Background Biological agents targeting tumor necrosis factor (TNF) have recently been successful in treating rheumatoid arthritis (RA). However, 20–40% of patients have inadequate responses to these agents, and novel therapeutic interventions with new modes of action are urgently required to treat RA. Interleukin-6 (IL-6) is a proinflammatory cytokine that is abundantly expressed and detectable in the joints and circulation of patients during the active phases of RA. Tocilizumab is a humanized anti-human IL-6R monoclonal antibody (Mab) that inhibits the binding of IL-6 to IL-6R or sIL-6R. However, the clinical benefit and safety of switching from anti-TNF agent to tocilizumab have not been defined.
Objectives This study determined the effectiveness of tocilizumab between patients with RA who switched from anti-TNF agents, and compared the effectiveness between the switched for inefficacy patients and for adverse events patients.
Methods This retrospective study investigated that 61 patients had already been treated with anti-TNF agents (46 patients for inefficacy and 15 patients for adverse events). Treatment responses to tocilizumab at week 12 and 24 were compared between the switched for inefficacy groups and for adverse events groups using the disease activity score 28 (DAS28) and EULAR response criteria.
Results Thirty seven (80.4%) and 13 (86.6%) patients in the switched for inefficacy groups and for adverse events group, respectively, completed 24 weeks of tocilizumab treatment. The DAS28-ESR and DAS28-CRP values at weeks 12 and 24 compared to baseline decreased significantly for both groups. The DAS28-ESR and DAS28-CRP values at weeks 12 and 24 were decreased in the switched for adverse events groups, compared to the switched for inefficacy group, but not significantly. Disease activity was improved in the switched for adverse events patients compared to the switched for inefficacy patients. Among the therapeutic outcomes of tocilizumab using the EULAR response criteria, the ratios (%) of good responses at week 24 were 50.0% (23 patients) and 60.0% (9 patients) in the switched for inefficacy group and the switched for adverse event group, respectively. The incidence of a good response was higher in the switched for adverse event group, than in the switched for inefficacy group. Disease activity was improved more and remission rates were better in the switched for adverse event (66.7%) than the switched for inefficacy group (47.8%).
Conclusions Tocilizumab was safe, tolerable, and clinically effective for patients with inadequate responses to anti-TNF therapy. Disease activity and remission rates were improved by treatment with tocilizumab in the switched to anti-TNF agents for adverse events patients with rheumatoid arthritis compared to the switched for inefficacy patients. A targeted blockade of IL-6 signaling is a highly effective and promising means of decreasing RA disease activity.
Disclosure of Interest None Declared
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