Bay-Jensen AC, Platt A, Byrjalsen I, et al., Effect of tocilizumab combined with methotrexate(Drug information on methotrexate) on circulating biomarkers of synovium, cartilage, and bone in the LITHE study. Seminars in Arthritis and Rheumatism (2013). Epub August 6
Tocilizumab (TCZ) combined with methotrexate (MTX) appears to be a strong inhibitor of circulating biomarkers of joint tissue remodeling at sites of inflammation in patients with moderate-to-severe rheumatoid arthritis (RA), a phase III study suggests.
In addition, the LITHE biomarker study suggests specific profiles of patients who will or will not respond well to the drug combination. This is the latest of numerous reports from the LITHE study of TCZ. An earlier publication announced a possible biomarker of fast RA progression detected using the same data.
LITHE-biomarker is a double blind, placebo-controlled parallel group study comparing the effects of two approved doses of TCZ combined with MTX or with placebo on different biomarkers of joint destruction in RA patients non-responsive to DMARDs. The current sub-study evaluated serum samples from a one-year, double blinded study that randomized 704 patients (mostly women in their 50s) to intravenous TCZ at doses of 4 mg/kg (TCZ 4) or 8 mg/kg (TCZ 8) or IV placebo, all with a stable concurrent dose of MTX (10–25 mg/week), over 4 weeks:
Patients whose swollen or tender joints had not improved by 20% from baseline by week 16 or later could receive blinded rescue therapy in a stepwise fashion between weeks 16 and 28 (escape patients).
Serum biomarkers were tested at baseline,and at weeks 4, 16, 24, and 52. Patients who had a 50% improvement in swollen and tender joints according to American College of Rheumatology criteria (ACR50) were classified as responders. Others were described as either early non-responders (tje escape patients) or as non-responders.
A year later, among the responders, TCZ8 had inhibited C-reactive protein (CRP) to 4% of baseline levels and TCZ4 had brought it down to 40% of baseline. CRP was inhibited the most among ACR50 responders, but with wide variations.
Other biomarkers also decreased significantly at week 52 among responders, but not among non-responders, suggesting a specific response profile for TCZ early ,and that the specific biomarkers may possess predictive properties for TCZ response.
Dose-dependent biomarker profiles were significantly different between ACR50 responders, non-responders, and early non-responders.