A recent study has identified obesity as a significant contributor to the reduced long-term efficacy of biologic therapies in patients with severe plaque psoriasis, highlighting the need for more personalized treatment strategies.
Study Overview
Conducted at Gachon University Gil Medical Center in Incheon, South Korea, this cross-sectional study analyzed data from 87 adult patients with severe plaque-type psoriasis. The treatment period spanned January 2012 to December 2022.
At study entry, all patients had a Psoriasis Area and Severity Index (PASI) score greater than 10 and body surface area (BSA) involvement exceeding 10%, despite having undergone conventional therapies for at least three months. All patients received biologic treatment for a minimum of 24 months. Data analysis took place from December 2023 to September 2024.
Treatment resistance was defined as failure to maintain a 75% improvement in PASI score (PASI 75) and the need to switch biologics due to loss of efficacy within the 24-month treatment period.
Key Findings
Of the 87 patients, 16 (18.4%) were classified as treatment-resistant, having required a switch to alternative biologics due to diminished effectiveness. Among all the clinical variables assessed, obesity—defined as a body mass index (BMI) of 25 or higher—was the only independent factor significantly associated with biologic resistance. Other variables, such as baseline disease severity or the duration of psoriasis prior to biologic therapy initiation, showed no significant differences between the treatment-resistant and treatment-sustained groups.
To better understand why biologics may be less effective in patients with obesity, researchers performed spatial transcriptomic analysis on skin samples from six individuals who had not yet started biologic treatment. These samples were analyzed alongside publicly available single-cell RNA sequencing data using advanced genetic tools to identify which immune pathways were most active in the affected skin.
The analysis identified increased transcriptional activity in epidermal clusters 2, 3, and 8, as well as dermal inflammatory cluster 5. These areas showed signs of heightened inflammation, driven by pathways like IL-17, IL-36, Th1/Th2 responses, and toll-like receptors.
These findings suggest that an overactive innate immune response in the skin, particularly involving neutrophils, may interfere with how well biologics work over time. Since current biologic treatments mainly target a different part of the immune system, this could explain why some patients—especially those with obesity—don’t get lasting results.
Clinical Implications
This study underscores the importance of considering obesity as a modifiable risk factor when selecting and managing biologic therapies for psoriasis. It also supports potentially incorporating therapies that target innate immune pathways alongside traditional biologic treatments.
As precision medicine continues to advance, clinicians may need to tailor treatment strategies to account for patient-specific factors like BMI, immune pathway profiles, and underlying inflammatory signatures to optimize outcomes for individuals with severe plaque psoriasis.
Sources:
- Association of Obesity and Innate Immune Markers with Resistance to Biologic Therapy in Psoriasis. (n.d.). JAMA Dermatology. https://jamanetwork.com/journals/jamadermatology/article-abstract/2832061
- Study Links Obesity to Biologic Failure in Psoriasis. (n.d.). medscape.com. https://www.medscape.com/viewarticle/study-links-obesity-biologic-failure-psoriasis-2025a1000893
