The evidence for adding small-molecule drugs to an ongoing biologic treatment is sparse, but combination therapies appear to be advantageous in appropriately selected patients with psoriasis. To our knowledge, efficacy and safety of combination therapy with apremilast and biologics has not previously been reviewed.

A literature search was performed on Medline (PubMed), Embase, Web of Science, and the Cochrane Library. Inclusion criteria were a diagnosis of psoriasis, age ≥ 18 years, concomitant treatment with apremilast and a specified biologic agent, and available safety and/or efficacy results. All papers written in English and published from database inception to August 2021 were included. No limit was set regarding study size.

The literature search yielded 447 citations. Of these, 19 studies published from 2015 to 2020 were included in the review. All papers referred to retrospective studies, comprising case reports (n = 9), case series (n = 8), or cohort studies (n = 2). A total of 172 patients with psoriasis were identified. Clinical subtypes included plaque psoriasis (n = 164), palmoplantar pustulosis (n = 7), and acute pustular psoriasis (n = 1). The observation period ranged from 3 weeks to 24 months. Geographical origin of studies was North America (n = 11), Europe (n = 4), and Asia (n = 4). In general, apremilast-biologic combination therapy was reported to be safe; across papers, one serious adverse event was registered (hospitalization due to weight loss). Adverse events (AEs) were otherwise mostly mild and gastrointestinal. No differences in AEs were observed in studies comparing apremilast mono- and combination therapy. In several papers, sufficient information about AEs was not reported or could not be extracted. Clinical response to combination treatment was evaluated at various time points, and only few studies used validated scores. In the remaining papers, efficacy data were descriptive and/or in photographic form, or not available. In total, two patients discontinued therapy due to lack of efficacy.

Evidence for combined treatment with apremilast and biologics is limited and restricted to retrospective studies of various quality. Based on available data, apremilast may constitute an efficacious and safe add-on treatment to biologic therapy, but properly conducted clinical investigations are needed.