Combined Cytokine Inhibition More Effective in Rheumatoid Arthritis Inflammation

Combined Cytokine Inhibition More Effective in Rheumatoid Arthritis Inflammation

rheumatoid arthritisA combination of specific cytokine inhibitors was shown to be effective as a potential treatment for patients with Rheumatoid Arthritis (RA). These findings were derived from a study, entitled, “Combined Inhibition of Tumor Necrosis Factor α and Interleukin-17 As a Therapeutic Opportunity in Rheumatoid Arthritis: Development and Characterization of a Novel Bispecific Antibody” recently published in the journal of the American College of Rheumatology, Arthritis & Rheumatogy.

Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints, causing synovial inflammation, and cartilage and bone destruction. Multiple mechanisms are involved in the pathogenesis of RA, including mesenchymal cell activation, and recruitment of cells of the innate and adaptive immune system.

Evidence has shown that cytokines are involved in the onset and progression of the disease, based on treatments that inhibit tumor necrosis factor α (TNFα) and interleukin-6 receptor (IL-6R). In this regard, treatments classified as anticytokines have been found to improve RA in patients that have failed to respond traditional antirheumatic agents.

However, single cytokine inhibition in patients with RA has been found to be clinically meaningful to only about half of treated patients, with loss of response over time. Combined inhibition treatments of different cytokine targets may overcome this challenge, permitting more effective suppression of inflammation, and halting, or even reversing, joint destruction.

A team of researchers from University of Erlangen–Nuremberg, Erlangen, Germany, in collaboration with Roche Pharmaceutical Research and Early Development, examined the anti-inflammatory potential and antiarthritic effects of combined TNFα and IL-17 inhibition (a proinflammatory cytokine), using human primary mesenchymal cells.

Georg Schett and colleagues assessed the additive/synergistic effects of TNFα and IL-17, and measured the proinflammatory effect through cytokine secretion by human fibroblast-like synoviocytes (FLS). They found this combined approach was more effective in inhibiting cytokine activity, and resulted in matrix enzyme responses, compared to a single blockage approach.

Furthermore, the researchers examined the impact of a combined inhibition of TNFα and IL-17 in vivo, using a robust arthritis model, and developed bispecific antibodies targeting TNFα and IL-17 by using different molecular formats for an optimal therapeutic approach. Results revealed that bispecific anti–TNFα/IL-17 antibodies have superior efficacy in the treatment of arthritis, and may overcome the limited therapeutic responses obtained from single cytokine neutralization.

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