Joel M Kremer1, Ricardo Blanco2, Anne-Marie Halland3, Marek Brzosko4, Ruben Burgos-Vargas5, Christopher M Mela6, Lucy Rowell6, Roy M Fleischmann7. 1. Albany Medical College, Albany, New York, USA. jkremer@joint-docs.com. 2. Hospital Marques de Valdecilla, IDIVAL, Santander, Spain. 3. Panorama Medical Center, Cape Town, South Africa. 4. Rheumatology and Internal Diseases Clinic, Pomeranian Medical University, Szczecin, Poland. 5. Hospital General de México and Universidad Nacional Autónoma de México, Mexico City, Mexico. 6. Roche Products Ltd., Welwyn Garden City, UK. 7. Metroplex Clinical Research Center, Dallas, Texas, USA.
Abstract
OBJECTIVES: To report 5-year efficacy and safety in rheumatoid arthritis (RA) patients with active disease treated withtocilizumab. 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.
RCT Entities:
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 RApatients (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 tocilizumabpatients 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.
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