FOREMOST trial: Apremilast shows promise in early oligoarticular psoriatic arthritis management

The FOREMOST trial results published in the Annals of the Rheumatic Diseases demonstrated the potential of apremilast in significantly improving outcomes for patients in the early stages of oligoarticular psoriatic arthritis (PsA). 

Conducted across multiple centers, the trial included 308 participants with symptom durations of five years or less. Patients had between two to eight active joints affected by PsA and were randomized in a 2:1 ratio to receive apremilast 30 mg twice daily or a placebo for 24 weeks.  

The study results revealed that 33.9% of patients treated with apremilast reached minimal disease activity (MDA) for sentinel joints by week 16, compared to only 16% in the placebo group. When examining all joints, 21.3% of apremilast recipients achieved MDA, outpacing the 7.9% in the placebo cohort. Beyond joint health, apremilast demonstrated broader benefits. Patients reported greater reductions in clinical disease activity and improvements in skin involvement, further underscoring its potential as a comprehensive treatment option. 

PsA is a prevalent clinical condition that significantly diminishes health-related quality of life and is associated with serious medical comorbidities. The disease is driven by chronic inflammatory processes at both local and systemic levels. Current biologic therapies focus on targeting specific inflammatory mediators, such as tumor necrosis factor-α (TNF-α), within the broader inflammatory signaling cascade. To intervene earlier in the inflammatory response or target upstream mechanisms, researchers have investigated the potential of phosphodiesterase-4 (PDE4) inhibitors. PDE4 plays a key role in degrading cyclic adenosine monophosphate (cAMP), a critical intracellular messenger that regulates a complex network of pro-inflammatory and anti-inflammatory mediators. By inhibiting PDE4, intracellular cAMP levels increase, leading to modulation of these mediators in both immune and non-immune cells. 

Apremilast, an orally administered PDE4 inhibitor, has demonstrated the ability to modulate a wide spectrum of inflammatory mediators involved in psoriasis and PsA. Its effects include reducing the expression of pro-inflammatory factors such as inducible nitric oxide synthase, TNF-α, and interleukin (IL)-23, while simultaneously enhancing anti-inflammatory cytokines like IL-10. This dual action supports a rebalancing of the inflammatory environment, offering a promising approach to managing PsA and restoring homeostasis. 

The FOREMOST trial marks a significant milestone as the first randomized controlled study focused on early oligoarticular PsA. Its findings suggest that timely intervention with apremilast can alter the trajectory of the disease, providing better outcomes for patients with this often-overlooked subtype of PsA. These results may influence future treatment strategies, offering a much-needed framework for rheumatologists seeking effective options for early oligoarticular PsA. The trial highlights the importance of early diagnosis and targeted therapy in achieving meaningful improvements in disease management. 

References 

1. Vasandani J, Pinter A, Merola JF, Kavanaugh A, Reddy J, Wang R, et al. Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial. Ann Rheum Dis. 2024 Oct 21;83(11):1480-1488.  
2. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012 Jun 15;83(12):1583-90.