Early clinical response as a predictor of subsequent response to ixekizumab treatment: results from a phase II study of patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Early identification of responsiveness to biologic treatments in psoriasis has significant clinical and economic implications.

OBJECTIVES: To evaluate whether early clinical improvements in Psoriasis Area and Severity Index (PASI) scores could predict subsequent clinical responses in patients treated with ixekizumab, an anti-interleukin-17 monoclonal antibody.

METHODS: This post hoc analysis was derived from a phase II study in patients with moderate-to-severe plaque psoriasis (n = 114) who received multiple doses of ixekizumab 10, 25, 75 or 150 mg subcutaneously over 20 weeks. PASI score improvements from baseline to weeks 2, 4 and 6 were evaluated to determine the optimal threshold for predicting subsequent PASI responses at week 12.

RESULTS: Early clinical improvement in disease symptoms at weeks 4 and 6 was predictive of ≥ 75% improvement in PASI score (PASI 75) at week 12 with ≥ 90% predictability. A 40-50% improvement in PASI (PASI 40 to PASI 50) from baseline to weeks 4 and 6 was the optimum range for predicting PASI 75 response at week 12. For all doses combined, achieving PASI 40 at week 4 or week 6 was associated with high negative predictive values (NPVs) (80% and 95%, respectively) and positive predictive values (PPVs) (89% and 84%, respectively). For all doses combined, achieving PASI 50 at week 4 or week 6 was associated with NPVs of 71% and 89% and PPVs of 94% and 89%, respectively. Sensitivity analysis with the high-dose group (75 and 150 mg) results confirmed these findings.

CONCLUSIONS: Early clinical responses (and nonresponse) may help predict later clinical responses in patients treated with ixekizumab.