Association of Pso with incident VTE and PVD
Today’s report also covers risk factors for Dx of psoriatic arthritis, the AMAGINE-2 and -3 trials, and more (1,400 words, 7 minutes 5 seconds)
The Vender on Psoriasis e-newsletter is supported by an unrestricted grant from Sun Pharma Canada
Good morning and welcome to the first of a new series of Special Reports: Skin Spectrum Weekly presents “Vender on Psoriasis.” This series is based on Dr. Vender’s popular column appearing in each edition of The Chronicle of Skin & Allergy, which offers expert commentary and opinions on current clinical developments in Pso. We’d love to get your feedback and suggestions and invite you to be in touch. Please write to us at health@chronicle.org
While psoriasis, venous thromboembolism (VTE), and peripheral vascular disease (PVD) share similar mechanisms involving chronic inflammation, the associations between psoriasis and VTE or PVD remain unclear. The authors of this meta-analysis, published in JAMA Dermatology (doi:10.1001/jamadermatol.2021.4918) performed a literature search to identify relevant publications; 13 studies met the selection criteria for qualitative review, and nine of these studies were acceptable for quantitative analysis. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratios (HRs) with the corresponding confidence intervals for incident VTE and PVD. Subgroup analyses for arthritis status, psoriasis severity, sex, and geographic location were also performed.
The 13 cohort studies included 12,435,982 participants. The analysis showed a significantly increased risk for incident VTE (pooled HR, 1.26; 95%CI, 1.08-1.48) and PVD (pooled HR, 1.27; 95%CI, 1.16-1.40) among patients with psoriasis. Subgroup analyses showed an increased risk for incident VTE among participants with psoriatic arthritis (pooled HR, 1.24; 95%CI, 1.01-1.53), women (pooled HR, 1.89; 95%CI, 1.36-2.61), and those in Asia (pooled HR, 2.02; 95%CI, 1.42-2.88) and Europe (pooled HR, 1.28; 95%CI, 1.06-1.53).
The authors conclude there is an increased risk for incident VTE and PVD in patients with psoriatic disease. They note that risk factors such as obesity, physical inactivity, smoking and varicose veins should be identified and treated in patients with psoriasis, and hormone-related therapies should be prescribed with caution.
Comment: With this increased risk of VTE and PVD in patients with psoriatic disease, the list continues to grow for comorbidities associated with this devastating chronic inflammatory immune-mediated skin condition. The interest may have stemmed from the advent of newer medications such as JAK inhibitors used to treat psoriatic arthritis. As of yet, there are no JAK inhibitors approved to treat skin psoriasis but there are drugs available in this class to treat psoriatic disease. Already there is a risk with JAK inhibitors for VTE, and this is certainly concerning. The prescribing physician must be aware of the rare side effects of this class of medication when treating patients with psoriatic arthritis and add this to the risk that already exists as a baseline in these patients, as this study confirmed.
Risk factors for diagnosis of psoriatic arthritis, psoriasis, rheumatoid arthritis, and ankylosing spondylitis: A set of parallel case-control studies
In this study in The Journal of Rheumatology (Aug. 2021, jrheum.210006; DOI: https://doi.org/10.3899/jrheum.210006), researchers utilized four parallel case-control studies to compare potential risk factors for psoriatic arthritis (PsA), psoriasis, rheumatoid arthritis (RA) and ankylosing spondylitis (AS). They used data collected between 1994 and 2015.
Patients with incident PsA (n=7,594), psoriasis (n=111,375), RA (n=28,341), and AS (n=3, 253) were identified and matched to controls (75,930, 1,113,345, 282,226, and 32,530 respectively). The median age of diagnosis was 48 years. Analysis showed that there were some shared and some different risk factors: PsA was associated with obesity, pharyngitis and skin infections; PsA and psoriasis were associated with obesity and moderate alcohol intake; PsA and AS were associated with uveitis; and PsA and RA were associated with preceding gout. Current smoking, former moderate drinking, anemia, osteoporosis and inflammatory bowel disease were associated with RA and AS. According to the authors, all individuals had former or current smoking as a risk factor. The use of statins was inversely associated with all four diseases.
Comment: This is an interesting analysis of risk factors for developing psoriatic arthritis. There are items mentioned that are certainly unusual such as pharyngitis and skin infections as a risk factor for arthritis. We know comorbidities are associated with inflammatory disease such as psoriasis and psoriatic arthritis but interesting conditions such as gout are innovative and unusual to discover. Quite often the risk factors for psoriatic arthritis include scalp psoriasis, nail psoriasis, gluteal psoriasis, as well as genital psoriasis. This adds more clues as to the risk factors that can be involved. However, it is suggested that all patients be screened for arthritis when they have psoriasis. Occasionally psoriatic arthritis is not associated with psoriasis and ankylosing spondylitis or rheumatoid arthritis. More commonly osteoarthritis is associated with psoriasis especially in the elderly population. However, knowing that psoriasis and psoriatic arthritis are associated diseases, it is important that we continue to screen our patients to provide better care for them.
AMAGINE-2 and -3: Complete clearance and PASI response for brodalumab and ustekinumab by previous Tx history
The authors of this study note that some patients with psoriasis may experience inadequate response to therapy. The response is partly dependent upon disease severity, and patients who repeatedly fail therapy may have limited options (J Eur Acad Dermatol Venereol 2021 Oct; 35(10):2034-2044; e-pub Jul 24, 2021: doi: 10.1111/jdv.17433). In the study, they conclude that patients treated with brodalumab showed higher levels of complete clearance and greater cumulative benefit over time compared to ustekinumab in patients with moderate-to-severe psoriasis, regardless of the patients’ prior treatment experience.
The researchers analyzed data from two phase 3, randomized, controlled, 52-week AMAGINE trials of brodalumab for patients who achieved complete clearance as measured by PASI 100, and then categorized them by prior treatment subgroup (naïve to systemic and biologic treatment, treated with a systemic but biologic-naïve, biologic-treated without failure, and biologic-treated with failure).
Results showed the 52-week cumulative incidence of patients achieving PASI 100 were consistently higher for brodalumab vs. ustekinumab across the treatment pathway subgroups (76% vs. 58% in systemic/biologic-naïve patients, 78% vs. 55% in systemic-treated/biologic-naïve patients, 75% vs. 41% in biologic-treated patients without failure, and 70% vs. 30% in biologic-treated patients with failure). They also noted that rates of inadequate response were lower with brodalumab compared to ustekinumab across all subgroups. Cumulative treatment benefit was also higher for all subgroups treated with brodalumab compared to those treated with ustekinumab.
Comment: Brodalumab is a commonly used anti-IL-17 agent. It is different from other anti-IL-17 inhibitors by acting on the receptor. This seems to increase the efficacy without jeopardizing the safety of this agent. With an every two week dosing that remains consistent throughout induction and maintenance phases, it is simple to administer. Although in North America it is not approved for psoriatic arthritis, it is often used for its indication of moderate to severe psoriasis. Its efficacy is superior to p40 agents such as ustekinumab. This study confirms that point. No direct head-to-head study has been done comparing brodalumab with other anti-IL-17 agents such as ixekizumab or secukinumab. The best comparative study, head to head, would be brodalumab versus bimekizumab. There are advantages and disadvantages to both. A black box warning creates a dark cloud over brodalumab. Unfortunately, it has been tainted with the suicides that occurred in phase 3 clinical studies which were shown on further analysis to be unrelated to this drug.
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Upcoming events and learning opportunities
Registration is open for the 2022 Indigenous Skin Spectrum Summit which will be held on Sat. June 11, 10:00 AM to 2:00 PM EDT.
First held in March 2021, the Indigenous Skin Spectrum Summit is a special session of the Skin Spectrum Summit addressing specific challenges in treating Canada’s Indigenous community.
The second Indigenous Skin Spectrum Summit will be held during National Indigenous History Month in Canada. As we recognize the history, heritage and diversity of First Nations, Inuit and Métis peoples in Canada, we must also acknowledge the persistent health gaps that these communities experience.
Learning objectives for the event are:
Be able to identify skin disorders in richly pigmented skin and recognize prevalent dermatologic diseases in Indigenous populations
Improve diagnosis of dermatologic conditions in First Nations, Inuit, and Métis patients
Understand how historical and systemic factors contribute to health gaps for Indigenous people
Understand how NIHB program coverage works for treating skin conditions
Adopt an experience-based approach to more effectively manage Indigenous patients and the unique treatment challenges they may face
Register for the 2022 Indigenous Skin Spectrum Summit here: