Evidence map›Paper›PMID 25975452›Full record

SynthesisLancet (London, England)2015

Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis.

Jasvinder A Singh, Chris Cameron, Shahrzad Noorbaloochi, Tyler Cullis, Matthew Tucker, Robin Christensen, Elizabeth Tanjong Ghogomu, Doug Coyle, Tammy Clifford, Peter Tugwell and 1 more

Abstract readSystematic ReviewNetwork Meta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Lancet (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 290 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
290citing papers in PubMed, 10 pooled it
47.2field-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

290 citing papers in PubMed, 10 syntheses or guidelines pooled it, 621 citations in OpenAlex.

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  4. Tumor necrosis factor (TNF) inhibitors for psoriatic arthritis.The Cochrane database of systematic reviews · 2025
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230 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Jasvinder A SinghBirmingham Veterans Affairs Medical Center, Birmingham, AL, USA; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA. Electronic address: jasvinder.md@gmail.com.
Chris CameronSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, ON, Canada; University of Ottawa Heart Institute, Ottawa, ON, Canada.
Shahrzad NoorbaloochiAmerican University, Washington, DC, USA.
Tyler CullisDivision of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Matthew TuckerDivision of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Robin ChristensenMusculoskeletal Statistics Unit, The Parker Institute, Department of Rheumatology, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Denmark.
Elizabeth Tanjong GhogomuSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, ON, Canada.
Doug CoyleSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, ON, Canada.
Tammy CliffordSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, ON, Canada.
Peter TugwellSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, ON, Canada.
George A WellsSchool of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, ON, Canada; University of Ottawa Heart Institute, Ottawa, ON, Canada.
University of Ottawa · CAUniversity of Alabama at Birmingham · USAmerican University · USCopenhagen University Hospital · DK

Funding

Multicenter Osteoarthritis Study (MOST) Second Renewal - UAB Clinical CenterU01AG018947 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LEWIS, CORA E · 2001 to 2020
$13.2M
The Effects of Urate Lowering Therapy on Inflammation, Endothelial function, andP50AR060772 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SINGH, JASVINDER A · 2012 to 2021
$12.8M
UAB Deep South Arthritis and Musculoskeletal CERTsU19HS021110 · AHRQ · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SAAG, KENNETH G · 2011 to 2015
$4.1M
ACOSOG Community Clinical Oncology Program (CCOP) Research BaseU10CA149950 · NCI · MAYO CLINIC ROCHESTER · PI NELSON, HEIDI, SLOAN, JEFF A. · 2011 to 2014
$3.9M
Effectiveness of DiscontinuinG bisphosphonatEs Study (EDGE)U34AR062891 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SAAG, KENNETH G · 2013 to 2014
$647k
AHRQ HHS U19 HS021110CIHR 116573CIHR CGV 121171Intramural VA VA999999NCI NIH HHS U10 CA149950NIAMS NIH HHS P50 AR060772NIAMS NIH HHS U34 AR062891NIA NIH HHS U01 AG018947
6 · The paper itself

Abstract

backgroundSerious infections are a major concern for patients considering treatments for rheumatoid arthritis. Evidence is inconsistent as to whether biological drugs are associated with an increased risk of serious infection compared with traditional disease-modifying antirheumatic drugs (DMARDs). We did a systematic review and meta-analysis of serious infections in patients treated with biological drugs compared with those treated with traditional DMARDs.

methodsWe did a systematic literature search with Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to Feb 11, 2014. Search terms included "biologics", "rheumatoid arthritis" and their synonyms. Trials were eligible for inclusion if they included any of the approved biological drugs and reported serious infections. We assessed the risk of bias with the Cochrane Risk of Bias Tool. We did a Bayesian network meta-analysis of published trials using a binomial likelihood model to assess the risk of serious infections in patients with rheumatoid arthritis who were treated with biological drugs, compared with those treated with traditional DMARDs. The odds ratio (OR) of serious infection was the primary measure of treatment effect and calculated 95% credible intervals using Markov Chain Monte Carlo methods.

findingsThe systematic review identified 106 trials that reported serious infections and included patients with rheumatoid arthritis who received biological drugs. Compared with traditional DMARDs, standard-dose biological drugs (OR 1.31, 95% credible interval [CrI] 1.09-1.58) and high-dose biological drugs (1.90, 1.50-2.39) were associated with an increased risk of serious infections, although low-dose biological drugs (0.93, 0.65-1.33) were not. The risk was lower in patients who were methotrexate naive compared with traditional DMARD-experienced or anti-tumour necrosis factor biological drug-experienced patients. The absolute increase in the number of serious infections per 1000 patients treated each year ranged from six for standard-dose biological drugs to 55 for combination biological therapy, compared with traditional DMARDs.

interpretationStandard-dose and high-dose biological drugs (with or without traditional DMARDs) are associated with an increase in serious infections in rheumatoid arthritis compared with traditional DMARDs, although low-dose biological drugs are not. Clinicians should discuss the balance between benefit and harm with the individual patient before starting biological treatment for rheumatoid arthritis.

fundingRheumatology Division at the University of Alabama at Birmingham.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidBiological FactorsHumansOpportunistic InfectionsRandomized Controlled Trials as TopicRisk FactorsAntirheumatic AgentsBiological Factors

Identifiers

PMID25975452
PMCPMC4580232
OpenAlexW1596092785

What OpenQuestion holds

Textmetadata
LicenceTDM
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.