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.