Subcutaneous tocilizumab for the treatment of rheumatoid arthritis

ABSTRACT

Rheumatoid arthritis (RA) is characterized by inflammatory synovitis and is mediated by several cytokines; this includes interleukin-6, whose receptor has been successfully targeted by the humanized monoclonal antibody tocilizumab. Intravenous tocilizumab (TCZ-IV) is registered for use in RA (alone or as combination therapy), systemic juvenile idiopathic arthritis and Castleman disease. Subcutaneous tocilizumab (TCZ-SC) is a desirable alternative to existing subcutaneous biological disease modifying antirheumatic drugs (bDMARDs) targeting tumor necrosis factor. TCZ-SC efficacy has been evaluated in three randomized controlled trials. BREVACTA demonstrated superiority to placebo, and both MUSASHI and SUMMACTA demonstrated non-inferiority to TCZ-IV. TCZ-SC has a similar safety profile to TCZ-IV apart from increased rates of injection site reactions and development of anti-TCZ antibodies (the latter of uncertain clinical significance). TCZ-SC 162 mg fortnightly is equivalent to TCZ-IV 4 mg/kg fourth weekly; TCZ-SC 162 mg weekly is equivalent to TCZ-IV 8 mg/kg fourth weekly. TCZ-SC is a suitable bDMARD for RA, particularly when monotherapy is preferred.

KEYWORDS:

• IL-6
• rheumatoid
• tocilizumab
• subcutaneous
• trial

Financial & competing interests disclosure

G Jones has received honoraria from Roche, the manufacturer of tocilizumab; however, this publication was not sponsored by any pharmaceutical company. The National Health and Medical Research Council (NHMRC), Australia, contributes to the Graeme Jones' author's salary. Graeme Jones has board membership on Novartis, Roche, Amgen, Abbott, Merck Sharpe & Dohme, Bristol -Myer Squibb, UCB, Pfizer, Janssen and Servier, and has received honoraria for educational presentations from Servier and MSD. He has also received honoraria from Novartis, Roche, Amgen, Abbott, MSD, BMS, UCB, Pfizer, Janssen and Servier for consultancy and lectures. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Tocilizumab is a humanized interleukin-6 receptor antibody licensed for intravenous use in rheumatoid arthritis (RA).

• Tocilizumab is currently one of two targeted therapies for RA which are used as monotherapy, along with the oral janus kinase inhibitor, tofacitinib.

• Subcutaneous tocilizumab is similarly efficacious to intravenous tocilizumab (TCZ-IV) and less expensive to administer.

• Safety profiles are similar between subcutaneous (SC) and TCZ-IV apart from local injection site reactions and neutralizing antibodies with SC treatment.

• It is unclear whether neutralizing antibodies will affect efficacy long-term; in six-month data, there was no effect on efficacy.