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. What's already known about this topic? There are no established biomarkers or other measures for reliably predicting response to psoriasis therapy. What does this study add? This study sets a framework for identification of a measure, early treatment response, that is reliably predictive of longer-term treatment response with a novel therapeutic agent, ixekizumab, for psoriasis. Once confirmed in larger studies, this may have important implications for ixekizumab use in clinical practice. See also the Commentary by Strober