Evidence map›Paper›PMID 29556418›Full record

ArticleRMD open2018

Identification of sarilumab pharmacodynamic and predictive markers in patients with inadequate response to TNF inhibition: a biomarker substudy of the phase 3 TARGET study.

Cem Gabay, Jérôme Msihid, Moshe Zilberstein, Caroline Paccard, Yong Lin, Neil M H Graham, Anita Boyapati

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in RMD open, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01709578 (A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 6% 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.

NCT01709578 phase3completednot on this map

A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing the Efficacy and Safety of Sarilumab Added to Non-biologic DMARD Therapy in Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF-α Antagonists

TypeinterventionalSponsorSanofiRan2012 to 2015Enrolled546ConditionsRheumatoid ArthritisArmsSarilumab, placebo, hydroxychloroquine, methotrexate, sulfasalazine
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

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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

7 authors at 4 institutions in 3 countries.

Cem GabayUniversity Hospitals of Geneva, Geneva, Switzerland.
Jérôme MsihidSanofi R&D, Chilly-Mazarin, France.
Moshe ZilbersteinSanofi R&D, Bridgewater, New Jersey, USA.
Caroline PaccardSanofi R&D, Chilly-Mazarin, France.
Yong LinSanofi Genzyme, Bridgewater, New Jersey, USA.
Neil M H GrahamRegeneron Pharmaceuticals, Inc, Tarrytown, New York, USA.
Anita BoyapatiRegeneron Pharmaceuticals, Inc, Tarrytown, New York, USA.
Regeneron (United States) · USSanofi (France) · FRSanofi (United States) · USUniversity Hospital of Geneva · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionInterleukin-6 (IL-6) orchestrates formation of an inflammatory pannus, leading to joint damage in rheumatoid arthritis (RA). Sarilumab is a human monoclonal antibody blocking the IL-6Rα. In TARGET (NCT01709578), a phase 3 study in adults with moderate-to-severe RA and inadequate response or intolerance to tumour necrosis factor inhibitors, subcutaneous sarilumab 200 mg or 150 mg every 2 weeks (q2w) plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) significantly reduced disease activity versus placebo plus csDMARDs.

methodsCirculating levels of biomarkers associated with synovial inflammation (matrix metalloproteinase 3 (MMP-3), collagen type I MMP-cleaved fragment (C1M), collagen type III MMP-cleaved fragment (C3M)), myeloid (soluble intercellular adhesion molecule 1 (sICAM-1), IL-8 and calprotectin) and lymphoid activation (chemokine, CXC motif, ligand 13 (CXCL13), CXCL10, B cell-activating factor) and bone remodelling (receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin and osteocalcin) were evaluated in patients from a TARGET substudy.

resultsSarilumab significantly decreased C1M, C3M, CXCL13, MMP-3 and total RANKL levels at week 24 versus placebo; some markers were significantly suppressed at week 2 and normalised to levels in healthy controls. Levels of sICAM-1 were predictive of disease activity score by C-reactive protein and clinical disease activity index low disease activity (LDA) response in the sarilumab 200 mg q2w group at week 12. A trend was observed in which patients with lower sICAM-1 levels at baseline had better response compared with patients with higher sICAM-1.

conclusionsSarilumab plus csDMARDs decreased circulating biomarkers of synovial inflammation and bone resorption; sICAM-1 was predictive of achieving LDA with sarilumab. TRIAL REGISTRATION NUMBER: NCT01709578; Post-results.

Indexed as

dmards (biologic)rheumatoid arthritistreatment

Identifiers

PMID29556418
PMCPMC5856917
OpenAlexW2790022206

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.