Findings from published reports demonstrate therapeutic benefit of interleukin (IL)-17/T-helper 17 (Th17) axis inhibitors in patients with generalized pustular psoriasis (GPP). Establishing a role of these biologic agents in the management of GPP, however, will require additional research assessing their efficacy and safety, according to Plachouri et al. who undertook a systematic review of the available evidence on this topic.
In their report, the investigators stated that other conventional systemic therapies (i.e., retinoids, cyclosporine, and methotrexate) and other biologics (i.e., tumor necrosis factor α inhibitors and IL-12/23 inhibitors) have been associated with variable results when used to treat GPP. They noted that the pathogenesis of GPP is not fully understood, but that mutations in the IL36RN gene that encodes the IL-36 receptor antagonist protein and in CARD14 (caspase recruitment domain-containing protein) are thought to be associated.
Interest in IL-17 inhibition relates to reports that serum and mRNA levels of IL-17 are significantly higher in patients with pustular psoriasis than in patients with nonpustular disease. Plachouri et al. pointed out that because IL-17 is a potent neutrophilic chemotactic factor, the elevated levels of serum and mRNA levels of IL-17 in patients with pustular psoriasis is consistent with the increased neutrophilic infiltration seen in this particular psoriatic subtype.
What’s in the literature?
To examine the evidence for IL-17 blockade as a treatment for GPP, the authors performed a review following recommendations of the Preferred Reporting Items for Systemic Reviews. They searched the Embase, MEDLINE (PubMed), and Scopus databases for English language articles published between 2012 and 2019 to identify papers relating to GPP and the use of secukinumab, ixekizumab and brodalumab. The search identified 88 articles; 38 fit the inclusion criteria for review, and the authors summarized their findings.
Secukinumab was evaluated in a Japanese open-label phase III study enrolling 12 adult patients, of which only 3 received secukinumab as monotherapy. Treatment with secukinumab was associated with early benefit, significant improvement at the week 16 endpoint, durable responses through week 52, and no unexpected adverse events.
Plachouri KM, Chourdakis V, Georgiou S. The role of IL-17 and IL-17 receptor inhibitors in the management of generalized pustular psoriasis. Drugs Today. 2019;55(9):587-593.