Tocilizumab shows low immunogenic potential
Use of tocilizumab—through the intravenous (TCZ-IV) or subcutaneous (TCZ-SC) route and either as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)—carries a low risk of immunogenicity in rheumatoid arthritis (RA), a study has shown.
Researchers pooled data from five TCZ-SC and eight TCZ-IV phase III clinical trials and 1 TCZ-IV clinical pharmacology safety study (>50,000 samples) to evaluate the immunogenicity profile of the agent. The overall population comprised 8,974 RA patients in total.
Antidrug antibody (ADA) measurements were performed following TCZ-SC or TCZ-IV treatment as monotherapy or in combination with csDMARDs, and after dosing interruptions or in TCZ-washout samples. The correlation of ADAs with clinical response, adverse events or pharmacokinetics (PK) was estimated.
ADAs developed in 1.5 percent of patients in the TCZ-SC cohort and in 1.5 percent in the TCZ-IV cohort. ADA development was comparable between patients who received TCZ as a monotherapy and those who received TCZ in combination with csDMARDs (0.7 to 2.0 percent).
ADA development was not associated with pharmacokinetic or safety events, such as anaphylaxis, hypersensitivity or injection-site reactions. Furthermore, there were no reports of loss of TCZ efficacy in patients who developed ADAs.
The low immunogenicity of TCZ might be attributed to the downregulation of B cell activities due to the inhibition of IL-6 signalling, as well as to molecule-related factors—including mAb structure (eg, a specific molecular structure with an idiotype of low immunogenic potential) and manufacturing processes.
In light of the finding that the incidence of ADA development is low among TCZ-treated RA patients, regardless or route of administration and whether used as monotherapy or in combination with csDMARDS, routine ADA testing is unnecessary for the clinical use of TCZ in RA management.