Complete clearance and psoriasis area and severity index response for brodalumab and ustekinumab in AMAGINE-2 and-3

Background Modern biologics achieve complete skin clearance [100% improvement in psoriasis area and severity index (PASI 100)] in 30-45% of psoriasis patients. Cumulative benefit considering rapidity, frequency and sustainability of response has not been thoroughly investigated. Objectives Compare the frequency, rapidity and sustainability of PASI 90 and 100 response in patients with moderate-to-severe psoriasis treated with brodalumab or ustekinumab. Methods Integrated analyses of the brodalumab Phase III AMAGINE-2 (NCT01708603) and -3 (NCT01708629) trials were performed to determine proportion of patients achieving PASI response per visit; corresponding odds ratios (OR) were calculated. Cumulative clinical benefit of treatment was determined with area-under-the-curve (AUC) analysis. Cumulative incidence of response was analysed using a competing risk model of PASI response or rescue. Sustained response was evaluated by time to inadequate response using Kaplan-Meier methods. Proportion of time spent in different response states was descriptively analysed. Association between PASI response and health-related quality of life [Dermatology Life Quality Index (DLQI)] was assessed using data from all treatment groups from AMAGINE-1, -2 and -3. Results A significantly higher proportion of patients treated with brodalumab achieved PASI 100 vs. ustekinumab (Week 52: 51% vs. 28%; OR [95% CI] 2.8 [2.1, 3.7];P < 0.0001), with significant differences observed from Week 4. Cumulative benefit through 52 weeks was 69% higher with brodalumab (AUC ratio: 1.69;P < 0.001). Brodalumab patients were also significantly more likely to achieve a PASI 100 at least once over 52 weeks vs. ustekinumab (76% vs. 52%;P < 0.0001). Once response was achieved, brodalumab patients had a low likelihood of failure or need for rescue. There was significant positive association between PASI response level and DLQI0/1 achievement (P < 0.0001). Conclusion Brodalumab treatment resulted in significantly higher levels of skin clearance, longer sustained response and greater cumulative treatment benefit vs. ustekinumab.

Automated summary

Modern biologics can achieve complete skin clearance in 30-45% of psoriasis patients. This study compared the effectiveness of brodalumab and ustekinumab in achieving PASI 90 and 100 responses, finding that brodalumab resulted in significantly higher levels of skin clearance, longer sustained response, and greater cumulative treatment benefit compared to ustekinumab. Additionally, there was a significant positive association between PASI response level and health-related quality of life.