Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies

Abstract

The diverse clinical picture of PsA suggests the need to identify suitable therapies to address the different combinations of clinical manifestations. This review aimed to classify the available biologic agents and new small molecule inhibitors (licensed and nonlicensed) based on their proven efficacy in treating different clinical manifestations associated with psoriasis and PsA. This review presents the level of evidence of efficacy of different biologic treatments and small molecule inhibitors for certain clinical features of treatment of PsA and psoriasis, which was graded in categories I–IV. The literature searches were performed on the following classes of biologic agents and small molecules: TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), anti-IL12/IL23 (ustekinumab), anti-IL17 (secukinumab, brodalumab, ixekizumab), anti-IL6 (tocilizumab), T cell modulators (alefacept, efalizumab, abatacept, itolizumab), B cell depletion therapy (rituximab), phosphodiesterase 4 inhibitor (apremilast) and Janus kinase inhibitor (tofacitinib). A comprehensive table including 17 different biologic agents and small molecule inhibitors previously tested in psoriasis and PsA was generated, including the level of evidence of their efficacy for each of the clinical features included in our review (axial and peripheral arthritis, enthesitis, dactylitis, and nail and skin disease). We also proposed a limited set of recommendations for a sequential biologic treatment algorithm for patients with PsA who failed the first anti-TNF therapy, based on the available literature data. There is good evidence that many of the biologic treatments initially tested in psoriasis are also effective in PsA. Further research into both prognostic biomarkers and patient stratification is required to allow clinicians the possibility to make better use of the various biologic treatment options available. This review showed that there are many potentially new treatments that are not included in the current guidelines that can be used for selected categories of patients based on their disease phenotype, clinician experience and access to new biologic therapies.

Therapeutic challenges in a case of psoriasis with nail onset

“…In the same study,patients treated with cyclosporine showed a 37% mean improvement in the NAPSI score (21 (25). The efficacy of etanercept in nail psoriasis has also been supported by other studies (7,26,27). In our case, there was a rapid response to etanercept with a significant reduction in the NAPSI score.…”

Dual Role of Act1 in Keratinocyte Differentiation and Host Defense: TRAF3IP2 Silencing Alters Keratinocyte Differentiation and Inhibits IL-17 Responses

“…TRAF3 and TRAF4 negatively regulate IL-17 signaling by competing for Act1 binding with TRAF6 and IL17RA, respectively (Wu et al, 2015, Zepp et al, 2012, Zhu et al, 2010). Although IL-17 alone regulates the expression of a relatively small subset of approximately 40 genes in cultured keratinocytes (Chiricozzi et al, 2011, Nograles et al, 2008), biologics targeting IL-17 and its receptors are very effective treatments for psoriasis (Elyoussfi et al, 2016, Lowes et al, 2014). …”

Recent advances in understanding and managing psoriatic arthritis

“…Fortunately for PsA patients, TNF inhibitors (TNFi) became available at the beginning of the millennium and have demonstrated excellent efficacy in patients with PsA 53 . Five TNFi agents are now available, including etanercept, adalimumab, infliximab, golimumab, and certolizumab 54 . Certolizumab is the most recent addition to the list and has proven to be efficacious in TNFi failures 55 .…”

“…All have been proven to be effective for signs and symptoms as well as for preventing radiographic progression of PsA. Infliximab, golimumab, and certolizumab have been proven to be effective for enthesitis and dactylitis in pivotal randomized controlled trials (RCT), while etanercept and adalimumab have been shown to control enthesitis and dactylitis in subsequent studies 54 .…”

“…A recent systematic review summarizes therapies for PsA and provides the level of evidence for the efficacy of each of the drugs, together with their level of efficacy 54 . Results of the SPIRIT-1 study, which tested ixekizumab, another anti-IL-17A agent, in a phase III RCT which included adalimumab as an active comparator, were recently published 60 .…”