Ustekinumab is an IL-12/23 inhibitor approved for moderate-to-severe plaque psoriasis.17 Few studies have shown the utility of brodalumab in patients who experienced inadequate response or intolerance. Langley et al assessed brodalumab rescue in 124 patients who had inadequate responses to ustekinumab vs 149 patients who continued ustekinumab despite no response at week 16.27 PASI75, PASI90, and PASI100 response rates for the brodalumab rescue group were 72.6%, 58.1%, and 36.3%, respectively, whereas those in the ustekinumab continuation group were 61.7%, 25.5%, and 5.4%, respectively. Furthermore, exposure-adjusted rates of adverse events were similar between the two groups.
Brodalumab rescue therapy was also assessed in patients who were refractory to anti-IL-17A inhibitors. A retrospective study by Gasslitter et al assessed patients with moderate-to-severe psoriasis who did not respond satisfactorily to an IL-17A inhibitor and switched to another biologic in the same class.28 There were 7 cases of secukinumab switches to brodalumab, of which 4 cases (57%) achieved PASI75, 1 case (14%) achieved PASI50, and 2 cases (28%) did not achieve success by week 12. Ixekizumab was switched to brodalumab in 3 cases of which 2 (66%) achieved PASI75. Kimmel et al also assessed the efficacy of brodalumab in patients who failed anti-IL-17A therapies in moderate-to-severe psoriasis.29 Failure to an IL-17A agent (ie, secukinumab, ixekizumab) was defined as either lack of PASI75 response or a 50% loss of original improvement by week 12. Thirty-nine patients were enrolled with 34 patients receiving brodalumab and completing all visits through week 16. As-observed results showed 71% of patients achieved sPGA score of 0 (clear) or 1 (almost clear) and 76%, 50%, and 32% achieved PASI75, PASI90, and PASI100, respectively, indicating that the majority of patients who failed IL-17A inhibitors experienced significant improvement in their psoriasis with brodalumab.
Brodalumab rescue therapy was also assessed in patients who were refractory to anti-IL-17A inhibitors. A retrospective study by Gasslitter et al assessed patients with moderate-to-severe psoriasis who did not respond satisfactorily to an IL-17A inhibitor and switched to another biologic in the same class.28 There were 7 cases of secukinumab switches to brodalumab, of which 4 cases (57%) achieved PASI75, 1 case (14%) achieved PASI50, and 2 cases (28%) did not achieve success by week 12. Ixekizumab was switched to brodalumab in 3 cases of which 2 (66%) achieved PASI75. Kimmel et al also assessed the efficacy of brodalumab in patients who failed anti-IL-17A therapies in moderate-to-severe psoriasis.29 Failure to an IL-17A agent (ie, secukinumab, ixekizumab) was defined as either lack of PASI75 response or a 50% loss of original improvement by week 12. Thirty-nine patients were enrolled with 34 patients receiving brodalumab and completing all visits through week 16. As-observed results showed 71% of patients achieved sPGA score of 0 (clear) or 1 (almost clear) and 76%, 50%, and 32% achieved PASI75, PASI90, and PASI100, respectively, indicating that the majority of patients who failed IL-17A inhibitors experienced significant improvement in their psoriasis with brodalumab.
Similar findings were noted by Kromer et al who found that ~48% of anti-IL-17A nonresponders achieved PASI75 after switching to brodalumab at week 12.30 Yeung et al also performed a multicenter retrospective study in Canada of 47 patients who failed to achieve PASI75 with either secukinumab or ixekizumab and switched to brodalumab.31 At week 16, 61.7%, 46.8%, and 42.5% of patients achieved PASI75, PASI90, and PASI100, respectively. Interestingly, they observed that a significant proportion of patients who previously failed 3 biologics achieved PASI90 with brodalumab.
Brodalumab in the Treatment of Nail, Scalp, and Palmoplantar Psoriasis
Psoriasis involvement of the nail, scalp, and palms/soles further contributes to poor quality of life. With respect to nail psoriasis, a post hoc analysis of phase 3 clinical trials assessing patients with moderate-to-severe nail psoriasis treated with either brodalumab or ustekinumab for 52 weeks found brodalumab to exhibit significantly greater rates of NAPSI 0 (complete clearance of nail psoriasis) at week 12 (7.9%) and week 52 (63.8%) compared to ustekinumab (2.2% and 39.1%, respectively).4 An open-label, single-center unblinded study also assessed response of severe nail psoriasis of the fingers and toes separately.32 Brodalumab treatment resulted in statistically significant reductions in NAPSI for bother fingers and toes compared to baseline at weeks 12 and 24. In addition, a real-world case series of 4 patients with psoriatic nail involvement achieved significant or complete clearance after 12 to 20 weeks of treatment.33
Regarding scalp involvement, brodalumab exhibited significant improvement rates from baseline in mean Psoriasis Scalp Severity Index (PSSI) scores at week
