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Psoriasis News

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Top Manuscripts

Manuscript summary and expert opinion

Every 6 months, IPC's board and councilors suggest and vote on articles that make the greatest impact on psoriasis research. Please find summaries and commentaries of those Top 5 articles searchable by topic in the list below.

Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials.

Gordon KB, Strober B, Lebwohl M, et al. Lancet. 2018 Aug 25;392(10148):650-661. Epub 2018 Aug 7. 2019
Summary

Risankizumab is a humanized IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23. It therefore inhibits this cytokine, which plays a key role in psoriatic inflammation. The aim of this study was to compare the efficacy and safety of risankizumab with placebo and with ustekinumab in moderate to severe chronic plaque psoriasis. Two replicate, multi-center, phase 3 studies across 14 countries involved 506 and 491 patients who were randomly assigned (3:1:1) to risakizumab 150 mg, ustekinumab 45 or 90 mg, or placebo for the initial double-blind 16 weeks. At week 16, the placebo group switched to risankizumab and the other patients continued on their original drug up to week 52. A Psoriasis Area and Severity Index (PASI) score of 90 was achieved at 16 weeks by 75.3% in the first study and 74.8% in the second study of patients on risakizumab, by 42% and 47.5% respectively, of patients on ustekinumab, and by 4.9% and 2.0% of patients on placebo. Confidence intervals were reported and demonstrated clear differences between the treatment groups. Secondary outcome measures included the Dermatology Life Quality Index (DLQI)* and the Psoriasis Symptom Scale (PSS), which scores the severity of pain, redness, itching, and burning. A DLQI score of 0 or 1 was achieved at week 16 by 66% and 67% of patients on risakizumab, by 43% and 46% on ustekinumab, and by 8% and 4% patients on placebo. A PSS score of 0 was achieved at 16 weeks by 29% and 31% of patients on risakizumab, 15% and 15% patients on ustekinumab, and 2% and 0% patents on placebo. Treatment-emergent adverse events were similar across patients treated with risakizumab, ustekinumab, and placebo.

IPC Expert Commentary

This is another well-organized and well-reported study adding major new evidence of the outstanding effectiveness of risankizumab and of superior effectiveness compared to ustekinumab. Interleukin- (IL-) 23 drives the development of psoriasis by stimulating T-helper-17 and innate immunity cells, which are major sources of pro-inflammatory cytokines. Whereas ustekinumab blocks the p40 subunit that both IL-12 and IL-23 share, risankizumab targets the p19 subunit, specific for only IL-23. The study is notable and especially valuable clinically, as it is one of the very few major studies to directly compare, head-to-head, two biologics with differing modes of action. Clinicians are now overwhelmed with choice of biologics for psoriasis, all providing greater benefit than our previous systemics. For each, the evidence of individual effectiveness may be clear, but the clinician needs to know how they directly compare: We need many more similar head-to-head studies. Pharmaceutical companies Boehringer Ingelheim and AbbVie closely cooperated over this study: Boehringer Ingelheim had sold the commercialization rights of risankizumab to AbbVie in 2016. It is not stated whether the maker of ustekinumab was involved in the study. The baseline demographics table reveals that 72% of the 996 patients weighed >100kg, regrettably reflecting accurately the reality of this comorbidity in patients with severe psoriasis. However, the ethnic origin of study participants in these international studies was 78% white, 17% Asian and only 1.6% black or African-American. This raises the general broader question of what steps clinical study organizers take to ensure recruitment of an appropriate racial mix. – Andrew Y. Finlay

*Dr. Finlay is joint copyright owner of the DLQI. He and Cardiff University receive royalties.

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Clinical and genetic differences between pustular psoriasis subtypes.

Twelves S, Mostafa A, Dand N, et al. J Allergy Clin Immunol. 2019 Mar;143(3):1021-1026. 2019
Summary

Pustular psoriasis can be defined as the heterogenous family of pustular skin diseases that are associated with psoriasis vulgaris (PV). According to this generous definition of pustular psoriasis, even palmoplantar pustulosis (PPP) is included. Mutations in the IL36RN and AP1S3 genes have been described in this group. Pustular psoriasis manifests with repeated eruptions of neutrophil-filled pustules. The most severe form of this condition is generalized pustular psoriasis (GPP). Acrodermatitis continua of Hallopeau (ACH) affects the tips of fingers and toes and palmoplantar pustulosis (PPP) affects the palms and soles. In this study, the clinical and genetic features of pustular psoriasis were investigated by the analysis of an extended patient cohort. A total of 863 unrelated patients with pustular psoriasis were clinically investigated (GPP=251, PPP=560, ACH=28, multiple diagnoses=24). Psoriasis vulgaris occurred in about half of patients with GPP or ACH (54% GPP; 46% ACH) but only in 16% of PPP cases. The percentage of female patients was greater in PPP (77%) than in GPP (63%); likewise, the percentage of smokers was greater in PPP (80%) than in GPP (28%). GPP patients had the lowest mean onset age, 31 years (PPP 44 years and ACH 52 years). Mutation screening was performed in a subset of this cohort comprising 475 patients. IL36RN disease alleles were associated with earlier age of onset in all subtypes (P=0.003). IL36RN mutations were more common in GPP patients (0.19) and ACH patients (0.16) compared to PPP patients (0.03). AP1S3 alleles had similar frequency (0.03 - 0.05) across disease subtypes.

IPC Expert Commentary

This is an important study, as the rarity of generalized pustular psoriasis and acrodermatitis continua of Hallopeau has previously limited this kind of combined genetic and clinical analysis across the extended pustular psoriasis family. This study underlines the clinical and genetic differences between PPP on the one hand and GPP and ACH on the other. Facts such as the comparatively weak association of PPP with psoriasis vulgaris and its strong association with smoking has earlier led to the conclusion that PPP should be separated from the psoriasis family and be seen as a unique entity on its own. This genetic investigation does not enlighten us on this question. IL36RN disease alleles were associated with earlier age of onset in all subtypes, pointing toward a disease-promoting function. However, the relative rarity of IL36RN mutations among patients with PPP may imply that future treatments with IL36 inhibitors are more likely to be therapeutically relevant in the group of GPP and ACH patients. In March 2019, the first-in-class investigational treatment with the monoclonal antibody BI 655130 against the interleukin-36 receptor was published in The New England Journal of Medicine.1 In this proof-of-concept study, 7 GPP patients were treated with a single, open-label, intravenous dose. Only 3 patients carried the IL36RN mutation. The pustules were completely cleared in 6 patients by week two. The efficacy of BI 655130 regardless of the presence of the IL36RN mutation suggests that the interleukin-36 pathway may play a pathogenic role among patients with generalized pustular psoriasis with different genetic backgrounds, including those without target mutations. This could imply that IL36RN screening before treatment is not necessary. – Marcus Schmitt-Egenolf

1 Bachelez H, Choon SE, Marrakchi S, et al. N Engl J Med. 2019 Mar 7;380(10):981-983. doi: 10.1056/NEJMc1811317.

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Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis.

Papp K, Gordon K, Thaçi D, et al. N Engl J Med. 2018 Oct 4;379(14):1313- 1321. Epub 2018 Sep 11. 2019
Summary

The strategy of identifying and targeting various key signaling pathways in psoriasis pathogenesis has been outstandingly successful in bringing powerful new therapies to benefit patients. Papp et al report on yet another approach, aiming at the enzyme tyrosinase kinase 2 (TYK2). Normally, TYK2 activates transcription (STAT)-dependent gene expression and activates functional responses of interleukin-12, interleukin-23, and type I and III interferon receptors. These pathways are involved in the pathogenesis of psoriasis and other immune-mediated disorders; hence, the logic of aiming at TYK2. BMS-986165 is the current catchy name of this latest creation from Bristol-Myers Squibb. It binds to the “pseudokinase” domain of TYK2, blocking further signal transduction. This study was a phase 2, double-blind trial, comparing 5 different dose regimens and one placebo group. As often in these early phase 2 studies, there were only 12 weeks of active therapy, with a 30-day follow-up. Randomization was stratified with respect to geographic region (Japan or the rest of the world), though the reason for this was not given. The study reported on a total of 267 patients. A Psoriasis Area and Severity Index (PASI) score of 75 was reached in 7% of the placebo group, 9% of the lowest-dose group (3 mg per day), and 75% of the highest-dose group (12 mg per day). There was a clear relationship between dose and effectiveness. There were 3 serious adverse events in patients receiving the active drug, as well as 1 case of malignant melanoma 96 days after the start of treatment. Eight patients (3%) developed mild to moderate acne and 12 (4.5%) reported diarrhea.

IPC Expert Commentary

Results of this study showed that in the highest-dose group, which had an average age of 47 years, 4 out of 44 patients developed mild to moderate acne. The authors speculate that this could be due to the inhibition of cytokines involved in resistance to these organisms, resulting in proliferation of commensal bacteria and inflammation in the pilosebaceous units. Or, it might be chance. At the highest-dose investigated, 12 mg daily, 75% of 44 patients reached a 75% reduction in PASI and 64% reached a Dermatology Life Quality Index (DLQI)* score of 0 or 1. This sounds very promising, especially for a drug taken by mouth, but as the authors cautiously conclude: Safety and durability of effect remain to be determined. And this highest-dose group experienced the highest percentage of adverse effects.

Note: A recent article in the British Journal of Dermatology praised the New England Journal of Medicine for most often reporting confidence intervals (CIs) rather than p values in dermatology reports.1 The gist of that BJD article was to encourage wider reporting of CIs by researchers to improve clinical interpretation of study results. So, it’s disappointing that in this NEJM article about TYK2, p values are given prominence. CIs provide a range in which the true value lies with a certain degree of probability as well as the strength and direction of the effect. So, statistical plausibility and clinical relevance of the study can be inferred. Admittedly, p values may appear to be clearer, but the 2 methods are complementary.

It was good to see that the investigators correctly defined the use of a “handprint” rather than a “palm,” as approximately 1% of body surface area. I admit I am biased over this, having struggled (mostly unsuccessfully) to help people understand this often wrongly or imprecisely defined concept. – Andrew Y. Finlay

* Dr. Finlay is joint copyright owner of the DLQI. He and Cardiff University receive royalties.
1 Hopkins ZH, Moreno C, Secrest AM. Lack of confidence interval reporting in dermatology: a call to action. Br J Dermatol. 2019 Apr;180(4):910-915.

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Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients.

Patrick MT, Stuart PE, Raja K, et al. Nat. Commun. 2018 Oct 9;9(1):4178. 2019
Summary

Psoriatic arthritis (PsA) occurs in about one-third of psoriasis patients. In this study, the authors use state-of-the-art statistical and machine-learning techniques to capitalize on the multitude of differences in the genetic architecture between PsA and cutaneous-only psoriasis (PsC) to predict the risk of developing PsA in the PsC population. The genetic data that populated their model were derived from 6 combined cohorts, resulting in 7,000 genotyped PsA and PsC patients. In their best predictions, the investigators achieved >90% precision with 100% specificity and 16% recall for predicting PsA among PsC patients, using conditional inference forest or shrinkage discriminant analysis, proving that genetic differences can potentially be used to predict PsA risk.

IPC Expert Commentary

This study shows that despite the lack of a relevant single genetic marker for PsA, a multitude of markers can be employed to predict this risk with impressive precision. Given the fast development and diminishing analysis costs in the fields of genetics and machine learning, personalized diagnostics for PsA may well enter clinical praxis soon and inform treatment decisions. From a clinical point of view, it would be interesting to be able to predict the risk of PsA in advance of symptoms and signs in PsC patients. However, as physicians, we should remember that genetic-derived statistical risk prediction does not necessarily translate to real-world clinical risk. We should not see the disease course of the patient in front of us in a deterministic way. On the contrary, we should always encourage and empower our patients, as lifestyle decisions have a value both within and far beyond the treatment of psoriasis. – Marcus Schmitt-Egenolf

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A skewed pool of resident T cells triggers psoriasis-associated tissue responses in never-lesional skin from patients with psoriasis.

Gallais Sérézal I, Hoffer E, Ignatov B et al. J Allergy Clin Immunol. 2019 Apr;143(4):1444-1454. Epub 2018 Sep 27. 2019
Summary

Resident lesional T cells in moderate to severe psoriasis are well studied. Less is known about T cells in never-lesional skin from patients with mild psoriasis (NLP), investigated here by confocal imaging and flow cytometry. Tissue responses to T cell stimulation were furthermore measured by multiplex and NanoString technology. Interestingly, T cell activation ex vivo triggered psoriasiform and type I interferon tissue responses in NLP psoriasis. NLP-derived keratinocytes responded to IFN-g stimulation with myxovirus 1 expression and IFN-a release. CCR6-expressing resident T cells producing IFN-g and IL-17 were enriched in NLP-epidermis. Keratinocytes from NLP exposed to IL-17 and skin explants exposed to common fungal antigens responded with upregulation of the CCR6 ligand CCL20. Taken together, this implies that epidermal resident T cells capable of triggering psoriasiform tissue responses accumulate in NLP-epidermis. The interaction of the microbial microenvironment with genetically susceptible keratinocytes appears to shape the NLP T cells.

IPC Expert Commentary

The microbial microenvironment has in the last years been one of the main interests in medicine, and psoriasis is not excluded from this trend. In order to investigate the early changes in the complex etiology of psoriasis, this study went not to the crowded place of T cells in the established plaque in moderate to severe psoriasis but tried to analyze the early events by focusing on never-lesional skin from patients with mild psoriasis. The clear disturbance of T cells and microenvironment described here encourages the search for therapeutic options that, following the intellectual concept behind the design of this study, might be able to interfere in these early subclinical stages of psoriasis or maybe even the microenvironment itself. – Marcus Schmitt-Egenolf

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Association between skin and aortic vascular inflammation in patients with psoriasis: a case-cohort study using positron emission tomography/computed tomography.

Dey AK, Joshi AA, Chaturvedi A, et al. JAMA Cardiol. 2017 Sep 1;2(9):1013-1018. doi: 10.1001/jamacardio.2017.1213. Clinical trials 2018
Summary

Vascular inflammation demonstrated by fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) is an important biomarker of cardiovascular risk, and psoriasis, especially in its severe forms, has been associated with vascular inflammation by FDG PET/CT, suggesting a relationship between skin inflammation and vascular disease.

This is an observational prospective cohort study intended to investigate the association between improvement in skin disease and consequent improvement in aortic vascular inflammation, as well as to characterize the impact of anti-TNF therapy on vascular inflammation.

Using vascular inflammation by FDG PET/CT as a primary outcome, the authors hypothesized that improvement of psoriasis severity would be associated with improvement of vascular inflammation at one year. A total of 115 patients were recruited and followed up to a year. The study group was middle-aged (mean 50.8 years), predominately male, had a formal diagnosis of moderate plaque psoriasis (mean PASI score 5.2), and were at low cardiovascular risk by the Framingham Risk Score. All of the patients underwent FDG PET/CT scans at baseline and at 1 year, and all the scans were read in a blinded fashion to patient characteristics.

Psoriasis was treated with different therapeutic modalities, including topical, phototherapy, systemic, and biologic treatments. Psoriasis severity was associated with vascular inflammation at baseline. At 1-year follow-up, the cohort had an improvement in different inflammatory biomarkers, including high-density lipoprotein cholesterol level and high-sensitive C-reactive protein. Reduction in skin disease severity was associated with reduction in vascular inflammation and the greater the improvement in psoriasis severity (PASI > 75) the greater the improvement in vascular inflammation. A subgroup analysis of anti-TNF-treated patients demonstrated significant reduction in psoriasis severity as well as significant improvement in vascular inflammation.

IPC Expert Commentary

This study offers further evidence of the systemic nature of psoriasis and how its control provides a beneficial effect on vascular inflammation, shown by the improvement demonstrated by highly sensitive vascular imaging modalities, in this case FDG PET/CT, as well as amelioration in inflammatory biomarkers. Though not designed to prove causality, the findings in this study suggest that reduction in severity or clearance of the disease can have potential impact in decreasing future cardiovascular events and, hence, cardiovascular morbidity-mortality. Some observational studies have already reported a reduction in the incidence of vascular disease in patients with well-controlled psoriasis. Randomized clinical trials with prolonged observation periods will be needed to confirm this hypothesis. – Nancy Powdosa, Mexico

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Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study

Lerman JB, Joshi AA, Chaturvedi A, et al. Circulation. 2017 Jul 18;136(3):263-276. doi: 10.1161/ CIRCULATIONAHA.116.026859. Guidelines 2018
Summary

This important paper by Lerman et al looks to further establish the connection between inflammation in psoriasis and the risk of coronary artery disease. While it is known that psoriasis is associated with an increased risk of myocardial infarction and a variety of coronary risk markers, this study compares imaging of the coronary arteries in patients with psoriasis and controls to assess relative damage. Patients with psoriasis, patients with hyperlipidemia who were approximately 10 years older than the psoriasis patients, and healthy volunteers all underwent coronary computed-tomography angiography to assess for total coronary plaque burden, noncalcified burden, and the presence of high-risk plaques. Total burden and noncalcified burden have previously been established to prospectively predict cardiac events. Patients with psoriasis exhibited significantly more total burden, noncalcified burden, and high-risk plaques than healthy volunteers. Psoriasis was strongly associated with high-risk plaque formation (about 6 times higher than the healthy population and independent of traditional cardiac risk factors). Compared to older patients with hyperlipidemia, psoriasis patients had increased noncalcified plaque burden and a similar number of high-risk plaques despite being younger and having fewer traditional risk factors. The first 50 patients with psoriasis were followed for 1 year and then re-imaged. Interestingly, when the Psoriasis Area and Severity Index (PASI) had improved over that year, there was a significant improvement in both the total plaque burden and the noncalcified burden after adjustment for other coronary risk factors. When the PASI worsened during the year, there was an increase in noncalcified plaque burden. 

IPC Expert Commentary

This paper adds significantly to the increasing evidence that psoriasis is not only associated with coronary disease, but that inflammation is at the heart of both conditions. Psoriasis may be a “hidden risk factor” that, so far, is not commonly considered alongside lipids, blood pressure, and obesity. Even when a patient with psoriasis has few traditional cardiac risk factors, it is important for dermatologists and other physicians to consider that patient’s cardiac risk similar to that of a higher-risk, older patient. Prevention (diet, exercise), cardiac monitoring, and possibly even interventions (such as statins) may be necessary in patients with psoriasis when they would not be in a similar patient who does not have psoriasis. The other key message of this paper is that treating psoriasis successfully shows, even in just one year, improvement in signs of cardiac risk. As we consider how aggressively to treat moderate to severe psoriasis, we must consider the mounting evidence that reducing body-wide inflammation will not only help the patient’s skin and joints, but also may lower the risk of serious and even fatal comorbidities. Psoriasis is a systemic disease, and dermatologists must continue to look to educate colleagues and monitor patients using a team approach to treat not only the skin, but the serious potential complications of chronic inflammation. – Colby Evans, USA

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An analysis of IL-36 signature genes and individuals with IL1RL2 knockout mutations validates IL-36 as a psoriasis therapeutic target.

Mahil SK, Catapano M, Di Meglio P, et al. Sci Transl Med. 2017 Oct 11;9(411).pii:eaan2514.doi:10.1126/scitranslmed.aan2514. Clinical trials 2018
Summary

Interleukin (IL)-36 (α, β and γ) are a family of IL-1 cytokines (usually produced in response to viral infection or skin trauma) sharing a common receptor with immunomodulatory effects. Loss-of-function mutations of an antagonist of the IL-36 receptor gene have been found in generalized pustular psoriasis, suggesting a role for IL-36 activation in the disease. There are also multiple lines of genetic and laboratory evidence connecting IL-36 to plaque psoriasis. This study aimed to further the analysis of IL-36 as a potential target for new therapies in psoriasis.

The first portion of the study treated keratinocytes with IL-36 and found that the genes upregulated after exposure were those genetically mapped to psoriasis but not to other diseases used as negative controls, implying that increasing levels of IL-36 have the potential to trigger psoriasis. Further analysis showed that 56% of keratinocyte genes upregulated by IL-17 (a fundamental cytokine in psoriasis pathogenesis) were also in the set upregulated by IL-36 exposure. Keratinocytes exposed to IL-36 also demonstrated further increases in IL-36 production (a positive feedback loop) and attracted TH17 cells and potentiated IL-17 production, which may help explain the continuous inflammation seen in psoriatic plaques.

The authors then analyzed mice that were pretreated with an IL-36 inhibitor and exposed to imiquimod to induce psoriasiform dermatitis. Mice so treated demonstrated significantly (30%) less acanthosis as well as less neutrophil infiltration compared to those treated with imiquimod alone. Although blunted, treatment with IL-36 blockade did not prevent psoriasiform dermatitis in this model.

Lastly, using a genetic registry, the authors identified 12 individuals who had homozygous mutations in the IL-36 receptor gene to ascertain if loss of IL-36 function might be dangerous. Reviews of their medical histories found no pattern of infections or cancers. Six of these patients underwent further testing, including normal blood tests and appropriate increase in levels of IL-17 when their peripheral blood mononuclear cells were exposed to vaccines.

IPC Expert Commentary

Future improvements in psoriasis treatment will likely rely on the discovery of new immunologic pathways involved in the pathogenesis of different disease subtypes. This study cleverly demonstrates the potential relevance of IL-36 in psoriasis pathophysiology and the immunologic health of patients who are genetically deprived of its function. Although it is far from demonstrating clinical relevance and safety, IL-36 blockade may be an avenue to consider for the next line of psoriasis treatment, especially in pustular psoriasis, where few convincingly effective treatments exist. – Colby Evans, USA

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Psoriasis and suicidality: a systematic review and meta-analysis.

Singh S, Taylor C, Kornmehl H, Armstrong AW. J Am Acad Dermatol. 2017 Sep;77(3):425-440.e2. doi: 10.1016/j.jaad.2017.05.019. Comorbidities 2018
SummaryAlthough psoriasis has been associated with a high prevalence of a wide range of psychiatric comorbidities, including all aspects of suicidality (ideation, suicidal attempts, and completed suicides), few studies have addressed the relationship between psoriasis and the latter.

In order to shed light on the epidemiological association between psoriasis and suicidality, the authors conducted a systematic review and meta-analysis of PubMed, EMBASE, PsyclNFO, and Cochrane databases. The search was limited to English-written studies and included studies published from database inception (1946) to 2017. Inclusion criteria applied were noninterventional studies, study participants 18 years or older, documented psoriasis diagnosis, and documented suicidality, which had to be a primary or secondary endpoint and assessed in conjunction with psoriasis and numerically reported.

Eighteen studies were identified with a total of 1,767,583 participants, of whom 18.6% had psoriasis. The study showed that patients with psoriasis have increased odds of all aspects of suicidality compared to the general population, with suicidal ideation the most pronounced. Patients with psoriasis are twice as likely to contemplate suicide and have a 32% higher likelihood of attempting suicide and 20% higher likelihood of completed suicide. A subanalysis demonstrated that the prevalence of suicidality presents a direct relation with the severity of the disease and that younger patients were more likely to experience suicidality than older patients, putting them especially at risk of suicidal behavior.

IPC Expert Commentary

Despite the fact that many reports have confirmed a higher prevalence of depression and anxiety among psoriatic patients, few have addressed suicidality, and many of these studies have claimed that the risk of suicidal ideation and/or suicidal behavior is not increased in this population. Nevertheless, the present study, despite some limitations, shows that psoriasis can have a substantial emotional impact on an individual, with high rates of suicidality among patients with the disease.

Besides direct effects of psoriasis (isolation, itch, sleeplessness, etc) contributing to psychiatric comorbidity in these patients, shared inflammatory pathways and/or an elevated inflammatory state provided by psoriasis may affect the development and progression of psychiatric diseases, including suicidality.

This finding has important implications in the integral management of psoriasis. Dermatologists and others involved in the care of patients with psoriasis should consider and recognize this association so that those suffering from suicidality can be identified. Then, effective interventions can be established aimed at controlling and reducing the severity of the skin disease as well as this potentially lethal comorbidity. – Nancy Podoswa, Mexico

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Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing αβ T cell clones.

Matos TR, O’Malley JT, Lowry EL, et al. J Clin Invest. 2017 Nov 1;127(11):4031-4041. doi: 10.1172/JCI93396. Epub 2017 Sep 25. Clinical trials 2018
Summary

Much has been learned in recent years about the local pathogenesis in psoriatic plaques, including the development of targeted treatments to influence the underlying biology. This study looked at plaques that were clinically resolved after treatment to assess the local T-cell population and presence of Interleukin (IL)-17, a key cytokine in the pathogenesis of psoriasis. Oligoclonal populations of T cells were analyzed to try to discern and quantify putative pathogenic T-cell clones. Skin samples were obtained from psoriatic plaques, resolved plaques (successfully treated with either etanercept or phototherapy), unaffected skin in psoriatic patients, and normal controls undergoing cosmetic procedures. High-throughput screening of the CDR3 region of the T-cell receptor and immunostaining for clonality and cytokine production were applied to these specimens. These techniques compared the same plaque before and after clearance with treatment and found oligoclonal populations of T cells in both. Clonal T cells were most common in the active plaques but were more common in the resolved plaques (93% reduction from active disease) than in normal skin of the same patient. This finding may imply that these residual T-cell clones set the stage for recurrence of disease at the same site if treatment is stopped. Further study of these clonal T cells in both active and resolved plaques demonstrated that they produce IL-17 and IL-22, key mediators of psoriasis, and that they have a psoriasis-specific TCR repertoire which was not seen in normal skin or other skin diseases.

IPC Expert Commentary

Our understanding of the cellular and cytokine activity in active psoriatic plaques has grown tremendously in the last 20 years. Furthering that understanding will require studies such as this that look at the immunologic tableau during or after treatment and in recurrence. This study establishes that populations of long-lived clonal T cells exist in active psoriatic plaques but also in resolved plaques and therefore may stand ready to reinitiate the inflammatory cascade if triggered or if treatment is withdrawn. Even in clinically resolved lesions, these clonal T cells continue to produce IL-17, indicating that they have not been destroyed or deactivated but simply suppressed by the successful treatment. As the authors point out, better understanding of these persistent clonal T cell populations could potentially lead to treatments that can kill or inactivate these populations, possibly leading to longer-term control of psoriasis. – Colby Evans, USA

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Psoriasis News

8/20/2019 10:08:00 AM
Eli Lilly and Company (NYSE: LLY) announced that Taltz® (ixekizumab) met the primary and all major secondary endpoints up to week 12 in the Phase 4 IXORA-R study, which evaluated the efficacy and safety of Taltz versus TREMFYA® (guselkumab) in people living with moderate to severe plaque psoriasis (PsO).
8/6/2019 11:36:00 AM
Celgene Corporation (NASDAQ:CELG) today announced that the U.S. Food and Drug Administration (FDA) has approved OTEZLA® (apremilast) 30 mg twice daily (BID) for the treatment of adult patients with oral ulcers associated with Behçet’s Disease.
8/1/2019 7:19:00 AM
On 25 May 2019, the World Health Assembly officially adopted the eleventh revision of the International Classification of Diseases (ICD-11). The ICD-11 will come into effect on 1 January 2022.
8/1/2019 7:09:00 AM
Samsung Bioepis Co., Ltd. today announced that the U.S. Food and Drug Administration (FDA) has approved HADLIMA™ (adalimumab-bwwd), a biosimilar referencing HUMIRA® (adalimumab)i , for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. Please see full indications and Boxed Warning for HADLIMA™, below.
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