The Immunogenicity of Branded and Biosimilar Infliximab in Rheumatoid Arthritis According to Th9-Related Responses.

Abstract

Our objective was to evaluate the immunogenicity of branded and biosimilar infliximab by detecting changes in T-helper-9 (Th9) percentages induced by an in vitro stimulation test.

METHODS:

Peripheral blood mononuclear cells collected from 55 consecutive rheumatoid arthritis (RA) outpatients (15 drug free, 20 successfully treated with branded infliximab, 20 branded infliximab inadequate responders) and 10 healthy controls were cultured, with or without 50 μg/mL of infliximab originator (Remicade®) or 50 μg/mL of infliximab biosimilar (Remsima®) for 18 h. Th9 lymphocytes were identified by means of flow cytometry as PU.1 and IRF4-expressing, IL-9-secreting CD4⁺ T cells. Furthermore, the markers CCR7 and CD45RA were used to distinguish naïve from memory IL-9 producer cells.

RESULTS:

Under unstimulated conditions, the drug-free RA patients had the highest percentages of Th9 lymphocytes. Following stimulation with branded infliximab, the percentages of PU.1 and IRF4-expressing Th9 cells, CCR7⁺, CD45RA- (central memory) and CCR7-, CD45RA- (effector memory) cells significantly increased in the group of inadequate responders, but no significant variation was observed after exposure to the biosimilar of infliximab.

CONCLUSIONS:

Th9 cells seem to be involved in the immune response to the epitopes of branded, but not biosimilar, infliximab, and this may depend on the recall and stimulation of both central and effector memory cells.

• Authors: Rossella Talotta, Angela Berzi, Andrea Doria, Alberto Batticciotto, Maria Chiara Ditto, Fabiola Atzeni, Piercarlo Sarzi-Puttini, Daria Trabattoni
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 18 Issue 10 (Oct 12 2017) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 29023386 (Publication Type: Journal Article)

Chemical References

• Antirheumatic Agents
• Autoantibodies
• Autoantigens
• Biomarkers
• Infliximab

Topics

• Adult
• Aged
• Antirheumatic Agents (adverse effects, immunology, therapeutic use)
• Arthritis, Rheumatoid (drug therapy, immunology, metabolism)
• Autoantibodies (immunology)
• Autoantigens (immunology)
• Biomarkers
• Female
• Humans
• Immunophenotyping
• Infliximab (adverse effects, immunology, therapeutic use)
• Male
• Middle Aged
• T-Lymphocytes, Helper-Inducer (drug effects, immunology, metabolism)
• Treatment Outcome