- Il presente studio ha valutato l’associazione tra apremilast e infiammazione vascolare aortica alla tomografia ad emissione di positroni/tomografia computerizzata con 18F-FDG (FDG-TC-PET), marcatori cardiometabolici (obiettivi primari a 16 settimane) e composizione del tessuto adiposo addominale.
- I risultati di questo trial non randomizzato suggeriscono che apremilast abbia un’associazione neutrale con l’infiammazione aortica, associazioni variabili, ma generalmente positive, con un sottogruppo di biomarcatori cardiometabolici e riduzioni del tessuto adiposo viscerale e sottocutaneo, con un effetto benefico globale per i pazienti con malattia cardiometabolica e psoriasi.
Abstract
Importance
Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss.
Objective
To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition.
Design, setting, and participants
A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites in the United States. A total of 101 patients with moderate to severe psoriasis were screened, 70 enrolled, 60 completed week 16, and 39 completed week 52.
Intervention
Apremilast, 30 mg, twice daily.
Main outcomes and measures
Aortic vascular inflammation (measured by FDG-PET/CT), 68 cardiometabolic biomarkers, and abdominal fat composition (measured by CT) at week 16 and week 52 compared with baseline.
Methods
Data from SPIRIT-P1 and SPIRIT-P2 were analysed to evaluate the effect of ixekizumab on achievement of low disease activity (LDA) and remission with the minimal disease activity (MDA) and very low disease activity (VLDA) composite, Disease Activity index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score, GRAppa Composite ScorE and modified Composite Psoriatic Disease Activity Index (mCPDAI). Performance was compared by quantifying residual symptom burden and the impact of structural damage and functional disability.
Results
The mean (SD) age of the 70 patients was 47.5 (14.6) years, 54 were male (77.1%), 4 were Black (5.7%), and 58 were White (82.9%). There was no change in aortic vascular inflammation at week 16 (target to background ratio, -0.02; 95% CI, -0.08 to 0.05; p = 0.61) or week 52 (target to background ratio, -0.07; 95% CI, -0.15 to 0.01; p = 0.09) compared with baseline. At week 16, potentially beneficial decreases in interleukin 1b, valine, leucine, isoleucine, fetuin A, and branched-chain amino acids were observed. At week 52 compared with baseline, potentially beneficial decreases in ferritin, β-hydroxybutyrate, acetone, and ketone bodies, with an increase in apolipoprotein A-1, were observed, but there was a reduction in cholesterol efflux. There was an approximately 5% to 6% reduction in subcutaneous and visceral adiposity at week 16 that was maintained at week 52.
Conclusions and relevance
The findings of this nonrandomized clinical trial suggest that apremilast has a neutral association with aortic vascular inflammation, variable but generally beneficial associations with a subset of cardiometabolic biomarkers, and associations with reductions in visceral and subcutaneous fat, indicating that the drug may have an overall benefit for patients with cardiometabolic disease and psoriasis.
Trial registration
ClinicalTrials.gov Identifier: NCT03082729.