Interleukin-23p19 Inhibitors: Current Perspectives
Selective inhibitors of the interleukin-23p19 (IL-23p19) subunit have emerged as highly effective therapies for patients with moderate to severe plaque psoriasis. The IL-23 inhibitors offer efficacy for plaque psoriasis that is comparable to that of the IL-17 inhibitors with less frequent maintenance dosing.
Clinical Professor and Medical Director
“The high degree of efficacy of these agents for plaque psoriasis is similar to that of the IL-17 blockers, and the safety of both drug classes is excellent.”
IL-23 has been recognized as a crucial player in the pathogenesis of autoimmune diseases in general and psoriasis in particular. At this time, the IL-23p19 blockers that are available for the treatment of plaque psoriasis include guselkumab, tildrakizumab, and risankizumab. The high degree of efficacy of these agents for plaque psoriasis is similar to that of the IL-17 blockers, and the safety of both drug classes is excellent. The IL-23p19 inhibitors work reasonably fast, and the small number of injections is a big plus. Maintenance dosing with guselkumab is every 8 weeks, while tildrakizumab and risankizumab are given every 12 weeks.
The importance of psoriatic arthritis in dermatology has been increasingly recognized since the advent of the tumor necrosis factor (TNF) blockers. An interesting but still unanswered question is whether treating psoriasis early on with effective systemic therapy will prevent the subsequent development of psoriatic arthritis in those who may be at risk. We need to improve our ability to identify those patients who are at increased risk of developing arthritis, and this continues to be an active area of research.
Inhibitors of IL-17A or TNF are efficacious in the treatment of cutaneous, peripheral, and axial inflammation. Direct IL-23 inhibition also improves outcomes in the skin and peripheral joints. However, Baeten et al found that blocking IL-23 with risankizumab was not effective in treating active ankylosing spondylitis. The specific molecular and cellular mechanisms that may underlie these observations remain poorly defined.
Favorable data with tildrakizumab were recently reported in a phase 2 trial in patients with active psoriatic arthritis, and we will be interested to see the phase 3 data. Guselkumab recently became the first IL-23 inhibitor approved for the treatment of psoriatic arthritis based on 2 phase 3 trials. TNF inhibitor agents are effective and safe for most people in the context of psoriatic arthritis, as are some IL-17 inhibitor agents (eg, secukinumab and ixekizumab) that have also been shown to prevent radiographic progression.
Another interesting aspect of the clinical development of the IL-23 blockers is that they are being investigated in the treatment of inflammatory bowel disease (IBD). This would be a significant advancement if IL-23 blockers were to become a US Food and Drug Administration–approved treatment option for IBD. Psoriasis and IBD may be present in the same patient, and one would not use an IL-17 blocker in a patient with psoriasis and a history or family history of IBD. In a similar vein, one would not use a TNF inhibitor in someone with a history or family history of demyelinating disease.
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