Evidence map›Paper›PMID 30014359›Full record

ArticleClinical rheumatology2019

Clinically important neutralizing anti-drug antibodies detected with an in-house competitive ELISA.

Manca Ogrič, Polona Žigon, Katja Lakota, Sonja Praprotnik, David Drobne, Borut Štabuc, Snezna Sodin-Semrl, Saša Čučnik

Abstract read
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In one paragraph

Article in Clinical rheumatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
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

8 authors at 3 institutions in 1 country.

Manca OgričDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000, Ljubljana, Slovenia.
Polona ŽigonDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000, Ljubljana, Slovenia.
Katja LakotaDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000, Ljubljana, Slovenia.
Sonja PraprotnikDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000, Ljubljana, Slovenia.
David DrobneDepartment of Gastroenterology, University Medical Centre Ljubljana, SI-1000, Ljubljana, Slovenia.
Borut ŠtabucDepartment of Gastroenterology, University Medical Centre Ljubljana, SI-1000, Ljubljana, Slovenia.
Snezna Sodin-SemrlDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000, Ljubljana, Slovenia.
Saša ČučnikDepartment of Rheumatology, University Medical Centre Ljubljana, SI-1000, Ljubljana, Slovenia. sasa.cucnik@guest.arnes.si.
Ljubljana University Medical Centre · SIUniversity of Ljubljana · SIUniversity of Primorska · SI

Funding

Javna Agencija za Raziskovalno Dejavnost RS P3-0314
6 · The paper itself

Abstract

Therapeutic drug monitoring of TNF-alpha inhibitors is crucial for evaluating patients with inflammatory diseases on a personalized level. It has been clinically observed that many patients receiving TNF-alpha inhibitors, with negative drug and anti-drug antibody results from bridging ELISA (bELISA), lose their drug response over time, despite dose optimization. Our aims were to develop innovative in-house competitive ELISAs (cELISAs) for the detection of neutralizing antibodies against infliximab and adalimumab and compare their results to reporter gene assay (RGA) and in-house bELISA. Furthermore, we aimed to evaluate patient anti-drug antibody results in regard to their clinical records and potential benefits of therapeutic drug monitoring with the novel cELISAs. Sera of patients treated with infliximab (n = 46) or adalimumab (n = 31), having undetectable drug levels, were tested with our in-house cELISA. Briefly, samples were incubated with a fixed amount of drug and the neutralizing capacity of the samples was determined. The cELISA results were compared to RGA and bELISA results using Spearman's correlation coefficient. Additionally, patient clinical data were evaluated in line with the results of cELISA, bELISA, and RGA using the Kaplan-Meier analysis and the Log Rank test. Both anti-infliximab and anti-adalimumab cELISAs showed very good correlation to RGA (r = 0.932, p < 0.0001 and r = 0.947, p < 0.0001, respectively). Furthermore, a positive result in anti-infliximab cELISA can predict treatment failure in 100% of patients with negative bELISA, while a positive result in anti-adalimumab cELISA can predict treatment failure in 80% of patients with negative bELISA. Taken together, we developed innovative cELISAs enabling quantification of functional and neutralizing anti-drug antibodies, comparable to RGA. The association between cELISA results and loss of drug response in patients identified clinically important anti-drug antibodies, as measured by cELISA.

Indexed as

Enzyme-Linked Immunosorbent AssayAdalimumabAdultAgedAged, 80 and overAntibodies, NeutralizingDrug MonitoringFemaleGenes, ReporterHumansInflammatory Bowel DiseasesInfliximabKaplan-Meier EstimateMaleMiddle AgedPredictive Value of TestsAdalimumabAntibodies, NeutralizingInfliximabTumor Necrosis Factor-alphaAnti-adalimumab antibodiesAnti-infliximab antibodiesCompetitive ELISAReporter gene assay

Identifiers

PMID30014359
OpenAlexW2883270563

What OpenQuestion holds

Textmetadata
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.