Early Onset of Clinical Improvement with Ixekizumab in a Randomized, Open-label Study of Patients with Moderate-to-severe Plaque Psoriasis

Abstract

Objective: The purpose of this study was to evaluate the speed of onset of clinical response to ixekizumab (IXE) and assess the progression of visible improvement in patients with moderate-to-severe plaque psoriasis. Design: This was an interventional, randomized, open-label, Phase IIIb clinical trial. Setting: This was a single center study at the Mount Sinai School of Medicine. Participants: Twelve patients were randomized at a ratio of 1:1 to receive 80mg of ixekizumab every two (IXE Q2W) or four (IXE Q4W) weeks following a starting dose of 160mg of ixekizumab. After Week 12, all patients received 80mg IXE Q4W through Week 44. Measurements: Clinical response was measured using the Patient's Global Assessment (PatGA), the Psoriasis Area and Severity Index (PASI), the static Physician's Global Assessment (sPGA), and the Itch Numeric Rating Scale (Itch NRS). Sequential patient photographs were taken at regular intervals during the study to evaluate visible improvement in plaque psoriasis. Results: The median time to an improvement of at least 1 point or 2 points from baseline in PatGA score was 5.0 and 10.0 days for patients randomized to IXE Q2W and 6.0 and 13.5 days for patients randomized to IXE Q4W. All patients achieved at least a 50- or 75-percent improvement in PASI from baseline by Weeks 2 and 4, respectively. At least half of the patients achieved at least a 4-point improvement from baseline in Itch NRS by Day 14. Improvement in disease was visibly evident within one week of treatment in patient photographs. Conclusion: Ixekizumab results in a rapid and visible improvement in plaque psoriasis in as early as one week of treatment.

Keywords: Phase IIIb; Plaque psoriasis; early onset; ixekizumab; photographs; randomized.

Conflict of interest statement

FUNDING:Funding provided by Eli Lilly and Company. DISCLOSURES:Dr. Khattri has received grant/research support from and is an investigator for Eli Lilly and Company. Dr. Lebwohl is an employee of Mount Sinai, which receives research funds from AbGenomics, Amgen, Anacor, Boehringer Ingelheim, Celgene, Ferndale, Janssen Biotech, Kadmon, LEO Pharma, Eli Lilly and Company, Medimmune, Novartis, Pfizer, Sun Pharma, and Valeant. Dr. Goldblum, Ms. Solotkin, Ms. Ridenour, and Dr. Yang own stock and are employees of Eli Lilly and Company. Dr. Amir and Dr. Min have no conflicts of interest relevant to the content of this article.

Figures

FIGURE 1.

Rapid onset of clinical response to ixekizumab—Response rates are presented as the percentage of patients achieving the indicated treatment outcomes at each visit. PASI 50 (blue circles), PASI 75 (red squares), PASI 90 (purple triangles), PASI 100 (inverted green triangles, dotted line), sPGA 0/1 (orange diamonds), and sPGA 0 (open black squares) response rates are shown for patients receiving A) 80mg IXE Q2W/Q4W (N=6) or B) 80mg IXE Q4W/Q4W (N=6) treatment regimens; C) Response rates for patients achieving an itch NRS improvement of at least 4 points from baseline (for patients with a baseline score of ≥4) are shown for both the IXE Q2W/Q4W (N=6, blue circles) and IXE Q4W/Q4W (N=5, red squares) treatment regimens. Because of a decreased frequency of patient visits between Weeks 12 and 48, the x-axis scale is condensed after Week 12. Missing values were imputed as nonresponse. All patients achieved PASI 50 and 75 by Weeks 2 and 4, respectively. IXE: ixekizumab; NRS: numeric rating scale; PASI: Psoriasis Area and Severity Index; Q2W: every 2 weeks; Q2W/Q4W, 80mg IXE Q2W during the induction dosing period and Q4W during the maintenance dosing period; Q4W: every 4 weeks; Q4W/Q4W, 80mg IXE Q4W during both the induction and maintenance dosing periods; sPGA: static Physician’s Global Assessment

FIGURE 2.

Visible clearance of psoriatic plaques over 48 weeks of treatment with IXE Q2W/Q4W—A 37-year-old man, with baseline PASI score of 32.5 and baseline BSA of 58%, achieved PASI 75 at Week 4 and PASI 90 at Week 12, which was maintained through Week 48. BSA: body surface area; IXE: ixekizumab; PASI: Psoriasis Area and Severity Index; Q2W: every two weeks; Q2W/Q4W, 80mg IXE Q2W during the induction dosing period and Q4W during the maintenance dosing period; Q4W: every four weeks

FIGURE 3.

Visible clearance of psoriatic plaques over 48 weeks of treatment with IXE Q2W/Q4W—A 40-year-old man with a baseline PASI score of 13 and a 10% BSA achieved PASI 75 at Week 3, PASI 90 at Week 4, and PASI 100 at Week 8, which was maintained through Week 48. BSA: body surface area; IXE: ixekizumab; PASI: Psoriasis Area and Severity Index; Q2W: every 2 weeks; Q2W/Q4W, 80mg IXE Q2W during the induction dosing period and Q4W during the maintenance dosing period; Q4W: every 4 weeks

FIGURE 4.

Visible clearance of psoriatic plaques over 48 weeks of treatment with IXE Q2W/Q4W—A 27-year-old woman with baseline PASI score of 19.2 and 12-percent BSA. Patient achieved PASI 75 at Week 4 and PASI 90 at Week 36, which was maintained through Week 48. BSA: body surface area; IXE: ixekizumab; PASI: Psoriasis Area and Severity Index; Q2W: every two weeks; Q2W/Q4W, 80mg IXE Q2W during the induction dosing period and Q4W during the maintenance dosing period; Q4W: every four weeks