The Food and Drug Administration has expanded its approval of tocilizumab to include labeling claims regarding the biologic drug’s effects on joint damage, physical function, and major clinical response in people with rheumatoid arthritis, according to the manufacturer, Genentech Inc.
On Jan. 5, Genentech announced that the FDA had approved the addition of the following information to the tocilizumab prescribing label, based on data from the LITHE (Tocilizumab Safety and the Prevention of Structural Joint Damage) study: inhibition and slowing of structural joint damage, improvement of physical function, and achievement of major clinical response in adults with moderately to severely active RA treated with tocilizumab and methotrexate.
The supplemental approval comes a year after the FDA approved tocilizumab, an interleukin-6 receptor inhibitor, for the treatment of adults with moderately to severely active RA who have had an inadequate response to one or more tumor necrosis factor antagonist therapies. It can be used alone or in combination with methotrexate or other disease modifying antirheumatic drugs (DMARDs) and is administered intravenously every 4 weeks.
LITHE was an international randomized, double-blind placebo-controlled study. It was designed to determine how the efficacy of the two approved tocilizumab doses (4 mg/kg or 8 mg/kg) every 4 weeks in combination with methotrexate compared with methotrexate plus placebo in 1,196 patients with moderately to severely active RA who had an inadequate response to methotrexate alone over 2 years. The 52-week results, according to Genentech, include the following:
• Sixty-three percent of the patients on the 8-mg/kg dose plus methotrexate and 60% of those on the 4-mg/kg dose plus methotrexate achieved a "clinically relevant" improvement on the Health Assessment Questionnaire-Disability Index (HAQ-DI), used to assess changes in physical function with questions about different categories of physical functioning, compared with 53% of those on methotrexate plus placebo, a significant difference between the treatment and placebo groups.
• Changes from baseline in Genant-modified Sharp scores, a radiographic score based on evaluation of different sites for bone erosion and joint space narrowing, indicated that the 4-mg/kg dose "slowed" the progression of structural joint damage (less than 75% inhibition compared with the control group) and that the 8-mg/kg dose "inhibited" the progression of structural damage (at least 75% inhibition compared with the control group).
• Seven percent of those on the 8-mg/kg dose and 4% of those on 4-mg/kg dose plus methotrexate had achieved a major clinical response (a 70% improvement in American College of Rheumatology response criteria for a continuous 24-week period) compared with 1% of those on placebo plus methotrexate.
Safety was similar to that in previous studies of the drug. Because of the increased risk for serious, potentially fatal infections associated with treatment, tocilizumab was approved in 2010 with a Risk Evaluation and Mitigation Strategy (REMS) to minimize this risk.
The recommended starting dose of tocilizumab is 4 mg/kg, increasing to 8 mg/kg based on the patient’s clinical response, according to the prescribing information. Tocilizumab is marketed as RoActemra in the European Union and is also approved in India, Brazil, Switzerland, and Australia, and several other countries, according to Genentech. It was approved in Japan in 2005.
Serious adverse reactions to tocilizumab can be reported to the FDA’s MedWatch program online or at 800-332-1088.