Dataset Information

Clinical Improvements as Predictors of Improvements in Patient-Reported Outcomes: Post Hoc Analysis of a Randomized, Open-Label Study of Etanercept in Latin American Patients with Rheumatoid Arthritis.

ABSTRACT: Background:In rheumatoid arthritis (RA), little is known about clinical responses to treatment as predictors of patient-reported outcome (PRO) changes. In this post hoc analysis, we examined the relationship between clinical outcomes at week 12 and PRO changes at week 24 in patients with RA. Methods:In an open-label study, Latin American patients with moderate-to-severe RA and an inadequate response to methotrexate (MTX) were randomized to receive etanercept 50 mg/week plus MTX (ETN+MTX; n=281) or an additional conventional disease-modifying anti-rheumatic drug (DMARD) plus MTX (DMARD+MTX; n=142) for 24 weeks. The PROs included Health Assessment Questionnaire Disability Index (HAQ-DI), 36-item Short Form (SF-36), Physician and Patient Global Assessment scores (PGA, PtGA), Physician and Patient Satisfaction, and an activity impairment assessment. PRO changes at week 24 were calculated by week-12 improvements using the American College of Rheumatology criteria (ACR <20, ?20 to <50, ?50 to <70, and ?70) and the 28-joint Disease Activity Scores (DAS28 ?3.2, ?2.6 to <3.2, and <2.6). Observed-cases data were analyzed using an ANCOVA model with linear contrast, adjusted for baseline PRO and ACR/DAS28 values. Results:For both ETN+MTX- and DMARD+MTX-treated patients, there was a significant linear trend between week-12 changes in ACR and DAS28 responses and week-24 changes in HAQ-DI (P<0.001 for all), with numerical improvements generally favoring ETN+MTX. Similar relationships were observed for SF-36, PGA, PtGA, Physician Satisfaction, Patient Satisfaction, and activity impairment. Conclusions:In patients with RA, clinical response after 12 weeks of treatment with ETN+MTX or DMARD+MTX could be a predictor of week-24 response for several PROs. Trial registration:ClinicalTrials.gov, NCT00848354.

SUBMITTER: Guerra Bautista G

PROVIDER: S-EPMC6913264 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical Improvements as Predictors of Improvements in Patient-Reported Outcomes: Post Hoc Analysis of a Randomized, Open-Label Study of Etanercept in Latin American Patients with Rheumatoid Arthritis.

Guerra Bautista Generoso G Xavier Ricardo Machado RM de la Vega Maria M Simón-Campos J Abraham JA Solano Gastón G Pedersen Ronald D RD Vlahos Bonnie B Borlenghi Cecilia C

Open access rheumatology : research and reviews 20191212

<h4>Background</h4>In rheumatoid arthritis (RA), little is known about clinical responses to treatment as predictors of patient-reported outcome (PRO) changes. In this post hoc analysis, we examined the relationship between clinical outcomes at week 12 and PRO changes at week 24 in patients with RA.<h4>Methods</h4>In an open-label study, Latin American patients with moderate-to-severe RA and an inadequate response to methotrexate (MTX) were randomized to receive etanercept 50 mg/week plus MTX (E ...[more]

PMID: 31849542

Similar Datasets

Project description:Smoking produces substances that activate proinflammatory, prothrombotic and vasoconstrictive mediators via posttranslational carbamylation of proteins. As a new consequence of carbamylation, induction of anti-carbamylated autoantibodies were observed in rheumatoid arthritis (RA) patients, sometimes prior to onset of the disease. The overall aim of this study was to characterize the reactivity of different isotypes of autoantibodies against carbamylated antigens of vimentin in relation to established rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and markers of disease activity in a so far largely uncharacterized population of Latin American (Cuban) patients with RA. Antigenic properties of carbamylated vimentin as well as vimentin peptides were analyzed in 101 patients with RA, 50 disease controls and 51 healthy controls. The diagnostic performance was compared with established commercial ELISA rheumatoid factor, anti-cyclic citrullinated peptide antibodies of second generation (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies. Prevalence of anti-MCV IgG (86 %), anti-carbamylated vimentin (carbVIM) IgG (77 %) and anti-carbamylated MCV (carbMCV) IgG antibodies (65 %) was higher than the classical RF IgM (60 %) and anti-CCP2 IgG (52 %) in this RA cohort. Of note, smoking status was associated with positive IgG antibody reactivity against CCP2 in 75.0 % and against MCV in 90 % of patients. Furthermore, IgM antibody response against carbMCV and carbVIM was observed in 80 and 90.0 % of smokers, respectively. Due to a high sensitivity of the IgM antibody isotype of anti-carbVIM of 85.2 %, the combination of ACPA with anti-carbVIM IgM provided the best diagnostic performance so far achieved in a RA cohort of this ethnic origin. We demonstrate a high prevalence of anti-carbVIM antibodies and correlation with smoking in Latin American (Cuban) RA patients. Anti-carbVIM IgM represents an useful marker in ACPA-negative patients and, in combination with ACPA IgG assays, optimizes the strategy for autoantibody testing.

Project description:BACKGROUND:Although long-term data are available from biologic studies in North American/European populations with rheumatoid arthritis (RA), long-term findings in Latin American RA populations are limited. OBJECTIVE:To examine long-term safety/efficacy of etanercept, methotrexate, and/or other disease-modifying anti-rheumatic drugs (DMARDs) in Latin American patients with moderate-to-severe active RA. METHODS:In the first phase of this open-label study, patients were randomized to etanercept 50 mg weekly plus methotrexate or conventional DMARD (hydroxychloroquine or sulfasalazine) plus methotrexate for 24 weeks. At the start of the second phase (week 24), investigators selected a treatment regimen that included any combination/dosage of etanercept, methotrexate, hydroxychloroquine, or sulfasalazine based on previous treatment response, preference, and local product labeling, and was continued for the 104-week extension. RESULTS:In the extension, in the group previously randomized to etanercept-plus-methotrexate therapy, etanercept was continued in 259/260 patients; methotrexate continued in 260/260; and hydroxychloroquine and sulfasalazine added in 8/260 and 3/260, respectively. In the group previously randomized to conventional DMARD-plus-methotrexate therapy, conventional DMARD was discontinued in 86/126 and etanercept added in 105/126. Among etanercept-exposed patients (total exposure, 798.1 patient-year [PY]), rates of adverse events, serious adverse events, and serious infections per PY were 1.7, 0.07, and 0.02 events per PY. In both groups, after treatment modification was permitted, clinical response rates and improvements in clinical/patient-reported outcomes from baseline were sustained to week 128. CONCLUSION:After investigators were permitted to modify treatment, etanercept was part of the treatment regimen in 95% of patients. Continuation or addition of etanercept in the 2-year extension resulted in a consistently good risk:benefit profile. TRIAL REGISTRATION:Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy; ClinicalTrials.gov, number NCT00848354; https://clinicaltrials.gov/ct2/show/NCT00848354.

Project description:ObjectivePatients with rheumatoid arthritis (RA) in whom remission is achieved following combination therapy with methotrexate plus etanercept face an ongoing medication burden. This study was undertaken to investigate whether sustained remission achieved on combination therapy can be maintained with either methotrexate or etanercept monotherapy, as assessed following discontinuation of one or the other medication from the combination.MethodsOf the 371 adult patients with RA who received combination therapy with methotrexate plus etanercept, remission (defined as a Simplified Disease Activity Index [SDAI] score of ≤3.3) was sustained in 253 patients through a 24-week open-label period. These 253 patients then entered a 48-week, double-blind period and were randomized to receive either 1) methotrexate monotherapy (n = 101), 2) etanercept monotherapy (n = 101), or 3) methotrexate plus etanercept combination therapy (n = 51). Patients who subsequently experienced disease-worsening received rescue therapy with the combination regimen at the same dosages as used in the initial run-in period. The primary end point was the proportion of patients in whom SDAI-defined remission was maintained without disease-worsening at week 48 in the etanercept monotherapy group as compared to the methotrexate monotherapy group. Secondary end points included time to disease-worsening, and the proportion of patients in whom SDAI-defined remission was recaptured after initiation of rescue therapy.ResultsBaseline demographic and clinical characteristics of the RA patients were similar across the treatment groups. At week 48, SDAI-defined remission was maintained in significantly more patients in the etanercept monotherapy group than in the methotrexate monotherapy group (49.5% versus 28.7%; P = 0.004). Moreover, as a secondary end point, sustained SDAI-defined remission was achieved in significantly more patients who received combination therapy than in those who received methotrexate monotherapy (52.9% versus 28.7%; P = 0.006). Time to disease-worsening was shorter in those who received methotrexate monotherapy than in those who received etanercept monotherapy or those who received combination therapy (each P < 0.001 versus methotrexate monotherapy). Among the patients who received rescue therapy, SDAI-defined remission was recaptured in 70-80% in each treatment group. No new safety signals were reported.ConclusionThe efficacy of etanercept monotherapy was superior to that of methotrexate monotherapy and similar to that of combination therapy in maintaining remission in patients with RA. SDAI-defined remission was recaptured in most of the patients who were given rescue therapy. These data could inform decision-making when withdrawal of therapy is being considered to reduce treatment burden in patients with well-controlled RA.

Project description:BACKGROUND:The aim was to analyze characteristics that predict remission induction and subsequent loss of remission in patients with moderately active rheumatoid arthritis (RA) who received full-dose combination etanercept plus methotrexate induction therapy followed by reduced-dose etanercept or etanercept withdrawal. METHODS:Patients with Disease Activity Score based on 28-joint count (DAS28) >3.2 and ?5.1 received open-label etanercept 50 mg once weekly (QW) plus methotrexate for 36 weeks. Those who achieved DAS28 low disease activity by 36 weeks were randomized to double-blind treatment with etanercept 50 mg or 25 mg QW plus methotrexate or placebo plus methotrexate for 52 weeks. All analyses were adjusted for the continuous baseline variables of their respective remission outcomes. RESULTS:Younger age, body mass index (BMI) <30 kg/m2, and lower Health Assessment Questionnaire (HAQ) score at baseline were significant predictors of week-36 remission (P?<?0.05) based on DAS28, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). Baseline DAS28, SDAI, and CDAI were significantly predictive of all three remission endpoints (P?<?0.05). For all three treatments, the strongest predictors of loss of DAS28 remission included failure to achieve sustained remission (DAS28?<?2.6 at weeks 12, 20, 28, and 36) with induction therapy, higher DAS28/SDAI/CDAI at randomization and at 1 month, increase in DAS28/SDAI/CDAI at 1 month, and increase in DAS28/CDAI/SDAI components and patient-reported outcomes (PROs) at 1 month. With the exception of not achieving sustained remission, very similar significant predictors were observed for loss of SDAI and CDAI remission. CONCLUSION:These findings suggest that patients with moderately active RA who are younger and have lower BMI, lower HAQ, and lower disease activity at baseline are most likely to achieve remission when receiving combination etanercept and methotrexate induction therapy. In addition, patients who fail to achieve sustained remission with induction therapy and those with worse disease activity and PROs at early time points after initiating maintenance therapy with a full-dose or reduced-dose etanercept-methotrexate regimen or methotrexate monotherapy are most likely to lose remission across all treatment arms. These findings may help guide clinicians' decision-making as they treat patients to remission and beyond. TRIAL REGISTRATION:ClinicalTrials.gov, NCT00565409 . Registered on 28 November 2007.

Dataset Information

Clinical Improvements as Predictors of Improvements in Patient-Reported Outcomes: Post Hoc Analysis of a Randomized, Open-Label Study of Etanercept in Latin American Patients with Rheumatoid Arthritis.

Publications

Clinical Improvements as Predictors of Improvements in Patient-Reported Outcomes: Post Hoc Analysis of a Randomized, Open-Label Study of Etanercept in Latin American Patients with Rheumatoid Arthritis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure