A recent review looked at the immunopathogenesis of psoriasis, identified key mediators of psoriatic plaques that are being targeted by new and emerging biologic therapies, and highlighted the latest efficacy and safety data from trials of these new agents.
Treatment of psoriasis has come a long way in a short time. The development of new biologic drugs that target specific mediators in the immunopathogenesis of plaque psoriasis has transformed management of the disease and has increased the range of treatment options. These options now include the old standbys—immunosupressants such as cyclosporine and methotrexate—as well as tumor necrosis factor alpha (TNF-α) inhibitors (etanercept, infliximab, adalimumab); interleukin-12/interleukin-23 (IL-12/23) inhibitors (ustekinumab), and an IL-17 inhibitor (secukinumab).
Biologic therapies come with great potential and some significant downside risk; safety concerns, including the risk of serious infections such as tuberculosis and major adverse cardiovascular events, still limit their use. A recent review article in Dermatologic Therapy looked at the immunopathogenesis of psoriasis, identified key mediators of psoriatic plaques that are being targeted by new and emerging biologic therapies, and highlighted the latest efficacy and safety data from trials of these new agents.
The article is a thorough summary of key efficacy results from Phase II and Phase III studies of interleukin (IL)-23— and IL-17–targeted biologic therapies in patients with moderate-to-severe chronic plaque psoriasis. It then breaks down each of the biologics one by one for both efficacy and safety/tolerability. The medications reviewed include tildrakizumab, guselkumab, secukinumab, ixekizumab,and brodalumab.
The specific results for the biologics are promising on their own, but a larger, macro view of the current state of psoriasis treatments illustrates how exciting this new avenue of treatment is fast becoming. As the study authors note, “Initial results from the phase 2 studies of the selective IL-23 inhibitors indicate that this efficacy may be maintained for up to 40 weeks (guselkumab) or 52 weeks (tildrakizumab)… The three selective IL-17 inhibitors have also all shown convincing efficacy over 12 weeks, although the 1-year results of large-scale phase 3 studies have only been reported for secukinumab. In these studies, the efficacy of secukinumab was not only superior to placebo, but also to etanercept.”
Safety and tolerability, of course, are longer-term measures, so fully evaluating profiles for these biologics will require both longer-term research and real-world evidence gathered over an extended period. “Although pivotal trials are powered to evaluate efficacy and common [adverse events], AEs of special interest require broader patient populations and longer time periods to detect,” the review authors note. “However, these new biologic therapies show great promise and, if approved, would increase the range of options for patients with plaque psoriasis.”