Objectives: To report 5-year efficacy and safety in rheumatoid arthritis (RA) patients with active disease treated with tocilizumab.
Methods: LITHE was a 2-year, randomised, placebo-controlled study of tocilizumab in RA patients (ClinicalTrials.gov, NCT00106535), with an additional 3-year, open-label extension. Patients were randomly assigned to tocilizumab (4 or 8 mg/kg IV) or placebo every 4 weeks + methotrexate. They could receive rescue with tocilizumab from week 16; after week 52, patients could switch to open-label tocilizumab 8 mg/kg. Radiographs were analysed by randomized treatment using the Genant-modified Total Sharp Score (GmTSS). Patients with at least baseline, week 104 and post-week 104 radiographs were included. Clinical and safety data were pooled for all patients who received ≥1 dose of tocilizumab; results are presented from the first tocilizumab dose.
Results: 1,149 patients were included with 4,380 patient-years of exposure; 34% received 5 years of treatment. Mean 5-year change in GmTSS revealed greater inhibition of radiographic progression in tocilizumab patients than placebo patients (1.34 vs. 3.02), with the greatest annualised progression rate in year 1. Overall, 53% of tocilizumab and 35% of placebo patients experienced no progression (GmTSS ≤0). Clinical benefit was maintained - determined by ACR response, DAS28-ESR <2.6, EULAR good/moderate response and Boolean remission - as was physical function. The safety profile over 5 years was similar to that over 2 years.
Conclusions: Over 5 years, tocilizumab + MTX inhibited radiographic progression and maintained improvements in signs and symptoms and physical function in MTX-inadequate responders with active disease; no new safety signals occurred.