Association between cumulative methotrexate dose and liver fibrosis in patients with a history of moderate to severe psoriasis
Today's report also covers systemic anti-psoriatic treatments, efficacy and safety of bimekizumab, and more (1,800 words, 7 minutes, 30 seconds)
The Vender on Psoriasis e-newsletter is supported by an unrestricted grant from Sun Pharma Canada
Good morning and welcome to the fourteenth issue 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
Association between cumulative methotrexate dose and liver fibrosis in patients with a history of moderate to severe psoriasis
A recent cross-sectional study published in The British Journal of Dermatology has shed new light on the relationship between methotrexate use and liver fibrosis (LF) in patients with moderate to severe psoriasis. The research, conducted in the U.K., challenges long-held concerns about methotrexate's hepatotoxic effects and offers valuable insights for dermatologists managing psoriasis patients.
The study evaluated 204 adults with a history of moderate to severe chronic plaque psoriasis, using transient elastography to assess liver stiffness measurements (LSM) as an indicator of LF. Researchers found a high prevalence of LF in the cohort, ranging from 17% to 36% depending on the LSM cutoff values used.
Surprisingly, the study found no significant association between cumulative methotrexate dose and LF. This finding contradicts historical concerns that led to recommendations for liver biopsies at certain cumulative dosing intervals. Instead, the research identified other risk factors as more predictive of LF in psoriasis patients.
Body mass index (BMI), waist circumference, metabolic syndrome, and diabetes emerged as significant predictors of higher LSM values and, consequently, more severe LF. Notably, a BMI ≥28 kg/m², when combined with diabetes and metabolic syndrome, proved to be a more sensitive indicator of moderate to severe LF than the widely used FIB-4 score.
The study's findings have important implications for clinical practice. While methotrexate remains a first-line systemic treatment for psoriasis in many parts of the world, these results suggest that patient selection based on metabolic risk factors may be more crucial than monitoring cumulative methotrexate dose when assessing LF risk.
Dr. Ruth McTighe, commenting on the study, emphasized that while the results support the lack of association between cumulative methotrexate dose and LF in psoriasis patients, physicians should consider alternative therapies for those with identified risk factors for LF. She is a dermatology resident at the University of Mississippi Medical Center in Jackson, Miss.
This research provides a new perspective on liver health monitoring in psoriasis patients undergoing methotrexate therapy. It suggests that dermatologists may need to shift their focus from cumulative methotrexate dose to patient-specific metabolic risk factors when assessing the appropriateness of methotrexate treatment and the need for additional liver health assessments.
As psoriasis treatment continues to evolve, with biologics becoming increasingly available, this study offers valuable guidance for optimizing the use of methotrexate in appropriate patient populations while minimizing unnecessary concerns about hepatotoxicity in low-risk individuals.
Comment: Dr. Ruth McTighe, a dermatology resident at the University of Mississippi Medical Center, highlights the practical implications of these findings. She emphasizes the importance of evaluating alternative therapies for psoriasis patients with identified metabolic risk factors forLF. This perspective aligns with the study’s suggestion that patient selection for methotrexate therapy should prioritize metabolic health over cumulative drug dose.
As the landscape of psoriasis treatment evolves, particularly with the advent of biologic therapies, the insights from this study are invaluable. They advocate for a more nuanced approach to methotrexate use, where patient-specific risk factors are meticulously evaluated to optimize treatment outcomes while minimizing the risk of hepatotoxicity. This approach not only enhances patient safety but also ensures that methotrexate remains a viable and effective option for those without significant metabolic risks.
In conclusion, this study presents a paradigm shift in the management of liver health in psoriasis patients treated with methotrexate. By prioritizing metabolic risk factors over cumulative drug dose, dermatologists can make more informed decisions, potentially improving patient outcomes and reducing unnecessary interventions. This research marks a significant step forward in the personalized treatment of psoriasis, promising better health and quality of life for patients.
Does systemic anti-psoriatic treatment impact the risk of cardiovascular disease?
This comprehensive review (Dermatol Ther (Heidelb) 2024; 14:303–321) examined the impact of systemic anti-psoriatic treatments on cardiovascular disease (CVD) risk, focusing on cardiovascular imaging studies. The authors analyzed 24 studies, including 16 observational cohort studies and eight randomized controlled trials (RCTs), investigating various imaging biomarkers as surrogates for subclinical atherosclerosis.
The observational studies, encompassing 1,406 patients with psoriasis and/or psoriatic arthritis, predominantly explored the effects of biologic therapies. Most studies reported significant improvements or reduced progression of cardiovascular imaging biomarkers during follow-up. Notably, anti-TNF treatments were associated with improved aortic vascular inflammation and reduced psoriasis severity after one year, independent of traditional CVD risk factors.
Imaging modalities used as surrogates for subclinical atherosclerosis included vascular inflammation assessment, myocardial dysfunction evaluation, endothelial dysfunction markers, coronary, carotid, brachial, and femoral atherosclerosis measurements, coronary artery plaque burden quantification, and arterial stiffness assessment.
The RCTs, involving 3,042 patients, primarily focused on the effects of IL-17 inhibitors. These studies generally showed no significant differences in vascular inflammation or coronary artery calcium scores between treatment and placebo groups. However, the authors note that the short duration of these trials (12 to 52 weeks) may limit their ability to detect meaningful changes in atherosclerosis progression.
The review highlights the potential of anti-inflammatory therapies in reducing CVD risk in psoriasis patients. It emphasizes the concept of the “psoriatic march,” where chronic systemic inflammation in psoriasis enhances endothelial dysfunction, leading to atherosclerosis and cardiovascular events.
While the majority of studies suggest a beneficial effect of systemic anti-psoriatic treatments on subclinical atherosclerosis, the authors caution that the heterogeneity in study designs, small sample sizes, and varying follow-up periods limit definitive conclusions. They stress the need for larger, long-term studies to establish causal relationships between anti-psoriatic treatments and reduced CVD risk.
This review provides valuable insights for dermatologists and cardiologists managing psoriasis patients with elevated CVD risk. It underscores the potential of cardiovascular imaging biomarkers in assessing treatment efficacy beyond skin clearance, potentially guiding more personalized therapeutic approaches in this high-risk population.
Comment: A key concept emphasized in the review is the ‘psoriatic march’ which describes the pathway from chronic systemic inflammation in psoriasis to endothelial dysfunction, atherosclerosis, and ultimately cardiovascular events. This concept reinforces the importance of addressing systemic inflammation in psoriasis to mitigate cardiovascular risk.
Despite the promising findings, the review highlights several limitations, including heterogeneity in study designs, small sample sizes, and varying follow-up periods. These factors hinder the ability to draw definitive conclusions regarding the causal relationship between anti-psoriatic treatments and reduced CVD risk. The authors call for larger, long-term studies to better establish these relationships and guide clinical practice.
This review provides critical insights for dermatologists and cardiologists managing psoriasis patients with elevated CVD risk. It underscores the potential of cardiovascular imaging biomarkers in assessing treatment efficacy beyond skin clearance, paving the way for more personalized therapeutic approaches. As systemic anti-psoriatic treatments continue to evolve, this review highlights the need for an integrated approach to managing both psoriasis and cardiovascular health, ultimately improving patient outcomes in this high-risk population.
The efficacy and safety of bimekizumab for plaque psoriasis: An expert consensus panel review
In a comprehensive expert consensus panel, dermatologists have provided new guidance on the use of bimekizumab for treating moderate to severe plaque psoriasis (Dermatol Ther (Heidelb) 2024; 14:323–339). The panel, comprised of nine leading experts in psoriasis management, conducted a thorough literature review and developed 14 consensus statements using a modified Delphi process.
Bimekizumab, a monoclonal antibody that selectively inhibits both IL-17A and IL-17F, has shown remarkable efficacy in clinical trials. Over 50% of patients achieve Psoriasis Area and Severity Index (PASI) 100 at the end of 16 weeks of treatment, surpassing the performance of other biologics.
The panel emphasized the unmet need for additional psoriasis treatments, noting that many patients continue to search for regimens offering long-term disease control. They highlighted bimekizumab's rapid onset of action and sustained efficacy, with some patients achieving PASI 90 as early as week 4.
Regarding safety, the experts noted that bimekizumab has a favourable safety profile comparable to other IL-17 inhibitors. The most common adverse event is oral candidiasis, which is generally mild to moderate and manageable. The panel recommended monitoring for inflammatory bowel disease, as IL-17 inhibition has been associated with exacerbation of Crohn's disease in some cases.
The consensus statements also addressed the use of bimekizumab in special populations. The experts agreed that bimekizumab is effective for treating psoriatic arthritis and may be considered for patients with both skin and joint involvement. They also noted its potential efficacy in difficult-to-treat areas such as the scalp, nails, and palmoplantar regions.
The panel discussed the importance of individualized treatment decisions, considering factors such as comorbidities, prior treatment history, and patient preferences. They emphasized the need for shared decision-making between physicians and patients when selecting biologic therapies.
This expert consensus provides valuable guidance for dermatologists and rheumatologists in optimizing the use of bimekizumab for psoriasis treatment. As more real-world data becomes available, these recommendations may be further refined to ensure the best outcomes for patients with moderate to severe plaque psoriasis.
Comment: This expert consensus provides invaluable insights and practical guidance for the use of bimekizumab in treating moderate to severe plaque psoriasis. By addressing both efficacy and safety, as well as considerations for special populations and individualized treatment, the panel’s recommendations offer a comprehensive framework for optimizing patient care. As more data becomes available, these guidelines will help ensure that patients receive the most effective and appropriate treatments, improving outcomes and quality of life for those living with psoriasis.
If you find the contents of this newsletter interesting, please check out the Vender on Psoriasis podcast. It’s available at Apple iTunes, Stitcher, Spotify, or wherever you get your podcasts.
Dr. Ron Vender is a Hamilton-based certified dermatologist with over 30 years of clinical practice experience and over 100 clinical trials in psoriasis. He is founder and director of Dermatrials Research Incorporated and Venderm Consulting, specializing in treatments and management solutions for individuals with psoriasis.
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