Evidence map›Paper›PMID 25169728›Full record

Trial reportAnnals of the rheumatic diseases2015

Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study.

T W J Huizinga, Philip G Conaghan, Emilio Martin-Mola, Georg Schett, Howard Amital, Ricardo M Xavier, Orrin Troum, Maher Aassi, Corrado Bernasconi, Maxime Dougados

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of the rheumatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00810199 (Randomized Placebo-controlled Study of Two Treatment Strategies Based on Tocilizumab), which is not on this map. Cited by 48 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 9 pooled it
–field-weighted citation impact
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.

NCT00810199 phase3completednot on this map

Randomized Placebo-controlled Study of Two Treatment Strategies Based on Tocilizumab (TCZ) With or Without Methotrexate (MTX) and Possible Addition of Other Disease-modifying Anti-rheumatic Drugs (DMARDs) in Patients...

TypeinterventionalSponsorHoffmann-La RocheRan2009 to 2013Enrolled556ConditionsRheumatoid ArthritisArmstocilizumab [RoActemra/Actemra], methotrexate, placebo
3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 9 syntheses or guidelines pooled it.

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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.

T W J HuizingaDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Philip G ConaghanNIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Emilio Martin-MolaDepartment of Rheumatology, Hospital Universitario La Paz, Madrid, Spain.
Georg SchettDepartment of Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany.
Howard AmitalDepartment of Medicine 'B', Sheba Medical Center, Tel Hashomer, Israel.
Ricardo M XavierDivision of Rheumatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Orrin TroumDivision of Rheumatology, University of Southern California Keck School of Medicine, Santa Monica, California, USA.
Maher AassiF.Hoffmann-La Roche Ltd, Basel, Switzerland.
Corrado BernasconiF.Hoffmann-La Roche Ltd, Basel, Switzerland.
Maxime DougadosRheumatology B Department, Paris-Descartes University, Cochin Hospital, Paris, France.

Funding

Medical Research Council MR/L01629X/1
6 · The paper itself

Abstract

objectiveTo assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission.

methodsACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR <2.6 at two consecutive visits 12 weeks apart) discontinued TCZ and were assessed every 4 weeks for 1 year. If sustained remission was maintained, added csDMARDs, then MTX/PBO, were discontinued.

resultsOf the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%).

conclusionsTreat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement. TRIAL REGISTRATION NUMBER: NCT00810199.

Indexed as

AdultAgedAntibodies, Monoclonal, HumanizedAntirheumatic AgentsArthritis, RheumatoidBlood SedimentationDisease ProgressionDouble-Blind MethodDrug Therapy, CombinationFemaleFoot JointsHand JointsHumansInduction ChemotherapyLongitudinal StudiesMaintenance ChemotherapyAntibodies, Monoclonal, HumanizedAntirheumatic AgentsMethotrexatetocilizumabDMARDs (biologic)MethotrexateRheumatoid Arthritis

Identifiers

PMID25169728
PMCPMC4283697

What OpenQuestion holds

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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.