Tumor necrosis factor inhibitors in psoriatic arthritis

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory disease that can result in significant disability. With the emergence of tumor necrosis factor inhibitors (TNFi), therapeutic outcomes in PsA have improved substantially. The clinical efficacy and the inhibition of radiographic progression demonstrated by TNFi have transformed the management of PsA. However, there is still an unmet need for a subset of patients who do not respond adequately to TNFi. Areas covered: This review provides an overview of the pharmacokinetics of TNFi, the efficacy of TNFi in PsA, and the role of immunogenicity of TNFi in the treatment of PsA. In addition, we address the use of TNFi in the setting of other medications utilized in the treatment of PsA and the potential future role of biosimilars. Expert commentary: Monoclonal antibodies exhibit complex and widely variable pharmacokinetics. The study of factors that can affect the pharmacokinetics, such as immunogenicity, is valuable to further define and understand the use of TNFi in PsA, especially in the subset of patients who do not respond adequately to these agents or lose effectiveness over time.

Keywords: Adalimumab; certolizumab; etanercept; golimumab; immunogenicity; infliximab; methotrexate; monoclonal antibodies; psoriatic arthritis; tumor necrosis factor inhibitors.

Figure 1.

Simplified GRAPPA treatment recommendations [4]. *combination csDMARDS and TNFi common in clinical practice. **Conditional recommendations: At the time these recommendations were published, these drugs were not approved or recommendations were based on data from abstracts. csDMARD, conventional synthetic DMARD; CSA, cyclosporin A; GRAPPA, Group for Research and Assessment of Psoriasis and Psoriatic Arthritis; IL-17i, interleukin-17 inhibitor; IL-12/23i, interleukin-12/23 inhibitor; LEF, leflunomide; MTX, methotrexate; NSAIDS, nonsteroidal anti-inflammatory drugs; PDE-4i, phosphodiesterase 4 inhibitor; SSZ, sulfasalazine; tsDMARD, targeted synthetic DMARD; TNFi, tumor necrosis factor inhibitor

Figure 2.

Simplified EULAR treatment recommendations [19]. *bDMARD includes TNFi, IL-12/23i, IL-17i. The preference initially is a TNFi, but if contraindicated, can consider one of the others or a PDE-4i. **no adverse prognostic factors: can try a second csDMARD or combination therapy. bDMARD, biologic DMARD; csDMARD, conventional synthetic DMARD; CI, contraindicated; EULAR, European League Against Rheumatism; IL-17i, interleukin-17 inhibitor; IL-12/23i, interleukin-12/23 inhibitor; LEF, leflunomide; MTX, methotrexate; NSAIDS, nonsteroidal anti-inflammatory drugs; PDE-4i, phosphodiesterase 4 inhibitor; SSZ, sulfasalazine; tsDMARD, targeted synthetic DMARD; TNFi, tumor necrosis factor inhibitor

Figure 3.

Pathogenesis of psoriatic arthritis. The Th1 and Th17 pathways are important pathways involved in the pathogenesis of PsA. TNF, a pro-inflammatory cytokine, is a key player in osteoclastogenesis via RANK-L and in inhibition of osteoblastogenesis via Dkk-1. Both processes eventually lead to bone erosions [42]. In addition, IL-22 is involved in the pathologic formation of new bone (osteoproliferation) [43]. APC, antigen presenting cell; Dkk-1, dickkopf-related protein 1; IFNγ, interferon gamma; IL-12, interleukin-12; IL-17, interleukin-17; IL-22, interleukin-22; IL-23, interleukin-23; RANK-L, receptor activator of nuclear factor-κB ligand; T cell, T lymphocyte; Th1, type 1 T helper cell; Th17, T helper 17 cell; TNF, tumor necrosis factor

Figure 4.

Simplified structures of TNFi. Fab, fragment antigen-binding; Fc, fragment crystallizable region; IgG1, immunoglobulin G1; PEG, polyethylene glycol; TNF, tumor necrosis factor; TNFR2, tumor necrosis factor receptor 2