Long‐term safety profile of ixekizumab in patients with moderate‐to‐severe plaque psoriasis: an integrated analysis from 11 clinical trials

Langley, Richard; Kimball, Alexa B.; Nak, H.; Xu, Wen; Pangallo, Beth A.; Osuntokun, Olawale; Agada, Noah; Reich, Kristian

doi:10.1111/jdv.15242

Cited by 55 publications

(57 citation statements)

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“…Upon medical review, no deaths were attributed to IXE by the sponsor. These findings are consistent with previous reports in the larger psoriasis IXE-treated population [9].…”

Section: Discussionsupporting

confidence: 94%

“…AE: adverse event; CEC: Clinical Events Committee; CI: confidence interval; IBD: inflammatory bowel disease; IR: incidence rate; IXE: ixekizumab; MACE: major adverse cardiovascular events; MedDRA: Medical Dictionary for Regulatory Activities; Ns: number of patients entered in each time interval; n: number in group; PBO: placebo; PY: patient-years; Q2W: every 2 weeks; Q4W: every 4 weeks; TEAEs: treatment-emergent adverse events frequent TEAEs [7]; the IR for these events decreased with an increase in the duration of IXE exposure. This is consistent with the pattern observed in the psoriasis clinical trials and with the findings associated with the use of secukinumab in PsA [9,10]. This is similar to the reports for biologic agents neutralizing TNF [11].…”

Section: Discussionsupporting

confidence: 90%

“…were 2.1 and 0.1, respectively; most were mild or moderate in nature and there was no discontinuation due to candida infections. Consistent with reports from the psoriasis program and with studies on other IL-17 inhibitors, there were no deep organ or blood stream fungal infections [9,12].…”

Section: Discussionsupporting

confidence: 82%

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Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis

et al. 2020

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Background: The long-term safety was assessed in patients with psoriatic arthritis who were treated with ixekizumab in three clinical trials (SPIRIT-P1/-P2/-P3). Methods: Integrated safety data from three trials (controlled and uncontrolled), including two pivotal phase 3, randomized, double-blind clinical trials: SPIRIT-P1 and SPIRIT-P2, were assessed. Safety data were integrated from the all ixekizumab exposure safety population (defined as all patients receiving ≥ 1 dose of ixekizumab). We report exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at 1-year intervals up to 3 years for adverse events. Results: Total exposure to IXE reached 1822.2 PY (1118 patients). The IRs/100 PY for the following treatment discontinuations were as follows: adverse events (5.3); serious infections (1.3); injection-site reactions (12.7); infections (34.2); and deaths (0.3). The IRs for treatment-emergent adverse events decreased or remained stable over time, the most common being upper respiratory tract infection, nasopharyngitis, and injection-site reactions. The IRs for serious adverse events and serious infections remained stable over time, whereas for injection-site reactions and general infections, IRs decreased with longer ixekizumab exposure. Opportunistic infections were limited to oral and esophageal candida and localized herpes zoster. No suicide or self-injuryrelated behaviors were reported. The IRs/100 PY for safety topics of special interest included inflammatory bowel disease (adjudicated; 0.1), depression (1.6), malignancies (0.7), and major adverse cardiovascular events (0.6). Conclusions: The findings of this integrated safety analysis in patients with psoriatic arthritis are consistent with the known safety profile of ixekizumab. No unexpected safety signals were observed with ixekizumab treatment in patients with psoriatic arthritis.

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“…Upon medical review, no deaths were attributed to IXE by the sponsor. These findings are consistent with previous reports in the larger psoriasis IXE-treated population [9].…”

Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 90%

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Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis

et al. 2020

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“…By contrast, IXORA‐R was designed to assess eight of the nine primary and major secondary time points in the first 12 weeks of the study, with one major secondary time point (PASI 100 at week 24) remaining to be disclosed after the trial finishes. IXORA‐R did not measure long‐term efficacy and safety because previous trials have demonstrated efficacy and safety of ixekizumab with up to 4 and 5 years of continuous treatment, respectively . The focus on early responses allowed direct comparison of the speed at which improvements in psoriasis occur for patients treated with ixekizumab vs. guselkumab.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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* Summary Background Patients with psoriasis value rapid and complete skin clearance. No head-tohead 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 < 0Á001]. 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.

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“…В отношении ингибиторов ИЛ-17 накоплены убедительные данные об их долгосрочной безопасности [13,14], которые говорят о низкой частоте случаев побочных реакций тяжелой токсичности. Известно, что ингибиторы ИЛ-17 могут способствовать развитию инфекций, однако длительный опыт применения этих препаратов у пациентов с псориазом демонстрирует развитие инфекций преимущественно легкой степени у небольшого Таблица 7.…”

Section: Discussionunclassified

Netakimab — new IL-17а inhibitor: 12-week results of phase III clinical study BCD-085-7/PLANETA in patients with moderate-tosevere plaque psoriasis

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et al. 2019

Vestnik dermatologii i venerologii

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Netakimab, the original monoclonal antibody against IL-17A, is an innovative drug for the treatment of moderate-to-severe plaque psoriasis in patients who have indications for systemic therapy or phototherapy. Netakimab was approved in Russian Federation, registration certificate number ЛП-005439 from 04.04.2019. This article outlines the first 12-week results of a phase III clinical trial in patients with psoriasis.Materials and methods. The BCD-085-7 study (PLANETA) is a comparative, randomized, double-blind, placebo-controlled phase 3 clinical study of the efficacy and safety of netakimab in patients with moderate-to-severe plaque psoriasis. This review presents the results of the first 12 weeks. The study is ongoing at the moment, the total duration of treatment for each patient is 3 years (154 weeks). Patients were randomized in a ratio of 2:2:1 into one of three arms: group 1 received netakimab subcutaneously at a dose of 120 mg once a week for the first three weeks (induction) and then once every 2 weeks up to week 10, group 2 received netakimab subcutaneously at a dose of 120 mg once a week for the first three weeks (induction) and then once every 4 weeks up to week 10, group 3 received a placebo subcutaneously on day 1 at weeks 0, 1, 2, 4, 6, 8 10. In order to maintain a double-blind design, placebo was administered to patients in group 2 at weeks 4 and 8.Results. Both netakimab groups showed a significant superiority over placebo (p < 0.001) and the absence of statistically significant differences between the two regimens of therapy (p > 0.05) across all endpoints. PASI 75 at week 12 was reached by 77.65 % of patients using netakimab once every 2 weeks and 83.33 % of patients using netakimab once every 4 weeks (ITT population). The rate of clear and almost clear skin (sPGA 0–1) was reached by 81.18 and 79.76 % of patients using netakimab once every 2 weeks and once every 4 weeks, respectively. The safety assessment showed no statistically significant differences between the groups, the incidence rate of adverse events in netakimab arms was not higher than in the placebo arm. There were no cases of early withdrawal due to adverse events and cases of grade 4 toxicity according to CTCAE 4.03. During the 12 weeks of the study, one serious adverse event was registered in group 2 (pneumonia grade 3), which was recovered without any consequences. The immunogenicity assessment showed binding antibodies formation at week 12 in one patient who received BCD-085 every 2 weeks. Neutralizing antibodies were not detected. Conclusion. Netakimab showed high efficacy in the treatment of psoriasis, more than 80 % of patients achieved PASI 75 and sPGA 0–1 (clear and almost clear skin) by the week 12 of treatment. The drug showed a favorable safety profile and low immunogenicity. Based on the study results the regimen once a week during the first 3 weeks (induction), then once every 4 weeks was chosen for medical use in patients with psoriasis.

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Long‐term safety profile of ixekizumab in patients with moderate‐to‐severe plaque psoriasis: an integrated analysis from 11 clinical trials

Abstract: The 3-year, long-term maintenance treatment with ixekizumab did not show any new safety signals in patients with moderate-to-severe plaque psoriasis.

Cited by 55 publications

References 24 publications

Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis

Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis

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

Netakimab — new IL-17а inhibitor: 12-week results of phase III clinical study BCD-085-7/PLANETA in patients with moderate-tosevere plaque psoriasis

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