Low immunogenicity of tocilizumab in patients with rheumatoid arthritis

Abstract

ObjectiveSubcutaneous (SC) and intravenous formulations of tocilizumab (TCZ) are available for the treatment of patients with rheumatoid arthritis (RA), based on the efficacy and safety observed in clinical trials. Anti-TCZ antibody development and its impact on safety and efficacy were evaluated in adult patients with RA treated with intravenous TCZ (TCZ-IV) or TCZ-SC as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).MethodsData from 5 TCZ-SC and 8 TCZ-IV phase III clinical trials and 1 TCZ-IV clinical pharmacology safety study (>50 000 samples) were pooled to assess the immunogenicity profile of TCZ-SC and TCZ-IV (8974 total patients). The analysis included antidrug antibody (ADA) measurement following TCZ-SC or TCZ-IV treatment as monotherapy or in combination with csDMARDs, after dosing interruptions or in TCZ-washout samples, and the correlation of ADAs with clinical response, adverse events or pharmacokinetics (PK).ResultsThe proportion of patients who developed ADAs following TCZ-SC or TCZ-IV treatment was 1.5% and 1.2%, respectively. ADA development was also comparable between patients who received TCZ monotherapy and those who received concomitant csDMARDs (0.7–2.0%). ADA development did not correlate with PK or safety events, including anaphylaxis, hypersensitivity or injection-site reactions, and no patients who developed ADAs had loss of efficacy.ConclusionsThe immunogenicity risk of TCZ-SC and TCZ-IV treatment was low, either as monotherapy or in combination with csDMARDs. Anti-TCZ antibodies developed among the small proportion of patients had no evident impact on PK, efficacy or safety.

Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial

“…Only nine patients tested positive for neutralising anti-TCZ antibodies, none of whom withdrew because of insufficient therapeutic response or loss of efficacy, consistent with previous reports. 13 Because of the complexity of multiple comparisons, all week 104 analyses were exploratory, which is a limitation of this study. Post-week 52 data for the 4 mg/kg TCZ+MTX and placebo+MTX groups should be interpreted with caution given the large number of patients switching to escape therapy.…”

Translating IL-6 biology into effective treatments

“…One safety concern of biologic therapies is the development of anti-drug antibodies, which can lead to loss of efficacy and/or immune-mediated adverse reactions 174 . A study evaluating the immunogenicity of tocilizumab in patients with RA found that the incidence of antibodies to tocilizumab was low, regardless of the route of administration of tocilizumab or whether it was used as monotherapy or in combination with csDMARDs; moreover, antibodies to tocilizumab were mostly transient, and their development did not correlate with pharmacokinetics, safety events or loss of efficacy 174 .…”

A Review of Recent Advances Using Tocilizumab in the Treatment of Rheumatic Diseases

“…The PK profile [28,29,31]. In a pooled analysis of data from 13 phase 3 clinical trials (8 TCZ-IV, 5 TCZ-SC) and one TCZ-IV safety study, antidrug antibodies were identified in 47 of 3094 (1.5%) and 69 of 5806 (1.2%) patients treated with TCZ-SC and TCZ-IV, respectively [76]; neutralizing antidrug antibodies were confirmed in 40 of 3094 (1.3%) and 54 of 5806 (0.9%) of these patients, respectively [76].In summary, the safety, PK, and immunogenicity of TCZ-SC appear to be similar to those for TCZ-IV. …”