Progress in understanding and utilizing TNF-α inhibition for the treatment of psoriatic arthritis

ABSTRACT

The improved recognition of pathogenetic molecular mechanisms has led to the use of drugs targeting cytokines in different inflammatory arthropathies as well psoriatic arthritis (PsA). In particular, the progress in knowledge on tumor necrosis factor (TNF)-α in the pathogenesis of PsA has changed the therapeutic approach by use of direct and receptor cytokine antagonists. Currently, infliximab (IFX), adalimumab, etanercept, golimumab and certolizumab pegol represent the five anti-TNF-α available for the treatment of PsA. This review describes evidence on treatment aimed at neutralizing TNF-α in PsA patients, from the first study in 2000 until today, mainly derived from randomized clinical trials. In comparison with traditional therapies, anti-TNF-α agents have shown to have more efficacy both in treating clinical aspects, including enthesitis, dactylitis, joint pain and swelling, axial involvement, nail and skin lesions, and in reducing radiographic progression. Moreover, anti-TNF-α agents have been demonstrated to be reasonably safe in PsA, as confirmed by data derived by different registries.

KEYWORDS:

• TNF-α
• anti-TNF-α
• adalimumab
• etanercept
• infliximab
• golimumab
• certolizumab
• psoriatic arthritis
• therapy

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy in which tumor necrosis factor (TNF)-α represents a key pathogenetic molecule.

• The progressive improvement in knowledge on TNF-α, in the pathogenesis of PsA, has changed the recent therapeutic approach by use of cytokine antagonists.

• Currently, infliximab, adalimumab, etanercept, golimumab and certolizumab pegol represent the five anti-TNF-α available for the treatment of PsA.

• In comparison with nonsteroidal anti-inflammatory drugs, glucocorticoids and traditional disease-modifying antirheumatic drugs (DMARDs), anti-TNF-α agents are more efficacious both in treating clinical aspects and in reducing radiographic progression.

• Anti-TNF-α agents have been also demonstrated to be safe in PsA.

• Anti-TNF-α agents are effective in different aspects of the disease, including enthesitis, dactylitis, joint pain and swelling, axial involvement, nail and skin lesions, and radiographic progression.

• DMARDs have been found efficacious in treating several aspects of the disease but show a lower level of evidence both in treating clinical aspects and in reducing radiographical progression when compared with anti-TNF-α agents.

• In future, increasing studies on cytokines other than TNF-α could lead to development of new drugs targeting different pathways.

• Agents targeting pro-inflammatory molecules other than TNF-α could represent new alternative therapeutic strategies in patients with absence, loss and contraindication to anti-TNF-α.