Longterm safety and effectiveness of the anti-interleukin 6 receptor monoclonal antibody tocilizumab in patients with systemic juvenile idiopathic arthritis in Japan.

Abstract

OBJECTIVE:

To assess the longterm safety and effectiveness of tocilizumab (TCZ) in systemic-onset juvenile idiopathic arthritis (sJIA).

METHODS:

The longterm extension phase of 2 pivotal studies (phase II with 11 patients and phase III with 56 patients) in patients with active sJIA was analyzed. Patients received open-label TCZ (8 mg/kg, every 2 weeks) without concomitant use of disease-modifying antirheumatic drugs.

RESULTS:

In total, 67 patients were enrolled. All patients received corticosteroid at baseline. Median duration of exposure to TCZ was 3.4 years. Nine patients withdrew from the study [4 because of adverse events (AE), 4 because of the development of anti-TCZ antibodies, and 1 because of inadequate response]. Rates of AE and serious AE were 803.7/100 patient-years (PY) and 34.7/100 PY, respectively. The most common serious AE were infections (13.2/100 PY). No cases of malignancy or death were reported. Two serious infusion reactions were reported in patients testing negative for anti-TCZ antibodies. One definite macrophage activation syndrome (MAS) case and 1 potential MAS case were identified. American College of Rheumatology (ACR) response rates attained early in the TCZ treatment period were maintained throughout the study: at Week 168, JIA ACR 30, 50, 70, 90, and 100 response rates were 80.3%, 80.3%, 75.4%, 60.7%, and 18.0%, respectively. In total, 22 of 67 patients (32.8%) completely discontinued corticosteroids without flare.

CONCLUSION:

TCZ has demonstrated durability of effectiveness in the longterm treatment of children with sJIA and has shown good tolerability and a low discontinuation rate associated with AE, development of anti-TCZ antibodies, or inadequate response. (ClinicalTrials.gov NCT00144599 and NCT00144612). (First Release March 15 2014; J Rheumatol 2014;41:759-67; doi:10.3899/jrheum.130690).

• Authors: Shumpei Yokota, Tomoyuki Imagawa, Masaaki Mori, Takako Miyamae, Syuji Takei, Naomi Iwata, Hiroaki Umebayashi, Takuji Murata, Mari Miyoshi, Minako Tomiita, Norihiro Nishimoto, Tadamitsu Kishimoto
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 41 Issue 4 Pg. 759-67 (Apr 2014) ISSN: 0315-162X [Print] Canada
• PMID: 24634205 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Receptors, Interleukin-6
• tocilizumab

Topics

• Adolescent
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Arthritis, Juvenile (diagnosis, drug therapy)
• Child
• Child, Preschool
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Infusions, Intravenous
• Japan
• Male
• Maximum Tolerated Dose
• Patient Safety
• Receptors, Interleukin-6 (immunology, therapeutic use)
• Risk Assessment
• Severity of Illness Index
• Time Factors
• Treatment Outcome