Evidence map›Paper›PMID 24297381›Full record

Trial reportAnnals of the rheumatic diseases2014

Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial.

Tom W J Huizinga, Roy M Fleischmann, Martine Jasson, Allen R Radin, Janet van Adelsberg, Stefano Fiore, Xiaohong Huang, George D Yancopoulos, Neil Stahl, Mark C Genovese

Registry-linked trialAbstract 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 NCT01061736 (A Randomized, Double-blind, Placebo-controlled, Multicenter, Two-part, Dose Ranging and Confirmatory Study With an Operationally Seamless Design, Evaluating Efficacy and Safety of SAR153191 on Top of Methotrexate), which is not on this map. Cited by 100 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed, 4 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.

NCT01061736 phase2 / phase3completednot on this map

A Randomized, Double-blind, Placebo-controlled, Multicenter, Two-part, Dose Ranging and Confirmatory Study With an Operationally Seamless Design, Evaluating Efficacy and Safety of SAR153191 on Top of Methotrexate (MTX) in Patients With Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy

TypeinterventionalSponsorSanofiRan2010 to 2013Enrolled1,675ConditionsRheumatoid ArthritisArmsSarilumab, Placebo (for sarilumab), Methotrexate, Folic Acid
3 · Its place in the literature

Who cites it

100 citing papers in PubMed, 4 syntheses or guidelines pooled it.

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

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.

Tom W J HuizingaDepartment of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Roy M FleischmannDepartment of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Martine JassonDivision of Rheumatology, Department of Medicine, University of Texas Southwestern Medical Center and Metroplex Clinical Research Center, Dallas, Texas, USA.
Allen R RadinDepartment of Research and Development, Sanofi, Paris, France.
Janet van AdelsbergRegeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
Stefano FioreRegeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
Xiaohong HuangDepartment of Research and Development, Sanofi, Bridgewater, New Jersey, USA.
George D YancopoulosDepartment of Research and Development, Sanofi, Bridgewater, New Jersey, USA.
Neil StahlRegeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
Mark C GenoveseDepartment of Immunology and Rheumatology, Stanford University Medical Center, Palo Alto, California, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA).

methodsIn this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100 mg q2w, 150 mg q2w, 100 mg qw, 200 mg q2w, 150 mg qw for 12 weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed.

resultsThe proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150 mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150 mg q2w (67%; unadjusted (nominal) p=0.0363) and 200 mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab ≥150 mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors.

conclusionsSarilumab improved signs and symptoms of RA over 12 weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150 mg and sarilumab 200 mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III.

Indexed as

AdultAgedAntibodies, Monoclonal, HumanizedAntirheumatic AgentsArthritis, RheumatoidBiomarkersC-Reactive ProteinDose-Response Relationship, DrugDrug Administration ScheduleDrug Therapy, CombinationFemaleHumansInjections, SubcutaneousMaleMethotrexateMiddle AgedAntibodies, Monoclonal, HumanizedAntirheumatic AgentsBiomarkersC-Reactive ProteinMethotrexateReceptors, Interleukin-6sarilumabCytokinesDMARDs (biologic)Rheumatoid ArthritisTreatment

Identifiers

PMID24297381
PMCPMC4145418

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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.