Evidence map›Paper›PMID 30894208›Full record

Trial reportArthritis research & therapy2019

Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a randomized, placebo-controlled phase III trial in Japan.

Yoshiya Tanaka, Kazuteru Wada, Yoshinori Takahashi, Owen Hagino, Hubert van Hoogstraten, Neil M H Graham, Hideto Kameda

Erratum issued Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02293902 (A Randomized, Double-blind, Multicenter Study With a Placebo-controlled Period Assessing the Efficacy and Safety of Sarilumab Added to Methotrexate), which is not on this map. Cited by 15 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 4 pooled it
5.2field-weighted citation impact, top 4% 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.

NCT02293902 phase3completednot on this map

A Randomized, Double-blind, Multicenter Study With a Placebo-controlled Period Assessing the Efficacy and Safety of Sarilumab Added to Methotrexate (MTX) in Japanese Patients With Moderately to Severely Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy

TypeinterventionalSponsorSanofiRan2014 to 2016Enrolled243ConditionsRheumatoid ArthritisArmsSarilumab SAR153191 (REGN88), Placebo (for sarilumab), Methotrexate, Folic acid
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 4 syntheses or guidelines pooled it, 45 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Observational
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Role of Interleukin 6 Inhibitors in the Management of Rheumatoid Arthritis.Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases · 2021
    Article
  13. Review
  14. Article
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 6 institutions in 2 countries.

Yoshiya TanakaThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, 807-8555, Japan. tanaka@med.uoeh-u.ac.jp.ORCID 0000-0002-0807-7139
Kazuteru WadaSanofi K.K, Opera City Tower 3-20-2 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 163-1488, Japan.
Yoshinori TakahashiSanofi K.K, Opera City Tower 3-20-2 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 163-1488, Japan.
Owen HaginoSanofi, 55 Corporate Drive, Bridgewater, NJ, 08807, USA.
Hubert van HoogstratenSanofi-Genzyme, 500 Kendall St, Cambridge, MA, 02142, USA.
Neil M H GrahamRegeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA.
Hideto KamedaDivision of Rheumatology, Department of Internal Medicine, School of Medicine, Toho University, 2-22-36 Ohashi, Meguro-ku, Tokyo, 153-8515, Japan.
Sanofi (Japan) · JPGenesys (United States) · USRegeneron (United States) · USSanofi (United States) · USToho University · JPUniversity of Occupational and Environmental Health Japan · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSarilumab is a human immunoglobulin G1 anti-interleukin-6 (IL-6) receptor monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor α. This bridging study assessed the efficacy and safety of sarilumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR).

methodsIn this phase III study, 243 patients were randomized 2:2:1:1 to receive subcutaneous sarilumab 150 mg every 2 weeks (q2w), sarilumab 200 mg q2w, placebo switching to sarilumab 150 mg q2w + MTX at 24 weeks, or placebo switching to sarilumab 200 mg q2w at 24 weeks, all in combination with MTX, for a total of 52 weeks (double-blind, placebo-controlled 24-week period followed by a single-blind 28-week extension). The primary endpoint was the proportion of patients achieving American College of Rheumatology 20% improvement criteria (ACR20) responses at week 24.

resultsACR20 response rates at week 24 were 67.9%, 57.5%, and 14.8% for sarilumab 150 mg, sarilumab 200 mg, and placebo, respectively. Serious treatment-emergent adverse events were reported by 9.9%, 6.3%, 0%, and 13.3% of patients in the sarilumab 150 mg, sarilumab 200 mg, placebo to sarilumab 150 mg, and placebo to sarilumab 200 mg groups, respectively. No deaths occurred. The incidence of infections ranged from 52.5 to 67.9%, with five serious infections for the sarilumab 150 mg group and one for the group switched from placebo to 200 mg sarilumab. Absolute neutrophil count < 1.0 Giga/l occurred in 13.6% and 7.5% of patients in the sarilumab 150 and 200 mg groups, respectively, and was not associated with infection.

conclusionsIn Japanese MTX-IR RA patients treated with sarilumab (150 and 200 mg q2w) in combination with MTX, sustained clinical efficacy was shown by significant improvement in signs, symptoms, and physical function; bridging between this and a previous global study was achieved. At week 52, the safety profiles of both doses of sarilumab were generally similar, as previously observed and as expected based on IL-6 class.

trial registrationClinicalTrials.gov, NCT02293902 . Registered on 19 November 2014.

Indexed as

AdultAgedAntibodies, Monoclonal, HumanizedAntirheumatic AgentsArthritis, RheumatoidDose-Response Relationship, DrugDrug Therapy, CombinationFemaleHumansMaleMethotrexateMiddle AgedNasopharyngitisNeutropeniaSeverity of Illness IndexTreatment OutcomeAntibodies, Monoclonal, HumanizedAntirheumatic AgentsMethotrexatesarilumabAntibodyAnti-IL-6 receptorJapanMTX-IRPhase IIIRheumatoid arthritisSarilumab

Identifiers

PMID30894208
PMCPMC6425658
OpenAlexW2924795555

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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.