Tocilizumab reduces complement C3 and C4 serum levels in rheumatoid arthritis patients

Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, is known to be able to rapidly reduce acute phase reactants. Although complement components are part of the acute phase, no data are available on a possible effect of tocilizumab on complement proteins. Serum levels of complement components C3 and C4 were retrospectively assessed in 19 consecutive rheumatoid arthritis patients eligible for tocilizumab treatment. Tocilizumab was found to reduce all known acute phase reactants, including C3 and C4 levels. C3 and C4 were found to decrease as early as 4 weeks after the first tocilizumab infusion. On average, C3 decreased by 24.02, 27.35, 33.62, and 32.81%, as compared to pre-treatment values, after 1, 3, 6, and 12 months of therapy, respectively; likewise, C4 decreased by 44.74, 43.40, 54.33, and 54.56% at the same time points with respect to pre-treatment values. A discrete proportion of patients (38.46 and 30.76% for C3 and C4, respectively) displayed subnormal complement serum levels early (4 weeks) after initiation of tocilizumab treatment, which raised suspicion for complement consumption. However, no circulating immunocomplexes were found nor did any patient ever display clinical features of immunocomplex disease during a median follow-up of 38 months. After 12 months of therapy, 68.75 and 56.25% of patients had abnormally low C3 and C4 serum levels, respectively. Reduction in C3 and C4 serum levels should be included among the anti-inflammatory effects exerted by tocilizumab and are thus to be considered as an expected outcome of the mechanism of action of this drug.