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A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab and tildrakizumab for the treatment of moderate to severe plaque psoriasis
<p><b>Objective:</b> To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis.</p> <p><b>Methods and results:</b> Twenty-four randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82β29.54, <i>p</i>β<β.00001) and 14.55 (10.42β20.31, <i>p</i>β<β.00001) for ustekinumab 90βmg, 13.75 (8.49β22.28, <i>p</i>β<β.00001) and 9.81 (5.70β16.89, <i>p</i>β<β.00001) for ustekinumab 45βmg, 17.65 (12.38β25.17, <i>p</i>β<β.00001) and 26.13 (16.05β42.53, <i>p</i>β<β.00001) for secukinumab 300βmg, 15.36 (10.76β21.94, <i>p</i>β<β.00001) and 20.91 (12.82β34.13, <i>p</i>β<β.00001) for secukinumab 150βmg, 18.22 (10.63β31.23, <i>p</i>β<β.000001) and 18.82 (10.36β34.16, <i>p</i>β<β.00001) for ixekizumab 80βmg every 4βweeks, 19.83 (11.07β35.52, <i>p</i>β<β.00001) and 20.41 (11.01β37.81, <i>p</i>β<β.00001) for ixekizumab 80βmg every 2βweeks, 14.79 (9.86β22.16, <i>p</i>β<β.00001) and 21.93 (15.52β31.01, <i>p</i>β<β.00001) for brodalumab 210βmg, 11.55 (7.77β17.18, <i>p</i>β<β.00001) and 16.59 (11.72β23.49, <i>p</i>β<β.00001) for brodalumab 140βmg, 12.40 (8.87β17.34, <i>p</i>β<β.00001) and 10.84 (7.91β14.85, <i>p</i>β<β.00001) for guselkumab 100βmg, 11.45 (7.45β17.58, <i>p</i>β<β.00001) and 10.97 (6.44β18.69, <i>p</i>β<β.00001) for tildrakizumab 200βmg, 11.02 (7.17β16.93, <i>p</i>β<β.00001) and 10.03 (6.45β15.59, <i>p</i>β<β.00001) for tildrakizumab 100βmg. Similar outcomes were seen for PASI-90. Safety was satisfactory for each therapy at any dose, but a slightly increased risk of withdrawal due to toxicity was observed in individuals receiving ixekizumab compared to placebo.</p> <p><b>Conclusion:</b> Ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab were highly efficacious and generally well-tolerated when used as treatments for moderate to severe plaque psoriasis.</p