PURPOSE: Both brodalumab and guselkumab improve skin clearance in patients with moderate-to-severe plaque psoriasis after inadequate response to ustekinumab. In the absence of a direct head-to-head comparison, the relative efficacy of brodalumab and guselkumab in non-responders to ustekinumab were compared using a matching-adjusted indirect comparison (MAIC). PATIENTS AND METHODS: Individual patient data for brodalumab (n = 121) were pooled from the AMAGINE-2 and -3 trials and adjusted using a propensity score reweighting method, so that baseline and week 16 characteristics matched the aggregate published data of patients with an inadequate response to ustekinumab who switched to guselkumab (n = 135) in the NAVIGATE trial. RESULTS: After inadequate response to ustekinumab, brodalumab resulted in significantly higher psoriasis area and severity index (PASI) 90 rates versus guselkumab at post-treatment switch week 12 (62.7% vs 48.1%, relative difference 14.6% [95% confidence interval [CI] 5.3-23.9], p = 0.002 [number needed to treat [NNT] = 6.8]) and week 36 (63.7% vs 51.1%; relative difference 12.6% [95% CI 4.1-21.0]; p = 0.004 [NNT = 7.9]) and PASI 100 rate at week 36 (40.3% vs 20.0%; relative difference 20.3% [95% CI 11.8-28.7]; p < 0.001 [NNT = 4.9]). CONCLUSION: In this MAIC, brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab. Switching to brodalumab in such patients may be a more effective strategy than switching to guselkumab.