0 (22.7% vs 13.4%; P<0.001).4 Notably, over the first 12 weeks in AMAGINE-1, brodalumab vs placebo was also associated with statistically significant improvements in anxiety and depression (measured by Hospital Anxiety and Depression Scale scores).14
In the integrated AMAGINE-1/-2/-3 studies, the PSI item score for pruritus significantly improved for patients receiving brodalumab 210 mg Q2W vs placebo as early as week 2 (36.1% vs 7.8%; P<0.001) and through week 12 (71.3% vs 13.2%; P<0.001). In AMAGINE-2/-3, brodalumab 210 mg Q2W vs ustekinumab induced rapid and sustained improvements in PSI item scores for pruritus and pain. Onset of significantly greater improvements began at week 2 for pruritus (36.4% vs 17.1%; P<0.01)4 and week 2 for pain (62.4% vs 44.4%; P<0.01; Figure 2).24 Significant treatment differences in response rates were observed with brodalumab vs ustekinumab through week 12 for pruritus (P<0.01) and through week 10 for pain (P<0.01).24 Overall, brodalumab achieved rapid-onset milestones for the PSI total score, as well as for pain and pruritus scores, more quickly than comparators (placebo and ustekinumab).
Quality of Life
The dermatology life quality index (DLQI) is a 10-item, patientreported measure of the social and psychologic impact of dermatologic disease. Total scores range from 0 to 30, with lower scores indicating a less severe impact on quality of life. In a secondary analysis of a phase 2 study, brodalumab (140 or 210 mg Q2W or 280 mg Q4W) vs placebo was associated with clinically meaningful improvements in DLQI (≥5.7-point reduction) as early as week 4 of treatment. At 12 weeks, DLQI scores were significantly improved in patients treated with brodalumab vs placebo.6 Moreover, pooled analysis of phase 3 trials of brodalumab (AMAGINE-1/-2/-3) demonstrated that patients who achieved complete skin clearance with brodalumab (PASI 100) were more likely to have a DLQI score of 0 or 1 compared with those who almost achieved complete skin clearance (PASI 90 through PASI 100; 80.2% vs 62.7%, respectively).7 These robust DLQI responses suggest that the time to response of brodalumab regarding physical signs of psoriasis may also correlate with timely achievement of quality-of-life improvement.
However, it is difficult to fully grasp the clinical implications of these DLQI data, as the approaches to measuring quality-of-life improvements vary across trials. For example, quality-of-life outcomes may be reported as achievement of a DLQI score of 0 or 1 vs a score of >1, as in a post hoc analysis of secukinumab, etanercept, and ustekinumab trials.25 In AMAGINE-1, changes in DLQI were reported as the proportion of patients achieving a ≥5-point improvement from baseline to week 12 (brodalumab 210 mg, 83.6%; placebo, 21.6%), whereas in a trial of ixekizumab, changes were reported as the total change in DLQI score from baseline to week 12 (ixekizumab, -10.7; placebo, -2.6 ).26,27 Although DLQI data for brodalumab are promising, more evidence is needed to determine the magnitude of effect compared with other IL-17 and IL-23 biologics.
An Indirect Comparison of the Onset of Response of Brodalumab and Other Biologics
In addition to studies directly comparing brodalumab with ustekinumab, time to response of brodalumab has been indirectly compared with that of other biologics. A 2020 meta-
