Dataset Information

Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3).

ABSTRACT: Patients with psoriasis who have an inadequate response to one biologic may benefit from switching to a new biologic, such as ixekizumab, a high affinity monoclonal antibody that selectively targets interleukin (IL)-17A.Our aim was to assess the response to ixekizumab in patients with moderate-to-severe plaque psoriasis who did not respond adequately to etanercept using a post-hoc analysis in two phase III studies.For the subanalyses in two phase III trials (UNCOVER-2 and -3), non-response was defined by either failure to have a static physician global assessment (sPGA) of 0/1 in UNCOVER-2 or failure to have at least 75% improvement in psoriasis area and severity index (PASI 75) in UNCOVER-3 at Week 12 of each study. Non-responders treated with twice-weekly etanercept 50 mg in the first 12 weeks received two injections of placebo at Week 12 (4-week wash-out period), followed by ixekizumab every 4 weeks (Q4W) for Weeks 16-60. Non-responders to placebo in the first 12 weeks were administered ixekizumab 160 mg at Week 12, followed by ixekizumab Q4W for Weeks 16-60.After switching to ixekizumab Q4W, a substantial proportion of patients with moderate-to-severe psoriasis who did not respond to etanercept experienced rapid and durable improvement in all efficacy evaluations. Among sPGA 0/1 (UNCOVER-2) and PASI 75 (UNCOVER-3) non-responders to etanercept, 73.0% achieved sPGA 0/1 and 78.2% achieved PASI 75, respectively, after 12 weeks of ixekizumab treatment. Safety profiles in patients switched from etanercept to ixekizumab were similar to those in patients switched from placebo to ixekizumab.Patients who were non-responders to etanercept after 12 weeks, as defined by failure to meet sPGA 0/1 (UNCOVER-2) or PASI 75 (UNCOVER-3), achieved high levels of response 12 weeks after switching to ixekizumab. Studies are registered with ClinicalTrials.gov (NCT01597245 and NCT01646177).

SUBMITTER: Blauvelt A

PROVIDER: S-EPMC5884910 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3).

Blauvelt Andrew A Papp Kim A KA Griffiths Christopher E M CEM Puig Luis L Weisman Jamie J Dutronc Yves Y Kerr Lisa Farmer LF Ilo Dapo D Mallbris Lotus L Augustin Matthias M

American journal of clinical dermatology 20170401 2

<h4>Background</h4>Patients with psoriasis who have an inadequate response to one biologic may benefit from switching to a new biologic, such as ixekizumab, a high affinity monoclonal antibody that selectively targets interleukin (IL)-17A.<h4>Objective</h4>Our aim was to assess the response to ixekizumab in patients with moderate-to-severe plaque psoriasis who did not respond adequately to etanercept using a post-hoc analysis in two phase III studies.<h4>Methods</h4>For the subanalyses in two ph ...[more]

PMID: 28074446

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Project description:BackgroundChronic psoriasis may require medication adjustments over time.ObjectivesTo evaluate the efficacy/safety of tildrakizumab in subgroups from the reSURFACE studies (N = 1862) that received continuous dosing, higher/lower dosing, treatment interruption/reinitiation and initiation.MethodsResponders [Psoriasis Area and Severity Index (PASI) ≥ 75%] and partial responders (PASI ≥ 50% to < 75%) in Part 3 of the reSURFACE studies (weeks 28-52 or week 64) who received tildrakizumab 200 mg or 100 mg were rerandomized to the same dosage (T100/T100 or T200/T200), a higher/lower dosage (T100/T200 or T200/T100) or placebo (PBO) (T100/PBO or T200/PBO). Patients receiving PBO who relapsed were reinitiated to tildrakizumab. Etanercept (ETN) week-28 partial responders and nonresponders (PASI < 50%) received tildrakizumab 200 mg (ETN/T200).ResultsAmong T100/T100 and T200/T200 week-28 partial responders, the proportion of patients who achieved as-observed PASI 75 responses increased over time. Among T100/T200 week-28 partial responders, PASI 75 responses increased from week 32 (38·5%) to week 52 (63·2%) and remained consistent in T200/T100 week-28 responders. Among patients who relapsed in the T100/PBO and T200/PBO groups, 86% and 83% of those who reinitiated tildrakizumab achieved PASI 75 by week 64, respectively. Among ETN/T200 week-28 partial responders, PASI 75 responses (nonresponder imputation) increased from week 32 (24·1%) to week 52 (74·7%). PASI 90, PASI 100 and Physician's Global Assessment responses were consistent with PASI 75 results. Treatment was well tolerated.ConclusionsPatients generally fared well with tildrakizumab maintenance, reinitiation, dose adjustment or initiation. What's already known about this topic? Tildrakizumab demonstrated significant efficacy vs. placebo with a positive safety profile during the first 28 weeks of treatment in two randomized double-blind trials. What does this study add? Treatment scenarios with tildrakizumab, such as long-term continuous dosing (up to 64 weeks), treatment interruption/reinitiation and switching from another biologic, can be part of the management of plaque psoriasis with a reasonable expectation of efficacy and tolerability.

Project description:BACKGROUND:Plaque psoriasis affects children and adults, but treatment options for paediatric psoriasis are limited. OBJECTIVES:To evaluate the efficacy and safety of ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, for moderate-to-severe paediatric psoriasis. METHODS:In a randomized, double-blind, placebo-controlled, phase III study (IXORA-PEDS), patients aged 6 to < 18 years with moderate-to-severe plaque psoriasis were randomized 2 : 1 to weight-based dosing of IXE every 4 weeks (IXE Q4W, n = 115) or placebo (n = 56) through week 12, followed by open-label IXE Q4W. Coprimary endpoints were the proportions of patients at week 12 achieving ? 75% improvement in Psoriasis Area and Severity Index (PASI 75) and those achieving a static Physician's Global Assessment score of 0 or 1 (sPGA 0,1). RESULTS:IXE was superior (P < 0·001) to placebo for both coprimary endpoints of PASI 75 (IXE Q4W, 89%; placebo, 25%) and sPGA (0,1) (IXE Q4W, 81%; placebo, 11%). IXE was also superior for all gated secondary endpoints, including PASI 75 and sPGA (0,1) at week 4, improvement in itch, and complete skin clearance. IXE Q4W provided significant (P < 0·001) improvements vs. placebo in quality of life and clearance of scalp and genital psoriasis. Responses at week 12 were sustained or further improved through week 48. Through week 12, 45% (placebo) and 56% (IXE) of patients reported treatment-emergent adverse events. One serious adverse event was reported (IXE), one patient discontinued due to an adverse event (placebo) and no deaths were reported. CONCLUSIONS:IXE was superior to placebo in the treatment of moderate-to-severe paediatric psoriasis, and the safety profile was generally consistent with that observed in adults. What is already known about this topic? Paediatric psoriasis affects approximately 1% of children and can negatively impact health-related quality of life. Treatment options for paediatric psoriasis are typically limited to off-label treatments and approved systemic biologics. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for moderate-to-severe plaque psoriasis in adults and was recently approved by the US Food and Drug Administration for moderate-to-severe paediatric psoriasis. What does this study add? Ixekizumab resulted in rapid and statistically significant improvements over placebo in skin involvement, itch and health-related quality of life, which persisted through 48 weeks of treatment in paediatric patients with moderate-to-severe plaque psoriasis. The safety profile of ixekizumab was generally consistent with that seen in adults. Ixekizumab may be an additional potential therapeutic option and an additional class of biologic therapy (interleukin-17A antagonist) for the treatment of moderate-to-severe paediatric psoriasis. Plain language summary available online.

Project description:IntroductionPsoriasis, an incurable chronic inflammatory disease, affects over 6 million people in China. Ixekizumab, a monoclonal antibody against interleukin-17A, has demonstrated efficacy and safety for the treatment of moderate-to-severe plaque psoriasis, although limited data are available regarding its use in routine clinical practice in China. We investigated the real-world application of ixekizumab in China.MethodsAdults (≥ 18 years) with moderate-to-severe plaque psoriasis prescribed ixekizumab in routine clinical practice were enrolled in this prospective, observational, single-arm, multicenter, post-marketing surveillance study. The primary endpoint was the safety of ixekizumab at week 12. The effectiveness of ixekizumab, based on the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), was assessed as a secondary endpoint.ResultsIn total, 666 patients were enrolled; 663 were included in the safety analysis, and 612 in the effectiveness analysis. At least one adverse event (AE) was reported by 42.7% (283/663) of patients, most of which were mild (242/283, 85.5%), and 32.7% (217/663) of patients reported AEs related to study treatment. The most frequently reported AEs were injection site reactions. AEs led to discontinuation in five patients (0.8%). Only three patients had a serious AE. Mean ± standard deviation (SD) change from baseline in PASI score was reduction in 10.79 ± 9.55 at week 2 and 16.80 ± 12.15 at week 12. At week 2, 63.7% of patients achieved PASI 50. At week 12, 93.2%, 77.4%, and 45.1% of patients achieved PASI 75, PASI 90, and PASI 100, respectively. Mean ± SD change from baseline in DLQI was reduction in 5.91 ± 6.27 at week 2 and 9.76 ± 7.16 at week 12. DLQI 0/1 was achieved by 19.8% and 59.9% of patients at week 2 and 12, respectively.ConclusionIxekizumab was well tolerated and effective in real-world clinical practice in Chinese adults with moderate-to-severe plaque psoriasis.

Dataset Information

Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3).

Publications

Efficacy and Safety of Switching to Ixekizumab in Etanercept Non-Responders: A Subanalysis from Two Phase III Randomized Clinical Trials in Moderate-to-Severe Plaque Psoriasis (UNCOVER-2 and -3).

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