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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:IntroductionThis article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators.MethodsThis integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years).ResultsMedian treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs.ConclusionRates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA.Trial registrationClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.

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.

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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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