Integrated safety analysis of treatment-emergent eczematous reactions in patients with moderate-to-severe psoriasis treated with ixekizumab, etanercept and ustekinumab.
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ABSTRACT:
SUBMITTER: Brunner PM
PROVIDER: S-EPMC8518506 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
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Integrated safety analysis of treatment-emergent eczematous reactions in patients with moderate-to-severe psoriasis treated with ixekizumab, etanercept and ustekinumab.
Brunner P M PM Conrad C C Vender R R Grond S S Schuster C C Patel H H Xu W W Carrascosa Carrillo J M JM
The British journal of dermatology 20210810 4
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Project description:Objectives: To asses skin clearance and patient-reported outcomes for ixekizumab treatment. Methods: IXORA-R enrolled adults with moderate-to-severe plaque psoriasis, defined as static Physician’s Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. The trial was registered with ClinicalTrials.gov (NCT03573323).
2023-04-10 | GSE178228 | GEO
Project description:IntroductionPatients with plaque psoriasis often have nail psoriasis, which is difficult to treat. Ixekizumab (IXE) and ustekinumab (UST) are biologics with established efficacy in nail psoriasis. We present post hoc data from a head-to-head trial of IXE and UST (IXORA-S) to examine the efficacy in nail psoriasis in patients with moderate-to-severe plaque psoriasis over 52 weeks.MethodsIn IXORA-S, randomised patients received IXE (N = 136) or UST (N = 166) per label for 52 weeks. Eighty-four (61.8%) and 105 (63.3%) of the patients treated with IXE or UST, respectively, had baseline fingernail psoriasis (Nail Psoriasis Severity Index [NAPSI] > 0); of these, 54 (64.3%) and 63 (60.0%) patients, respectively, had significant baseline fingernail psoriasis (defined as NAPSI ≥ 16 with ≥ 4 fingernails involved). The proportion of patients achieving NAPSI = 0, a NAPSI score change from baseline and correlations in Psoriasis Area of Severity Index (PASI) and NAPSI improvement over 52 weeks were examined.ResultsProgressive improvement occurred in both treatment groups over 52 weeks. Statistically significantly more patients achieved NAPSI = 0 with IXE versus UST by week 16-20, and the proportions continued to increase through week 52 among patients with baseline nail psoriasis (61.9 vs. 28.6%, respectively; P < 0.001), including those with significant nail psoriasis (57.4 vs. 17.5%, respectively; P < 0.001). Similar results were observed for NAPSI score improvement from baseline to week 52. Interestingly, the presence of nail psoriasis was associated with lower skin response with UST but not with IXE.ConclusionsIxekizumab was superior to UST in the clearance of nail psoriasis, with earlier improvement continued through 52 weeks regardless of baseline nail severity.Trial registrationClinicalTrials.gov identifier; NCT02561806.
| S-EPMC7367982 | biostudies-literature
Project description:BackgroundPersonal treatment goals have been systematically investigated in psoriasis patients with active but not in controlled disease.ObjectivesTo explore patient needs in psoriasis patients with controlled disease due to biologic therapy with adalimumab, etanercept or ustekinumab.MethodsTreatment needs in patients on adalimumab, etanercept or ustekinumab with a stable low disease activity for ≥ 6 months and preferably a Psoriasis Area and Severity Index (PASI) < 5, were explored with the Patient Needs Questionnaire (PNQ). Goal importance was expressed as overall mean importance score, percentage of patients that reported a goal to be quite/very important, and per PNQ subscale. Data were analysed separately for treatment, gender, age group (< 50 vs. ≥ 50 years), biologic naivety and willingness to participate in a pragmatic dose-reduction strategy.ResultsSixty-five patients were included. 'To be free of itching', 'to be healed of all skin defects' and 'to have confidence in the therapy' were rated quite/very important in 78.5% of the patients, followed by 'to have no fear the disease will progress' (75.4%) and 'to get better skin quickly' (75.4%). Goals related to the subscale 'confidence in healing' were still of high importance in controlled disease. Least importance was attributed towards social goals. For female patients, it was significantly more important than for males to 'feel less depressed' and 'be comfortable showing yourself more in public'.ConclusionsPsoriasis patients with controlled disease still report substantial treatment needs, with high importance ascribed to confidence in healing. To apply personalized medicine, treatment needs should be explored on an individual level.
| S-EPMC8128951 | biostudies-literature
Project description:BackgroundDose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients.ObjectivesTo evaluate the implementation of protocolized biologic DR in daily practice.MethodsA pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review.ResultsThe implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR.ConclusionAdditional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.
| S-EPMC10013325 | biostudies-literature
Project description:Statins, an example of the most commonly prescribed medications to the elderly, are not without side effects. Dermatologic events are often overlooked as arising from medications, particularly those which are taken chronically. Moreover, elderly patients are prone to pharmacologic interactions due to multiple medications. In this report, we describe a case of a statin-induced eczematous dermatitis with a psoriasis-like clinical presentation and review the skin manifestations that may arise from statin therapy.An 82-year-old man with gout and hypercholesterolemia presented to dermatology clinic with new onset of pruritic, scaly erythematous plaques bilaterally on the extensor surfaces of his arms. He had never had similar lesions before. Despite various topical and systemic treatments over several months, the rash continued to evolve. The patient was then advised to discontinue his long-term statin, which led to gradual resolution of his symptoms. He was subsequently diagnosed with statin-induced eczematous dermatitis.This case report describes an adverse cutaneous reaction to statins that is rarely reported in the literature. Medications, including longstanding therapies, should be suspected in cases of refractory dermatologic lesions.
| S-EPMC5555012 | biostudies-other
Project description:BackgroundThere is increasing concern about the risk of latent tuberculosis infection (LTBI) reactivation during the use of biologics for psoriasis. Although ustekinumab had been documented with low risk of tuberculosis, the long-term follow-up of LTBI as determined by QuantiFERON-TB Gold (QFT-G) testing in patients treated with ustekinumab is limited.ObjectivesThis study aims to use serial QFT-G testing as a screening method for detecting LTBI in patients with psoriasis from an intermediate tuberculosis burden country.MethodsThis retrospective review investigated 134 psoriatic patients in whom ustekinumab was prescribed for at least one year between 2010 and 2016 in National Taiwan University Hospital. All patients underwent annular QFT-G testing during ustekinumab therapy.ResultsAmong the 134 enrolled patients, baseline LTBI rate was 13.4% (18/134). Indeterminate QFT-G result was noted in 5.2% (7/134) of patients and 71.4% (5/7) of them turn to be QFT-G negative during the next testing. 81.3% (109/134) of patients had a negative QFT-G at baseline and the seroconversion rate was 7.3% (8/109) in the serial QFT-G. All the patients in the conversion group were referred to a pulmonologist for evaluation and 81.5% (22/27) of them underwent chemoprophylactic therapy while on ustekinumab. No active TB infection was noted during further follow-up with or without chemoprophylaxis.ConclusionsThis study revealed that psoriatic patients receiving long-term ustekinumab therapy had a low QFT-G conversion rate (7.3%). The clinical significance of QFT-G conversion remains controversial and needs larger scale trials to investigate.
| S-EPMC5590912 | biostudies-literature
Project description:ImportanceDrug survival of biologic therapies for psoriasis is a proxy for longer-term treatment effectiveness and safety. Patient factors that are associated with the survival of each biologic differently (effect modifiers) may inform the decision to choose between biologics.ObjectiveTo assess the drug survival associated with the effectiveness and safety of commonly used biologics for psoriasis in the UK and Ireland and identify effect modifiers for these biologics and their survival.Design, setting, and participantsWe conducted a prospective cohort study of patients with psoriasis using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2021.ExposuresAdalimumab, ustekinumab, secukinumab, guselkumab, ixekizumab.Main outcomes and measuresWe conducted a survival analysis and fitted separate flexible parametric models for drug survival as a proxy for effectiveness and safety.ResultsA total of 16 122 treatment courses were included: 6607 (41.0%) in which treatment with adalimumab was initiated, 5405 (33.5%) with ustekinumab, 2677 (16.6%) with secukinumab, 730 (4.5%) with guselkumab, and 703 (4.4%) with ixekizumab. The crude survival functions at year 1 for measures of effectiveness for treatment with adalimumab was 0.81 (95% CI, 0.80-0.82), 0.89 for ustekinumab (95% CI, 0.88-0.89), 0.86 for secukinumab (95% CI, 0.85-0.87), 0.94 for guselkumab (95% CI, 0.92-0.96), and 0.86 for ixekizumab (95% CI, 0.83-0.89). The adjusted survival curves from the multivariable model for effectiveness showed that treatment with guselkumab had the higher survival (adjusted hazard ratio, 0.13; 95% CI, 0.03-0.56) and adalimumab had the lower survival (adjusted hazard ratio, 2.37; 95% CI, 2.03-2.76) compared with ustekinumab. Secukinumab and ixekizumab had similar survival curves over time. Psoriatic arthritis, previous biologic exposure, nail involvement, and ethnicity were effect modifiers for survival in association with treatment effectiveness. The crude survival functions at year 1 for safety were 0.91 for treatment with adalimumab (95% CI, 0.90-0.91), 0.94 for ustekinumab (95% CI, 0.94-0.95), 0.94 for secukinumab (95% CI, 0.92-0.94), 0.96 for guselkumab (95% CI, 0.94-0.98), and 0.92 for ixekizumab (95% CI, 0.89-0.94). Guselkumab, ustekinumab, and secukinumab had similar adjusted survival curves for safety, while adalimumab (adjusted hazard ratio, 1.66; 95% CI, 1.46-1.89) and ixekizumab (adjusted hazard ratio, 1.52; 95% CI, 1.13-2.03) had lower survival compared with ustekinumab.Conclusions and relevanceThe results of this cohort study suggest that guselkumab had the highest drug survival in BADBIR of the included biologics for treatment persistence that was associated with effectiveness, and guselkumab had highest drug survival for safety compared with other biologics except ustekinumab. Psoriatic arthritis, nail involvement, previous biologic exposure, and ethnicity were effect modifiers for biologics and their survival in association with treatment effectiveness. This information on longer-term treatment persistence, safety, and tolerability may help patients and their clinicians make an informed decision to initiate treatment with a biologic therapy.
| S-EPMC9260644 | biostudies-literature
Project description:ImportancePsoriasis in children is increasingly treated with systemic medications, yet their risk of serious infection is not well characterized in clinical practice. Pediatric clinical trials for these medications were often small and placebo controlled.ObjectiveTo estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.Design, setting, and participantsThis cohort study used insurance claims data from clinical practices across the US on children aged 17 years or younger with psoriasis who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. The analysis was stratified by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021). Patient follow-up started 1 day after initiating treatment and ended at 6 months.ExposuresNew treatment with ustekinumab, etanercept, and methotrexate.Main outcomes and measuresDuring follow-up, the frequency of inpatient serious infections and outpatient infections requiring treatment was compared. Event rates and rate ratios were estimated after propensity score decile stratification.ResultsAfter exclusions, we identified 2338 patients (1368 girls [57.8%]) who initiated new treatment with a targeted immunomodulating agent. In all, 379 patients started treatment with ustekinumab, 779 patients started treatment with etanercept, and 1180 patients started treatment with methotrexate from 2009 through 2021. The propensity score-adjusted incidence rate of serious infection was 18.4 per 1000 person-years (3 events) for ustekinumab users, 25.6 per 1000 person-years (9 events) for etanercept users, and 14.9 per 1000 person-years (8 events) for methotrexate users. The adjusted rate of outpatient infections was 254.9 per 1000 person-years (39 events) for ustekinumab users, 435.7 per 1000 person-years (139 events) for etanercept users, and 433.6 per 1000 person-years (209 events) for methotrexate users. The adjusted rate ratio of outpatient infections was 0.58 (95% CI, 0.41-0.83) for ustekinumab vs etanercept, 0.66 (95% CI, 0.48-0.91) for ustekinumab vs methotrexate, and 0.95 (95% CI, 0.75-1.21) for etanercept vs methotrexate. Rate ratios were similar during the off-label use era and after pediatric labeling.Conclusions and relevanceAmong children with psoriasis who started treatment with immunomodulating agents, serious infections were infrequent. This cohort study suggests that there was no increase in the risk of outpatient infections for children who started treatment with ustekinumab compared with etanercept or methotrexate.
| S-EPMC9909570 | biostudies-literature
Project description:BackgroundPatients 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.ObjectiveOur 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.MethodsFor 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.ResultsAfter 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.ConclusionPatients 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).
| S-EPMC5884910 | biostudies-literature
Project description:IntroductionWe evaluated baseline itch and its impact on the efficacy of ixekizumab (IXE) in clearing psoriasis and improving quality-of-life measures, and we explored the relationship between itch and psoriatic skin improvement.MethodsData were analyzed from two double-blind, randomized, controlled phase III studies (UNCOVER-2/3) comparing etanercept (ETN), IXE, and placebo (PBO) in patients with moderate-to-severe plaque psoriasis. Long-term analysis included UNCOVER-3 data from week 0 to week 156.ResultsAt week 12, a clinically meaningful improvement in itch [Itch Numeric Rating Scale (NRS) reduction ≥ 4] was seen in 70.0%, 88.6%, and 90.8% of the IXE-treated patients in the baseline Itch NRS 4-6, 7-8, and 9-10 groups, respectively (all itch severity groups p < 0.001 versus ETN and PBO). Also, 68.9%, 67.1%, and 73.6% of the IXE-treated patients in the baseline Itch NRS 4-6, 7-8, and 9-10 groups, respectively, showed an improvement of ≥ 90.0% in the Psoriatic Area and Severity Index (PASI) at week 12 as compared to the baseline (PASI 90) (all itch severity groups p < 0.001 versus ETN and PBO). For most patients, itch reduction preceded psoriatic plaque improvement. Sustained effects of IXE on itch and PASI were observed during 3 years of treatment.ConclusionsRegardless of baseline itch severity, IXE treatment provided a rapid improvement in itch followed by clinically meaningful improvements in psoriasis.FundingEli Lilly and Company.Trial registrationClinicalTrials.gov identifiers, NCT01597245 and NCT01646177.
| S-EPMC6261114 | biostudies-literature