Background LITHE was a 2-y, randomised, double-blind, placebo-controlled study of TCZ in pts with moderate to severe RA who were inadequate responders to methotrexate (MTX) with an additional 3 y of open-label extension.
Objectives To report radiographic, efficacy and safety data in RA pts treated with TCZ in LITHE at 5 y of follow up.
Methods In LITHE, 1190 pts were randomised (1:1:1) to receive TCZ (4 mg/kg [TCZ4] or 8 mg/kg [TCZ8]) or placebo every 4 wks + MTX (10-25 mg/wk). Mean duration of RA at study entry was 8.96 to 9.43 y in the 3 arms. Pts could receive rescue with TCZ from wk 16; after wk 52, pts could switch to open-label TCZ8. Radiographs were analysed by Genant-modified Total Sharp Score (GmTSS) at baseline (BL) and at wks 52, 104, 152, 200 and 260 by original randomised group. Pts with at least BL, wk 104 and post-wk 104 radiographs were included in the analysis; linear extrapolation was used to impute any additional missing time points. Signs and symptoms and safety data were pooled for all pts who received ≥1 dose of TCZ (All TCZ) with data presented from the first dose of TCZ. LOCF was used for missing tender and swollen joint counts; no imputation was used for missing HAQ-DI score, CRP, ESR and VAS assessments. The proportions of pts who maintained an ACR20/50/70, DAS28-ESR, EULAR or HAQ-DI response consecutively for ≥24 wks at any time point during the study were summarised (Table).
Results 1149 pts received ≥1 dose of TCZ with 4379.6 pt-y (PY) of exposure, and 34% received 5 y of treatment (All TCZ). Mean duration in the All TCZ population was 3.81 y with half the pts participating for ≥4.69 y. Radiographic data were assessed in 803 pts: 545 initially assigned to TCZ and 258 initially assigned to placebo. The mean change in GmTSS over 5 y showed a 56% greater inhibition of joint damage in pts randomised to TCZ vs those initially randomised to placebo, with greatest APR in y 1 (Table). 53% of TCZ pts had no progression (GmTSS≤0) during the 5 y vs 35% of placebo pts (placebo pts might have switched to TCZ as early as wk 16). Clinical benefit was maintained, as measured by maintenance of ACR response, DAS28-ESR remission and EULAR good/moderate response (Table). Overall rates/100PY of serious adverse events and serious infections were 11.67 and 3.42, respectively. The safety profile at 5 y was similar to that observed at 2 y.1
Conclusions 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 of TCZ at 5 y was similar to that previously observed.1
Ann Rheum Dis 2010;69(suppl 3):387
Disclosure of Interest J. Kremer Grant/research support from: Genentech, Consultant for: Genentech, A.-M. Halland: None Declared, M. Brzosko: None Declared, R. Burgos-Vargas Grant/research support from: Abbott, Consultant for: Abbott, BMS, Janssen, Pfizer, Roche, Speakers bureau: Abbott, BMS, Janssen, Pfizer, Roche, C. Mela Employee of: Roche, E. Vernon Employee of: Roche, R. Fleischmann Grant/research support from: Abbott, Amgen, Janssen, UCB, BMS, Roche, Genentech, Lexicon, Sanofi Aventis, Lilly, MSD, Pfizer, Regeneron, Consultant for: Abbott, Amgen, Janssen, UCB, BMS, Roche, Genentech, Lexicon, Sanofi Aventis, Lilly, MSD, Pfizer, Regeneron