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Andrew Blauvelt - One of the best experts on this subject based on the ideXlab platform.
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a head to head comparison of Ixekizumab vs guselkumab in patients with moderate to severe plaque psoriasis 12 week efficacy safety and speed of response from a randomized double blinded trial
British Journal of Dermatology, 2020Co-Authors: Alice B. Gottlieb, Laura K Ferris, R G Langley, Andrew Blauvelt, K A Papp, A Jarell, K Reich, Catherine Maari, Kenneth B Gordon, Yayoi TadaAbstract:BACKGROUND Patients with psoriasis value rapid and complete skin clearance. No head-to-head studies have focused on early responses to interleukin (IL)-17 vs. IL-23 inhibitors. OBJECTIVES To compare early and complete skin clearance by the IL-17A inhibitor Ixekizumab vs. the IL-23p19 inhibitor guselkumab. METHODS IXORA-R, a 24-week, randomized, double-blinded study, enrolled adults with moderate-to-severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous Ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran-Mantel-Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported. RESULTS In total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met [215/520 Ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001]. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified. CONCLUSIONS Ixekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate-to-severe plaque psoriasis by week 12. Adverse events were similar to previous Ixekizumab and guselkumab studies. Compared with the IL-23 inhibitor guselkumab, Ixekizumab can offer complete skin clearance more rapidly to patients with moderate-to-severe plaque psoriasis. What's already known about this topic? Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long-term efficacy, safety and durability of response. Clinical trial data and systematic reviews have suggested that IL-17 inhibitors can improve a patient's psoriasis more rapidly than IL-23 inhibitors. What does this study add? The head-to-head study design directly compares the efficacy and speed of response of Ixekizumab and the IL-23 inhibitor guselkumab in moderate-to-severe plaque psoriasis. The primary end point was met, showing superiority of Ixekizumab over guselkumab for achieving complete skin clearance at week 12. The safety profile of Ixekizumab was consistent with previous studies. Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab.
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Comparison of Real-World Treatment Patterns Among Psoriasis Patients Treated with Ixekizumab or Adalimumab.
Patient preference and adherence, 2020Co-Authors: Andrew Blauvelt, Orin Goldblum, Chen-yen Lin, Baojin Zhu, Russel Burge, Mwangi J. Murage, Nianwen Shi, William N. Malatestinic, Carolyn R. Lew, Nicole M. ZimmermanAbstract:Background There is lack of real-world treatment pattern comparison data between Ixekizumab and adalimumab which are approved for the treatment of moderate-to-severe plaque psoriasis. Objective To compare real-world treatment patterns among psoriasis patients initiating Ixekizumab or adalimumab in the United States. Methods Psoriasis patients with ≥1 claim for Ixekizumab or adalimumab between March 1, 2016, and May 31, 2018, were identified (index date = date of first Ixekizumab or adalimumab claim) from the IBM Watson Health MarketScan® databases. Patients were required to be continuously enrolled for ≥12 months before the index date and followed for a minimum of 6 months until inpatient death, enrollment end, or study end, whichever occurred first. Treatment persistence, adherence, discontinuation, restart, and switching were analyzed. Inverse probability of treatment weighting and multivariable regression modeling were employed to address cohort imbalances and estimate the adjusted risk of non-persistence, discontinuation, and switching, and the odds of adherence. Results A total of 646 Ixekizumab and 3668 adalimumab users were included and followed for a mean of 14.0 and 16.5 months, respectively. Compared to adalimumab, Ixekizumab was associated with 19% lower risk of non-persistence (hazard ratio [HR]=0.81, 95% confidence interval [CI]: 0.69-0.95), 26% lower risk of discontinuation (HR=0.74, 95% CI: 0.62-0.88), and 28% lower risk of switching (HR=0.72, 95% CI: 0.57-0.91). Ixekizumab users had higher odds of medication possession ratio ≥80% (odds ratio [OR]=1.36, 95% CI: 1.10-1.69) but similar odds by proportion of days covered ≥80% (OR=1.22, 95% CI: 0.98-1.53). Conclusion Psoriasis patients treated with Ixekizumab demonstrated longer persistency, higher adherence and were less likely to discontinue or switch treatment compared to adalimumab users. However, while patients achieving highly adherent threshold significantly differed by MPR ≥80%, it did not by PDC ≥80%; hence, further analysis using fixed-length follow-up is required.
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safety of Ixekizumab treatment for up to 5 years in adult patients with moderate to severe psoriasis results from greater than 17 000 patient years of exposure
Dermatologic Therapy, 2020Co-Authors: April W Armstrong, C. Paul, Christopher E M Griffiths, Luis Puig, Kim Papp, Wolfhenning Boehncke, Michael R Freeman, Hideshi Torii, Andrew BlauveltAbstract:Long-term safety data are critical for evaluating therapies for psoriasis. Ixekizumab has demonstrated efficacy and is well tolerated for the treatment of moderate-to-severe plaque psoriasis. We examined the safety and tolerability of up to 5 years of Ixekizumab therapy in patients with psoriasis. Integrated safety data were analyzed from 13 Ixekizumab clinical studies. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for the 12-week induction period in the combined pivotal studies, and for all pooled studies by year(s) of therapy and overall, reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (p-y) and/or frequencies. Total Ixekizumab exposure was 17,003.4 p-y (N = 5898); 2749 patients had ≥ 4 years of exposure. When compared across years of exposure, rates for AEs remained largely stable or declined, including TEAEs leading to discontinuation (3.8/100 p-y in year 1, declining to 2.0/100 p-y in year 5); SAEs (range 6.2–7.0/100 p-y); serious infections (range 1.3–1.7/100 p-y); nonmelanoma skin cancer (ranging from 0.5/100 p-y in year 1 to 0.2/100 p-y in years 4–5); other malignancies (range 0.4–0.6/100 p-y); inflammatory bowel disease including ulcerative colitis and Crohn’s disease (IR 0.2/100 p-y); and major adverse cardiovascular events (MACE) (range 0.3–0.7/100 p-y). Candidiasis was reported in 327 patients (IR 1.9/100 p-y), with the majority identified as mucocutaneous. The rate of injection site reactions was 15.5/100 p-y during year 1 and 2.0–2.3/100 p-y by years 3–5. The decrease in rates of TEAEs and the stable rates of SAEs, other malignancies and MACE during up to 5 years of Ixekizumab dosing are consistent with previous reports describing a favorable safety profile of Ixekizumab following shorter durations of exposure. Eli Lilly and Company.
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Comparison of real-world treatment patterns among patients with psoriasis prescribed Ixekizumab or secukinumab
Journal of the American Academy of Dermatology, 2019Co-Authors: Andrew Blauvelt, Orin Goldblum, Chen-yen Lin, Baojin Zhu, Russel Burge, Mwangi J. Murage, Nianwen Shi, William N. Malatestinic, Carolyn R. Lew, Nicole M. ZimmermanAbstract:Background Real-world data on treatment patterns associated with use of interleukin-17A inhibitors in psoriasis are lacking. Objective To compare treatment patterns between Ixekizumab or secukinumab users in clinical practice. Methods A retrospective cohort study included patients with psoriasis aged ≥18 years treated with Ixekizumab or secukinumab between March 1, 2016, and May 31, 2018 in IBM MarketScan (IBM Corp, Armonk, NY) databases. Inverse probability of treatment weighting and multivariable models were used to address cohort imbalances and estimate the risks of nonpersistence (60-day gap), discontinuation (≥90-day gap), switching, and the odds of adherence. Results The study monitored 645 Ixekizumab users for 13.7 months and 1152 secukinumab users for 16.3 months. Ixekizumab users showed higher persistence rate (54.8% vs 45.1%, P Limitations Disease severity and clinical outcomes were unavailable. Conclusion Ixekizumab users demonstrated longer drug persistence, lower discontinuation rate and risk of discontinuation, higher likelihood of adherence, and similar risk of switching compared with secukinumab users in clinical practices.
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efficacy and safety of Ixekizumab in a randomized double blinded placebo controlled phase iiib study of patients with moderate to severe genital psoriasis
British Journal of Dermatology, 2018Co-Authors: Caitriona Ryan, Alan Menter, Robert Bissonnette, Lyn Guenther, Gil Yosipovitch, Andrew Blauvelt, K A P Meeuwis, John Sullivan, Jennifer Clay Cather, A B GottliebAbstract:BACKGROUND Genital psoriasis (GenPs) is a common, debilitating and difficult-to-treat manifestation of plaque psoriasis. However, few controlled, interventional studies of GenPs exist. OBJECTIVES To determine the efficacy of Ixekizumab vs. placebo in patients with moderate-to-severe GenPs with ≥ 1% involved body surface area (BSA). METHODS Patients with moderate-to-severe GenPs, defined as a baseline static Physician's Global Assessment of Genitalia (sPGA-G) score of ≥ 3, with BSA ≥ 1% were randomized 1 : 1 to receive placebo (n = 74) or the recommended dosing of Ixekizumab (n = 75). Major outcomes included the percentage of patients achieving 0 or 1 scores on the sPGA-G (primary end point), overall sPGA, GenPs Sexual Frequency Questionnaire (GenPs-SFQ) item 2, and ≥ 3-point improvement from baseline on the GenPs itch numerical rating scale. RESULTS At week 12, Ixekizumab was superior to placebo for sPGA-G 0/1 (73% vs. 8%, P < 0·001), overall sPGA 0/1 (73% vs. 3%, P < 0·001), GenPs-SFQ item 2 score of 0 or 1 (78% vs. 21%, P < 0·001) and genital itch (60% vs. 8%, P < 0·001). No candidiasis was reported, no deaths occurred and one (1%) serious adverse event was reported in a patient receiving placebo. CONCLUSIONS Ixekizumab was superior to placebo for the treatment of moderate-to-severe GenPs with BSA ≥ 1%. The safety profile of Ixekizumab was consistent with previous studies in moderate-to-severe plaque psoriasis.
Kristian Reich - One of the best experts on this subject based on the ideXlab platform.
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Ixekizumab provides superior efficacy compared with ustekinumab over 52 weeks of treatment results from ixora s a phase 3 study
Journal of The American Academy of Dermatology, 2019Co-Authors: C. Paul, Christopher E M Griffiths, Yves Dutronc, Lluís Puig, Kristin Hollister, Peter C.m. Van De Kerkhof, Carsten Henneges, Martin Dossenbach, Kristian ReichAbstract:Background Biologics targeting interleukin 17A (IL-17A) allow for rapid clearance of psoriatic plaques, with a clinically favorable safety profile. Objectives To compare the safety and efficacy of Ixekizumab, an IL-17A antagonist, with the safety and efficacy of the IL-12/23 inhibitor ustekinumab through 52 weeks of treatment in the head-to-head trial IXORA-S. Methods Patients were randomized to Ixekizumab (n = 136) or ustekinumab (n = 166) and dosed per the approved labels. After 1 year, efficacy was assessed via improvements in Psoriasis Area and Severity Index (PASI) score (with PASI 90 indicating a 90% or greater improvement from baseline PASI score) and a static Physician's Global Assessment (sPGA) response of either 0 or 0 or 1, with dropouts counted as nonresponders. Safety analyses included treatment-emergent adverse events (AEs). Results At week 52, significantly more Ixekizumab-treated patients (P Limitations This study was not designed to compare safety end points related to rare events. Conclusions Compared with ustekinumab, Ixekizumab showed superior efficacy and comparable safety outcomes through 52 weeks of treatment.
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Ixekizumab Pharmacokinetics, Anti-Drug Antibodies, and Efficacy through 60 Weeks of Treatment of Moderate to Severe Plaque Psoriasis
The Journal of investigative dermatology, 2018Co-Authors: Kristian Reich, Lisa Kerr, Susan Ball, Kimberley Jackson, Sandra Garces, Laiyi Chua, Talia M. Muram, Andrew BlauveltAbstract:Ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, is efficacious for moderate to severe plaque psoriasis. We examined relationships between serum Ixekizumab concentrations, treatment-emergent anti-drug antibodies (TE-ADAs), and efficacy during 60 weeks of treatment in a randomized, controlled, phase 3 study. Steady-state Ixekizumab serum trough concentrations were rapidly achieved and associated with high clinical responses at week 12 with a starting dose of 160 mg followed by 80 mg every 2 weeks. During the long-term extension period dosage of 80 mg every 4 weeks, stable serum trough concentrations maintained high clinical responses through week 60. Most (82.6%, 308/373) patients never developed TE-ADA. In TE-ADA–positive patients (17.4%, n = 65), variations in ADA titers, neutralizing capacity, and persistence were observed. Fifty-six patients (15%) developed low or moderate maximum titers, with serum concentrations and efficacy comparable to those of TE-ADA–negative patients. Nine patients (2.4%) developed high titers, with variable individual clinical responses; four of these nine patients achieved at least PASI 75 at week 60. Median serum concentrations in the TE-ADA-high titer group were generally comparable to the median serum concentrations in the lower titer groups. For most patients, TE-ADA had a negligible impact on Ixekizumab serum concentrations and efficacy. Clinicaltrials.gov: NCT01646177
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Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site Reactions from 11 Clinical Trials.
Journal of drugs in dermatology : JDD, 2018Co-Authors: Kristian Reich, Craig L Leonardi, Mamitaro Ohtsuki, Melinda Gooderham, Andrew Blauvelt, Neil H. Shear, Carle Paul, Beth Pangallo, Susan BallAbstract:BACKGROUND: Injection-site reactions (ISRs) are reported with biologic therapies. The objective of this study was to comprehensively characterize ISRs among moderate-to-severe psoriasis patients treated with Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A. METHODS: ISRs are presented from UNCOVER-1, UNCOVER-2, and UNCOVER-3 (12 weeks) and all Ixekizumab-exposed patients in 11 controlled and uncontrolled trials (156 weeks). RESULTS: At week 12, reported ISR frequency with 80 mg Ixekizumab every 2 weeks (IXE Q2W, 16.8%) was comparable with etanercept twice weekly (16.4%); both were significantly higher than placebo (3.3%). With IXE Q2W, ISRs were mild (12.3%), moderate (3.9%), or severe (0.7%), typically reported in the first 2 weeks (median onset, 6.6 days), and most commonly characterized as nonspecified, erythema, and pain. Generally, erythema onset was delayed, whereas pain occurred around drug administration. Discontinuation from Ixekizumab due to ISRs (0.4%) occurred in the first 12 weeks. After 2 weeks, ISR frequency decreased and remained stable (≤4.2%) through week 156. No ISR-related serious adverse events were reported in Ixekizumab-treated patients. ISR data were solicited if patients reported injection-associated events. Since nonspecified ISR was the most commonly reported term, specific types might be underreported. CONCLUSIONS: ISRs have been reported with Ixekizumab during clinical trials. These reactions are typically tolerable, manageable, and decrease over time. Clinicaltrials.gov: NCT01474512 (UNCOVER-1); NCT01597245 (UNCOVER-2); NCT01646177 (UNCOVER-3); NCT01777191 (UNCOVER-A); NCT01624233 (UNCOVER-J); NCT01107457 (I1F-MC-RHAJ); NCT02561806 (I1F-MC-RHBS); NCT02387801 (I1F-US-RHBO);NCT02513550 (I1F-MC-RHBP); NCT02634801 (I1F-EW-RHBZ) J Drugs Dermatol. 2018;17(2):200-206. THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS. .
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efficacy and safety of Ixekizumab for the treatment of moderate to severe plaque psoriasis results through 108 weeks of a randomized controlled phase 3 clinical trial uncover 3
Journal of The American Academy of Dermatology, 2017Co-Authors: Andrew Blauvelt, L. Zhang, Melinda Gooderham, Lars Iversen, Susan Ball, Noah Agada, Kristian ReichAbstract:Background Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin 17A, is efficacious in treating moderate-to-severe plaque psoriasis through 60 weeks. Objective To evaluate the efficacy and safety of Ixekizumab through 108 weeks of treatment in UNCOVER-3. Methods Patients (N = 1346) were randomized 2:2:2:1 to 80 mg Ixekizumab every 2 or 4 weeks, 50 mg etanercept twice weekly, or placebo. At week 12, patients switched to Ixekizumab every 4 weeks during a long-term extension (LTE) period. Efficacy data were summarized using as-observed, multiple imputation (MI), and modified MI (mMI) methods. Results For patients (N = 385) receiving the recommended dose (Ixekizumab every 2 weeks on weeks 0-12 and every 4 weeks during LTE), the 108-week as-observed, MI, and mMI response rates were 93.4%, 88.3%, and 83.6%, respectively, for patients achieving ≥75% improvement from baseline in the Psoriasis Area and Severity Index, and the 108-week as-observed, MI, and mMI response rates were 82.6%, 78.3%, and 74.1%, respectively, for patients with a static Physician's Global Assessment score of 0 or 1. During LTE, 1077 (84.5%) patients reported ≥1 treatment-emergent adverse event, and 85% were mild or moderate in severity. Discontinuation because of adverse events occurred in 6.4% of patients. Limitations There was no comparison treatment group after week 12. Conclusion Ixekizumab is well tolerated and demonstrates persistent efficacy through 108 weeks.
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efficacy of Ixekizumab compared to etanercept and placebo in patients with moderate to severe plaque psoriasis and non pustular palmoplantar involvement results from three phase 3 trials uncover 1 uncover 2 and uncover 3
Journal of The European Academy of Dermatology and Venereology, 2017Co-Authors: Alan Menter, Yukari Okubo, Joseph F. Merola, David Shrom, R B Warren, R G Langley, L N Kerr, Ellen B Dennehy, David Amato, Kristian ReichAbstract:Background Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat. Objective To evaluate the efficacy of Ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis and moderate-to-severe non-pustular palmoplantar involvement. Methods In three phase 3, double-blind, placebo-controlled trials, patients with moderate-to-severe non-pustular plaque psoriasis [UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224), UNCOVER-3 (N = 1346)] were randomized to subcutaneous 80 mg Ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160-mg starting dose, or placebo through week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg etanercept biweekly. Patients entering the open-label long-term extension (UNCOVER-3) received Ixekizumab Q4W weeks 12–60. Moderate-to-severe palmoplantar involvement was defined as Palmoplantar Psoriasis Area and Severity Index (PPASI) ≥8. Results Twenty-eight percent of UNCOVER-1, UNCOVER-2 and UNCOVER-3 patients had baseline palmoplantar involvement (PPASI ≥0, n = 1092) and 9.1% (n = 350) had moderate-to-severe involvement, with mean baseline PPASI ~20, PASI ~24, and most (>60%) had static Physician's Global Assessment ≥4. Higher percentages of patients treated with Ixekizumab vs. placebo or etanercept achieved PPASI 50 (approximately 80% vs. 32.9%, 67.8%; Ixekizumab, placebo, etanercept, respectively) and PPASI 75 (approximately 70% vs. 18.8%, 44.1%; Ixekizumab, placebo, etanercept, respectively) at week 12 (all P < 0.05). PPASI 100 was achieved by higher percentages of Ixekizumab-treated patients vs. placebo (approximately 50% vs. 8.2%, P < 0.001) and Ixekizumab Q2W-treated patients vs. etanercept (51.8% vs. 32.2%, P < 0.05). Outcomes were maintained or improved in patients continuing on Ixekizumab Q4W through week 60. Differences between Ixekizumab and placebo or etanercept were statistically significant as early as week 1. Conclusion In a subpopulation analysis of patients from phase 3 trials with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis, Ixekizumab treatment resulted in greater and more rapid improvements than placebo and etanercept at week 12; improvements were sustained with continued treatment.
Lisa Kerr - One of the best experts on this subject based on the ideXlab platform.
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withdrawing Ixekizumab in patients with psoriatic arthritis who achieved minimal disease activity results from a randomized double blind withdrawal study
Arthritis & Rheumatism, 2021Co-Authors: Laura C Coates, Lisa Kerr, Masato Okada, Sreekumar G Pillai, Hasan Tahir, Ivo Valter, Vinod Chandran, Hideto Kameda, Denise Alves, So Young ParkAbstract:OBJECTIVE To evaluate the effect of withdrawing Ixekizumab in patients with psoriatic arthritis (PsA) who had achieved minimal disease activity (MDA) after open-label Ixekizumab treatment. METHODS SPIRIT-P3 was a multicenter, randomized, double-blind withdrawal study that enrolled biologic-naive adult patients with PsA to open-label Ixekizumab (160 mg at week 0, 80 mg every two weeks [IXE Q2W]) for 36 weeks. Patients sustaining MDA for >3 consecutive months were randomized (between weeks 36-64) 1:1 to blinded IXE Q2W withdrawal (placebo) or continued IXE Q2W treatment up to week 104. The primary efficacy endpoint was time to relapse (loss of MDA) for randomized patients. Patients who relapsed were retreated with IXE Q2W until week 104. RESULTS A total of 394 patients were enrolled and received open-label IXE Q2W. Of those, 158 (40%) patients achieved sustained MDA and were randomized to IXE Q2W withdrawal (placebo; N=79) or continued IXE Q2W treatment (N=79). Patients relapsed more rapidly with treatment withdrawal (median 22.3 weeks [95% CI 16.1-28.3]) vs continued IXE Q2W treatment (median not estimable, p<0.0001); 67 (85%) patients vs 30 (38%) patients relapsed, respectively. Median time to re-achieving MDA on retreatment was 4.1 weeks (95% CI 4.1-4.3); 64 (96%) of 67 patients who relapsed with treatment withdrawal re-achieved MDA on retreatment. Safety was consistent with the known safety profile for Ixekizumab. CONCLUSION Continued Ixekizumab therapy is superior to Ixekizumab withdrawal in maintaining low disease activity in biologic-naive patients with PsA. Retreatment with Ixekizumab following relapse may restore disease control in case of treatment interruption.
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withdrawing Ixekizumab in patients with psoriatic arthritis who achieved minimal disease activity results from a randomized double blind withdrawal study
Arthritis & Rheumatism, 2021Co-Authors: Laura C Coates, Lisa Kerr, Masato Okada, Sreekumar G Pillai, Hasan Tahir, Ivo Valter, Vinod Chandran, Hideto Kameda, Denise Alves, So Young ParkAbstract:OBJECTIVE To evaluate the effect of withdrawing Ixekizumab in patients with psoriatic arthritis (PsA) in whom minimal disease activity (MDA) has been achieved after open-label Ixekizumab treatment. METHODS SPIRIT-P3 was a multicenter, randomized, double-blind withdrawal study of biologic treatment-naive adult patients with PsA who were treated with open-label Ixekizumab for 36 weeks (160 mg at week 0, then 80 mg every 2 weeks). Patients in whom MDA was sustained for >3 consecutive months were randomized 1:1, between weeks 36 and 64, to undergo blinded withdrawal of Ixekizumab treatment (placebo) or to continue Ixekizumab treatment every 2 weeks up to week 104. The primary efficacy end point was time to relapse (loss of MDA) for randomized patients. Patients who experienced a relapse were re-treated with Ixekizumab every 2 weeks up to week 104. RESULTS A total of 394 patients were enrolled and received open-label Ixekizumab every 2 weeks. Of those patients, 158 (40%) achieved sustained MDA and were randomized to undergo withdrawal of Ixekizumab treatment (placebo every 2 weeks; n = 79) or to continue Ixekizumab treatment every 2 weeks (n = 79). Disease relapse occurred more rapidly with treatment withdrawal (median 22.3 weeks [95% confidence interval (95% CI) 16.1-28.3]) compared to those who continued treatment with Ixekizumab (median not estimable; P < 0.0001). Sixty-seven patients (85%) compared to 30 patients (38%) experienced relapse in the placebo group and the continued treatment group, respectively. Median time to achieving MDA again with re-treatment was 4.1 weeks (95% CI 4.1-4.3); in 64 of 67 patients (96%) who experienced relapse with treatment withdrawal, MDA was achieved again with re-treatment. Safety was consistent with the known safety profile for Ixekizumab. CONCLUSION Continued Ixekizumab therapy is superior to Ixekizumab withdrawal in maintaining low disease activity in biologic treatment-naive patients with PsA. Re-treatment with Ixekizumab following a relapse may restore disease control in cases of treatment interruption.
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safety and efficacy of Ixekizumab in patients with psa and previous inadequate response to tnf inhibitors week 52 results from spirit p2
Rheumatology, 2018Co-Authors: Mark C. Genovese, Frank Behrens, Joel M Kremer, Tsenfang Tsai, Lisa Kerr, Benard Combe, David H. Adams, Peter NashAbstract:To assess the long-term safety and efficacy of Ixekizumab, an IL-17A antagonist, in patients with active PsA. In SPIRIT-P2 (NCT02349295), patients (n = 363) with previous inadequate response to TNF inhibitors entered the double-blind period (weeks 0-24) and received placebo or Ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) following a 160-mg starting dose at week 0. During the extension period (weeks 24-156), patients maintained their original Ixekizumab dose, and placebo patients received IXEQ4W or IXEQ2W (1:1). We present the accumulated safety findings (week 24 up to 156) at the time of this analysis for patients who entered the extension period (n = 310). Exposure-adjusted incidence rates (IRs) per 100 patient years are presented. ACR responses are presented on an intent-to-treat basis using non-responder imputation up to week 52. From week 24 up to 156 (with 228 patient years of Ixekizumab exposure), 140 [61.3 IR] and 15 (6.6 IR) patients reported infections and serious adverse events, respectively. Serious adverse events included one death and four serious infections. In all patients initially treated with IXEQ4W and IXEQ2W at week 0 (non-responder imputation), ACR20 (61 and 51%), ACR50 (42 and 33%) and ACR70 (26 and 18%) responses persisted out to week 52. Placebo patients re-randomized to Ixekizumab demonstrated efficacy as measured by ACR responses at week 52. During the extension period, the overall safety profile of Ixekizumab remained consistent with that observed with the double-blind period, and clinical improvements persisted up to 1 year.
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Safety and efficacy of Ixekizumab in patients with PsA and previous inadequate response to TNF inhibitors: week 52 results from SPIRIT-P2
Rheumatology, 2018Co-Authors: Frank Behrens, Tsenfang Tsai, Lisa Kerr, Benard Combe, Chin Lee, Mark Genovese, Joel Kremer, David Adams, Peter NashAbstract:Objectives: To assess the long-term safety and efficacy of Ixekizumab, an IL-17A antagonist, in patients with active PsA. Methods: In SPIRIT-P2 (NCT02349295), patients (n = 363) with previous inadequate response to TNF inhibitors entered the double-blind period (weeks 0-24) and received placebo or Ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) following a 160-mg starting dose at week 0. During the extension period (weeks 24-156), patients maintained their original Ixekizumab dose, and placebo patients received IXEQ4W or IXEQ2W (1:1). We present the accumulated safety findings (week 24 up to 156) at the time of this analysis for patients who entered the extension period (n = 310). Exposure-adjusted incidence rates (IRs) per 100 patient years are presented. ACR responses are presented on an intent-to-treat basis using non-responder imputation up to week 52. Results: From week 24 up to 156 (with 228 patient years of Ixekizumab exposure), 140 [61.3 IR] and 15 (6.6 IR) patients reported infections and serious adverse events, respectively. Serious adverse events included one death and four serious infections. In all patients initially treated with IXEQ4W and IXEQ2W at week 0 (non-responder imputation), ACR20 (61 and 51%), ACR50 (42 and 33%) and ACR70 (26 and 18%) responses persisted out to week 52. Placebo patients re-randomized to Ixekizumab demonstrated efficacy as measured by ACR responses at week 52. Conclusion: During the extension period, the overall safety profile of Ixekizumab remained consistent with that observed with the double-blind period, and clinical improvements persisted up to 1 year.
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Ixekizumab Pharmacokinetics, Anti-Drug Antibodies, and Efficacy through 60 Weeks of Treatment of Moderate to Severe Plaque Psoriasis
The Journal of investigative dermatology, 2018Co-Authors: Kristian Reich, Lisa Kerr, Susan Ball, Kimberley Jackson, Sandra Garces, Laiyi Chua, Talia M. Muram, Andrew BlauveltAbstract:Ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, is efficacious for moderate to severe plaque psoriasis. We examined relationships between serum Ixekizumab concentrations, treatment-emergent anti-drug antibodies (TE-ADAs), and efficacy during 60 weeks of treatment in a randomized, controlled, phase 3 study. Steady-state Ixekizumab serum trough concentrations were rapidly achieved and associated with high clinical responses at week 12 with a starting dose of 160 mg followed by 80 mg every 2 weeks. During the long-term extension period dosage of 80 mg every 4 weeks, stable serum trough concentrations maintained high clinical responses through week 60. Most (82.6%, 308/373) patients never developed TE-ADA. In TE-ADA–positive patients (17.4%, n = 65), variations in ADA titers, neutralizing capacity, and persistence were observed. Fifty-six patients (15%) developed low or moderate maximum titers, with serum concentrations and efficacy comparable to those of TE-ADA–negative patients. Nine patients (2.4%) developed high titers, with variable individual clinical responses; four of these nine patients achieved at least PASI 75 at week 60. Median serum concentrations in the TE-ADA-high titer group were generally comparable to the median serum concentrations in the lower titer groups. For most patients, TE-ADA had a negligible impact on Ixekizumab serum concentrations and efficacy. Clinicaltrials.gov: NCT01646177
Ricardo Romiti - One of the best experts on this subject based on the ideXlab platform.
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infections from seven clinical trials of Ixekizumab an anti interleukin 17a monoclonal antibody in patients with moderate to severe psoriasis
British Journal of Dermatology, 2017Co-Authors: Kim Papp, Mamitaro Ohtsuki, Daniel K Braun, Andrew Blauvelt, Lotus Mallbris, Hervé Bachelez, Kevin L. Winthrop, Ricardo Romiti, Nayan Acharya, F. ZhaoAbstract:SummaryBackground Infections are associated with biological therapies in psoriasis. Objectives To summarize the incidence of infections in patients with moderate-to-severe psoriasis treated with Ixekizumab, an anti-interleukin-17A monoclonal antibody. Methods Infections are summarized from an integrated database of seven controlled and uncontrolled Ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0–12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12–60; UNCOVER-1 and UNCOVER-2), and all patients exposed to Ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported. Results Overall, 4209 patients were treated with Ixekizumab (6480 PY). During induction (weeks 0–12), overall infection rates were higher in patients treated with Ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer-term exposure. For all patients treated with Ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation. Conclusions Overall, infections occurred in a higher percentage of patients treated with Ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups.
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sustained response with Ixekizumab treatment of moderate to severe psoriasis with scalp involvement results from three phase 3 trials uncover 1 uncover 2 uncover 3
Journal of Dermatological Treatment, 2017Co-Authors: Kristian Reich, Yukari Okubo, Lisa Kerr, Mark Lebwohl, Orin Goldblum, Craig L Leonardi, Ellen B Dennehy, Ricardo Romiti, Francisco A Kerdel, Howard SofenAbstract:AbstractBackground: Scalp is a frequently affected and difficult-to-treat area in psoriasis patients.Objective: We assessed the efficacy of Ixekizumab in the treatment of patients with scalp psoriasis over 60 weeks using the Psoriasis Scalp Severity Index (PSSI).Methods: In three Phase 3, multicenter, double-blind, placebo-controlled trials, patients with moderate-to-severe psoriasis in UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224) and UNCOVER-3 (N = 1346) were randomized to subcutaneous 80 mg Ixekizumab every two weeks (Q2W) or every four weeks (Q4W) after a 160 mg starting dose, or placebo through Week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg bi-weekly etanercept through Week 12. Patients entering the open-label long-term extension (LTE) (UNCOVER-3) received Ixekizumab Q4W; UNCOVER-1 and UNCOVER-2 included a blinded maintenance period in which static physician global assessment (sPGA) 0/1 responders were re-randomized to placebo, Ixekizumab Q4W, or 80 mg Ixekizumab every 12 w...
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Comparison of Ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study
Actas dermo-sifiliograficas, 2017Co-Authors: Fernando Valenzuela, Ricardo Romiti, C. De La Cruz Fernandez, R.l. Galimberti, S. Gürbüz, M. Mckean-matthews, L GoncalvesAbstract:Abstract Background and objectives Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. Patients and methods Analysis included 102 Latin American patients randomized to receive placebo (n = 14), etanercept 50 mg twice weekly (n = 30), or Ixekizumab 160-mg starting dose followed by 80 mg every 2 weeks (Q2W; n = 29) or every 4 weeks (Q4W; n = 29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with Ixekizumab Q4W. Results At week 12, Psoriasis Area and Severity Index (PASI) 100 scores were 0%, 20.0% (p = 0.075 vs placebo), 62.1% (p Conclusions In Latin American patients, both Ixekizumab dosing regimens demonstrated greater efficacy than etanercept for treating psoriasis over 12 weeks. The safety profile of Ixekizumab through 60 weeks was well tolerated and consistent with the overall profile.
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inflammatory bowel disease among patients with psoriasis treated with Ixekizumab a presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials
Journal of The American Academy of Dermatology, 2017Co-Authors: Kristian Reich, Craig L Leonardi, Mamitaro Ohtsuki, R B Warren, Hervé Bachelez, Ricardo Romiti, Nayan Acharya, Richard G Langley, Wen Xu, Kathleen SolotkinAbstract:Background Inflammatory bowel disease (IBD) occurs more frequently in patients with psoriasis. The 2 diseases have significant genetic overlap, but the pathogenesis underlying their co-occurrence is unknown. Objective We sought to report adjudicated IBD cases (Crohn's disease [CD] and ulcerative colitis [UC]) in patients exposed to Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. Methods Adverse events (AEs) integrated from 7 randomized controlled and uncontrolled trials were analyzed for the controlled induction period, controlled maintenance period, and all Ixekizumab-treated patients. Suspected IBD cases were reviewed by blinded external experts using internationally recognized criteria (Registre Epidemiologique des Maladies de l'Appareil Digestif registry). Results In all, 4209 patients (6480 patient-exposure years) were exposed to Ixekizumab. Suspected CD (N = 12) or UC (N = 17) AEs were reported; 19 were adjudicated as definite/probable IBD (CD, N = 7, incidence rate = 1.1/1000 patient-exposure years; UC, N = 12, incidence rate = 1.9/1000 patient-exposure years). Among these, 3 occurred during induction (CD, N = 1; UC, N = 2) and 7 during maintenance (CD, N = 4; UC, N = 3). Twelve of 16 patients with reported IBD history have not had an IBD treatment-emergent AE/serious AE to date. Limitations Clinical review (adjudication) was not prespecified. AE data collected post-hoc may have been limited by length of time from occurrence. Conclusion From an integrated database of 7 Ixekizumab psoriasis trials, CD and UC cases were uncommon (
Daniel K Braun - One of the best experts on this subject based on the ideXlab platform.
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infections from seven clinical trials of Ixekizumab an anti interleukin 17a monoclonal antibody in patients with moderate to severe psoriasis
British Journal of Dermatology, 2017Co-Authors: Kim Papp, Mamitaro Ohtsuki, Daniel K Braun, Andrew Blauvelt, Lotus Mallbris, Hervé Bachelez, Kevin L. Winthrop, Ricardo Romiti, Nayan Acharya, F. ZhaoAbstract:SummaryBackground Infections are associated with biological therapies in psoriasis. Objectives To summarize the incidence of infections in patients with moderate-to-severe psoriasis treated with Ixekizumab, an anti-interleukin-17A monoclonal antibody. Methods Infections are summarized from an integrated database of seven controlled and uncontrolled Ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0–12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12–60; UNCOVER-1 and UNCOVER-2), and all patients exposed to Ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported. Results Overall, 4209 patients were treated with Ixekizumab (6480 PY). During induction (weeks 0–12), overall infection rates were higher in patients treated with Ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer-term exposure. For all patients treated with Ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation. Conclusions Overall, infections occurred in a higher percentage of patients treated with Ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups.
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short and long term safety outcomes with Ixekizumab from 7 clinical trials in psoriasis etanercept comparisons and integrated data
Journal of The American Academy of Dermatology, 2017Co-Authors: Bruce E Strober, C. Paul, Mark Lebwohl, Craig L Leonardi, Kim Papp, Ulrich Mrowietz, Mamitaro Ohtsuki, Robert Bissonnette, Laura K Ferris, Daniel K BraunAbstract:Background Safety of biologics is important when treating patients with psoriasis. Objective We sought to determine the safety of Ixekizumab in psoriasis. Methods Integrated safety data are presented from a 12-week induction period, a 12- to 60-week maintenance period, and from all Ixekizumab-treated patients from 7 clinical trials. Exposure-adjusted incidence rates (IRs) per 100 patient-years are reported. Results Overall, 4209 patients received Ixekizumab (total exposure: 6480 patient-years). During the induction period, the IRs of patients experiencing 1 or more treatment-emergent adverse event (AE) were 251 and 236 among Ixekizumab- and etanercept-treated patients, respectively, and for serious AEs was 8.3 in both groups. During maintenance, for Ixekizumab, the IRs of treatment-emergent AEs and serious AEs were 100.4 and 7.8, respectively. Among all Ixekizumab-treated patients from 7 trials, the IR of Candida infections was 2.5. The IRs of treatment-emergent AEs of special interest (including serious infections, malignancies, major adverse cardiovascular events) were comparable for Ixekizumab and etanercept during the induction period. Limitations Additional long-term data are required. Conclusion Ixekizumab had an acceptable safety profile with no unexpected safety findings during Ixekizumab maintenance in psoriasis.
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Ixekizumab an interleukin 17a specific monoclonal antibody for the treatment of biologic naive patients with active psoriatic arthritis results from the 24 week randomised double blind placebo controlled and active adalimumab controlled period of the
Annals of the Rheumatic Diseases, 2017Co-Authors: Philip J Mease, Chen-yen Lin, Masato Okada, Catherine L Shuler, Daniel K Braun, Desiree Van Der Heijde, Christopher T Ritchlin, Raquel S Cuchacovich, Chin LeeAbstract:Objective To assess the safety and efficacy of Ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA). Methods Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), Ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or Ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both Ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24. Results Significantly more patients treated with Ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both Ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with Ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with Ixekizumab (65.7–66.4%) and adalimumab (64.4%) than placebo (47.2%) (p Conclusions In biologic-naive patients with active PsA, Ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo. Trial registration number NCT01695239; EudraCT2011-002326-49; Results.
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phase 3 trials of Ixekizumab in moderate to severe plaque psoriasis
The New England Journal of Medicine, 2016Co-Authors: Kenneth B Gordon, Kristian Reich, Thomas A. Luger, Kim Papp, Mamitaro Ohtsuki, David Amato, Andrew Blauvelt, Susan Ball, Richard G Langley, Daniel K BraunAbstract:BackgroundTwo phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, Ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. MethodsWe randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of Ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of Ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixeki...
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safety and efficacy of open label subcutaneous Ixekizumab treatment for 48 weeks in a phase ii study in biologic naive and tnf ir patients with rheumatoid arthritis
The Journal of Rheumatology, 2016Co-Authors: Mark C. Genovese, Daniel K Braun, Pierreyves Berclaz, Michael P Heffernan, Janelle S Erickson, Subhashis Banerjee, Hilde CarlierAbstract:Objective. To evaluate Ixekizumab, an anti-interleukin 17A monoclonal antibody, for safety and effectiveness through 64 weeks in biologic-naive and tumor necrosis factor–inadequate responder (TNF-IR) patients with rheumatoid arthritis. Methods. Patients completing the 16-week double-blind period of a phase II study were eligible to enter the open-label extension (OLE) for an additional 48 weeks of Ixekizumab treatment. After a treatment hiatus between weeks 10 to 16, 232 biologic-naive and 158 TNF-IR patients entered the OLE with all patients receiving 160 mg Ixekizumab at weeks 16, 18, and 20, and then every 4 weeks through Week 64. Results. A total of 201 (87%) biologic-naive and 99 (62%) TNF-IR patients completed the OLE. Treatment-emergent adverse events (AE) occurred in 168 (72%) biologic-naive and 115 (73%) TNF-IR patients during the OLE. Most AE were mild to moderate in severity and did not lead to study discontinuation. Serious AE (SAE) occurred in 17 (7%) biologic-naive patients, including 5 (2%) serious infections and 2 (1%) deaths. SAE occurred in 18 (11%) TNF-IR patients, including 4 (3%) serious infections and 1 (1%) death. No mycobacterial or invasive fungal infections were reported. Clinical responses [American College of Rheumatology (ACR) 20, ACR50, ACR70, and 28-joint Disease Activity Score with C-reactive protein] observed at Week 16 were maintained or improved through Week 64. Conclusion. Ixekizumab was well tolerated, and safety findings in the OLE were consistent overall with those in the double-blind period of this study. Clinical improvements observed with Ixekizumab through Week 16 were maintained or improved in patients participating in the OLE through Week 64. Trial registration number: [NCT00966875][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00966875&atom=%2Fjrheum%2F43%2F2%2F289.atom
