Tocilizumab (TCZ) treatment for rheumatoid arthritis (RA) was associated with a low risk of developing antidrug antibodies (ADAs), according to a study published in Annals of the Rheumatic Diseases. Low immunogenicity was observed when TCZ was administered intravenously, subcutaneously, as monotherapy, or in combination with conventional disease-modifying antirheumatic drugs (csDMARDs).
TCZ, which is available in intravenous (IV) and subcutaneous (SC) formulations, has been shown to be effective in RA as monotherapy or in combination with csDMARDs. However, since TCZ is a biologic DMARD (bDMARD), patients are at risk for developing ADAs, which may result in loss of efficacy or immune-mediated adverse events. The risk of forming ADAs may be affected by factors such as treatment duration, drug dose, concurrent csDMARD use, and route of administration.
High Yield Data Summary
- Results suggest that the development of antidrug antibodies was low in patients being treated with TCZ for RA, regardless of route of administration.
Gerd R. Burmester, MD, from the Department of Rheumatology and Clinical Immunology, Charité — University Medicine Berlin, Free University and Humboldt University of Berlin, and colleagues evaluated the immunogenicity of TCZ when administered SC vs IV or as monotherapy vs in combination with csDMARDs in patients with RA.
Data were derived from 5 SC TCZ (TCZ-SC) and 9 IV TCZ (TCZ-IV) clinical trials. A total of 3099 patients received TCZ-SC as monotherapy (n = 616) or in combination with csDMARDs (n = 2483), and 5875 received TCZ-IV as monotherapy (n = 753) or in combination with csDMARDs (n = 5122).
Similar proportions of patients in the TCZ-SC and TCZ-IV groups developed ADAs (1.5% and 1.2%, respectively). Comparable rates of ADA development were observed with TCZ monotherapy (2.0% and 0.7% for SC and IV, respectively) and with TCZ in combination with csDMARDs (1.4% and 1.3% for SC and IV, respectively).
No correlation was found between ADA development and adverse events, including hypersensitivity, anaphylaxis, and injection-site reactions. Loss of efficacy did not occur in ADA-positive patients.
Summary and Clinical Applicability
TCZ is approved for RA in IV and SC formulations and has demonstrated efficacy as monotherapy or in combination with csDMARDs. Because TCZ is a bDMARD, the development of ADAs, which may result in loss of efficacy or immune-mediated adverse events, remains a safety concern. The authors performed a pooled analysis of 9 clinical trials to evaluate the immunogenicity of TCZ when administered IV, SC, as monotherapy, or in combination with csDMARDs.
“Our pooled results from 8974 patients treated with TCZ indicated that the incidence of ADA development was low, regardless of [IV] or SC formulation and whether it was administered as monotherapy or in combination with csDMARDs. In patients who did develop ADAs, ADAs were mostly transient and no correlation to [pharmacokinetics], safety events, or loss of efficacy was observed,” the investigators wrote.
“Overall, our data suggest that routine ADA testing is unnecessary for the clinical use of TCZ in treating adult RA,” they concluded.
- The number of patients who developed ADAs was low (n = 116 overall), particularly in subgroups TCZ-SC monotherapy (n = 12) and TCZ-IV monotherapy (n = 5)
- In all but one study, hypersensitivity events were defined as all adverse events occurring within 24 hours of TCZ administration, regardless of whether they were clinically consistent with hypersensitivity.
Funding for this study was provided by Roche.
Burmester GR, Choy E, Kivitz A, et al. Low immunogenicity of tocilizumab in patients with rheumatoid arthritis [published online December 22, 2016]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2016-210297