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).
Sources:
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.