Evolution of cytokines and inflammatory biomarkers during infliximab induction therapy and the impact of inflammatory burden on primary response in patients with Crohn's disease.

Abstract

OBJECTIVE:

Primary non-response to infliximab in Crohn's disease is still incompletely understood. Our aim was to further characterize the role of inflammatory burden during infliximab induction therapy.

MATERIALS AND METHODS:

We studied a well-characterized cohort of 201 anti-TNF naive Crohn's disease patients treated with infliximab 5mg/kg at week 0, 2, 6 and 14 who had serum samples drawn just before every infusion. All serum samples were analyzed for CRP, albumin, TNF, IFN-γ, IL-6, IL-8, IL-10, infliximab trough concentrations (in-house-developed ELISA) and antibodies to infliximab (HMSA, Prometheus Laboratories Inc., San Diego, CA). Primary non-response was defined as the absence of clinical improvement at week 14.

RESULTS:

The incidence of primary non-response to infliximab was 8% (n = 16). IL-8 concentrations at baseline were higher (p = .01) and albumin at week 6 was lower in primary non-responders (p = .01) compared to responders. During induction, IFN-γ and IL-6 concentrations decreased significantly at week 2 and week 6 in responders compared to primary non-responders (p < .05). Serum TNF increased significantly after each infliximab infusion and this increase from week 0 to week 14 was more pronounced in responders (p = .03). Multiple logistic regression identified TNF/CRP ratio at baseline as predictive for primary non-response to infliximab at week 14 (OR 2.8 (95% CI 1.4-5.5; p = .003)).

CONCLUSIONS:

In this intensively sampled cohort of Crohn's disease patients, we demonstrate that inflammatory burden is more determining for primary non-response than drug exposure or immunogenicity. Our findings furthermore suggest that the contribution of TNF in inflammation might be higher in primary non-response, contradicting the non-TNF-driven concept.

• Authors: Thomas Billiet, Isabelle Cleynen, Vera Ballet, Karolien Claes, Fred Princen, Sharat Singh, Marc Ferrante, Gert Van Assche, Ann Gils, Severine Vermeire
• Journal: Scandinavian journal of gastroenterology (Scand J Gastroenterol) Vol. 52 Issue 10 Pg. 1086-1092 (Oct 2017) ISSN: 1502-7708 [Electronic] England
• PMID: 28622097 (Publication Type: Journal Article)

Chemical References

• Antibodies
• Biomarkers
• CXCL8 protein, human
• Cytokines
• Gastrointestinal Agents
• IL10 protein, human
• IL6 protein, human
• Interleukin-6
• Interleukin-8
• Serum Albumin
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interferon-gamma
• C-Reactive Protein
• Infliximab

Topics

• Adult
• Antibodies (blood)
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Crohn Disease (blood, drug therapy)
• Cytokines (blood)
• Female
• Gastrointestinal Agents (blood, immunology, therapeutic use)
• Humans
• Induction Chemotherapy
• Infliximab (blood, immunology, therapeutic use)
• Interferon-gamma (blood)
• Interleukin-10 (blood)
• Interleukin-6 (blood)
• Interleukin-8 (blood)
• Male
• Middle Aged
• Serum Albumin (metabolism)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (blood)