Currently Enrolling Trials
Actemra (tocilizumab) ) is an interleukin-6 (IL-6) receptor antagonist.
Actemra is specifically indicated to slow the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).
Actemra for this indication is supplied as a subcutaneous injection. The recommended dose of Actemra for adult patients with SSc-ILD is 162 mg given once every week as a subcutaneous injection. Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia.
The FDA approval of Actemra for SSc-ILD was based on data from the focuSSced trial, a Phase III randomized, double-blind, placebo-controlled clinical trial of 212 adults with systemic sclerosis. Supportive information was also used from the faSScinate trial, a Phase II/III, randomized, double-blind, placebo-controlled study in patients with SSc. There was not a statistically significant effect on the primary endpoint of mRSS in the faSScinate trial.
The focuSSced trial did not meet its primary endpoint of change from baseline to week 48 in the modified Rodnan Skin Score (mRSS), which is a standard outcome measure for skin fibrosis (the scarring or hardening of the skin) in SSc. However, in the overall population of the focuSSced study, patients treated with Actemra, as compared to placebo-treated patients, were observed to have less decline from baseline to week 48 in observed forced vital capacity (FVC), a common measure of lung function that assesses how much air can be exhaled, and percent predicted forced vital capacity (ppFVC), which compares the observed FVC to that expected for a healthy person of the same age, gender, race and height. FVC results were similar in the faSScinate study.
Of the 212 patients who were randomized into the focuSSced study, 68 patients (65%) in the Actemra arm and 68 patients (64%) in the placebo arm had SSc-ILD at baseline, as confirmed by a visual read of high resolution computed tomograph (HRCT) by blinded thoracic radiologists. Post-hoc exploratory analyses were performed to evaluate the results within the subgroups of patients with and without SSc-ILD. The ppFVC and FVC results in the overall population were primarily driven by results in the SSc-ILD subgroup. In that subgroup, patients in the Actemra group had a smaller decline in mean ppFVC than patients on placebo (0.07% vs. -6.4%, mean difference 6.47%), and a smaller decline in FVC compared to placebo (mean change -14 mL vs. -255 mL, mean difference 241 mL). The mean change from baseline to week 48 in mRSS in patients receiving Actemra compared to placebo was -5.88 vs. -3.77, mean difference -2.11.
Adverse effects associated with the use of Actemra may include, but are not limited to, the following:
- upper respiratory tract infections
- increased ALT
- injection site reaction
The Actemra drug label comes with the following Black Box Warning: Serious infections leading to hospitalization or death including tuberculosis (TB), bacterial, invasive fungal, viral, and other opportunistic infections have occurred in patients receiving Actemra. If a serious infection develops, interrupt Actemra until the infection is controlled. Perform test for latent TB; if positive, start treatment for TB prior to starting Actemra. Monitor all patients for active TB during treatment, even if initial latent TB test is negative.
Mechanism of Action
Actemra (tocilizumab) binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes.
For additional information regarding Actemra or SSc-ILD, please visit the Actemra website.