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Anti-Drug Antibodies, Drug Levels, Interleukin-6 and Soluble TNF Receptors in Rheumatoid Arthritis Patients during the First 6 Months of Treatment with Adalimumab or Infliximab: A Descriptive Cohort Study.
- Source :
-
PloS one [PLoS One] 2016 Sep 08; Vol. 11 (9), pp. e0162316. Date of Electronic Publication: 2016 Sep 08 (Print Publication: 2016). - Publication Year :
- 2016
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Abstract
- Objectives: With the present study we wanted to explore the impact of treatment with a tumor necrosis factor-α -inhibitor (TNFi) on levels of soluble biomarkers in rheumatoid arthritis (RA) patients and to identify predictors of impaired drug levels and development of anti-TNFi antibodies (anti-TNFi Abs).<br />Methods: Blood samples from 26 patients with established RA were taken at baseline and following 6 months of treatment with adalimumab or infliximab. Samples were analyzed for levels of TNFi, interleukin (IL)-6, and soluble TNF-receptors 1 and -2 (sTNF-R1 and -2) and for presence of anti-TNFi Abs. Clinical and demographic data were recorded as well.<br />Results: During the initial 6 months treatment, DAS28(CRP) (Disease activity score in 28 joints using C-reactive protein) and levels of IL-6 and sTNF-R2 decreased significantly in patients without anti-TNFi Abs and in patients retaining detectable drug levels. The levels of other tested cytokines (TNF-α, TNF-β, IL-1ra, IL-1b, IL-8, IL-10, IL-12(p70), IL-13, IL-17A, IL-17F, and IL-33) were generally below detection limits. Higher baseline levels of IL-6 associated with undetectable levels of TNFi at follow-up. Anti-TNFi Abs were associated with decreased drug levels, but no predictors for anti-TNFi Ab development could be found.<br />Conclusion: The effect of treatment with TNFi on RA disease activity depends on levels of active drug, and by presence of anti-TNFi Abs. In patients who retain detectable drug levels, and in the absence of anti-TNFi Abs, clinical outcome is improved during treatment, and circulating levels of IL-6 and sTNF-R2 decrease. Baseline levels of IL-6 may predict depletion of TNFi and may identify patients at risk of treatment failure.<br />Competing Interests: Dr. Eng has served as a speaker for Pfizer. Dr. Bendtzen has served as a speaker for Pfizer and Hospira, and owns stocks in Novo-Nordisk and Eurodiagnostica. Dr. Bliddal has received consulting fees, honoraria, research or institutional support, educational grants, equipment, services or expenses from: Abbott, Abbvie, Amgen, AstraZeneca, Aventis, Axellus, Bristol Myers Squibb, Cambridge Nutritional Foods, Dansk Droge, Eurovita, Ferrosan, GlaxoSmithKline, Hoechst, LEO, Lundbeck, MSD, Mundipharma, Norpharma, NOVO, NutriCare, Nycomed, Pfizer, Pharmacia, Pierre-Fabre, Proctor & Gamble, Rhone-Poulenc, Roche, Roussel, Schering-Plough, Searle, Serono, UCB, Wyeth. Dr. Bliddal is not employed by and holds no shares in any of these companies. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
- Subjects :
- Adalimumab blood
Adalimumab pharmacology
Adult
Antibody Formation drug effects
Arthritis, Rheumatoid blood
Biomarkers metabolism
Cohort Studies
Female
Humans
Infliximab blood
Infliximab pharmacology
Male
Middle Aged
Solubility
Tumor Necrosis Factor-alpha antagonists & inhibitors
Tumor Necrosis Factor-alpha metabolism
Adalimumab therapeutic use
Antibodies immunology
Arthritis, Rheumatoid drug therapy
Infliximab therapeutic use
Interleukin-6 metabolism
Receptors, Tumor Necrosis Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27606615
- Full Text :
- https://doi.org/10.1371/journal.pone.0162316