FRI0205 TOCILIZUMAB INHIBITS RADIOGRAPHIC PROGRESSION, IMPROVES PHYSICAL FUNCTION, AND GAINS EFFICACY OVER TIME: LITHE 2 YEAR

R. Fleischmann ^1,*R. Burgos-Vargas ²F. N. Skopouli ³Z.-G. G. Li ⁴P. Ambs ⁵E. Vernon ⁶J. Kremer ⁷

¹Metroplex Clinical Research Center, Dallas, United States, ²Hospital General de México, Universidad Nacional Autónoma de México, Mexico City, Mexico, ³Harokopio University and Euroclinic of Athens, Athens, Greece, ⁴Beijing University Medical School, Beijing, China, ⁵Roche, Basel, Switzerland, ⁶Roche, Welwyn, United Kingdom, ⁷Albany Medical College, Albany, United States

Background: RA patients (pts) treated for 1 year with tocilizumab (TCZ) 8 mg/kg or 4 mg/kg with methotrexate (MTX) experienced significant inhibition in progression of joint damage and improvement in RA signs/symptoms compared to MTX.

Objectives: To assess the efficacy of treatment with TCZ + MTX in year 2 (mostly open-label) of LITHE, a phase 3 study of TCZ in pts with moderate to severe RA who had a previous inadequate response to MTX.

Methods: Pts were randomly assigned to receive TCZ 4 or 8 mg/kg (TCZ4 or TCZ8) or placebo (control) every 4 weeks (wks) + MTX. From wk 16, stepwise blinded rescue therapy was allowed if pts had <20% improvement in SJC and TJC. At 52 wks, all pts (including rescue pts) with <70% improvement in SJC and TJC initiated open-label (OL) TCZ8; pts with ≥70% improvement could also initiate OL TCZ8 (decision made by investigator and pt). Primary end points were change from baseline to year 2 in Genant-modified Total Sharp Score (GmTSS) and physical function (AUC change from baseline to year 2 in HAQ-DI). Linear extrapolation (GmTSS) or standardization (HAQ-DI) was used for missing data. Post-rescue data were set to missing. Efficacy data were reported by original treatment group at randomization.

Results: The ITT population included 1,190 pts (393 control, 399 TCZ4, 398 TCZ8). At year 2, most pts in all treatment arms were on TCZ8 (Table). Radiographic progression was inhibited by 81% and 70% in the original TCZ8 and TCZ4 groups compared to the original control group. More TCZ8 and TCZ4 pts than controls experienced no radiographic progression. Physical function, assessed by HAQ-DI AUC, significantly improved in TCZ pts vs controls (Table). At year 2, proportions achieving ACR70 response were higher in pts randomized to TCZ4 or TCZ8 than in controls. Patients in DAS28 remission on TCZ8 increased during year 2 (48% [132/275] at year 1 vs 65% [156/241] at year 2). Safety analyses will be presented separately.

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Conclusion: Treatment with TCZ + MTX over 2 years resulted in inhibition of joint damage progression and improvement in physical function and in continuous reduction in signs and symptoms of RA.

Disclosure of Interest: R. Fleischmann Grant / Research Support from: RocheR. Burgos-Vargas Consultant for: Abbott, Roche, Schering-Plough, Wyeth, Pfizer Speakers Bureau: Abbott, Roche, Schering-Plough, Wyeth, PfizerF. Skopouli Grant / Research Support from: RocheZ.-G. Li: None DeclaredP. Ambs Employee of: RocheE. Vernon Employee of: RocheJ. Kremer Grant / Research Support from: Amgen, Abbott, BMS, Centocor, Genentech, Pfizer, Roche Consultant for: Amgen, Abbott, BMS, Centocor, Genentech, Pfizer, Roche, UCB