Dataset Information

Body Region Involvement and Quality of Life in Psoriasis: Analysis of a Randomized Controlled Trial of Adalimumab.

ABSTRACT: Psoriasis severity and treatment responsiveness vary by body region, which differentially impacts quality of life (QoL).The objective of the study was to examine adalimumab efficacy by body region and regional response and QoL relationship.Patients (n = 1212) with moderate-to-severe psoriasis were randomized 2:1 to 80 mg at week 0, followed by adalimumab 40 mg or placebo every other week for 16 weeks in the double-blind REVEAL study. Psoriasis Area and Severity Index (PASI) responses and Dermatology Life Quality Index outcomes were analyzed.Week 16 regional mean PASI improvements were significantly greater with adalimumab (83.1 ± 1.57, 81.3 ± 1.58, 75.7 ± 1.34, and 73.9 ± 1.26% in the trunk, head, upper extremities, and lower extremities, respectively; all p < 0.001 vs. placebo). Likewise, percentages of patients with regional PASI ?75/?90/100% reduction from baseline were significantly higher with adalimumab (all p < 0.001); adalimumab responses were greater for the trunk (77.9/65.0/59.1%) and head (74.6/66.1/62.8%; all p ? 0.0001 vs. lower) than upper (67.7/45.1/39.6%; p = 0.4, p = 0.04, p = 0.0005, respectively, vs. lower) and lower extremities (65.7/40.0/31.3%). Adalimumab significantly improved Dermatology Life Quality Index scores vs. placebo (8.2- vs 1.7-point decrease from baseline; p < 0.001).The study was a post hoc analysis.Adalimumab treatment resulted in statistically significant and clinically meaningful improvements in disease severity and QoL. QoL improvements were associated with PASI responses in all body regions.ClinicalTrials.gov identifier NCT00237887.

SUBMITTER: Armstrong AW

PROVIDER: S-EPMC5110581 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Body Region Involvement and Quality of Life in Psoriasis: Analysis of a Randomized Controlled Trial of Adalimumab.

Armstrong April W AW Villanueva Quintero Delfina Guadalupe DG Echeverría Cristina M CM Gu Yihua Y Karunaratne Mahinda M Reyes Servín Ofelia O

American journal of clinical dermatology 20161201 6

<h4>Background</h4>Psoriasis severity and treatment responsiveness vary by body region, which differentially impacts quality of life (QoL).<h4>Objective</h4>The objective of the study was to examine adalimumab efficacy by body region and regional response and QoL relationship.<h4>Methods</h4>Patients (n = 1212) with moderate-to-severe psoriasis were randomized 2:1 to 80 mg at week 0, followed by adalimumab 40 mg or placebo every other week for 16 weeks in the double-blind REVEAL study. Psoriasis ...[more]

PMID: 27815915

Similar Datasets

Project description:BackgroundBI 695501 is an FDA-approved biosimilar to adalimumab reference product (RP). VOLTAIRE-X was a randomized clinical trial to assess outcomes with a biosimilar monoclonal antibody in line with the FDA requirements for designation as an 'interchangeable' biosimilar.ObjectiveThe aim of this study was to assess whether multiple switches between adalimumab RP and BI 695501 lead to equivalent pharmacokinetics and a similar safety and immunogenicity profile compared with continuous adalimumab RP.MethodsWe conducted a phase III, double-blind, randomized controlled trial between July 19, 2017, and April 16, 2019. There were 49 investigational sites across Europe and North America. Of 323 screened patients with moderate-to-severe chronic plaque psoriasis, 259 were treated with adalimumab RP during the run-in period. Of these, 118 and 120 were randomized to the continuous or switching arms, respectively. Interventions consisted of a run-in period with adalimumab RP 80 mg subcutaneously (SC) on Day 1, then 40 mg SC every other week (EOW) Weeks 2-12. Patients were then randomized to receive adalimumab RP 40 mg EOW Weeks 14-48 (continuous arm) or BI 695501 40 mg Weeks 14 and 16, adalimumab RP 40 mg Weeks 18 and 20, and BI 695501 40 mg EOW Weeks 22 to 48 (switching arm); all interventions were given SC. Primary endpoints were pharmacokinetics parameters, area under the plasma concentration-time curve (AUCτ,30-32) and maximum observed drug plasma concentration (Cmax,30-32), measured after the third switch during the Week 30-32 dosing interval.Results238 patients (mean [standard deviation] age 44.9 [13.8]; 66.0% male) were treated in the switching (n = 118) or continuous arms (n = 120). Adjusted mean Cmax,30-32 was 7.08 and 7.00 μg/mL in the switching and continuous treatment arms, respectively; adjusted mean AUCτ,30-32 was 2025.8 and 1925.9 μg h/mL. Point estimate for mean ratio for AUCτ,30-32 was 105.2% (90.2% confidence interval [CI] 96.6-114.6), and 101.1% (90.2% CI 93.3-109.7) for Cmax,30-32. Both CIs were within a predefined bioequivalence range of 80.0-125.0%. Treatment-emergent adverse events led to discontinuation in 0.8% and 1.7% of patients in the switching and continuous treatment arms, and Psoriasis Area and Severity Index (PASI) scores were highly similar in the two arms across the entire trial period.ConclusionsPharmacokinetic equivalence was demonstrated, with highly similar efficacy and immunogenicity, and comparable safety observed in patients with chronic plaque psoriasis who received either adalimumab RP continuously or who switched between adalimumab RP and BI 695501.Trial registrationClinicalTrials.gov: NCT03210259 (registered July 2017); Eudract.ema.europa.eu: 2016-002254-20.

Project description:IntroductionHealth-related quality of life (HRQoL) is an important part of the clinical assessment and management of psoriasis. Few studies have investigated the effects of withdrawing treatment on the relationship between HRQoL and objective clinical manifestations of psoriasis. This post hoc subanalysis of a clinical trial (REVEAL) examined the relationship of HRQoL [assessed with the Dermatology Life Quality Index (DLQI)] and objective disease activity [assessed with the Psoriasis Area and Severity Index (PASI)] among patients before and after they underwent protocol-mandated discontinuation of psoriasis therapy.MethodsAdult patients with moderate-to-severe plaque psoriasis who received adalimumab from baseline and had 75% or greater improvement in the PASI score at weeks 16 and 33 were re-randomized to adalimumab 40 mg or placebo every other week from weeks 33 to 52. DLQI and PASI scores were compared at baseline (week 0), early in treatment (week 4), directly before randomized withdrawal (week 33), and up to 19 weeks after treatment discontinuation (week 52; last observations carried forward). Correlations between DLQI total score and PASI score at week 4 and week 52 were modeled by linear regression.ResultsIn the patients (N = 240) who underwent protocol-mandated discontinuation of psoriasis treatment after achieving PASI 75 response, mean PASI scores at week 52 were lower (i.e., better) compared with week 4, yet mean DLQI scores were higher (i.e., worse). An approximately twofold disproportionately greater degree of worsening of DLQI score compared with the degree of worsening of PASI was observed while patients underwent discontinuation of therapy (week 52) compared with early in treatment (week 4). There was a significant interaction (P < 0.0001) between the PASI-DLQI correlation and study period (week 4 or 52).ConclusionDiscontinuing therapy in patients who initially responded to treatment, as seen in this analysis with adalimumab, disproportionately worsened patient-reported HRQoL relative to the worsening of PASI.

Project description:IntroductionThe objective of this study was to demonstrate that BCD-057 is similar to innovator adalimumab (iADA) in terms of efficacy, safety, and pharmacokinetics in steady state in the target population of patients with moderate to severe plaque psoriasis (NCT02762955).MethodsPatients were randomized in 1:1 ratio to receive 80 mg of BCD-057 or iADA at week 0 and 40 mg thereafter every other week from week 1. At week 24 patients from iADA group were re-randomized (1:1) to continue iADA or to be switched to BCD-057. The primary efficacy endpoint was 75% improvement in Psoriasis Area and Severity Index from baseline (PASI 75), secondary endpoints included PASI percent improvement and relative change in affected Body Surface Area (BSA) from baseline at weeks 16, 24, 33, and 55. Safety was assessed through monitoring of adverse events (AEs) and antidrug antibodies. Pharmacokinetics was evaluated at steady state.ResultsOverall, 346 adult patients were included in the study (174/172 patients in BCD-057/iADA arms, respectively). At week 16 PASI 75 was achieved by 60.34% and 63.37% of patients in BCD-057 and iADA arms, respectively (p = 0.5622). Bounds of the calculated 95% confidence interval (CI) for the difference between PASI 75 responses in arms [-13.26%; 7.2%] fall within the equivalence margin [-15% to 15%] demonstrating equivalent efficacy of BCD-057 and iADA. At week 55 81.61%, 85.56%, and 80.49% of patients in BCD-057, iADA and iADA/BCD-057 arms achieved PASI 75. Comparison of the secondary endpoints did not show significant differences between arms. A comparable pharmacokinetics was shown at steady state. Safety profiles and proportions of patients with antidrug antibodies were similar between arms. The switch from the iADA to BCD-057 did not affect the immunogenicity profile.ConclusionObtained data demonstrate that BCD-057 and iADA are highly similar in clinical efficacy, pharmacokinetics, safety, and immunogenicity in patients with moderate to severe plaque psoriasis.

Project description:BackgroundThe introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases.MethodsThis is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past.DiscussionOPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy.Trial registrationNTR4499 . Registered on 7 April 2014.

Project description:ObjectiveTo evaluate the impact of adalimumab on health-related quality of life (HRQOL) for patients with moderate to severe plaque psoriasis.BackgroundPsoriasis is a chronic, inflammatory, immune-mediated disease that has a significant impact on patients' HRQOL. Adalimumab is a fully human monoclonal antibody that blocks tumor necrosis factor, a pro-inflammatory cytokine, and is effective and well-tolerated for patients with moderate to severe psoriasis.MethodsData were obtained for a secondary analysis of patients in a randomized, controlled Phase III trial evaluating the effect of adalimumab in patients with psoriasis (N = 1,205). Patients with moderate to severe psoriasis were randomized in a 2:1 ratio to adalimumab 80 mg (two 40 mg injections administered subcutaneously at baseline followed by one 40 mg injection every other week from Week 1 to Week 15) or placebo. Short Form-36 (SF-36) Health Survey scores of psoriasis patients were used to assess HRQOL and were compared with United States (US) population norms at baseline and Week 16.ResultsBaseline Physical Component Summary (PCS) scores for the placebo and adalimumab groups were similar to the general US population. Baseline mean Mental Component Summary (MCS) scores were significantly lower for the adalimumab and placebo groups compared with the general population (47.4, 47.7, and 50.8 points, respectively; p < 0.0001). PCS scores at Week 16 for patients receiving adalimumab had improved and were significantly greater than scores for the general US population (52.7 vs 48.9; p < 0.001). Compared with the general US population, MCS scores at Week 16 were similar for patients receiving adalimumab (51.2 vs 50.8; p = 1.000) and lower for patients receiving placebo (50.8 vs 48.7; p < 0.0001).ConclusionPsoriasis has a broad impact on patient functioning and well-being. Improvement in skin lesions and joint symptoms associated with adalimumab treatment was accompanied by improvements in HRQOL to levels that were similar to or greater than those of the general US population.Trial registrationClinicaltrials.gov NCT00237887.

Project description:ObjectiveTo evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis (SpA).MethodsABILITY-2 is an ongoing phase III, multicenter study of adalimumab treatment. Eligible patients age ≥18 years fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for peripheral SpA, did not have a prior diagnosis of psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis (AS), and had an inadequate response or intolerance to nonsteroidal antiinflammatory drugs (NSAIDs). Patients were randomized 1:1 to receive adalimumab 40 mg every other week or matching placebo for 12 weeks, followed by a 144-week open-label period. The primary end point was the proportion of patients achieving 40% improvement in disease activity according to the Peripheral SpA Response Criteria (PSpARC40) at week 12. This was defined as ≥40% improvement from baseline (≥20-mm absolute improvement on a visual analog scale) in patient's global assessments of disease activity and pain, and ≥40% improvement in at least one of the following features: swollen joint and tender joint counts, total enthesitis count, or dactylitis count. Adverse events were recorded throughout the study.ResultsIn total, 165 patients were randomized to a treatment group, of whom 81 were randomized to receive placebo and 84 to receive adalimumab. Baseline demographics and disease characteristics were generally similar between the 2 groups. At week 12, a greater proportion of patients receiving adalimumab achieved a PSpARC40 response compared to patients receiving placebo (39% versus 20%; P = 0.006). Overall, improvement in other outcomes was greater in the adalimumab group compared to the placebo group. The rates of adverse events were similar in both treatment groups.ConclusionTreatment with adalimumab ameliorated the signs and symptoms of disease and improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs, with a safety profile consistent with that observed in patients with AS, PsA, or other immune-mediated diseases.

Dataset Information

Body Region Involvement and Quality of Life in Psoriasis: Analysis of a Randomized Controlled Trial of Adalimumab.

Publications

Body Region Involvement and Quality of Life in Psoriasis: Analysis of a Randomized Controlled Trial of Adalimumab.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets