Keeping It Real: Real-World Brodalumab Outcomes in the Context of Pivotal Trials for Moderate-to-Severe Plaque Psoriasis

Abstract

Introduction Brodalumab is the only interleukin-17 (IL-17) receptor A blocker approved for moderate-to-severe plaque psoriasis and blocks downstream signaling of multiple IL-17 isoforms including IL-17A, IL-17F, IL-17C, IL-17E, and IL-17A/F. Here, we contextualize effectiveness and safety of brodalumab in adult patients in the Canadian Real-World Evidence (CARE) study alongside results from pivotal phase 3 trials. Methods CARE is a Canadian, 12-month, multi-center, prospective, observational phase 4 study (NCT05132231) in adult patients initiating brodalumab as part of routine clinical care. Results reported here reflect a prespecified interim analysis through month 6. In the AMAGINE-1, -2, and -3 phase 3 trials (NCT01708590, NCT01708603, NCT01708629), participants were initially randomized to receive brodalumab (140 or 210 mg) or placebo via subcutaneous injection every 2 weeks (Q2W) during a 12-week induction period. At week 12, brodalumab-treated patients were rerandomized to placebo or the same brodalumab dose (AMAGINE-1) or various brodalumab regimens (AMAGINE-2 and -3) through week 52. Brodalumab’s performance at the approved 210-mg dose was assessed with Psoriasis Area and Severity Index (PASI) scores and rates of adverse events (AEs). Real‑world effectiveness (3 and 6 months) and safety (6 months) are presented descriptively alongside pivotal trials efficacy and safety (3 months). No formal statistical testing was performed. Results In the CARE study, 351 patients (58% male, 74% Caucasian, mean age 51 y, baseline mean PASI score 14.1) completed the 6-month visit. At 3 months, PASI 75/90/100 were observed in 78.2% (265/339), 64.0% (217/339), and 43.4% (147/339) of patients, with improvements at 6 months to 82.1% (276/336), 72.6% (244/336), and 52.1% (175/336) of patients, respectively. Overall, 44.4% and 2.0% of patients reported AEs and serious AEs, respectively. In the phase 3 trials with brodalumab 210 mg (n=1458, 69%-73% male, 90%-91% Caucasian, mean age 45-46 y, baseline mean PASI score 19.4-20.4), PASI 75/90/100 were achieved in 83%-86%, 69%-70%, and 37%-44% of patients at 3 months (week 12). A total of 56.8%-59.0% and 1.0%-1.8% of patients experienced AEs and serious AEs, respectively. Conclusions Real‑world outcomes with brodalumab align closely with the efficacy and safety profile established in pivotal phase 3 trials. These results support the robustness and generalizability of brodalumab’s clinical profile across both controlled and routine‑care settings and its use as an effective treatment option for moderate‑to‑severe plaque psoriasis.