Researchers initially hoped that bimekizumab’s dual IL-17A/IL-17F blocking might pose less risk of inflammatory bowel disease than earlier anti-IL-17 therapies. Dr. Ogdie pointed out, however, that this has not been borne out, so clinicians must counsel patients on these risks; this entire class should be avoided in patients with preexisting inflammatory bowel disease. Dr. Ogdie also noted that bimekizumab may pose a higher risk of candida infection compared with other anti-IL-17 agents, particularly when given at the higher dosage recommended for psoriasis vs. psoriatic arthritis.5,6
Bimekizumab also contains a warning for suicidal ideation, although Dr. Ogdie noted that this was more prevalent in patients treated for psoriasis than for psoriatic arthritis. “It’s something to be aware of,” she said. “For all patients, ask about depression and anxiety at every visit.”
Researchers have also been exploring whether innovations in biologic size might improve response. At around 150 kilodalton (kDa) in size, current therapeutic biologic antibodies may not fully penetrate tissues.
Thus, sonelokimab is a novel nanoparticle agent (40 kDa) displaying dual inhibition of IL-17A and IL-17F. Dr. Ogdie shared that phase 2 trials in psoriatic arthritis showed similar efficacy and safety profile to what might be expected from an IL-17 inhibitor, but the current phase 3 study will yield more definitive information.7
Similarly, izokibep is an even smaller (14 kDa) particle designed to inhibit IL-17A with greater tissue penetration than current anti-IL-17 agents. Previous data and a phase 2b/3 study presented on Tuesday at ACR Convergence show the durability of response at 52 weeks, with a safety profile similar to previous anti-IL-17 therapies.8,9 “For all practical purposes it looks [like] secukinumab or ixekizumab,” said Dr. Ogdie.
New IL-23 Inhibitors
Two subcutaneous IL-23 inhibitors came on the market within the last five years: guselkumab followed by risankizumab. Another subcutaneous agent in this class, tildrakizumab, is currently approved for psoriasis, and like these previous agents also targets the p19 subunit of interleukin-23. Although the full results have not yet been released, the developer, Sun Pharma, has announced two positive phase 3 trials in psoriatic arthritis (INSPIRE-1 and INSPIRE-2), which may be presented at the next EULAR Congress.10,11
Dr. Ogdie noted that anti-IL-23 agents are known for their clean safety profile, and, so far, tildrakizumab looks very similar to other anti-IL-23 agents in this respect; however, its skin response, although good, might not be quite as effective as those seen in earlier therapies in this class.10,11
