Apremilast has demonstrated sustained and clinically meaningful improvements in signs and symptoms of psoriatic arthritis (PsA), as well as in physical function in patients who continued treatment over 5 years.
Apremilast is an oral phosphodiesterase 4 inhibitor that works intracellularly to regulate the inflammatory mediators associated with the pathogenesis of PsA (1). Long-term efficacy and safety of treatment with apremilast were evaluated for up to 5 years in patients with active PsA by using data from the Phase 3 PALACE 1, 2, and 3 studies. Apremilast continued to demonstrate a favorable safety profile and was generally well tolerated at 5 years.
Eligible patients had active PsA (duration >6 months, meeting CASPAR criteria, ≥3 swollen joints [SJC], and ≥3 tender joints [TJC]) despite prior conventional treatment with disease-modifying antirheumatic drugs (DMARDs) and/or biologics. A total of 1,493 patients were randomized at baseline (1:1:1) to receive placebo, apremilast 30 g BID, or apremilast 20 mg BID. Placebo subjects were re-randomized 1:1 to apremilast 30 mg BID or 20 mg BID at week 16 or week 24. All randomised subjects received ≥1 dose of study medication (placebo: n=496; apremilast 30 mg: n=497; apremilast 20 mg: n=500). Of those patients randomized to apremilast 30 mg at baseline, 44.5% completed week 260.
The results showed that at week 260, modified ACR20, ACR50, and ACR70 responses were achieved by 67.2%, 44.4%, and 27.4%, respectively. At week 260, mean percent changes were -82.3% for SJC and -72.7% for TJC in patients who continued apremilast 30 mg BID treatment. For patients who had enthesitis or dactylitis at baseline, the number who achieved a Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) of 0 or a dactylitis count of 0 increased over 52 weeks. It suggested maintenance of improvements through week 260 with continued apremilast 30 mg BID treatment. At week 260, 60.4% of patients achieved a Clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score ≤13 (which is indicative of low disease activity and remission), with continued apremilast 30 g BID treatment (2). Furthermore, mean improvement in the Health Assessment Questionnaire-Disability Index (HAQ-DI) of -0.33 at week 52 was maintained through week 260 (-0.42) in patients who received continuous apremilast 30 mg BID. In patients with baseline psoriasis body surface area (BSA) involvement ≥3% mean improvement in the Psoriasis Area and Surface Severity Index (PASI) score at week 52 (-3.54) was maintained throughout week 260 (-4.63) with continued apremilast 30 mg BID. At week 260, 65.8% and 43.6% of patients who received apremilast 30 mg BID achieved a PASI-50 or a PASI-75 response.
It needs to be noted that all efficacy results were similar for subjects receiving apremilast 20 mg BID. Finally, most AEs were mild to moderate in severity over weeks 0 to ≤52 and no new safety concerns or increases were observed with longer-term (up to 260 weeks) exposure to apremilast. AEs, occurring in ≥5% of apremilast-exposed patients during week 0 to ≤52, were diarrhea, nausea, headache, upper respiratory tract infection and nasopharyngitis (3).
1. Gossec L, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis 2016;75:499–510.
2. Edwards C, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomized, controlled trial (PALACE 3). Ann Rheum Dis 2016;75:1065-1073.
3. Kavanaugh A, et al. PAL 1-3, 5yr efficacy and safety of apremilast treatment in subjects with psoriatic arthritis: Pooled analysis of the PALACE studies. THU0294 EULAR 2018.