Dataset Information

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

ABSTRACT:

Background

Psoriasis severity and treatment responsiveness vary by body region, which differentially impacts quality of life (QoL).

Objective

The objective of the study was to examine adalimumab efficacy by body region and regional response and QoL relationship.

Methods

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.

Results

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).

Limitations

The study was a post hoc analysis.

Conclusions

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.

Trial registration

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

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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.

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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.

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Dataset Information

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

Background

Objective

Methods

Results

Limitations

Conclusions

Trial registration

Publications

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

Similar Datasets

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