Treatment with brodalumab was well tolerated and produced high levels of skin clearance over 120 weeks in patients with moderate to severe plaque psoriasis, according to results of a post hoc analysis of phase 2 and 3 clinical trials of brodalumab published in the Journal of the European Academy of Dermatology and Venereology.
To address potential concerns raised by previous research indicating biologic therapies may lose efficacy over time, study investigators conducted a post hoc analysis of the long-term safety and efficacy of brodalumab in treating plaque psoriasis using pooled data from the AMAGINE-2 and -3 clinical trials (ClinicalTrials.gov Identifiers: NCT01708603 and NCT01708629, respectively. For the post hoc analysis, the investigators evaluated the long-term efficacy and safety of 210 mg brodalumab every 2 weeks using observed data, nonresponder imputation (NRI), absolute psoriasis area severity index (PASI) scores, and other methods to account for missing data resulting from the early termination of the AMAGINE clinical trials.
For the current investigation, researchers analyzed response rates and safety outcomes through 120 weeks for pooled trial participants, who were divided into 3 groups: the “210 mg constant group” (N = 339), who received continuous brodalumab 210 mg every 2 weeks from week 0; the “140 mg switch group” (N = 337), who switched to brodalumab 210 mg every 2 weeks after receiving brodalumab 140 mg through week 12; and the “placebo switch group” (N = 595), who switched to brodalumab 210 mg every 2 weeks after receiving a placebo through week 12. The progress of the disease was measured using PASI and the safety of the treatment was analyzed by monitoring treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
With respect to PASI scores, the investigators observed high response rates in the 210 mg constant group through week 120, where 86% of patients reached PASI 90 and 74% reached PASI 100. In the 140 mg switch group, patients had lower response rates at week 12 compared to the 210 mg constant group, but achieved similar levels at week 20 and maintained comparable high response rates at week 120, 86% for PASI 90 and 74% for PASI 100.
In the safety analysis, the researchers found that the event rate of TEAEs per 100 patient-years among patients in the 210 mg constant group was 323.4; in the 140 mg switch group, the rate was 300; and in the placebo switch group, the rate was 323. Event rates for SAEs per 100 patient-years were 9.4 (constant), 7.7 (switch), and 7.9 (placebo switch); event rates per 100 patient-years for adverse events (AE) that lead to patient’s removal from the study were 2.9 (constant), 3 (switch), and 1 (placebo switch).
Limitations to the study included the sponsor’s decision to terminate the AMAGINE -2 and -3 trials early and the subsequent missing data, as well as the high percentage of biologic-naïve patients included in the AMAGINE-2 and -3 trials, who may have better response rates than biologic-experienced patients.
Researchers concluded that, “This study assessed the efficacy and safety of brodalumab over 2 years, and further supports primary results which demonstrated a treatment benefit for brodalumab 210 mg through 52 weeks in the AMAGINE-2 and -3 studies and through 120 weeks in the AMAGINE-2 study. High levels of skin clearance, as determined by absolute and relative PASI scores, were achieved, and largely maintained, from week 52 through week 120. In addition, brodalumab was generally well tolerated for over 2 years; rates of SAEs were low and similar to those observed through week 52 during the AMAGINE-2 and -3 trials.”
Reich K, Iverrsen L, Puig L, et al. Long-term efficacy and safety of brodalumab in moderate-to- severe plaque psoriasis: a post hoc pooled analysis of AMAGINE-2 and -3. JEAV. Published online March 13, 2022. doi:10.1111/jdv.18068