Councilor Professor Kristian Reich, Dermatologikum Hamburg, Germany, discussed findings from the observational LAPIS-PSO study, which assessed the long-term treatment effects of apremilast, an oral phosphodiesterase-4 inhibitor, on patients’ quality of life, clinical response, and tolerability in a real-world setting. Patients enrolled in the study received apremilast according to label instructions and were followed up to 52 weeks. The primary endpoint was the proportion of patients who achieved a Dermatology Life Quality Index (DLQI) of score ≤ 5 or improvement of DLQI score by >5 after 4 months of treatment. The outcomes were stratified by 1 vs >1 prior conventional systemic therapy. The primary endpoint was achieved by 66% vs 68% of patients with 1 vs > 1 prior conventional systemic treatment. At 1 year, the primary endpoint was met in 81% and 86% of patients, respectively. Secondary outcomes, such as Physician Global Assessment score of 0 or 1, changes in mean body surface area and skin pain visual analog scores showed considerable improvement as well.

Indirect comparisons of psoriasis treatments

IPC Councilor Professor Matthias Augustin, University Medical Center Hamburg-Eppendorf, Germany, discussed the value of indirect comparisons to enhance psoriasis treatment decisions in clinical practice. As therapeutic options for plaque psoriasis continue to grow, the complexity of treatment decisions for clinicians increases as well. Direct comparisons of all available treatments are impractical, so indirect comparisons are the most feasible approach for objective treatment comparisons. Several methodologies are available for indirect comparisons, such as matching-adjusted indirect comparisons (MAICs) and network meta-analyses. Professor Augustin presented findings from a systematic review that identified 9 network meta-analyses and 2 matching-adjusted indirect comparisons that assessed treatments in psoriasis. These 11 studies were based on data from randomized controlled trials and mostly assessed short-term treatment up to 16 weeks. The greatest variations between the identified studies was in the treatments included, data handling of treatment doses, and selected effect measures. Most studies included PASI 75 and PASI 90 as efficacy outcomes, but safety and quality of life outcomes varied considerably among the different studies. Professor Augustin concluded with the observation that the indirect comparison methodology provides valuable indirect evidence of available treatment options for psoriasis, though such studies need to be interpreted with caution, as safety outcomes and long-term outcome studies are often lacking.

Therapeutic inertia in psoriasis management

Dr. Bruno Halioua, dermatology consultant, Paris, France, discussed highlights from a study that evaluated patients’ perception of therapeutic inertia in psoriasis. Therapeutic inertia is defined as the failure of health care providers to initiate or intensify therapy when indicated. In a French online survey from 2019, 181 patients with psoriasis (70% female, mean age 52 years, mean disease duration 16 years) were asked to give their perception of therapeutic inertia. Of the 92 participants in which a treatment change took place – either from topical to oral therapy or from oral to injection therapy – 50% indicated that their doctor should have changed their treatment earlier. In the subgroup of patients without any change in treatment, the majority (69%) of patients would have liked their doctor to change their treatment. In terms of consequence of therapeutic inertia, 69% reported that the absence of a change of therapy had a negative impact on their quality of life and 41% reported that this resulted in a negative impact on their treatment adherence. Moreover, 71% patients indicated they had switched to a different health care provider.

Secukinumab/etanercept in patients with psoriasis and comorbidities

IPC Councilor Professor Alice Gottlieb, Icahn School of Medicine at Mount Sinai, New York, United States, presented data from a post-hoc analysis that assessed the clinical efficacy and safety of the anti-IL17A-biologic secukinumab and the TNF-alpha-inhibitor etanercept in patients with psoriasis and comorbidities. By pooling data from 4 phase 3 randomized controlled trials, the analysis involved data from 2,401 patients with psoriasis who were treated with either secukinumab (150 or 300 mg) or etanercept (50 mg) for 12 weeks. The efficacy and safety outcomes were stratified by the presence or absence of baseline comorbidity. Overall, the most common comorbidities were obesity (defined as a body mass index ≥ 30 kg/m2) present in 61%, followed by hypertension (37%) and psoriatic arthritis (18%). One finding was that patients with baseline comorbidity were on average older, heavier, and more likely to be biologic experienced than those without comorbidity. The efficacy and safety outcome analyses showed no statistically significant differences in treatment responses between patients with and without comorbidity. Secukinumab, and to a lesser extent etanercept, improved outcomes and were well tolerated despite the presence of baseline comorbid conditions. Only body weight ≥ 90 kg was consistently associated with a decreased likelihood of achieving clinical response. Expanding on these results, randomized controlled trials for secukinumab in obese patients are ongoing.

Adalimumab vs adalimumab with methotrexate

Dr. Gayle van der Kraaij, University of Amsterdam, the Netherlands, discussed 1-year results from a randomized controlled trial in which adalimumab monotherapy was compared to adalimumab plus methotrexate. The rationale behind this trial is that concomitant methotrexate could prevent antidrug antibody formation to adalimumab and thus could help to improve adalimumab’s efficacy and drug survival. In this multi-center, single-blinded controlled trial, 61 patients with psoriasis were randomized to receive either adalimumab or adalimumab plus methotrexate in a dose of 10 mg/week. Follow-up was every 12 weeks up to 3 years. At week 49, the proportion of patients with a PASI 75 response was statistically significantly higher in the adalimumab plus methotrexate group than the adalimumab monotherapy group, 58% vs 31%, respectively. For the safety outcomes, 6 patients on adalimumab plus methotrexate discontinued their treatment due to adverse events, compared to 4 patients on adalimumab monotherapy. The proportion of patients with antidrug antibodies at week 49 was significantly higher in patients treated with adalumumab alone (47%) than in those treated with adalimumab and methotrexate (16%). Dr. van der Kraaij concluded that the combination of adalimumab with methotrexate leads to less antidrug antibody formation and seems to enhance clinical efficacy and prolong drug survival. Based upon the interim findings of this trial, adding low-dose methotrexate to adalimumab should be considered.

Impact of IL-17A genetic variants on IL-17 blockade

Currently, 3 approved psoriasis biologics target interleukin (IL) 17: secukinumab, ixekizumab, and brodalumab. The efficacy of these IL-17-inhibiting drugs could be influenced by genetic variants in the IL-17A gene. Dr. Lieke van Vugt, Radboud University Medical Centre, Nijmegen, the Netherlands, undertook a pharmacogenetic analysis of all variants in the coding and noncoding regions of the IL-17A gene and assessed their impact on PASI response in a multicenter cohort of 134 patients treated with either secukinumab or ixekizumab. In this cohort, the investigators found 8 single nucleotide variants within the IL-17A gene; however, none were located in the coding regions. They selected 5 variants for further analyses based on a known or suspected functional effect. There were no associations between any of the variants and change in PASI at week 12 or week 24. The study concluded that clinical response to secukinumab and ixekizumab cannot be explained by genetic variants in the IL-17A gene.

Psoriasis pathogenesis update

IPC Councilor Professor Jörg Prinz, Ludwig Maximilians University, Munich, Germany, reviewed new insights into psoriasis pathogenesis. Previous analyses from genome-wide association studies have demonstrated gene-gene interactions between one specific HLA-class I-allele – ie, HLA-C*06.02 – with ERAP1 variants that affect the risk for psoriasis. The normal function of HLA-class I molecules is to present peptides to CD8+ T cells; ERAP1 is involved in the processing of peptides. In psoriasis, CD8+ T cells are known to be activated and infiltrate within the epidermis and thus are likely to be autoreactive. Professor Prinz’s work centered around elucidating the skin target of these autoreactive CD8+ T cells in psoriasis. A series of sophisticated experimental studies found that melanocytes were the target of the autoreactive T-cells and the HLA-C*06.02-restricted autoimmune response in psoriasis. The causative autoantigen is ADAMTSL5 and the antigen processing of this peptide is ERAP1-dependent. Professor Prinz concluded that these findings may explain the gene-gene interaction observed between ERAP1 variants and HLA-C*06.02 in psoriasis risk.

Challenges in diagnosing psoriasis

Pitfalls in diagnosing psoriasis were the topic discussed by IPC Councilor Professor Paolo Gisondi, University of Verona, Italy. Pitfalls, he said, may be common, as no definitive laboratory tests exist for psoriasis, lesions could be similar to other skin diseases, psoriasis could occur concomitantly to other skin diseases, and finally, because of atypical cases. On average, there is a delay of 2 years between onset of symptoms and establishing a psoriasis diagnosis. In addition, the list of potential differential diagnoses is extensive and includes Bowen disease, lichen planus, discoid and subacute forms of lupus erythematosus, parapsoriasis, and pityriasis rubra pilaris. Professor Gisondi concluded that clinicians should recognize pitfalls that may occur in diagnosing psoriasis as well as the importance of including a differential diagnosis of other papulosqamous skin diseases. In selected cases, obtaining a skin biopsy and culture examination could be helpful.

Topicals and phototherapy in disease management

IPC Councilor Professsor Wolf-Henning Boehncke, Hopital Universitaire de Genève, Switzerland, shared his clinical experience with topical therapy and phototherapies for psoriasis. Topical therapy remains an important component of disease management and includes use of emollients such as urea and salicylic acid. Topical therapeutic agents, including corticosteroids, vitamin D derivatives and calcineurin inhibitors, are indicated for mild psoriasis, but they can complement therapy for moderate to severe psoriasis and are additionally useful for difficult-to-treat conditions, such as palmoplantar, genital and scalp psoriasis. For phototherapy, narrowband ultraviolet (UV) B is the current gold standard. Phototherapy can be particularly advantageous in selected special patient populations, such as patients with contraindications for systemic therapy.

Therapeutic advances in psoriasis

IPC Councilor Professor James Krueger, Rockefeller University, New York, United States, presented an overview of therapeutic advances for psoriasis made over the past 3 decades. He described psoriasis as the most successful case of molecular therapeutic targeting in a human immune-mediated disease. With a single drug, psoriasis now can be well controlled in more than 90% of patients and with full disease resolution in about 50% of patients. These successes built upon work from the late 1980s that demonstrated the presence of specific subsets of immune cells, ie, CD3+ T cells, in psoriasis skin. Subsequently, a 1995 groundbreaking clinical trial demonstrated that by blocking T cell activation using an interleukin-2 (IL-2R) binding toxin (DAB389IL-2), psoriasis could improve clinically. These early therapeutic advances were expanded further with the arrival of the first-generation biologics targeting T cell activation and, far more successful, TNF-alpha. Professor Krueger expanded on the concept that psoriasis is caused by inappropriate activation of polar T cell subsets, ie, Th1, Th17, and Th22. The use of biologics to target IL-17 and IL-23 has increased the understanding of psoriasis pathogenesis, so that, at the moment, the IL-23/T17 axis is viewed as most crucial for sustaining psoriasis. Psoriasis is now best modeled as an IL-17-centered disease with “feed forward” inflammation and keratinocytes amplifying the response. Professor Krueger ended his presentation by sharing future aspirations for psoriasis treatment, including achieving a Psoriasis Area and Severity Index (PASI) 100 score for every patient with psoriasis, no residual molecular scar in clinically healed psoriasis lesions, improved health and longer lifespans by addressing disease-associated comorbidities, and, finally, disease modifications that lead to a cure.

Poster presentationsPatients with Psoriasis Remain Undertreated: Results from the DERMLINE Online Survey.
M. Schielein and colleagues, Technical University of Munich, Germany

• The DERMLINE survey investigated the impact of psoriasis on patients’ lives, their level of satisfaction, and potential reasons for undertreatment.
• DERMLINE was an online survey conducted in Germany between December 2018 and January 2019. Subjects were recruited via banner advertisement and completed a 52- to 60-item survey.
• In total, 650 questionnaires were completed. Mean age of participants was 43 years. 50% were female. Mean duration of disease was 15 years.
• The survey results showed a considerable impact of psoriasis on patients’ lives: 47% said they avoided stressful situations for fear of triggering symptoms; 40% hid skin with clothing despite weather conditions; 38% modified their diet; 34% avoided physical proximity to friends; and 33% reduced sporting activities.
• Only 54% were currently being treated by a physician. Reasons for not consulting a physician included thinking that the doctors take too little time (49%); thinking that doctors do not care about their illness (29%); and, finally, thinking that doctors are not well informed (26%).
• In terms of patient satisfaction with their current treatment, 34% were moderately satisfied, 19% not satisfied, and 6% not at all satisfied. Mean reasons for patient dissatisfaction were that the medications prescribed do not help (55%) or have too many side effects (29%).
• This study concluded that a striking proportion of patients with psoriasis seem to remain undertreated or dissatisfied with their treatments. 

Gender differences in the impact of psoriasis: Results from the World Psoriasis Happiness surveys
S. Mcbride and colleagues, Royal Free London NHS Foundation Trust, United Kingdom

• This international study explored the role gender plays in the impact of psoriasis on patient’s social and psychological well-being.
• Participants aged ≥16 years from 21 countries completed an app-based survey on well-being via the PsoHappy platform between July 2017 and August 2018. Validated questionnaires were used to assess social and psychological well-being.
• 89,778 responders participated. Most of the study’s participants (60%) were female and aged 25-54 years.
• Psoriasis affected social well-being as assessed by the Dermatology Life Quality Index (DLQI), with 22 percent reporting that the disease interfered with leisure, and that it affected routine activities (18%) and relationships with partners/friends (17%). Women more than men experienced a great impact on their social well-being.
• In terms of psychological well-being, psoriasis was associated with poorer life satisfaction and higher proportions of patients who experienced loneliness and stress. This was particularly the case for young women. Compared to men, women generally reported a higher occurrence of intense emotions and were more sensitive to negative emotions.
• This study concluded that the social and psychosocial well-being of patients with psoriasis requires greater attention, especially in young women. Given the differential impact of gender, approaches tailored to specific needs of men and women may be warranted.