Evidence map›Paper›PMID 34878629›Full record

ArticleRheumatology and therapy2022

Differential Changes in ACPA Fine Specificity and Gene Expression in a Randomized Trial of Abatacept and Adalimumab in Rheumatoid Arthritis.

Omar Jabado, Michael A Maldonado, Michael Schiff, Michael E Weinblatt, Roy Fleischmann, William H Robinson, Aiqing He, Vishal Patel, Alex Greenfield, Jasmine Saini and 2 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Rheumatology and therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00929864 (A Randomized, Head-to-Head, Single-Blind Study to Compare the Efficacy and Safety of Subcutaneous Abatacept Versus Subcutaneous Adalimumab, Both With Background Methotrexate, in Biologic-Naive Subjects With Rheumatoid Arthritis), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00929864 phase3completednot on this map

A Randomized, Head-to-Head, Single-Blind Study to Compare the Efficacy and Safety of Subcutaneous Abatacept Versus Subcutaneous Adalimumab, Both With Background Methotrexate, in Biologic-Naive Subjects With Rheumatoid Arthritis

TypeinterventionalSponsorBristol-Myers SquibbRan2009 to 2012Enrolled869ConditionsRheumatoid ArthritisArmsAbatacept, Adalimumab
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 1 country.

Omar JabadoBristol Myers Squibb, Princeton, NJ, USA.
Michael A MaldonadoBristol Myers Squibb, Princeton, NJ, USA.
Michael SchiffUniversity of Colorado, Denver, CO, USA.
Michael E WeinblattBrigham and Women's Hospital, Boston, MA, USA.
Roy FleischmannMetroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX, USA.
William H RobinsonStanford University School of Medicine, Stanford, CA, USA.
Aiqing HeBristol Myers Squibb, Princeton, NJ, USA.
Vishal PatelBristol Myers Squibb, Princeton, NJ, USA.
Alex GreenfieldBristol Myers Squibb, Princeton, NJ, USA.
Jasmine SainiBristol Myers Squibb, Princeton, NJ, USA.
David GalbraithBristol Myers Squibb, Princeton, NJ, USA.
Sean E ConnollyBristol Myers Squibb, B4290 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA. sean.connolly@bms.com.
Bristol-Myers Squibb (United States) · USBrigham and Women's Hospital · USStanford University · USThe University of Texas Southwestern Medical Center · USUniversity of Colorado Denver · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe biologics abatacept and adalimumab have different mechanisms of action (MoAs). We analyzed data from patients with rheumatoid arthritis treated in AMPLE (NCT00929864) to explore the pharmacodynamic effects of abatacept or adalimumab on anti-citrullinated protein antibodies (ACPAs) and gene expression.

methodsAMPLE was a phase IIIb, 2-year, randomized, head-to-head trial of abatacept versus adalimumab. Post hoc analyses of baseline anti-cyclic citrullinated peptide-2 (anti-CCP2, an ACPA surrogate) positive (+) status and ACPA fine-specificity profiles over time, as well as transcriptional profiling (peripheral whole blood), were performed.

resultsOf 646 patients treated (abatacept, n = 318; adalimumab, n = 328), ACPA and gene expression data were available from 508 and 566 patients, respectively. In anti-CCP2+ patients (n = 388), baseline fine specificities for most ACPAs were highly correlated; over 2 years, levels decreased with abatacept but not adalimumab. By year 2, expression of genes associated with T cell co-stimulation and antibody production was lower for abatacept versus adalimumab; expression of genes associated with proinflammatory signaling was lower for adalimumab versus abatacept. Treatment modulated the expression of T- and B-cell gene signatures, with differences in CD8+ T cells, activated T cells, plasma cells, B cells, natural killer cells (all lower with abatacept versus adalimumab), and polymorphonuclear leukocytes (higher with abatacept versus adalimumab).

conclusionsIn AMPLE, despite similar clinical outcomes, data showed that pharmacodynamic/genetic changes after 2 years of abatacept or adalimumab were consistent with drug MoAs. Further assessment of the relationship between such changes and clinical outcomes, including prediction of response, is warranted.

trial registrationClinicalTrials.gov identifier, NCT00929864.

Indexed as

AbataceptAdalimumabAnti-citrullinated protein autoantibodies (ACPAs)Disease-modifying antirheumatic drugs (DMARDs)Gene expressionRheumatoid arthritis

Identifiers

PMID34878629
PMCPMC8964842
OpenAlexW4200064864

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.