Long-Term Apremilast Monotherapy Is Safe and Effective Treatment for Psoriatic Arthritis

Long-Term Apremilast Monotherapy Is Safe and Effective Treatment for Psoriatic Arthritis

Results from the PALACE 4 trial indicate that apremilast, an oral phosphodiesterase inhibitor, is safe and effective as a first-line treatment for patients with psoriatic arthritis (PsA) who have not been previously treated with either conventional synthetic (cs) or biologic (b) disease-modifying antirheumatic drugs (DMARDs). In this trial, treatment with apremilast showed significantly greater improvement in American College of Rheumatology 20% (ACR20) improvement response criteria and Health Assessment Questionnaire Disability Index (HAQ-DI) scores at week 16 for 20- and 30-mg twice-daily doses compared with placebo (Wells AF, et al. Rheumatology. 2018 Apr 4. Epub ahead of print).

“PALACE 1, 2, and 3 evaluated apremilast in patients with active PsA who were considered inadequate responders to csDMARDs or bDMARDs, with benefits observed up to 156 weeks. PALACE 4 assessed apremilast use earlier in the treatment algorithm in patients with active PsA who were csDMARD-naïve and biologic-naïve,” wrote lead study investigator Alvin Wells, MD, PhD, Director, Rheumatology and Immunotherapy Center, Franklin, WI, and colleagues. The investigators noted that previous studies have shown that early control of PsA-related symptoms is important for overall effectiveness of treatment.

The PALACE 4 trial was a phase 3 parallel-group study over 5 years that randomized eligible patients in a 1:1:1 ratio to apremilast 20 mg twice daily, apremilast 30 mg twice daily, or placebo. Patients were evaluated at weeks 16, 24, and 52, at which point they were eligible for an open-label extension trial phase for 4 additional years.

The primary end point of the trial was ACR20 improvement in symptoms at week 16. The key secondary end point was the change in HAQ-DI scores at week 16. Other secondary end points included ACR50 and ACR70 responses and ≥50% and ≥70% improvement from baseline in the Psoriasis Area and Severity Index scores.

At week 16, patients treated with apremilast demonstrated significantly greater ability to achieve an ACR20 response (apremilast 20 mg, 28% [P = .0062]; apremilast 30 mg, 30.7% [P = .0010) than patients who received placebo (15.9%). Significant ACR20 responses were seen for both doses of apremilast versus placebo at 24 and 52 weeks.

Patients treated with apremilast also had significant improvements in functionality compared with placebo, as measured by the week 16 change in HAQ-DI scores (apremilast 20 mg, –0.17 [P = .0008]; apremilast 30 mg, –0.21 [P <.0001]; placebo, 0.03). Significantly more patients treated with apremilast achieved a minimal clinically important difference in HAQ-DI score improvement of ≥0.13 (20 mg) and ≥0.30 (30 mg) compared with placebo, and this improvement in HAQ-DI scores was sustained at 52-week follow-up with continued apremilast treatment.

The majority of adverse events (AEs) were mild or moderate in severity, and the incidence between the treatment arms and placebo were similar. The most frequently reported AEs (≥5%) in any treatment group were diarrhea, nausea, and headache. From weeks 0 to 52, 22 patients had a severe AE, with back pain being the only event reported by >1 patient (N = 2).

Dr Wells and colleagues acknowledged that one limitation to PALACE 4 was that many of the patients had long-term, active PsA. Therefore, the results may not fully apply to a population of patients with early PsA who have not received previous treatment with DMARDs. Despite this limitation, they believe apremilast may provide an important clinical benefit for specific populations of patients with PsA.

“The lack of monitoring requirements and the overall long-term benefit-risk profile with oral apremilast make it a therapeutic option for patients with active PsA whose systemic treatment choices may be limited by efficacy, frequent laboratory safety requirements and tolerability,” Dr Wells and colleagues concluded, adding that, “Given the favorable benefit-risk profile, apremilast may be a treatment option for DMARD-naïve patients with active PsA.”

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