Evidence map›Paper›PMID 21917824›Full record

Trial reportAnnals of the rheumatic diseases2012

Evaluation of abatacept administered subcutaneously in adults with active rheumatoid arthritis: impact of withdrawal and reintroduction on immunogenicity, efficacy and safety (phase Iiib ALLOW study).

Jeffrey Kaine, Geoffrey Gladstein, Ingrid Strusberg, Manuel Robles, Ingrid Louw, Sheila Gujrathi, Ramesh Pappu, Ingrid Delaet, Miranda Pans, Charles Ludivico

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of the rheumatic diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 31 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 6 pooled it
7.5field-weighted citation impact, top 2% 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.

NCT00533897 phase3completednot on this map

A Phase IIIb, Multi-Center, Randomized, Withdrawal Study to Evaluate the Immunogenicity and Safety of Subcutaneous Administered Abatacept in Adults With Active Rheumatoid Arthritis

TypeinterventionalSponsorBristol-Myers SquibbRan2007 to 2014Enrolled270ConditionsRheumatoid ArthritisArmsAbatacept, Placebo
NCT01846975 phase4completednot on this mapstarted 2013, after this paper: background citation

A Phase IV, Open Label Study Introducing a Single IV Treatment With Abatacept in Patients With Rheumatoid Arthritis Currently Receiving Weekly Injections of SC Abatacept to Simulate a Holiday or Patient Vacation

TypeinterventionalSponsorRüdiger B. MüllerRan2013 to 2015Enrolled49ConditionsRheumatoid ArthritisArmsIV Abatacept
3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 6 syntheses or guidelines pooled it, 73 citations in OpenAlex.

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  12. Assessing Immunogenicity of Biologic Drugs in Inflammatory Joint Diseases: Progress Towards Personalized Medicine.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022
    Review
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  20. Unintended Immunological Consequences of Biologic Therapy.Current allergy and asthma reports · 2016
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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

10 authors at 6 institutions in 4 countries.

Jeffrey KaineSarasota Arthritis Research Center, 1945 Versailles Street #101, Sarasota, FL 34239, USA. jkainemd@gmail.com
Geoffrey Gladstein
Ingrid Strusberg
Manuel Robles
Ingrid Louw
Sheila Gujrathi
Ramesh Pappu
Ingrid Delaet
Miranda Pans
Charles Ludivico
Bristol-Myers Squibb (United States) · USCape Town Science Centre · ZAInstituto Oncológico de Córdoba · ARInstituto Tecnológico de Toluca · MXNew England Research (United States) · USPrader Willi Syndrome Association · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo assess the effect of a temporary interruption in subcutaneous (SC) abatacept on immunogenicity, safety and efficacy in patients with active rheumatoid arthritis despite methotrexate in a phase III trial.

methodsFollowing a 12-week open-label introduction (period I; intravenous abatacept loading dose and weekly fixed-dose SC abatacept 125 mg), patients were randomised 2:1 to double-blind SC placebo or SC abatacept for 12 weeks (period II). At the end of period II, patients receiving SC abatacept continued treatment and patients on placebo were reintroduced to SC abatacept (12-week open-label period III). The co-primary end points were ELISA-detected immunogenicity rate and safety at the end of period II. Efficacy was also monitored.

resultsOf 167 patients entering period I, 72% qualified for period II; during periods II and III, three patients discontinued treatment. Mean (SD) disease duration was 6.6 (6.5) years and Disease Activity Score 28 was 4.8 (0.8). The primary end point was met, with a non-significant increase in immunogenicity upon withdrawal (7/73 placebo vs 0/38 abatacept in period II; p=0.119) which was reversed upon reintroduction of SC abatacept (2/73 vs 1/38, end period III). Safety was comparable regardless of withdrawal, with no unexpected events upon reintroduction. Two patients experienced reactions at the SC injection site. On withdrawal, patients experienced slight worsening in efficacy which improved following reintroduction.

conclusionsOverall immunogenicity to SC abatacept is low, consistent with intravenous abatacept, and is not significantly affected by a 3-month interruption and reintroduction. This stop-start schedule was well tolerated, with little impact on safety and efficacy. These are important considerations for the clinical use of SC abatacept. CLINICALTRIALS: gov Identifier NCT00533897.

Indexed as

Withholding TreatmentAbataceptAdultAntirheumatic AgentsArthritis, RheumatoidBiomarkersC-Reactive ProteinDrug Administration ScheduleFemaleHumansImmunoconjugatesInjections, SubcutaneousMaleMiddle AgedTreatment OutcomeAbataceptAntirheumatic AgentsBiomarkersC-Reactive ProteinImmunoconjugates

Identifiers

PMID21917824
PMCPMC3233696
OpenAlexW2126049604

What OpenQuestion holds

Textmetadata
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.