Potential patient benefit of a subcutaneous formulation of tocilizumab for the treatment of rheumatoid arthritis: a critical review

Patient Prefer Adherence. 2014 Aug 1;8:1051-9. doi: 10.2147/PPA.S34958. eCollection 2014.


Treatment of rheumatoid arthritis (RA) was revolutionized during the last decade with the development of new biologic disease-modifying anti-rheumatic drugs (DMARDs) enabling the targeting of immune cells and cytokines other than tumor necrosis factor (TNF). Subcutaneous formulations of the newer biologic DMARDs facilitate not only patients' emancipation from the hospital, but reduce both societal and medical costs. Intravenous tocilizumab (TCZ) in RA has an efficacy and safety profile similar to anti-TNF in both the short and long-term. However, TCZ can be administered in monotherapy without loss of efficacy when patients do not tolerate methotrexate or synthetic DMARDs. TCZ is consistently found superior to methotrexate and possibly superior to adalimumab in monotherapy in randomized controlled trials. Subcutaneous administration of TCZ is as effective and safe as its intravenous administration in RA patients during the first year of treatment. Similar to intravenous TCZ, patients' weight and possibly previous use of anti-TNF influence the efficacy of subcutaneous TCZ. Additionally, combination with synthetic DMARDs seems to expose RA patients to more adverse events independently of its administration route. Pharmacokinetics of different administration routes could potentially lead to differences in efficacy, adverse events, and auto-immunogenicity. The concentration of free TCZ before new TCZ dose (C trough) is higher in the subcutaneous route, while the maximal concentration of free TCZ is higher in the intravenous route. The subcutaneous dosages of TCZ 162 mg every week, and every 2 weeks in RA patients with low body weight (<60 kg) work well. Nevertheless, dosage and intervals of subcutaneous TCZ administration could be adjusted during the course of treatment since 80% of non-Japanese RA patients with usually higher body weight achieved similar efficacy with the low TCZ dosage in combination with a synthetic DMARD. Patients want effective, easy-to-administer therapy with sustained prolonged efficacy without the need of polypharmacy and with minimal to no side effects. Subcutaneous TCZ in RA patients in monotherapy seems to live up to patients' expectations.

Keywords: efficacy; pharmacokinetic; rheumatoid arthritis; safety; subcutaneous; tocilizumab.

Publication types

  • Review