What is more efficacious, intravenous (IV) or subcutaneous Actemra (Tocilizumab)?

From the Guidelines

Intravenous (IV) Actemra (tocilizumab) is generally more efficacious than subcutaneous administration for rapid control of severe inflammatory conditions, as it provides faster onset of action and higher peak concentrations in the bloodstream. This is particularly important in acute conditions like cytokine release syndrome or severe rheumatoid arthritis flares, where rapid control of inflammation is crucial. According to a study published in 2019 in Autoimmunity Reviews 1, tocilizumab, an IL-6 receptor antagonist, has been shown to lead to a rapid and sustained improvement in clinical and radiographic outcomes and health-related quality of life, with a low risk of immunogenicity.

The standard IV dosing is typically 4-8 mg/kg every 2-4 weeks, while subcutaneous dosing is usually 162 mg weekly or every other week, depending on weight. However, subcutaneous administration offers advantages of convenience, home administration, and similar long-term outcomes for maintenance therapy in conditions like rheumatoid arthritis. Key considerations for choosing between IV and subcutaneous routes include:

• Urgency of treatment
• Disease severity
• Patient preference
• Practical considerations like access to infusion facilities

Some key points to consider when deciding between IV and subcutaneous administration of Actemra include:

• IV administration requires healthcare facility visits and monitoring but provides a more immediate therapeutic effect
• Subcutaneous administration allows for more independence but with a slightly delayed onset of action
• Both routes have similar safety profiles, though injection site reactions are more common with subcutaneous administration, as noted in the study 1.

From the FDA Drug Label

The tocilizumab-SC data in rheumatoid arthritis (RA) includes 2 double-blind, controlled, multicenter studies Study SC-I was a non-inferiority study that compared the efficacy and safety of tocilizumab 162 mg administered every week subcutaneously and 8 mg/kg intravenously every four weeks in 1262 adult subjects with rheumatoid arthritis

The answer to the question of whether intravenous (IV) or subcutaneous Actemra (Tocilizumab) is more efficacious is not directly stated in the provided drug labels. However, Study SC-I compared the efficacy and safety of tocilizumab administered subcutaneously and intravenously, but the label does not provide a direct comparison of efficacy between the two routes of administration.

• The label states that Study SC-I was a non-inferiority study, implying that the subcutaneous route was compared to the intravenous route to determine if it was not significantly less effective.
• However, the label does not provide the results of this comparison, and therefore, no conclusion can be drawn about which route of administration is more efficacious 2.

From the Research

Efficacy Comparison of IV and Subcutaneous Actemra (Tocilizumab)

• The efficacy of intravenous (IV) and subcutaneous (SC) Actemra (Tocilizumab) has been compared in several studies 3, 4, 5, 6.
• Subcutaneous administration of Tocilizumab is as effective and safe as its intravenous administration in RA patients during the first year of treatment 3.
• The BREVACTA, MUSASHI, and SUMMACTA trials demonstrated the efficacy of SC Tocilizumab, with BREVACTA showing superiority to placebo and MUSASHI and SUMMACTA demonstrating non-inferiority to IV Tocilizumab 4.
• SC Tocilizumab 162 mg fortnightly is equivalent to IV Tocilizumab 4 mg/kg fourth weekly, and SC Tocilizumab 162 mg weekly is equivalent to IV Tocilizumab 8 mg/kg fourth weekly 4.
• A real-life clinical setting study found that SC Tocilizumab improved all efficacy parameters assessed, with improvement achieved as early as the second week of treatment 6.

Safety Profile

• The safety profile of SC Tocilizumab is similar to that of IV Tocilizumab, apart from increased rates of injection site reactions and development of anti-Tocilizumab antibodies 4.
• The most common adverse events associated with SC Tocilizumab are neutropenia, leukopenia, and increased hepatic enzymes 6.
• The rates of serious infections and adverse events leading to discontinuation were 4.8 and 11.9 events/100 patient-years, respectively 6.

Administration and Patient Preference

• SC Tocilizumab is a desirable alternative to existing subcutaneous biological disease modifying antirheumatic drugs (bDMARDs) targeting tumor necrosis factor 4.
• Patients prefer effective, easy-to-administer therapy with sustained prolonged efficacy without the need for polypharmacy and with minimal to no side effects 3.
• SC Tocilizumab in RA patients in monotherapy seems to live up to patients' expectations 3.