The phase IV FOREMOST trial demonstrated the efficacy of apremilast in treating early oligoarticular psoriatic arthritis, according to a new study.
In the randomized, placebo-controlled trial, published in Annals of the Rheumatic Diseases, researchers enrolled 308 patients with early oligoarticular psoriatic arthritis (PsA), defined as symptom duration ≤ 5 years and > 1 but ≤ 4 swollen and tender joints. The patients were randomly assigned 2:1 to receive 30 mg of apremilast twice daily (n = 203) or placebo (n = 105) for 24 weeks.
The FOREMOST trial was conducted at 80 sites across 10 countries from December 2018 to December 2022. Eligible patients had PsA according to the Classification Criteria for Psoriatic Arthritis, with > 1 but ≤ 4 swollen and tender joints (66/68 joint count). The majority of patients had ≤ 4 active joints at baseline.
Additional baseline characteristics included:
- Mean cDAPSA score: 16.2
- Mean PASDAS score: 4.9
- Mean body surface area affected: 6.7%
- Mean HAQ-DI score: 1.0
- Approximately 90% of patients had ≤ 4 active joints at baseline.
The researchers found that significantly more patients achieved minimal disease activity after receiving apremilast compared with placebo. At week 16, 33.9% of the apremilast-treated patients achieved minimal disease activity (MDA)-Joints response based on sentinel joints (primary endpoint) compared with 16.0% of the placebo-treated patients (treatment difference = 18.5%, 95% confidence interval [CI] = 8.9%–28.1%, P = .0008). In exploratory analyses assessing all joints, MDA-Joints response rates were 21.3% with apremilast vs 7.9% with placebo (treatment difference = 13.6%, 95% CI = 5.9%–21.4%, P = .0028).
Key secondary endpoints also favored apremilast at week 16:
- Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) remission or low disease activity: 70.2% vs 51.8% (P = .0017)
- Tender joint count ≤ 1: 66.2% vs 44.4% (P = .0003)
- Patient Global Assessment ≤ 20: 30.4% vs 19.1%
- Patient pain Visual Analogue Scale ≤ 15: 29.4% vs 13.1%
- Psoriatic Arthritis Impact of Disease (PsAID-12) score improvement: –1.5 vs –0.4
- Psoriatic Arthritis Disease Activity Score (PASDAS) good/moderate response: 59.9% vs 42.7%.
The primary endpoint was the proportion of patients achieving MDA-Joints at week 16, based on sentinel joints (those affected at baseline). Exploratory analyses of all joints showed consistent benefits with apremilast. At week 16, more apremilast-treated patients achieved swollen joint count ≤ 1 (57.9% vs 41.5%, P = .0068) and tender joint count ≤ 1 (38.0% vs 16.7%, P = .0002).
A post-hoc analysis revealed that fewer apremilast-treated patients with ≤ 4 active joints at baseline progressed to > 4 active joints at week 16 compared with placebo-treated patients (19.7% vs 34.9%). This halved the progression to polyarticular disease, highlighting the potential for early intervention in preventing disease worsening.
Treatment-emergent adverse events (TEAEs) occurred in 59.3% of the patients who received apremilast and 47.1% of those who received placebo. The most common TEAEs with apremilast were diarrhea (23.0% vs 10.6%, respectively), nausea (10.8% vs 3.8%), and headache (7.8% vs 2.9%).
Severe TEAEs occurred in 3.9% of the patients in the apremilast group and 3.8% of those in the placebo group. TEAEs leading to drug withdrawal were reported in 10.3% of the patients who received apremilast vs 6.7% of those who received placebo. Two deaths occurred in the apremilast group, both deemed unrelated to treatment by investigators.