Evidence map›Paper›PMID 24641941›Full record

Trial reportAnnals of the rheumatic diseases2014

Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study.

Mark C Genovese, Roy Fleischmann, Daniel Furst, Namieta Janssen, John Carter, Bhaskar Dasgupta, Judy Bryson, Benjamin Duncan, Wei Zhu, Costantino Pitzalis and 2 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of the rheumatic diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01242488 (Randomized, Double-blind, Placebo-controlled, Dose Ranging Study With an Active Comparator to Evaluate the Efficacy and Safety of CDP6038 Administered Subcutaneously for 12 Weeks to Subjects With Rheumatoid Arthritis Having Previously Failed TNF-blocker Therapy), which is not on this map. Cited by 68 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 13 pooled it
13.3field-weighted citation impact, top 1% 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.

NCT01242488 phase2completednot on this map

Randomized, Double-blind, Placebo-controlled, Dose Ranging Study With an Active Comparator to Evaluate the Efficacy and Safety of CDP6038 Administered Subcutaneously for 12 Weeks to Subjects With Rheumatoid Arthritis Having Previously Failed TNF-blocker Therapy

TypeinterventionalSponsorUCB PharmaRan2010 to 2012Enrolled221ConditionsRheumatoid ArthritisArmsCDP6038, Tocilizumab (Actemra or RoActemra), Placebo sc, Placebo iv
3 · Its place in the literature

Who cites it

68 citing papers in PubMed, 13 syntheses or guidelines pooled it, 137 citations in OpenAlex.

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8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 9 institutions in 3 countries.

Mark C GenoveseDivision of Immunology and Rheumatology, Stanford University Medical Center, Stanford, USA.
Roy FleischmannDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
Daniel FurstDepartment of Medicine, UCLA, Los Angeles, California, USA.
Namieta JanssenHouston Institute for Clinical Research, Houston, USA.
John CarterDivision of Rheumatology, University of South Florida Health, Tampa, Florida, USA.
Bhaskar DasguptaDepartment of Rheumatology, Southend University Hospital, Westcliff-on-Sea, UK.
Judy BrysonUCB Pharma, Raleigh, USA.
Benjamin DuncanUCB Pharma, Raleigh, USA.
Wei ZhuUCB Pharma, Raleigh, USA.
Costantino PitzalisWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Patrick DurezService et Pôle de Rhumatologie, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
Kosmas KretsosUCB Pharma, Slough, UK.
UCB Pharma (United States) · USCliniques Universitaires Saint-Luc · BEHouston Institute for Clinical Research · USSouthend University Hospital NHS Foundation Trust · GBStanford University · USThe University of Texas Southwestern Medical Center · USUCB Pharma (United Kingdom) · GBUniversity of South Florida · USWilliam Harvey Research Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThe aim of this 12-week Phase IIb study was to assess the efficacy and safety of olokizumab (OKZ), a humanised anti-IL6 monoclonal antibody, in patients with rheumatoid arthritis (RA) with moderate-to-severe disease activity who had previously failed tumour necrosis factor (TNF) inhibitor therapy. The dose-exposure-response relationship for OKZ was also investigated.

methodsPatients were randomised to one of nine treatment arms receiving placebo (PBO) or OKZ (60, 120 or 240 mg) every 4 weeks (Q4W) or every 2 weeks (Q2W), or 8 mg/kg tocilizumab (TCZ) Q4W. The primary endpoint was change from baseline in DAS28(C-reactive protein, CRP) at Week 12. Secondary efficacy endpoints were American College of Rheumatology 20 (ACR20), ACR50 and ACR70 response rates at Week 12. Exploratory analyses included comparisons of OKZ efficacy with TCZ.

resultsAcross 221 randomised patients, OKZ treatment produced significantly greater reductions in DAS28(CRP) from baseline levels at Week 12, compared to PBO (p<0.001), at all the OKZ doses tested (60 mg OKZ p=0.0001, 120 and 240 mg OKZ p<0.0001). Additionally, ACR20 and ACR50 responses were numerically higher for OKZ than PBO (ACR20: PBO=17.1-29.9%, OKZ=32.5-60.7%; ACR50: PBO=1.3-4.9%, OKZ=11.5-33.2%). OKZ treatment, at several doses, demonstrated similar efficacy to TCZ across multiple endpoints. Most adverse events were mild or moderate and comparable between OKZ and TCZ treatment groups. Pharmacokinetic/pharmacodynamic modelling demonstrated a shallow dose/exposure response relationship in terms of percentage of patients with DAS28(CRP) <2.6.

conclusionsOKZ produced significantly greater reductions in DAS28(CRP) from baseline at Week 12 compared with PBO. Reported AEs were consistent with the safety profile expected of this class of drug, with no new safety signals identified. TRIAL REGISTER NUMBER: NCT01242488.

Indexed as

Antibodies, Monoclonal, HumanizedAntirheumatic AgentsArthritis, RheumatoidBiological ProductsDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleFemaleHumansInterleukin-6 InhibitorsMaleMiddle AgedSeverity of Illness IndexTreatment FailureTreatment OutcomeTumor Necrosis Factor-alphaAntibodies, Monoclonal, HumanizedAntirheumatic AgentsBiological ProductsInterleukin-6 InhibitorsolokizumabtocilizumabTumor Necrosis Factor-alphaAutoimmune DiseasesDisease ActivityDMARDs (biologic)Rheumatoid Arthritis

Identifiers

PMID24641941
PMCPMC4145439
OpenAlexW2108062638

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.