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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

View Article: PubMed Central - PubMed

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).

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.

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.

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.

No MeSH data available.


Related in: MedlinePlus

Changes in levels of IL-6, sTNF-R1 and sTNF-R2 following 6 months of treatment with adalimumab or infliximab.Level of IL-6 and sTNF-R1 and sTNF-R2 were determined in 26 patients with rheumatoid arthritis, 15 patients treated with adalimumab, and 11 patients treated with infliximab. Levels were determined prior to treatment (Baseline) and following 6 months of treatment (Follow-up). Levels of IL-6 (A) and sTNF-R2 (C) decreased significantly during treatment. *p < 0.05. Medians and interquartile ranges are shown.
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pone.0162316.g002: Changes in levels of IL-6, sTNF-R1 and sTNF-R2 following 6 months of treatment with adalimumab or infliximab.Level of IL-6 and sTNF-R1 and sTNF-R2 were determined in 26 patients with rheumatoid arthritis, 15 patients treated with adalimumab, and 11 patients treated with infliximab. Levels were determined prior to treatment (Baseline) and following 6 months of treatment (Follow-up). Levels of IL-6 (A) and sTNF-R2 (C) decreased significantly during treatment. *p < 0.05. Medians and interquartile ranges are shown.

Mentions: A total of 26 patients with RA were included from the cohort (for the selection process, see Fig 1). Fifteen patients were treated with adalimumab, and 11 patients were treated with infliximab (for baseline characteristics, see Table 1). None of the participants were exposed to steroid treatment during the study, and only a few patients received sulfasalazine. The patients treated with adalimumab or infliximab did not differ in any of the baseline characteristics, neither did they differ in baseline levels of measured biomarkers. During the first 6 months of treatment with adalimumab or infliximab, DAS28(CRP) declined from 4.9 (4.2–5.7) to 3.5 (2.6–4.4) (p < 0.001) in the entire group, whereas the median level of CRP did not change significantly, from 5.0 (1.8–36)) mg/ml to 3.3 (1.4–9) mg/ml, respectively (p = 0.0535)). There was no difference in effect on DAS28(CRP),CRP, IL-6 or sTNF-R1 and -R2 between patients treated with adalimumab or infliximab. Both levels of IL-6 and sTNF-R2 decreased significantly during treatment (Fig 2). IL-6 decreased from 8 (1–36) pg/ml at baseline to 1 (1–5) pg/ml after 6 months treatment (p = 0.009). sTNF-R2 decreased from 3092 (2642–3750) pg/ml at baseline to 2604 (2361–3079) pg/ml at follow-up (p = 0.0071). Levels of sTNF-R1 did not change significantly during treatment from 1152 (976–1380) pg/ml to 1135 (919–1281) pg/ml (p = 0.2818). The levels of the other tested cytokines (TNF-α, IL-1b, IL-10, IL-17A, IL-17F, IL-33, TNF-β, IL-1ra, IL-8, IL-12(p70) and IL-13) were generally below detection limits of the kits (data not shown).


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
Changes in levels of IL-6, sTNF-R1 and sTNF-R2 following 6 months of treatment with adalimumab or infliximab.Level of IL-6 and sTNF-R1 and sTNF-R2 were determined in 26 patients with rheumatoid arthritis, 15 patients treated with adalimumab, and 11 patients treated with infliximab. Levels were determined prior to treatment (Baseline) and following 6 months of treatment (Follow-up). Levels of IL-6 (A) and sTNF-R2 (C) decreased significantly during treatment. *p < 0.05. Medians and interquartile ranges are shown.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5016088&req=5

pone.0162316.g002: Changes in levels of IL-6, sTNF-R1 and sTNF-R2 following 6 months of treatment with adalimumab or infliximab.Level of IL-6 and sTNF-R1 and sTNF-R2 were determined in 26 patients with rheumatoid arthritis, 15 patients treated with adalimumab, and 11 patients treated with infliximab. Levels were determined prior to treatment (Baseline) and following 6 months of treatment (Follow-up). Levels of IL-6 (A) and sTNF-R2 (C) decreased significantly during treatment. *p < 0.05. Medians and interquartile ranges are shown.
Mentions: A total of 26 patients with RA were included from the cohort (for the selection process, see Fig 1). Fifteen patients were treated with adalimumab, and 11 patients were treated with infliximab (for baseline characteristics, see Table 1). None of the participants were exposed to steroid treatment during the study, and only a few patients received sulfasalazine. The patients treated with adalimumab or infliximab did not differ in any of the baseline characteristics, neither did they differ in baseline levels of measured biomarkers. During the first 6 months of treatment with adalimumab or infliximab, DAS28(CRP) declined from 4.9 (4.2–5.7) to 3.5 (2.6–4.4) (p < 0.001) in the entire group, whereas the median level of CRP did not change significantly, from 5.0 (1.8–36)) mg/ml to 3.3 (1.4–9) mg/ml, respectively (p = 0.0535)). There was no difference in effect on DAS28(CRP),CRP, IL-6 or sTNF-R1 and -R2 between patients treated with adalimumab or infliximab. Both levels of IL-6 and sTNF-R2 decreased significantly during treatment (Fig 2). IL-6 decreased from 8 (1–36) pg/ml at baseline to 1 (1–5) pg/ml after 6 months treatment (p = 0.009). sTNF-R2 decreased from 3092 (2642–3750) pg/ml at baseline to 2604 (2361–3079) pg/ml at follow-up (p = 0.0071). Levels of sTNF-R1 did not change significantly during treatment from 1152 (976–1380) pg/ml to 1135 (919–1281) pg/ml (p = 0.2818). The levels of the other tested cytokines (TNF-α, IL-1b, IL-10, IL-17A, IL-17F, IL-33, TNF-β, IL-1ra, IL-8, IL-12(p70) and IL-13) were generally below detection limits of the kits (data not shown).

View Article: PubMed Central - PubMed

ABSTRACT

Objectives: With the present study we wanted to explore the impact of treatment with a tumor necrosis factor-&alpha; -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).

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.

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-&alpha;, TNF-&beta;, 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.

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.

No MeSH data available.


Related in: MedlinePlus