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Combination Therapy with Apremilast and Biologics for Psoriasis: A Systematic Review

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Abstract

Background

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.

Materials and Methods

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.

Results

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.

Conclusion

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.

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Authors and Affiliations

  1. Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte Hospitalsvej 15, 2900, Hellerup, Denmark

    Mette Gyldenløve, Farzad Alinaghi, Claus Zachariae & Lone Skov

  2. Department of Dermatology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Nielsine Nielsens Vej 9, 2300, Copenhagen, Denmark

    Alexander Egeberg

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  1. Mette Gyldenløve
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Corresponding author

Correspondence to Mette Gyldenløve.

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Funding

None.

Conflict of interest

M. Gyldenløve: None. F. Alinaghi: None. C. Zachariae: Investigator for AbbVie, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZeneca, Eli Lilly, Novartis, Regeneron, and LEO Pharma. Paid speaker for Eli Lilly, Novartis, CSL, and LEO Pharma. Consultant and/or advisory board member for AbbVie, Janssen Cilag, Novartis, Eli Lilly, LEO Pharma, UCB, Almirall, Takeda, Amgen, and CSL. L. Skov: Received research funding from Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the LEO Foundation, and the Kgl Hofbundtmager Aage Bang Foundation. Honoraria as consultant and/or speaker for AbbVie, Eli Lilly, Novartis, Pfizer, LEO Pharma, Janssen Cilag, UCB, Almirall, Bristol-Myers Squibb, and Sanofi. Investigator for AbbVie, Pfizer, Sanofi, Janssen Cilag, Boehringer Ingelheim, AstraZeneca, Eli Lilly, Novartis, Regeneron, Galderma, and LEO Pharma. A. Egeberg: Received research funding from Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation. Honoraria as consultant and/or speaker from AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and Janssen Pharmaceuticals.

Ethics approval, informed consent, and code availability

Not applicable.

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors’ contributions (credit taxonomy)

Conceptualization (MG), methodology (MG and FA), literature search and data extraction (MG, FA, and AE), resources (FA, CZ, and LS), writing—original draft (MG), writing—review and editing (FA, AE, LS, and CZ).

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Gyldenløve, M., Alinaghi, F., Zachariae, C. et al. Combination Therapy with Apremilast and Biologics for Psoriasis: A Systematic Review. Am J Clin Dermatol 23, 605–613 (2022). https://doi.org/10.1007/s40257-022-00703-1

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