Severe Psoriasis Linked To Increased Risk of Mortality

MedicalResearch.com Interview with:

Megan H. Noe MD, MPH Clinical Instructor and Post-Doctoral Research Fellow University of Pennsylvania, Department of Dermatology Perelman Center for Advanced Medicine Philadelphia, PA 19104

Dr. Megan Noe

Megan H. Noe MD, MPH
Clinical Instructor and Post-Doctoral Research Fellow
University of Pennsylvania, Department of Dermatology
Perelman Center for Advanced Medicine
Philadelphia, PA 19104

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous research has shown that patients with psoriasis have higher rates of hypertension, diabetes, cardiovascular disease and chronic kidney disease that may put them at an increased risk of death.

Our research found that patients with psoriasis covering more than 10% of their body had almost double the risk of death than people of the same age with similar medical conditions, but without psoriasis.

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Cardiovascular Events Rise With Increased Duration of Psoriasis

MedicalResearch.com Interview with:

Alexander Egeberg, MD PhD Gentofte Hospital Department of Dermatology and Allergy Kildegårdsvej 28 2900 Hellerup Denmark 

Dr. Egeberg

Alexander Egeberg, MD PhD
Gentofte Hospital
Department of Dermatology and Allergy
Kildegårdsvej 28
2900 Hellerup
Denmark

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The majority cardiovascular events in psoriasis occur in patients at low risk by traditional cardiovascular risk calculators. It has been speculated that long-term exposure to systemic inflammation may increase the risk of adverse cardiovascular outcomes. Therefore, clinically available historical features such as disease duration may identify those at higher risk for cardiovascular disease.

Using a translational epidemiological approach, combining 18F-fluorodeoxyglucose positron emission tomography computed tomography scanning with nationwide epidemiological data of more than four million individuals, we provide the first convincing evidence to suggest a detrimental effect of psoriasis duration on cardiovascular disease beyond traditional cardiovascular risk factors, even in patients deemed “low-risk” by conventional risk scores. We found a 1% increase in future major adverse cardiovascular event risk per additional year of disease duration. This finding has an effect size similar to smoking, a well-established cardiovascular risk factor.

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Secukinumab Provides Sustained Improvements in Dermatology-Specific Quality of Life in Moderate to Severe Psoriasis Patients Through 3 Years of Treatment

MedicalResearch.com
Eric Hughes
Global Development Franchise Head Immunology & Dermatology
Novartis

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Psoriasis is a chronic immune-mediated inflammatory disease that negatively impacts patients’ quality of life (QOL); therefore QOL outcomes are increasingly recognized as an important measure of efficacy in psoriasis, complementing traditional measures of severity such as the Psoriasis Area and Severity Index (PASI).

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), exhibits significant efficacy in the treatment of moderate-to-severe psoriasis, ankylosing spondylitis and psoriatic arthritis, demonstrating a rapid onset of action and a favorable safety profile.

Biologic therapies for psoriasis have previously been associated with a fall-off in efficacy over time; accordingly, extended follow-up is required to adequately evaluate novel therapeutic strategies like IL-17A inhibition. Recently, results from the extension of the SCULPTURE secukinumab trial showed that high responses initially achieved with secukinumab at year 1 in the SCULPTURE study were sustained over time up to 3 years with no new or unexpected safety concerns. In this analysis, we examined whether the sustained efficacy observed in SCULPTURE up to 3 years was translated into sustained effect of secukinumab on patient’s QOL measured by the Dermatology Life Quality Index (DLQI) questionnaire.

SCULPTURE, a multi-center extension study, was conducted with subjects who completed 52 weeks of treatment. Subjects were randomized into two maintenance dosing regimens; a fixed-interval schedule of secukinumab 300 mg every 4 weeks (Fixed interval dosing regimen (FI) cohort), and secukinumab retreatment-as-needed (Retreatment as needed (RAN) cohort), in which subjects received placebo until start of relapse, at which time secukinumab 300 mg every 4 weeks was re-initiated.

The analysis using as-observed data showed that at Year 3, improvements in the total score on DLQI was well sustained in both FI and RAN cohorts. Approximately two-thirds of the subjects in the FI cohort reported no impact of skin disease on QOL (corresponding to a score of 0 or 1 on DLQI). The proportion of patients in the RAN cohort reporting no impact of the disease on their QOL was well sustained through 3 years but remained consistently lower than those observed in the FI cohort. The results for each subscale of the DLQI questionnaire were consistent with those with DLQI total score i.e. showing high and sustained proportions of patients reporting no impact of the disease on different domains of health-related QOL in the two secukinumab cohorts with greater effect in the FI cohort compared to the RAN cohort.

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Secukinumab (Cosentyx) Provides Greater Improvement in Quality of Life, Work Productivity, and Daily Activity Than Ustekinumab (Stelara) in Moderate To Severe Psoriasis

MedicalResearch.com Interview with:
Eric Hughes, Global Head of Development, Immunology & Dermatology

Novartis Pharma AG
Basel, Switzerland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is well established that psoriasis negatively affects quality of life and work productivity. However, how the treatments affect psoriasis severity (based on skin clearance, itch, pain and scaling symptoms), health-related quality of life (HRQOL), work productivity, and daily activity directly or indirectly (via other factors) are still largely unknown.

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), exhibits significant efficacy in the treatment of moderate-to-severe psoriasis, ankylosing spondylitis, and psoriatic arthritis, demonstrating a rapid onset of action and a favorable safety profile.

In CLEAR, a Phase 3b head-to-head study versus ustekinumab, secukinumab demonstrated sustained superior efficacy in clearing skin through Week 52, greater improvement in symptoms and HRQOL, greater relief of work and activity limitations, and a comparable safety profile. In this sub-analysis of the CLEAR study, Novartis was interested in examining the relationships among multiple variables that are thought to be important to patients with psoriasis. The direct and indirect (i.e. mediated) effects of treatment (secukinumab or ustekinumab) on psoriasis severity and patients’ HRQOL, work productivity, and daily activity were examined. The evaluation was conducted using structural equation modeling (or path analysis) and compared these relationships for secukinumab versus ustekinumab at 16 and 52 weeks. Structural equation modeling or path analysis is a statistical method that models the direct and indirect relationship between multiple patient-relevant outcomes simultaneously.

Goodness-of-fit statistics for all models were excellent confirming the robustness of the results. Results at Week 16 and at Week 52 for different Psoriasis Area and Severity Index (PASI) response categories (e.g. PASI 75, PASI 90, PASI 100) indicated that psoriasis treatment indirectly affected HRQOL and work productivity and daily activity, measured with the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment (WPAI) questionnaires, respectively.

Actually, greater effect of secukinumab over ustekinumab on DLQI was mediated by greater improvement of secukinumab in PASI response as well as by greater improvement in psoriasis-related symptoms (itch, pain and scaling). Greater effect of secukinumab over ustekinumab on work productivity and daily activity was mediated by greater improvement of secukinumab in psoriasis-related symptoms.

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Psoriasis Patients At Higher Risk for Multiple Pathological Fractures

MedicalResearch.com Interview with:
Dr. Jonathan L. Silverberg MD PhD MPH

Assistant Professor in Dermatology
Medical Social Sciences and Preventive Medicine
Northwestern University, Chicago, Illinois

Dr. Jonathan L. Silverberg MD PhD MPH Assistant Professor in Dermatology Medical Social Sciences and Preventive Medicine Northwestern University, Chicago, Illinois

Dr. Jonathan Silverberg

Response: Psoriasis is associated with a number of potential risk factors for developing osteoporosis and pathological fractures, including including low vitamin D, chronic inflammation, higher rates of cigarette smoking and systemic corticosteroid usage. We hypothesized that adults with psoriasis have higher rates of osteoporosis and pathological fractures.

We examined data from the 2002-2012 National Inpatient Sample, which contains a representative 20% sample of all hospitalizations in the United States. We found that psoriasis was associated with higher odds of osteopenia, osteoporosis, osteomalacia, ankylosing spondylitis, and pathological fractures. In particular, psoriasis was associated with vertebral, pelvic, femoral and tibial/fibular fractures. The associations between psoriasis and pathological fractures were more pronounced in women than men.

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Psoriasis: Efficacy and Safety of Guselkumab vs Humira for Moderate to Severe Disease

MedicalResearch.com Interview with:

Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center

Dr. Blauvelt

Andrew Blauvelt, M.D., M.B.A.
President and Investigator
Oregon Medical Research Center

 MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Findings from the Phase 3 VOYAGE 1 study showed that patients with moderate to severe plaque psoriasis receiving guselkumab, an human anti-interleukin (IL)-23 monoclonal antibody, achieved significant improvement in skin clearance and in comparison with Humira® (adalimumab), a TNF blocker.  The Phase 3 study and head-to-head analysis of guselkumab vs. adalimumab showed the significant and durable efficacy of guselkumab as maintained through one year when compared with adalimumab, and the robust efficacy of this novel IL-23 targeted therapy in meeting all primary and major secondary endpoints.

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Musculoskeletal Symptoms May Mark Onset of Arthritis in Psoriasis Patients

MedicalResearch.com Interview with:

Lihi Eder MD PhD Rheumatologist, Women’s College Hospital Scientist, Women’s College Research Institute Assistant Professor of Medicine, University of Toronto Toronto, ON, Canada

Dr. Lihi Eder

Lihi Eder MD PhD
Rheumatologist, Women’s College Hospital
Scientist, Women’s College Research Institute
Assistant Professor of Medicine, University of Toronto
Toronto, ON, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There significant delays in the diagnosis of psoriatic arthritis (PsA) among patients with psoriasis. Many patients with psoriasis experience musculoskeletal symptoms. The majority of them do not have PsA, but other non-inflammatory conditions such as fibromyalgia or osteoarthritis.

In this study, we aimed to assess whether the presence and the degree of musculoskeletal symptoms in psoriasis patients predict the development of psoriatic arthritis. We analyzed a cohort of 410 psoriasis patients who were followed over a period of 9 years. These patients did not have arthritis at baseline. The patients were assessed annually by a rheumatologist for signs of PsA. A total of 57 patients developed psoriatic arthritis during the follow-up period.
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Guselkumab Potentially Increases Treatment Choices For Psoriasis

MedicalResearch.com Interview with:

Prof. Dr. med. Kristian Reich Dermatologie, Allergologie Psoriasis- und Neurodermitis-Trainer Hamburg

Prof.  Kristian Reich

Prof. Dr. med. Kristian Reich
Dermatologie, Allergologie
Psoriasis- und Neurodermitis-Trainer
Hamburg

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Ustekinumab is an antibody against the p40 molecule shared by IL-12 and IL-23. The antibody shows a favorable benfit-risk profile in the treatment of psoriasis. IL-23 is regarded a key driver in psoriasis pathology. It is speculated that antibodies against the IL-23-specific subunit p19 may produce even higher levels of clinical response than ustekinumab or the anti-TNF antagonist adalimumab. Guselkumab is the first IL-23p19 antibody to publish phase III data in psoriasis.   
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Guselkumab Bests Adalimumab in Psoriasis Study

MedicalResearch.com Interview with:

Andrew Blauvelt, M.D., M.B.A. President and Investigator Oregon Medical Research Center Portland, OR 97223

Dr. Andrew Blauvelt

Andrew Blauvelt, M.D., M.B.A.
President and Investigator
Oregon Medical Research Center
Portland, OR 97223

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Findings from the guselkumab Phase 3 VOYAGE 1 study showed that patients with moderate to severe plaque psoriasis receiving the anti-interleukin (IL)-23 monoclonal antibody (mAb) achieved significant improvements in skin clearance compared with patients receiving placebo and patients receiving Humira® (adalimumab), a TNF blocker. The Phase 3 study and head-to-head analysis of guselkumab vs. adalimumab in the treatment of moderate to severe plaque psoriasis also showed the significant efficacy of guselkumab maintained through week 48 compared with adalimumab, and the robust efficacy of guselkumab in meeting all primary and major secondary endpoints.

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Psoriasis Associated With Increased Risk of Avascular Bone Death

MedicalResearch.com Interview with:

Psoriasis

Psoriasis

Hsien-Yi Chiu, MD/
Tsen-Fang Tsai, MD

Department of Dermatology, National Taiwan University Hospital
Taipei, Taiwan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Psoriasis is a chronic, immune-mediated disorder, characterized by red, itchy and scaly skin patches. Over the past several years, accumulating research had shown the effects of psoriasis go far deeper than the skin and psoriasis is associated with multiple comorbidities.

Psoriasis shares the inflammatory pathways and several contributing factors with avascular necrosis (AVN), a bone disease presented with death of trabecular bone and collapse of the bony structure. However, previous studies mostly focus on evaluation the increased risk of cardiovascular diseases in patients with psoriasis. No large scale studies have previously explored a potential association between psoriasis and AVN.

Our nationwide population-based cohort study investigated this risk in 28268 patients with psoriasis registered in the Taiwan National Health Insurance Research Database. The patients were matched, by age and sex, with 113072 controls without psoriasis. Both the patients and controls were followed to identify those who subsequently diagnosed with an AVN. The results showed that psoriasis was associated with a disease severity–dependent increase in avascular necrosis risk. Moreover, AVN risk was positively associated with male sex, age younger than 30 years, corticosteroid use, severe psoriasis, and concomitant psoriatic arthritis. People with severe psoriasis were 3 times more likely to develop AVN compared with the control group.

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