Clinical Evaluation of Risankizumab-rzaa in the Treatment of Plaque Psoriasis.
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SUBMITTER: Reddy V
PROVIDER: S-EPMC6985981 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Clinical Evaluation of Risankizumab-rzaa in the Treatment of Plaque Psoriasis.
Reddy Vidhatha V Yang Eric J EJ Myers Bridget B Liao Wilson W
Journal of inflammation research 20200122
Risankizumab-rzaa (Skyrizi<sup>®</sup>; AbbVie) is a humanized IgG monoclonal antibody directed against interleukin-23p19 (IL-23p19) indicated for the treatment of moderate-to-severe psoriasis in adults who are candidates for systemic therapy or phototherapy. Four pivotal Phase III trials: UltIMMa-1, UltIMMa-2, IMMhance, and IMMvent have demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis. This review highlights important findings from these and other clinical t ...[more]
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Project description:Risankizumab, an anti-interleukin-23 monoclonal antibody, achieved significantly (P < 0.001) greater Psoriasis Area and Severity Index (PASI) and static Physician Global Assessment (sPGA) clear or almost clear (0/1) responses than adalimumab in a phase III trial in patients with moderate-to-severe psoriasis. Meta-analyses of the PASI 50, PASI 75, PASI 90, PASI 100, and sPGA0/1 responses after 16 weeks of treatment from eight (three for risankizumab and five for adalimumab) randomized, placebo-controlled trials were conducted to estimate the efficacy difference between risankizumab and adalimumab. For PASI 75, PASI 90, PASI 100, and sPGA0/1 responses, the estimated effect differences (95% confidence interval) between risankizumab and adalimumab were 15.2% (10.1%, 20.4%), 23.7% (15.7%, 31.2%), 20.8% (13.0%, 28.7%), and 20.1% (13.7%, 26.1%), respectively. These results were consistent with the observed efficacy difference from the head-to-head phase III trial, which was not included in the meta-analyses, providing independent, confirmatory evidence of the superior efficacy of risankizumab compared with adalimumab for treatment of moderate-to-severe psoriasis.
| S-EPMC7006886 | biostudies-literature
Project description:Risankizumab (Skyrizi®; risankizumab-rzaa) is a humanized immunoglobulin (Ig) G1 monoclonal antibody that specifically targets the p19 subunit of interleukin (IL)-23, thereby inhibiting IL-23-dependent cell signaling. Subcutaneous risankizumab is approved for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy (in the EU), those who are candidates for systemic therapy or phototherapy (in the USA) and those who have an inadequate response to conventional therapies (in Japan). In pivotal phase III trials (UltIMMa-1, UltIMMa-2, IMMvent and IMMhance), risankizumab was more effective than placebo, ustekinumab and adalimumab with regard to the proportion of patients achieving ≥ 90% improvement from baseline in Psoriasis Area and Severity Index score (PASI 90) and a static Physician's Global Assessment score of 0 or 1 at week 16, with these benefits maintained over the longer term. In supportive head-to-head trials, risankizumab was also superior to secukinumab and fumaric acid esters in terms of PASI 90 response rate. In an ongoing open-label extension study (LIMMitless), risankizumab was associated with durable and improved efficacy after switching from ustekinumab or adalimumab, as well as durable maintenance of efficacy through > 2.5 years of continuous exposure. Treatment with risankizumab improved health-related quality of life and was generally well tolerated, both in the short- and longer-term. In conclusion, risankizumab represents a useful new treatment option for patients with moderate to severe plaque psoriasis.
| S-EPMC7475056 | biostudies-literature
Project description:IntroductionRisankizumab has demonstrated efficacy and safety in phase 3 studies in patients with moderate to severe plaque psoriasis. This randomized clinical trial assessed the efficacy and safety of risankizumab in patients with moderate to severe plaque psoriasis in the Russian Federation.MethodsPatients with moderate to severe plaque psoriasis were randomized 4:1 to 16 weeks of double-blind treatment with risankizumab 150 mg or placebo (period A; dosing at baseline and week 4) followed by an open-label extension (period B) during which all patients received risankizumab 150 mg at weeks 16, 28, and 40 and were followed up to week 52. The primary study endpoint was the proportion of patients achieving ≥ 90% improvement in the Psoriasis Area and Severity Index (PASI 90) at week 16, and secondary endpoints included Static Physician's Global Assessment scores and the Dermatology Life Quality Index. Treatment-emergent adverse events were monitored throughout the two study periods.ResultsOf the 50 patients who entered period A, 41 were randomized to receive risankizumab and 9 to receive placebo. Forty-eight patients entered period B, and 47 completed the study. A significantly larger proportion of risankizumab-treated patients achieved PASI 90 at week 16 compared with placebo-treated patients [response rate difference: 38.8% (95% CI 7.8-69.7%; P = 0.035)]. Consistently higher proportions of risankizumab-treated patients achieved secondary endpoints compared with the placebo-treated patients. Safety profiles were similar between the treatment groups, and no patients discontinued the study drug owing to adverse events.ConclusionRisankizumab was efficacious and well tolerated in patients with moderate to severe plaque psoriasis in the Russian Federation.Trial registrationClinicalTrials.gov NCT03518047.
| S-EPMC9464287 | biostudies-literature
Project description:BackgroundRisankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials.ObjectivesTo evaluate safety data from risankizumab psoriasis phase I-III clinical trials.MethodsShort-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials.ResultsShort-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients.ConclusionsRisankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis.
| S-EPMC9298814 | biostudies-literature
Project description:ImportanceRisankizumab selectively inhibits interleukin 23, a cytokine that contributes to psoriatic inflammation.ObjectiveTo evaluate the efficacy and safety of risankizumab vs placebo and continuous treatment vs withdrawal in adults with moderate to severe plaque psoriasis.Design, setting, and participantsMultinational, phase 3, randomized, double-blind, placebo-controlled trial conducted from March 6, 2016, to July 26, 2018. A total of 507 eligible patients had stable moderate to severe chronic plaque psoriasis for 6 months or longer, body surface area involvement greater than or equal to 10%, Psoriasis Area and Severity Index (PASI) greater than or equal to 12, and a static Physician's Global Assessment (sPGA) score greater than or equal to 3. Intention-to-treat analysis was conducted.InterventionsPatients were randomized (4:1, interactive response technology) to risankizumab, 150 mg, subcutaneously, or placebo at weeks 0 and 4 (part A1). All patients received risankizumab at week 16. At week 28, patients randomized to risankizumab who achieved an sPGA score of 0/1 were rerandomized 1:2 to risankizumab or placebo every 12 weeks (part B).Main outcomes and measuresCo-primary end points for the part A1 phase included proportions of patients achieving greater than or equal to 90% improvement in PASI (PASI 90) and sPGA score of 0/1 at week 16. The PASI measures severity of erythema, infiltration, and desquamation weighted by area of skin involvement over the head, trunk, upper extremities, and lower extremities; scores range from 0 (no disease) to 72 (maximal disease activity). The sPGA assesses average thickness, erythema, and scaling of all psoriatic lesions; scores range from 0 (clear) to 4 (severe), with 0/1 indicating clear or almost clear. Primary and secondary end points in part B included proportion of rerandomized patients achieving an sPGA score of 0/1 at week 52 (primary) and week 104 (secondary).ResultsOf 563 patients screened, 507 were randomized to risankizumab (n = 407) or placebo (n = 100). Most patients were men (356 [70.2%]); median age was 51 years (interquartile range, 38-60 years). At week 16, 298 patients (73.2%) in the treatment group vs 2 patients (2.0%) receiving placebo achieved a PASI 90 response, and 340 patients (83.5%) receiving risankizumab vs 7 patients (7.0%) receiving placebo achieved sPGA 0/1 scores (placebo-adjusted differences: PASI 90: 70.8%; 95% CI, 65.7%-76.0%; sPGA 0/1: 76.5%; 95% CI, 70.4%-82.5%; P < .001 for both). At week 28, 336 responders were rerandomized to risankizumab (n = 111) or treatment withdrawal (n = 225). At week 52, the sPGA 0/1 score was achieved by 97 patients (87.4%) receiving risankizumab vs 138 patients (61.3%) receiving placebo. At week 104, the sPGA 0/1 score was achieved by 90 patients (81.1%) receiving risankizumab vs 16 patients (7.1%) receiving placebo (placebo-adjusted differences: week 52: 25.9%; 95% CI, 17.3%-34.6%; week 104: 73.9%; 95% CI, 66.0%-81.9%; P < .001 for both). Rates of treatment-emergent adverse events were similar between risankizumab (186 [45.7%]) and placebo (49 [49.0%]) in part A1 and remained stable over time.Conclusions and relevanceRisankizumab showed superior efficacy compared with placebo through 16 weeks and treatment withdrawal through 2 years. Risankizumab was well tolerated, with no unexpected safety findings during the 2-year trial.Trial registrationClinicalTrials.gov Identifier: NCT02672852.
| S-EPMC7142813 | biostudies-literature
Project description:Risankizumab, a humanized monoclonal antibody that targets interleukin-23 p19 subunit, was developed for the treatment of psoriasis. This work characterizes risankizumab pharmacokinetics in Japanese and Chinese healthy subjects compared with white healthy subjects and in Japanese patients with moderate to severe plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis. A phase 1, single-dose study evaluated risankizumab pharmacokinetics and safety/tolerability in healthy white (18 and 300 mg subcutaneous [SC]), Japanese (18, 90, and 300 mg SC and 200, 600, and 1200 mg intravenous [IV]), and Chinese (18, 90, and 300 mg SC) subjects; pharmacokinetic data were analyzed using noncompartmental methods. Risankizumab pharmacokinetic data from phase 2/3 studies in Japanese patients with plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis following multiple SC doses of 75 mg or 150 mg were analyzed using a population pharmacokinetic approach along with data from the phase 1 and global phase 1 to 3 studies. Risankizumab plasma exposures (peak plasma concentration and area under the concentration-time curve) were approximately dose-proportional across 18- to 300-mg SC or 200- to 1200-mg IV doses. Risankizumab terminal elimination half-life (harmonic mean 27-34 days) was comparable across doses and ethnicities. Risankizumab exposures were approximately 20% to 30% higher in Japanese and Chinese healthy subjects compared with white healthy subjects or in Japanese patients compared with non-Japanese patients. After accounting for body-weight differences, risankizumab exposures were comparable across ethnicities. Overall, there was no ethnic impact on risankizumab pharmacokinetics, and the small difference in exposure due to body weight has no clinical relevance.
| S-EPMC6852105 | biostudies-literature
Project description:IntroductionRisankizumab has demonstrated efficacy in treating moderate-to-severe psoriasis. The phase-3 IMMhance trial (NCT02672852) examined the effect of continuing versus withdrawing from risankizumab treatment on psoriasis severity, including the Psoriasis Area and Severity Index (PASI) and static Physician Global Assessment (sPGA). However, the effect of withdrawal on health-related quality of life (HRQL) was not assessed. Therefore, this study was conducted to evaluate the impact of risankizumab withdrawal on HRQL measured by the Dermatology Life Quality Index (DLQI). Because DLQI was not measured beyond week 16 in IMMhance, a machine learning predictive model for DLQI was developed.MethodsA machine learning model for DLQI was fitted using repeated measures data from three phase-3 trials (NCT02684370, NCT02684357, NCT02694523) (pooled N = 1602). An elastic-net algorithm performed automated variable selection among candidate predictors including concurrent PASI and sPGA, demographics, and interaction terms. The machine learning model was used to predict DLQI at weeks 28-104 of IMMhance among patients re-randomized to continue (N = 111) or withdraw from (N = 225) risankizumab after achieving response (sPGA = 0/1) at week 28.ResultsThe machine learning predictive model demonstrated good statistical fit during tenfold cross-validation and external validation against observed DLQI at weeks 0-16 of IMMhance (N = 507). Predicted improvements in DLQI from baseline were lower in the withdrawal versus the continuation cohort (mean DLQI change at week 104, -5.9 versus -11.5, difference [95% CI] = 5.6 [4.1, 7.3]). Predicted DLQI deteriorated more extensively than PASI (49.7% versus 36.4%) after treatment withdrawal.ConclusionsThe predicted DLQI score deteriorated more rapidly after risankizumab withdrawal than the PASI score, an objective measure of disease. These findings suggest that the deterioration in HRQL reflects more substantial impacts after risankizumab discontinuation than those measured by PASI only.
| S-EPMC8322223 | biostudies-literature
Project description:Psoriasis is a chronic immune-mediated disease involving complex interaction of T cells and keratinocytes. The comprehensive pathogenesis of psoriasis is not fully understood but the IL-23/Th17 axis is a central pathway in driving disease development. Guselkumab is the first treatment of moderate-to-severe psoriasis that specifically targets the p19 subunit of IL-23. The benefit of guselkumab has been established by a number of clinical trials including demonstration of greater long-term efficacy in recent comparator trials. This review addresses the results of head-to-head trials (ECLIPSE, IXORA-R, and POLARIS) that compared guselkumab to secukinumab, ixekizumab, and fumaric acid esters. The previously demonstrated long-term efficacy of guselkumab has been corroborated by many recently published studies. The effective and safe profile, convenient dosing, and improved quality of life in patients make gulselkumab a viable first-line treatment option for moderate-to-severe psoriasis.
| S-EPMC7815086 | biostudies-literature
Project description:BackgroundRisankizumab has demonstrated durable, high rates of efficacy in patients with moderate-to-severe plaque psoriasis as assessed by the achievement of relative Psoriasis Area and Severity Index (PASI) improvement and Dermatology Life Quality Index (DLQI) 0/1.ObjectivesThe aim of this post hoc analysis is to assess the achievement of absolute PASI thresholds and related improvements in health-related quality of life (HRQoL) in patients with moderate-to-severe plaque psoriasis treated with (i) risankizumab compared with ustekinumab, and (ii) long-term (>52 weeks to 172 weeks) risankizumab.MethodsData from patients randomised to 150 mg risankizumab or 45 or 90 mg ustekinumab in replicate randomised controlled trials UltIMMa-1 and UltIMMa-2 were analysed for the achievement of absolute PASI thresholds PASI ≤ 3, PASI ≤ 1, and PASI = 0, time to achieve these thresholds, and combined PASI and DLQI endpoints. Data from pat ients initially randomised to risankizumab who continued on risankizumab in the open-label extension study LIMMitless were analysed for the achievement of absolute PASI levels, mean DLQI scores, and DLQI 0/1.ResultsSignificantly greater proportions of patients treated with risankizumab compared with ustekinumab achieved PASI ≤ 3, PASI ≤ 1, and PASI = 0, as well as combined endpoints for absolute PASI and DLQI [(PASI ≤ 3 and DLQI ≤ 5) or (PASI ≤ 1 and DLQI 0/1)]. The median time to first achieve PASI ≤ 3, PASI ≤ 1, and PASI = 0 was significantly lower for risankizumab-treated patients compared with ustekinumab-treated patients. Among patients treated with long-term risankizumab, more than 90% achieved PASI ≤ 3 though week 172 and more than 80% achieved DLQI 0/1. Low absolute PASI scores corresponded with low mean absolute DLQI scores through week 172 of continuous risankizumab treatment.ConclusionsRisankizumab treatment demonstrated high rates of rapid and durable efficacy as measured by absolute PASI thresholds and improvements in patient HRQoL.
| S-EPMC9314097 | biostudies-literature
Project description:Spa therapy is considered an add-on treatment for psoriasis, but without any objective evaluation in the absence of randomized trials. This multicenter, open-label, randomized trial compared immediate spa therapy versus a control group having usual treatments until study assessments at 4.5 months. Spa therapy was proposed in five French spa resorts with standardized programs. Inclusion criteria were adults with plaque psoriasis, Dermatology Life Quality Index (DLQI) > 10, and stable medical treatment in the last 6 months. The main objective was DLQI ≤ 10 at 4.5 months after inclusion. VQ-Dermato and EQ5D-3L also assessed quality of life (QoL), Perceived Stress Scale (PSS) stress, and visual analogue scales (VAS) pain and pruritus. Between January 2015 and November 2018, 128 patients were randomized to either immediate spa therapy (64) (within 34 days, median) or usual treatments (61) until assessment at 4.5 months. Most were first-time spa users (71.2%). Mean DLQI and Psoriasis Area and Severity Index at inclusion were 16.7 and 10.5, respectively. Immediate spa therapy patients achieved the primary objective for 66.1% [95% CI 52.6% > 77.9%] vs 41.4% [95% CI 28.6% > 55.1%] control group patients (p = 0.007). VQ-Dermato scores and pruritus VAS significantly improved. Outcomes at 12-month follow-up of the immediate spa therapy group showed persistent improvement of DLQI, VQ-Dermato, and pruritus. This randomized controlled trial demonstrated that a cure of spa therapy improves QoL and alleviates certain symptoms of psoriasis, in short and long terms. This justifies its integration in the therapeutic strategies for psoriasis. Trial registration number: ClinicalTrials.gov Identifier: NCT02098213.
| S-EPMC9132808 | biostudies-literature