Tocilizumab inhibits radiographic progression and improves physical function in patients with rheumatoid arthritis at 5 years with maintenance of clinical efficacy over time

Background: LITHE was a 2-year, randomized, double-blind study of tocilizumab (TCZ) in patients (pts) with moderate to severe RA who were inadequate responders to MTX, with an additional 3 years of open-label (OL) extension. Methods: 1190 pts were randomized (1:1:1) to TCZ (4 mg/kg [TCZ4] or 8 mg/kg [TCZ8]) or placebo every 4 weeks+MTX (10-25 mg/week). Pts could receive rescue TCZ from week 16; after week 52, pts could switch to OL TCZ8. Radiographs were analysed by Genant-modified Total Sharp Score (GmTSS). Data were pooled for all pts who received ≥1 dose of TCZ (All TCZ). The proportions of pts who maintained efficacy responses consecutively for ≥24 weeks are summarized (Table 1). Results: 1149 pts received ≥1 dose of TCZ with 4379.6 patient-years (PY) of exposure, and 34% received 5 years of treatment (All TCZ). Mean duration in the All TCZ population was 3.81 years with half the pts participating for ≥4.69 years. The mean change in GmTSS over 5 years showed a 56% greater inhibition of joint damage in pts randomized to TCZ vs placebo, with greatest annualized progression rate (APR) in year 1. 53% of TCZ pts had no progression (GmTSS≤0) during the 5 years vs 35% of placebo pts (placebo pts may have switched to TCZ as early as week 16). Clinical benefit was maintained, as measured by ACR response, DAS28-ESR remission and EULAR good/moderate response. Overall rates/100PY of serious adverse events and serious infections were 11.67 and 3.42, respectively. Conclusion: During long-term treatment, TCZ+MTX continued to inhibit radiographic progression. Improvements in signs and symptoms and in physical function were maintained with continued TCZ treatment. The safety profile at 5 years was similar to that previously observed. (Table presented).