Risankizumab for the treatment of moderate-to-severe psoriasis: A multicenter, retrospective, 1 year real-life study.
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ABSTRACT:
SUBMITTER: Caldarola G
PROVIDER: S-EPMC9287038 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:New biologic agents targeting interleukin (IL)23/T-helper17 axis, such as tildrakizumab, have been developed for the treatment of plaque psoriasis. To analyze the efficacy and safety of tildrakizumab in a real life setting of patients affected by moderate-to-severe psoriasis over a 28-week treatment period. A multicentric retrospective study was conducted in patients who initiated tildrakizumab between February 2020 and March 2021. Psoriasis Area and Severity Index-PASI was measured at baseline and after 4, 16 and 28 weeks. The percentage change in PASI value from baseline to the considered time-points, proportion of patients with absolute PASI <3 at week 28 and the percentages of achieving a PASI75 or PASI90 response were assessed. Data about potential safety issues and adverse events (AEs) were collected. Statistical analysis were performed for establish clinical efficacy and for variables predicting clinical response. Fifty nine patients with psoriasis were included. Overall mean PASI percentage reduction was of 88% from baseline to week 28 and 47 out of 59 patients (79.7%) at week 28 had an absolute PASI <3. PASI75 and PASI90 responses at week 28 were achieved by 48 (81.40%) patients and 38 (64.4.0%) patients, respectively. No substantial associations between gender, body mass index - BMI, PASI at baseline and prior exposition to biological therapies and the efficacy endpoints were retrieved. No serious safety issues or discontinuations related to adverse events were reported. In our real-life study, tildrakizumab showed high efficacy and a favorable safety profile, regardless of patient- and disease-related factors.
| S-EPMC9287013 | 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:Psoriasis is a common disease, which has a considerable impact on patients and the health care system. Treatment approaches to the disease may be various because some issues are not definitely addressed. Moreover, the therapeutic paradigms are continuously changing because of the recent approval of new treatments for psoriasis such as interleukin (IL)-17 inhibitors and apremilast. In this review, the factors influencing psoriasis severity, the indications for systemic treatments, the overall parameters to be considered in the treatment choice, life style interventions, and the recommendations for the use, screening, and monitoring of systemic therapies available including acitretin, cyclosporine, methotrexate, apremilast, adalimumab, etanercept, infliximab, secukinumab, ixekizumab, and ustekinumab are discussed. Finally, treatment approaches in special patient populations including children, the elderly, pregnant women, patients with a history of neoplasm, and candidates for surgical procedures are reported.
| S-EPMC5713395 | biostudies-other
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: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: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: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: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:BackgroundPsoriasis imposes a significant treatment burden on patients, particularly impacting well-being and quality of life (QoL). The psychosocial impact of psoriasis treatments remains unexplored in most patient populations.ObjectiveTo assess the impact of adalimumab on health-related QoL (HRQoL) in Korean patients with psoriasis.MethodsThis 24-week, multicenter, observational study, assessed HRQoL in Korean patients treated with adalimumab in a real-world setting. Patient-reported outcomes (PROs) including European Quality of Life-5 Dimension scale (EQ-5D), EQ-5D VAS, SF-36, and DLQI were evaluated at week 16 and 24, versus baseline. Patient satisfaction was assessed using TSQM.ResultsAmong 97 enrolled patients, 77 were assessed for treatment effectiveness. Most patients were male (52, 67.5%) and mean age was 45.4 years. Median baseline body surface area and Psoriasis Area and Severity Index (PASI) scores were 15.00 (range 4.00~80.00) and 12.40 (range 2.70~39.40), respectively. Statistically significant improvements in all PROs were observed between baseline and week 24. Mean EQ-5D score improved from 0.88 (standard deviation [SD], 0.14) at baseline to 0.91 (SD, 0.17) at week 24 (p=0.0067). The number of patients with changes in PASI 75, 90, or 100 from baseline to week 16 and 24 were 65 (84.4%), 17 (22.1%), and 1 (1.3%); and 64 (83.1%), 21 (27.3%), and 2 (2.6%), respectively. Overall treatment satisfaction was reported, including effectiveness and convenience. No unexpected safety findings were noted.ConclusionAdalimumab improved QoL and was well-tolerated in Korean patients with moderate to severe psoriasis, as demonstrated in a real-world setting. Clinical trial registration number (clinicaltrials.gov: NCT03099083).
| S-EPMC10112372 | biostudies-literature