5-year safety assessment of apremilast in patients with psoriasis and psoriatic arthritis

Introduction

Apremilast, a small molecule inhibitor of phosphodiesterase-4 (involved in inflammatory signaling pathways), has been used to treat patients with psoriasis (Pso) or psoriatic arthritis (PsA). Following the European Medicine’s Agency (EMA) approval of apremilast for the treatment of adults with moderate-to-severe plaque psoriasis in 2015, a post-authorization safety study was requested.

Here, we summarize results from the 5-year longitudinal study by Persson et al.¹ examining safety signals in UK patients treated with apremilast compared with oral only, injectable only, or oral plus injectable treatments.

Study design

This was a prospective cohort study conducted using data from the UK Clinical Practice Research Datalink, the study design is shown in Figure 1.

Figure 1. Study design* 

AESI, adverse events of special interest; GP, general practitioner; Rx, prescription.
*Adapted from Persson, et al.¹

The four exposure groups included:

• apremilast
• oral only
• injectable only
• oral plus injectable

Each patient in the apremilast group was matched to ≤10 patients in the non-apremilast group for age (± 3 years), sex, year of record start (± 3 years or a longer history for the matches than the apremilast-exposed patient), and calendar time.

Results

As shown in Table 1, 341 apremilast treated patients were matched with non-apremilast patients with Pso or PsA. A decreased percentage of patients with PsA were included in the apremilast group compared with the oral plus injectable exposure group and comorbidity distribution was similar between the apremilast exposed and non-exposed groups.

Table 1. Baseline patient characteristics*

Patients treated with both injectable and oral treatments had more than double the number of treatments compared with the other exposure groups (Table 2). Apremilast was used in combination with another agent (often methotrexate or prednisolone) in 26% of patients.

Table 2. Treatment characteristics of patients in the apremilast and non-apremilast cohorts*

The apremilast group showed low levels of adverse events of special interest (AESI), with 18 infections and 11 hypersensitivity reactions recorded in the cohort of 341 patients (Table 3). No cases of vasculitis, blood cancer, non-melanoma skin malignancy or treated anxiety, depression, or suicidal behaviors were recorded for the apremilast group during the ≤59-month follow-up.

Incidence of major adverse cardiac events, tachyarrhythmias, solid malignancies was similar across all treated cohorts, as seen in Table 3. Patients treated with oral medicine only had the highest recorded number of events for each AESI. Patients treated with injectables had <5 events recorded for all AESI except all-cause death for which 6 events were noted.

Table 3. Incidence rate and incidence rate ratios of AESIs*

Conclusion 

The number of AESI in patients with Pso and/or PsA for the apremilast group was low compared with the non-apremilast treatment groups, with no new safety signals recorded. While the rate of opportunistic infections in the apremilast group was slightly higher than the injectable only group, rates were similar in the oral and oral + injectable groups. This 5-year prospective UK study demonstrated that the safety profile of apremilast in a real-world setting was comparable to what has been reported in clinical trials for patients with Pso and/or PsA.