Evidence mapPaperPMID 35213675Full record

ArticlePloS one2022

Antirheumatic therapy is associated with reduced complement activation in rheumatoid arthritis.

Thao H P Nguyen, Ingrid Hokstad, Morten Wang Fagerland, Tom Eirik Mollnes, Ivana Hollan, Mark W Feinberg, Gunnbjørg Hjeltnes, Gro Ø Eilertsen, Knut Mikkelsen, Stefan Agewall

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

8 citing papers in PubMed, 9 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

10 authors at 6 institutions in 2 countries.

Thao H P NguyenLillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway.ORCID 0000-0003-2597-4031
Ingrid HokstadDepartment of Laboratory medicine, Innlandet Hospital Trust, Lillehammer, Norway.
Morten Wang FagerlandOslo Centre for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
Tom Eirik MollnesDepartment of Immunology, Oslo University Hospital, Oslo, Norway.
Ivana HollanBeitostølen Health and Sport Centre, Beitostølen, Norway.
Mark W FeinbergHarvard Medical School, Boston, Massachusetts, United States of America.
Gunnbjørg HjeltnesDepartment of Internal Medicine, Innlandet Hospital Trust, Lillehammer, Norway.
Gro Ø EilertsenFaculty of Health Sciences, Department of Clinical Medicine, UIT-The Arctic University of Norway, Tromsø, Norway.
Knut MikkelsenVolvat Medical Center, Lillehammer, Norway.
Stefan AgewallUniversity of Oslo, Faculty of Medicine, Institute of Clinical Medicine, Oslo, Norway.
Oslo University Hospital · NOInnlandet Hospital Trust · NOBrigham and Women's Hospital · USNorwegian University of Science and Technology · NOUniversity Hospital of North Norway · NOUniversity of Oslo · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe complement system plays an important role in pathophysiology of cardiovascular disease (CVD), and might be involved in accelerated atherogenesis in rheumatoid arthritis (RA). The role of complement activation in response to treatment, and in development of premature CVD in RA, is limited. Therefore, we examined the effects of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) on complement activation using soluble terminal complement complex (TCC) levels in RA; and assessed associations between TCC and inflammatory and cardiovascular biomarkers.

methodsWe assessed 64 RA patients starting with MTX monotherapy (n = 34) or TNFi with or without MTX co-medication (TNFi±MTX, n = 30). ELISA was used to measure TCC in EDTA plasma. The patients were examined at baseline, after 6 weeks and 6 months of treatment.

resultsMedian TCC was 1.10 CAU/mL, and 57 (89%) patients had TCC above the estimated upper reference limit (<0.70). Compared to baseline, TCC levels were significantly lower at 6-week visit (0.85 CAU/mL, p<0.0001), without significant differences between the two treatment regimens. Notably, sustained reduction in TCC was only achieved after 6 months on TNFi±MTX (0.80 CAU/mL, p = 0.006). Reductions in TCC after treatment were related to decreased C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and interleukin 6, and increased levels of total, high and low-density lipoprotein cholesterol. Similarly, baseline TCC was significantly related to baseline CRP, ESR and interleukin 6. Patients with endothelial dysfunction had higher baseline TCC than those without (median 1.4 versus 1.0 CAU/mL, p = 0.023).

conclusionsPatients with active RA had elevated TCC, indicating increased complement activation. TCC decreased with antirheumatic treatment already after 6 weeks. However, only treatment with TNFi±MTX led to sustained reduction in TCC during the 6-month follow-up period. RA patients with endothelial dysfunction had higher baseline TCC compared to those without, possibly reflecting involvement of complement in the atherosclerotic process in RA.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidBlood SedimentationCholesterol, HDLCholesterol, LDLComplement ActivationComplement Membrane Attack ComplexC-Reactive ProteinDrug Administration ScheduleDrug Therapy, CombinationFemaleHumansInterleukin-6MaleMethotrexateMiddle AgedAntirheumatic AgentsCholesterol, HDLCholesterol, LDLComplement Membrane Attack ComplexC-Reactive ProteinInterleukin-6MethotrexateTumor Necrosis Factor Inhibitors

Identifiers

PMID35213675
PMCPMC8880951
OpenAlexW4214606478

What Socratic holds

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Registered trials

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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 Socratic graph.