IL-17 inhibitors have achieved rapid and substantial reductions in Psoriasis Area Severity Index (PASI) score, which takes into account the extent and severity of skin involvement, erythema (redness), induration (thickness), and desquamation (scaling) of psoriatic lesions. In the placebo-controlled phase 3 monotherapy trials of these inhibitors in adult moderate-to-severe plaque psoriasis, PASI75 response rates (ie, the proportion of patients achieving at least 75% reduction in PASI scores) at week 12 were comparable. PASI75 response rates range from 67% to 81% for secukinumab, 78% to 90% for ixekizumab, and 83% to 86% for brodalumab at week 12 in these trials.14-17 PASI90 response rates at week 12 ranged from 54% to 59%, 49% to 71%, and 70% to 72%, respectively (Figure 2). For the most stringent endpoint, PASI100 (complete clearance), response rates at week 12 ranged from 24% to 35%, 29% to 44%, and 40% to 44%, respectively.
Long-term data from phase 3 trials have also shown sustained efficacy profiles. Secukinumab has shown sustained PASI75 response rates ranging from 73% to 83% at 52 weeks.15 Similarly, ixekizumab has demonstrated PASI75 response rates of >80% at 52 weeks.18 Brodalumab has also shown sustained efficacy, with PASI75 response rates of 69% to 85% at 52 weeks.14,17 When comparing PASI75 response rates up to 5 years of treatment, results were also sustained. Secukinumab demonstrated a response rate of ~81%.19 Ixekizumab demonstrated a greater response rate of 90%.20 Brodalumab also demonstrated a similar response rate of over 80%.21 These findings suggest that IL-17 inhibitors may provide durable and sustained efficacy in the treatment of psoriasis for up to at least 260 weeks of treatment.
Brodalumab Achieves Rapid Clearance Relative to IL-17A Inhibitors
As treatment for plaque psoriasis has become more sophisticated, so have the expectations for treatment goals. Patients are expecting long-term remission from psoriasis and a rapid time frame to achieve a clinically acceptable endpoint. While no head-to-head comparative studies have been conducted comparing biologics within the IL-17 family, brodalumab appears to have the greatest efficacy by week 4 concerning PASI75 response rates. In the phase 3 trials, response rates ranged from 38.1% to 86.3%, 57.4% to 82.1%, and 85.1% to 100% for secukinumab, ixekizumab, and brodalumab, respectively. Investigator Global Assessment (IGA) response rates (achieving a score of clear [0] or almost clear [1] with ≥2 point improvement) at week 4 are as follows: 55.5% to 59.2%, 43.1% to 46.1%, and 83.3% to 84.6% for secukinumab, ixekizumab, and brodalumab, respectively. In performing an indirect comparison of time for 50% of patients receiving IL-17 or IL-23 antagonists to achieve PASI90, Fried et al found brodalumab to have the quickest mean time at 6.2 weeks, whereas ixekizumab and secukinumab both required greater than 7 weeks.22
Brodalumab Demonstrates High Levels of Recapture Response Among IL-17 Inhibitors
In real-world circumstances, patients may stop and restart treatment for a number of reasons such as cost, insurance barriers, inconveniences, psychological
