Evidence map›Paper›PMID 36109142›Full record

Trial reportAnnals of the rheumatic diseases2022

Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study.

Eugen Feist, Saeed Fatenejad, Sergey Grishin, Elena Korneva, Michael E Luggen, Evgeniy Nasonov, Mikhail Samsonov, Josef S Smolen, Roy M Fleischmann

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of the rheumatic diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02760433 (A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Tumor Necrosis Factor Alpha), which is not on this map. Cited by 18 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 4 pooled it
6.3field-weighted citation impact, top 3% 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.

NCT02760433 phase3completednot on this map

A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Tumor Necrosis Factor Alpha (TNF-α) Inhibitor Therapy

TypeinterventionalSponsorR-Pharm International, LLCRan2017 to 2019Enrolled368ConditionsRheumatoid ArthritisArmsOlokizumab, Placebo
3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 4 syntheses or guidelines pooled it, 38 citations in OpenAlex.

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  17. Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What Have We Learned?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  18. 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

9 authors at 7 institutions in 4 countries.

Eugen FeistRheumatology and Clinical Immunology, HELIOS Fachklinik Vogelsang/Gommern, Vogelsang, Sachsen-Anhalt, Germany Eugen.Feist@helios-gesundheit.de.
Saeed FatenejadSFC Medica LLC, Charlotte, North Carolina, USA.ORCID http://orcid.org/0000-0002-3005-9439
Sergey GrishinMedical, R-Pharm Group, Moscow, Russian Federation.
Elena KornevaMedical, CJSC R-Pharm, Moskow, Russian Federation.ORCID http://orcid.org/0000-0002-4085-5869
Michael E LuggenDepartment of Internal Medicine, Division of Rheumatology, Allergy, and Immunology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Evgeniy NasonovFSBSI V A Nasonov Research Institute of Rheumatology, Moscow, Russian Federation.ORCID http://orcid.org/0000-0002-1598-8360
Mikhail SamsonovMedical, CJSC R-Pharm, Moscow, Russian Federation.
Josef S SmolenDivision of Rheumatology, Department of Medicine, Medical University of Vienna, Wien, Austria.
Roy M FleischmannMedicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.ORCID http://orcid.org/0000-0002-6630-1477
R-Pharm (Russia) · RUAssociation of Rheumatologists of Russia · RUHelios Kliniken · DEMedical University of Vienna · ATMedica (United States) · USMetroplex Clinical Research Center · USUniversity of Cincinnati Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo assess the efficacy and safety of olokizumab (OKZ), a monoclonal antibody against the interleukin-6 (IL-6) cytokine, versus placebo (PBO) in patients with prior inadequate response to tumour necrosis factor inhibitors (TNFi-IRs).

methodsIn this 24-week multicentre, placebo-controlled, double-blind study, the patients were randomised in a 2:2:1 ratio to receive subcutaneously administered OKZ 64 mg once every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or PBO plus methotrexate. At week 16, the patients on PBO were randomised to receive either OKZ regime. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. Disease Activity Score 28-joint count C-reactive protein (DAS28 (CRP))<3.2 at week 12 was the major secondary efficacy endpoint. Safety and immunogenicity were assessed.

resultsIn 368 patients randomised, ACR20 response rates were 60.9% in OKZ q2w, 59.6% in OKZ q4w and 40.6% in PBO (p<0.01 for both comparisons). Achievement of DAS28 (CRP) <3.2 was significantly different, favouring the OKZ arms. Improvements in efficacy and patient-reported outcomes were maintained throughout 24 weeks and were noted after week 16 in patients who switched from PBO.Dose-related treatment-emergent serious adverse events were 7% in OKZ q2w, 3.2% in OKZ q4w and none in the PBO group.

conclusionsDirect inhibition of IL-6 with OKZ resulted in significant improvements in the signs and symptoms of rheumatoid arthritis compared with PBO in TNF-IR patients with a similar safety profile as observed for monoclonal antibodies to the IL-6 receptor. TRIAL REGISTRATION NUMBER: NCT02760433.

Indexed as

Antibodies, MonoclonalAntirheumatic AgentsArthritis, RheumatoidAntibodies, Monoclonal, HumanizedC-Reactive ProteinDose-Response Relationship, DrugDouble-Blind MethodDrug Therapy, CombinationHumansInterleukin-6MethotrexateTreatment OutcomeTumor Necrosis Factor InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntirheumatic AgentsC-Reactive ProteinInterleukin-6MethotrexateolokizumabTumor Necrosis Factor Inhibitorsantirheumatic agentsarthritis, rheumatoidautoimmune diseases

Identifiers

PMID36109142
PMCPMC9664111
OpenAlexW4295952264

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.