Concurrent Oral 1 - Rheumatoid Arthritis: Treatment [OP4-OP9]: OP4. Inhibition of Radiographic Progression and Improvements in Physical Function at 2 Years, with Increasing Clinical Efficacy Over Time, in Rheumatoid Arthritis (Ra) Patients Treated with Tocilizumab (Tcz): The Lithe Study

Abstract

Background: Patients with moderate to severe RA who remained on methotrexate (MTX) despite inadequate response were treated with TCZ in a double-blind, randomized, controlled phase 3 trial. Results of a 2-year planned analysis from this study are presented. Methods: Patients were randomized to treatment with TCZ 4 mg/kg + MTX (TCZ4), TCZ 8 mg/kg + MTX (TCZ8) or placebo + MTX (CON) every 4 weeks. If patients failed to respond (<20% improvement in swollen and tender joint count; SJC and TJC) then stepwise rescue therapy could begin at week 16. Patients with ≥ 70% improvement in SJC and TJC could continue the blinded therapy at the end of year 1 to week 104. For all other patients, open-label TCZ8 was initiated at week 52. Change from baseline in Genant-modified total Sharp score (GmTSS) and physical function (AUC of change from baseline in HAQ-DI) were the primary 2-year end points. Linear extrapolation (GmTSS) or standardization (change in HAQ-DI) was used for missing data. The impact of 2 years of treatment was examined by assessing efficacy end points over time for patients randomized to TCZ8, with the last observation carried forward for SJC and TJC in patients who received rescue therapy or withdrew. Results: The intention to treat population consisted of 398 TCZ8, 399 TCZ4 and 393 CON patients. At 2 years, exposure rates in patient-years (PY) were 1320.0, 521.9 and 284.8 in TCZ8, TCZ4 and CON patients, respectively. At year 2, patients in the TCZ8 group had 81% less radiographic progression vs CON patients (based on linear extrapolation of mean change in GmTSS). Significantly more TCZ8 patients had no radiographic progression vs CON patients (P ≤ 0.0001). AUC of change from baseline in HAQ-DI showed significant improvement in physical function in TCZ4 and in TCZ8 vs CON patients (P ≤ 0.0025). In patients initially randomized to TCZ8, a low disease activity score (LDAS; DAS28 < 3.2) was seen in > 60% of patients and the DAS28 remission (DAS28 < 2.6) rate was 48% at week 52 and continued to increase to week 104. By week 52, patients treated with TCZ8 had clinically significant improvements in SJC that were maintained through week 104. Rates per 100 PY for adverse events (AEs) were higher in TCZ8 and TCZ4 (263.6, 275.4) vs CON patients (251.4) while rates for serious AEs were comparable (11.4, 12.1, 10.9, respectively). Rates per 100 PY of AEs leading to withdrawal (7.4, 32.5, 4.8) and treatment modification (8.4, 30.7, 20.4) were higher in TCZ8 and TCZ4 vs CON patients, respectively and death rates were comparable (0.6, 0.2, 0.4). Conclusions: Treatment with TCZ + MTX inhibits radiographic progression over 2 years and improves physical function as shown by DAS28 remission, LDAS and low SJC, with a manageable safety profile. Disclosure statement: E.A., F. Hoffmann-La Roche - Employee. P.A., F. Hoffmann-La Roche - Employee. R.B.-V., F. Hoffmann-La Roche - Honoraria. R.F., Genentech - Research Funding, Honoraria. J.K., F. Hoffmann-La Roche - Research funding, Honoraria.