Evidence map›Paper›PMID 26585988›Full record

Trial reportAnnals of the rheumatic diseases2016

Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial.

Tsutomu Takeuchi, Yoshiya Tanaka, Naoki Ishiguro, Hisashi Yamanaka, Toshiyuki Yoneda, Takeshi Ohira, Naoki Okubo, Harry K Genant, Désirée van der Heijde

Open 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, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 5 pooled it
21.6field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 5 syntheses or guidelines pooled it, 162 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 8 institutions in 3 countries.

Tsutomu TakeuchiDivision of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Yoshiya TanakaFirst Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Naoki IshiguroDepartment of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Aichi, Japan.
Hisashi YamanakaInstitute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Toshiyuki YonedaDivision of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Takeshi OhiraDaiichi-Sankyo Co., Ltd., Tokyo, Japan.
Naoki OkuboDaiichi-Sankyo Co., Ltd., Tokyo, Japan.
Harry K GenantDepartments of Radiology, Medicine and Orthopaedic Surgery, University of California, San Francisco, California, USA.
Désirée van der HeijdeDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID http://orcid.org/0000-0002-5781-158X
Daiichi-Sankyo (Japan) · JPIndiana University School of MedicineKeio University · JPLeiden University Medical Center · NLNagoya University · JPTokyo Women's Medical University · JPUniversity of California, San Francisco · USUniversity of Occupational and Environmental Health Japan · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTo evaluate efficacy and safety of three different regimens of denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor kappa B (RANK) ligand (RANKL), for Japanese patients with rheumatoid arthritis (RA).

methodsIn this multicentre, randomised, placebo-controlled phase II study, 350 Japanese patients with RA between 6 months and <5 years, stratified by glucocorticoid use and rheumatoid factor status, were randomly assigned to subcutaneous injections of placebo or denosumab 60 mg every 6 months (Q6M), every 3 months (Q3M) or every 2 months (Q2M). All patients basically continued methotrexate treatment and had a supplement of calcium and vitamin D throughout the study. The primary endpoint was change in the modified Sharp erosion score from baseline to 12 months.

resultsDenosumab significantly inhibited the progression of bone erosion at 12 months compared with the placebo, and the mean changes of the modified Sharp erosion score at 12 months from baseline were 0.99, 0.27 (compared with placebo, p=0.0082), 0.14 (p=0.0036) and 0.09 (p<0.0001) in the placebo, Q6M, Q3M and Q2M, respectively. Secondary endpoint analysis revealed that denosumab also significantly inhibited the increase of the modified total Sharp score compared with the placebo, with no obvious evidence of an effect on joint space narrowing for denosumab. As shown in previous studies, denosumab increased bone mineral density. No apparent difference was observed in the safety profiles of denosumab and placebo.

conclusionsAddition of denosumab to methotrexate has potential as a new therapeutic option for patients with RA with risk factors of joint destruction. TRIAL REGISTRATION NUMBER: JapicCTI-101263.

Indexed as

AgedAntirheumatic AgentsArthritis, RheumatoidBone DensityBone Density Conservation AgentsDenosumabDouble-Blind MethodDrug Therapy, CombinationFemaleHumansJapanMaleMethotrexateMiddle AgedRheumatoid FactorAntirheumatic AgentsBone Density Conservation AgentsDenosumabMethotrexateRheumatoid FactorBone Mineral DensityRheumatoid ArthritisTreatment

Identifiers

PMID26585988
PMCPMC4893103
OpenAlexW2179986300

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.