Background: Secukinumab, a fully human anti-interleukin 17A monoclonal antibody, was evaluated in ERASURE and FIXTURE, two phase 3 multicenter double blind vs placebo clinical studies, for efficacy and safety in subjects with moderate to severe plaque psoriasis. Data from these trials provided an opportunity to evaluate the relationship between traditional clinical outcomes and patient-reported symptoms.
Methods: Patients aged = 18 years were randomized 1:1:1 in ERASURE to receive subcutaneous treatment with secukinumab 300 mg, secukinumab 150 mg, or placebo; and 1:1:1:1 in FIXTURE which included etanercept 50 mg twice-weekly. The co-primary endpoints were the Psoriasis Area and Severity Index (PASI) and Investigator’s Global Assessment Mod 2011 Rating Scale (IGA mod 2011). Symptom response was evaluated using the patient-completed Psoriasis Symptom Diary (PSD), which measures psoriasis-related disease characteristics which subjects have reported as important and relevant to their disease and treatment. Correlation coefficients were calculated at baseline, week 12, and change from baseline to week 12 between the PSD weekly itching, pain and scaling severity scores and the PASI and IGA mod 2011 scores. Logistic regression evaluated the relationship between itching, pain and scaling response (defined as improvement of at least 2.2 points for itching and pain and 2.3 points for scaling), and percent change in PASI at week 12.
Results: Approximately 40% of patients completed the voluntary PSD. For the pooled analysis (ERASURE n = 187, FIXTURE n = 266) of secukinumab data, correlation coefficients at baseline were positive but low in magnitude (0.11-0.21) and positive and stronger at week 12 (0.32-0.52). The change from baseline to week 12 correlation coefficients (0.18-0.30) were positive but lower in magnitude than week 12 values. Most coefficients were significant (P < 0.001). The logistic models showed that the percent change in PASI score was a significant predictor of PSD response. The likelihood of a response for psoriasis-related itching, pain, and scaling at week 12 increased from 77.7%, 65.9% and 77.7% with a 75% PASI change between baseline and week 12 to 85.9%, 72.6%, and 86.1% with a 90% PASI change.
Conclusion: PASI 90 provides greater symptom response as measured by the PSD than PASI 75. It is important to evaluate both patient-reported outcomes and clinical endpoints to understand the full benefits of a psoriasis treatment.
