Secukinumab: A Review in Moderate to Severe Pediatric Plaque Psoriasis.
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ABSTRACT:
SUBMITTER: Blair HA
PROVIDER: S-EPMC8599386 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:UnlabelledPsoriasis is a chronic immune-mediated inflammatory skin disease commonly categorized as mild, moderate, or severe. Moderate-to-severe psoriasis is associated with significant comorbidity and has been shown to severely impair quality of life. Moreover, psoriasis is associated with high costs, including those associated with treatment, which have increased recently with the inclusion of biological systemic agents (most recently secukinumab) as available treatment options. However, despite clear evidence of their value in the treatment of moderate-to-severe plaque psoriasis, in Italy access to the biological agents remains limited to dermatological centers originally involved in the Psocare network. The impact of secukinumab entry into the market in Italy is still to be determined, but we believe that it will be associated with significant changes in the way in which biological treatments for psoriasis are accessed and prescribed in Italy. It is noteworthy that in January 2015, the European Medicines Agency approved secukinumab as first-line systemic therapy in this indication.FundingNovartis, Italy.
| S-EPMC4906108 | 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, a chronic immune-mediated disease, is associated with an increased risk of cardiovascular events and mortality. Secukinumab selectively neutralizes IL-17A and has reported high efficacy with a favorable safety profile in various psoriatic disease manifestations. Subsequent to the 12-week randomized, placebo-controlled, double-blind treatment period, patients with moderate-to-severe psoriasis received secukinumab for 40 weeks. Vascular inflammation using 18F-2-fluorodeoxyglucose-positron emission tomography/computed tomography imaging and blood-based cardiometabolic was assessed at week 0, 12, and 52. The difference in change in aortic inflammation from baseline to week 12 for secukinumab (n = 46) versus placebo (n = 45) was -0.053 (95% confidence interval = -0.169 to 0.064; P= 0.37). Small increases in total cholesterol, low-density lipoprotein, and low-density lipoprotein particles, but no changes in markers of inflammation, adiposity, insulin resistance, or predictors of diabetes, were observed with secukinumab treatment compared with placebo. At week 52, reductions in TNF-α (P= 0.0063) and ferritin (P= 0.0354), and an increase in fetuin-A (P= 0.0024), were observed with secukinumab treatment compared with baseline. No significant changes in aortic inflammation or markers of advanced lipoprotein characterization, adiposity, or insulin resistance were observed with secukinumab treatment compared with baseline. Secukinumab exhibited a neutral impact on aortic vascular inflammation and biomarkers of cardiometabolic disease after 52 weeks of treatment.
| S-EPMC7434644 | biostudies-literature
Project description:BackgroundThe efficacy and safety of biologic treatments for children and adolescents with moderate to severe psoriasis should be examined over a considerable time period and in different subgroups.ObjectiveWe report the efficacy and safety of secukinumab low dose (LD) and high dose (HD) regimens in pediatric patients with moderate to severe psoriasis for up to Week 52.MethodsThis was a randomized, open-label, parallel-group, multicenter study in patients aged 6 to < 18 years. Patients were randomized in a 1:1 ratio to receive LD (75/75/150 mg; N = 42) or HD (75/150/300 mg; N = 42) subcutaneous secukinumab. At randomization, patients were stratified by weight (< 25, 25 to < 50, ≥ 50 kg) and disease severity (moderate/severe). The study is ongoing; the present analysis included data up to Week 52 collected from August 29, 2018 (first patient first visit) to May 28, 2020 (last patient last visit for Week 52). Efficacy was measured using Investigator's Global Assessment modified 2011 0/1 (IGA 0/1) and Psoriasis Area Severity Index (PASI) 75/90/100 response. Safety outcomes included assessment of adverse events.ResultsOf the 84 enrolled patients, 78 (92.9%) completed 52 weeks of treatment. Overall, response rates for PASI 75 and IGA 0/1 were similar between the LD (92.8/88.9%) and HD (93.3/84.7%) groups at Week 52. In the LD and HD groups, PASI 90/100 responses at Week 52 were 78.7/53.5% and 84.7/70.0%, respectively. The proportions of IGA 0/1 and PASI 75/90 responders were comparable for the age, body weight, and disease severity subgroups in the secukinumab LD and HD groups. Mean absolute PASI change from baseline at week 52 was - 17.3 ± standard deviation 5.0 and - 18.2 ± 7.0, a percentage change of - 94.3 and - 94.5% for the LD and HD groups, respectively. More than 70% of evaluable patients achieved Children's Dermatology Life Quality Index 0/1 at Week 52 (LD 70.7%; HD 70.3%). The safety profile was consistent with that in adults, with no new safety signals for either secukinumab dosing regimen.ConclusionA high proportion of pediatric patients with psoriasis responded to both dosing regimens of secukinumab and maintained clinical responses through 52 weeks of treatment. No clinical difference was observed in the efficacy of secukinumab across the pediatric subgroups. Safety events were consistent with the established safety profile of secukinumab.Trial registrationClinicalTrials.gov: NCT03668613.
| S-EPMC9205811 | biostudies-literature
Project description:IntroductionSecukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab.MethodsIn the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator's Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients' quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized.ResultsBoth co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p < 0.0001). PASI 90 responses were greater with secukinumab compared to ustekinumab from as early as Week 4 (16.7% vs. 4.0%) and out to Week 16 (76.6% vs. 54.2%). Similarly, IGA mod 2011 0/1 findings were greater with secukinumab at Week 4 (26.9% vs. 7.8%) and at Week 16 (78.6% vs. 59.1%). DLQI 0/1 response rates were also greater with secukinumab compared to ustekinumab at Week 4 (33.9% vs. 18.0%), Week 12 (64.0% vs. 51.7%), and Week 16 (68.4% vs. 55.9%).ConclusionThe results of this study confirm the superior efficacy of secukinumab over ustekinumab in treating patients with moderate to severe psoriasis.Trial registrationClinicaltrials.gov Identifier, NCT02826603.FundingNovartis Pharma AG, Basel, Switzerland.
| S-EPMC6261116 | biostudies-literature
Project description:Background The efficacy and safety of secukinumab in patients with psoriasis has been established in randomised clinical trials. However, data on effectiveness and safety of secukinumab in Latin American real-world settings are scarce.ObjectivesTo evaluate the effectiveness and safety of secukinumab in real-world settings in patients with psoriasis in Latin America.MethodsPURE is an ongoing multinational, prospective, observational study in patients with moderate-to-severe chronic plaque psoriasis in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab and other approved therapies. The study enrolled (1:1) patients treated with secukinumab versus other approved therapies (other Tx) per local standard of care from 81 community- and hospital-based speciality sites (21 in Latin America). Here, we report effectiveness and safety outcomes with secukinumab and other Tx for plaque psoriasis for up to 12 months in a Latin American population.ResultsOverall, 187 patients were included in the analysis, 89 of whom initiated secukinumab treatment and 98 of whom received other Tx. At month 12, 84.4%, 71.1% and 53.3% of patients treated with secukinumab achieved Psoriasis Area and Severity Index (PASI) 75/90/100, respectively, compared with 66.7%, 47.9% and 29.2% of patients who received other Tx. Investigator Global Assessment (IGA) 0/1 responders in secukinumab versus other Tx were 78.3% versus 36.7% at month 3 and 81.8% versus 66.7% at month 12, respectively. Overall, the proportion of patients achieving Dermatology Life Quality Index (DLQI) 0/1 improved from 6.9% at baseline to 76.5% at month 12 in patients treated with secukinumab versus 5.6% at baseline to 54.5% at month 12 in patients on other Tx. No unexpected adverse events were reported during the 12-month observation period.ConclusionSecukinumab demonstrated real-world effectiveness and improved dermatology quality-of-life in chronic plaque psoriasis patients from Latin America.Trial registrationPURE: NCT02786186.
| S-EPMC9823177 | 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:Secukinumab is a human monoclonal antibody with demonstrated efficacy for moderate to severe psoriasis; it binds to and neutralizes interleukin (IL)-17A. The pharmacokinetic (PK) parameters of secukinumab were best described by a 2-compartment model. Only weight was included in the final model, as other covariates did not affect clinical relevance. The estimated serum clearance of secukinumab was 0.19 L/day, with interindividual variability (IIV) of 32% coefficient of variation (CV), and low total volume of distribution (central compartment volume, 3.61 L with IIV of 30% CV; peripheral compartment volume, 2.87 L with IIV of 18% CV). The bioavailability of secukinumab after subcutaneous dosing was approximately 73%, with an absorption rate of 0.18/day with IIV of 35% CV. The PK profile of secukinumab was linear, with no evidence of a dose dependence of clearance. Clearance and volume of secukinumab varied with body weight in an allometric relationship. The time to maximum serum concentration at steady state occurred approximately 6 days after dosing for both secukinumab 300 mg and secukinumab 150 mg. Overall, the PK properties of secukinumab were typical of a 150-kDa human IgG1 antibody interacting with a soluble target.
| S-EPMC5485066 | biostudies-literature
Project description:IntroductionThe impact of psoriasis varies with the body region affected. In addition, patients have different perceptions of disease improvement and treatment satisfaction based on the location of skin clearance with treatment. The monoclonal antibody secukinumab selectively targets interleukin-17A-a central cytokine of psoriasis-and provides rapid and sustained clearance for moderate-to-severe psoriasis affecting all body regions. The objective of this study was to evaluate the efficacy of secukinumab on moderate-to-severe psoriasis affecting the trunk, upper limbs, and lower limbs.MethodsData were pooled from four phase 3 studies. To be included in the analysis for each body region, patients were required to have a Psoriasis Area and Severity Index (PASI) score ≥12 for that body region and psoriasis covering ≥10% of the surface area of that region. Secukinumab was administered at Baseline, Weeks 1, 2 and 3, and then every 4 weeks from Week 4 to 48.ResultsAcross the trunk, upper limbs, and lower limbs, initial PASI subscore responses were sustained to Week 52. At Week 52, trunk (T) PASI 90/100 responses were achieved by 78.4%/71.1% of patients receiving secukinumab 300 mg, respectively, and by 66.3%/56.9% of patients receiving secukinumab 150 mg, respectively. At Week 52, upper limb (UL) PASI 90/100 responses were achieved by 67.3%/59.1% of patients receiving secukinumab 300 mg, respectively, and by 50.3%/43.3% of patients receiving secukinumab 150 mg, respectively. At Week 52, lower limb (LL) PASI 90/100 responses were achieved by 63.9%/55.3% of patients receiving secukinumab 300 mg, respectively, and by 45.1%/36.4% of patients receiving secukinumab 150 mg, respectively. A 50% reduction in mean PASI subscore occurred after 2.8, 2.9, and 3.4 weeks with secukinumab 300 mg on the trunk, upper limbs, and lower limbs, respectively.ConclusionSecukinumab provided robust and sustained efficacy for moderate-to-severe psoriasis affecting the trunk, upper limbs, and lower limbs.FundingNovartis Pharmaceuticals Corporation.Trial registrationClinicalTrials.gov identifiers: NCT01365455, NCT01358578, NCT01555125, and NCT01636687.
| S-EPMC5120629 | biostudies-literature
Project description:BackgroundPsoriasis is a chronic inflammatory skin disease, affecting patients of a wide age range, including elderly patients. Elderly patients can respond differently to drug treatments and can be more vulnerable to adverse reactions. There are limited data on biologic therapies for psoriasis in elderly subjects. Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has proven significant efficacy in the treatment of moderate to severe psoriasis.AimsA post-hoc analysis of three phase III trials (ERASURE, FIXTURE and CLEAR) was performed to evaluate the efficacy and safety of secukinumab in elderly subjects.MethodsStudies were multicentre, randomized, parallel-group, double-blind, 52-week phase III trials in subjects with moderate to severe plaque psoriasis. For efficacy analyses, 67 elderly subjects (≥ 65 years) treated with secukinumab 300 mg were compared with 841 younger subjects (18-64 years). Psoriasis Area and Severity Index (PASI), Dermatological Life Quality Index (DLQI) and safety were analysed.ResultsElderly subjects had higher baseline frequencies of cardiovascular and metabolic disorders. Secukinumab efficacy in elderly subjects was comparable to that in younger subjects throughout 52 weeks of treatment. PASI 75 response was reached by 81.8% of elderly subjects and 79.4% of younger subjects at Week 52. Similar rates of DLQI 0/1 response were observed. The total rate of adverse events was similar between elderly and younger subjects.ConclusionsSecukinumab at the recommended dose (300 mg) is effective and acceptably safe in subjects aged ≥ 65 years with moderate to severe psoriasis, with quality-of-life benefits, despite an increased prevalence of cardiovascular and metabolic comorbidities in this population.
| S-EPMC5847154 | biostudies-literature