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Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity.

ABSTRACT: OBJECTIVES:To evaluate the relationship between radiographic progression and disease activity in subjects with PsA treated with adalimumab (ADA) or placebo (PBO) and the impact of concomitant MTX. METHODS:This was a post hoc analysis of the randomized, double-blind, PBO-controlled ADEPT trial. Subjects were categorized according to time-averaged (TA) disease activity (remission, low, moderate or high) based on Disease Activity Score of 28 joints with CRP [DAS28(CRP)], Disease Activity Index for Psoriatic Arthritis (DAPSA) or Psoriatic Arthritis Disease Activity Score (PASDAS), and achievement of minimal disease activity (MDA) at week 24. Radiographic progression was assessed as change in modified total Sharp score (?mTSS) from baseline to week 24. The analyses included interaction terms between disease activity and treatment on radiographic progression, comparison of radiographic progression in subjects categorized by disease activity and treatment, and correlation between disease activity and radiographic progression by treatment. RESULTS:The interaction terms for TA disease activity and treatment on ?mTSS were significant (P = 0.002-0.008). Irrespective of concomitant MTX, ?mTSS was lower with ADA vs PBO in all disease activity categories. Importantly, even in subjects having moderate or high disease activity or not achieving MDA, ?mTSS was significantly lower on ADA than PBO (P = 0.05-0.001 for TA-DAPSA, TA-PASDAS and MDA). Correlations between TA disease activity scores and ?mTSS were moderately positive and significant (P < 0.001) with PBO but non-significant with ADA. CONCLUSION:Among subjects with PsA treated with ADA, there was evidence of a 'disconnect' between disease activity and radiographic progression: inhibition of radiographic progression was greater than expected based on control of clinical disease activity alone. MTX had no added effect. TRIAL REGISTRATION:ClinicalTrials.gov, http://clinicaltrials.gov, NCT00646386.

SUBMITTER: Landewe R

PROVIDER: S-EPMC6532443 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity.

Landewé Robert R Ritchlin Christopher T CT Aletaha Daniel D Zhang Ying Y Ganz Fabiana F Hojnik Maja M Coates Laura C LC

Rheumatology (Oxford, England) 20190601 6

<h4>Objectives</h4>To evaluate the relationship between radiographic progression and disease activity in subjects with PsA treated with adalimumab (ADA) or placebo (PBO) and the impact of concomitant MTX.<h4>Methods</h4>This was a post hoc analysis of the randomized, double-blind, PBO-controlled ADEPT trial. Subjects were categorized according to time-averaged (TA) disease activity (remission, low, moderate or high) based on Disease Activity Score of 28 joints with CRP [DAS28(CRP)], Disease Acti ...[more]

PMID: 30608620

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Project description:BackgroundIn the GO-VIBRANT trial of intravenous golimumab in psoriatic arthritis (PsA), golimumab significantly inhibited radiographic progression. In post hoc analyses, we evaluated changes in total PsA-modified Sharp/van der Heijde scores (SHS) across levels of composite index-defined disease activity following treatment.MethodsIn this phase-3, double-blind, placebo-controlled trial, 480 bio-naïve patients with active PsA randomly received intravenous golimumab 2?mg/kg (N?=?241; week 0, week 4, every 8 weeks [q8w]) or placebo (N?=?239; week 0, week 4, week 12, week 20) followed by golimumab (week 24, week 28, q8w) through week 52. Week 24 and week 52 SHS changes in patient subgroups, defined by levels of disease activity as assessed by several composite measures (minimal disease activity [MDA], very low disease activity [VLDA], Psoriatic ArthritiS Disease Activity Score [PASDAS], Disease Activity in Psoriatic Arthritis [DAPsA], Clinical Disease Activity Index [CDAI]), were evaluated post hoc in 474 patients with evaluable radiographic data. Partially (last-observation-carried-forward methodology) and completely (nonresponder methodology) missing data were imputed.ResultsAcross indices, golimumab-treated patients demonstrated less radiographic progression than placebo-treated patients, regardless of disease activity state achieved via golimumab, from week 0 to 24 (e.g., mean changes in PsA-modified SHS were -?0.83 vs. 0.91, respectively, in patients achieving MDA and -?0.05 vs. 1.49, respectively, in those not achieving MDA). Treatment differences observed at week 24 persisted through week 52, despite placebo-randomized patients crossing over to golimumab at week 24 (e.g., mean changes in PsA-modified SHS from week 0 to 52 for golimumab- vs. placebo?golimumab-treated patients achieving MDA were -?1.16 vs. 1.19, respectively) and regardless of whether low disease activity was achieved (0.03 vs. 1.50, respectively, in those not achieving MDA). Consistent patterns were observed for disease activity assessed using VLDA, PASDAS, DAPsA, and CDAI composite endpoints.ConclusionsThe extent of structural damage inhibition afforded by up to 1?year of intravenous golimumab treatment paralleled levels of PsA activity, with greater progression of structural damage observed in patients with sustained higher disease activity. Among patients not achieving low levels of disease activity across several composite indices, golimumab-randomized patients appeared to exhibit far less progression of structural damage than placebo-randomized PsA patients, illustrating a potential disconnect between responses, wherein golimumab can inhibit structural damage independent of clinical effect.Trial registrationClinicalTrials.gov. NCT02181673. Registered 04 July 2014.

Project description:IntroductionThis study investigated the effectiveness of adalimumab treatment in improving Work Productivity and Activity Impairment (WPAI) in patients with psoriatic arthritis (PsA) in real-world settings in Japan.MethodsThis 24-week, single-arm, postmarketing surveillance study (2014-2017), conducted at 75 centers in Japan, enrolled adalimumab-naïve patients (paid workers, including part-time) meeting ClASsification criteria for Psoriatic ARthritis (CASPAR). The primary endpoint was improvement in overall work impairment (OWI) scores from baseline to week 24. Secondary endpoints included changes in WPAI-PsA (OWI, absenteeism, presenteeism, and activity impairment), Psoriasis Area and Severity Index (PASI), psoriatic arthritis screening and evaluation (PASE) scores, Disease Activity Scores in 28 joints using C-reactive protein (DAS28[CRP]), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and PASI75/90 and American College of Rheumatology (ACR) 20/50/70 rates.ResultsIn the effectiveness population (n = 106; 72.6% men; mean ± standard deviation [SD] age, 49.3 ± 10.7 years), OWI scores significantly improved (mean ± SD change, - 25.2 ± 35.3; p < 0.0001) from baseline to week 24. Other WPAI domain scores also improved significantly. Changes in OWI were significantly correlated (p < 0.0001) with PASE (r = 0.6284), DAS28(CRP) (r = 0.6059), BASDAI (r = 0.7281), and HAQ-DI (r = 0.6161) scores and were significantly influenced by previous nonsteroidal anti-inflammatory drug use (p = 0.0142), and baseline PASE (p = 0.0098), DAS28(CRP) (p = 0.0026), HAQ-DI (p = 0.0004), and BASDAI (p < 0.0001) scores. At the last evaluation, rate (95% confidence interval) of PASI 75 and 90 (n = 100) was 58.0% (47.7-67.8) and 39.0% (29.4-49.3), respectively, and that of ACR 20, 50, and 70 (n = 58) was 86.2% (74.6-93.9), 70.7% (57.3-81.9), and 53.4% (39.9-66.7), respectively. No new safety signals were observed in the safety population (n = 148).ConclusionAdalimumab treatment improved WPAI in patients with PsA. Improvements in OWI and joint symptoms were significantly associated.Trial registration numberClinicalTrials.gov identifier: NCT02414633.FundingAbbVie GK and Eisai Co., Ltd.

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Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity.

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Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity.

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