Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


LITHE: Tocilizumab (TCZ) Inhibits Radiographic Progression and Improves Physical Function in Rheumatoid Arthritis (RA) Patients (pts) at 3 Years with Maintenance of Clinical Efficacy over Time.

Kremer1,  Joel M., Furst6,  Daniel E., Burgos-Vargas3,  Ruben, Dudler2,  Jean, Mela5,  Christopher M., Vernon5,  Emma, Fleischmann4,  Roy M.

Albany Medical College, Albany, NY
Hôpital Orthopédique, Epalinges, Switzerland
Hospital General de México and Universidad Nacional Autónoma de México, Mexico City, México, Mexico
Metroplex Clinical Research Center, Dallas, TX
Roche, Welwyn, United Kingdom
UCLA Medical Center, Los Angeles, CA

Purpose:

To report 3-yr data from the extension of a 3-arm, randomized, double-blind, placebo-controlled, phase 3 trial of TCZ in pts with moderate to severe RA who were MTX inadequate responders.

Methods:

A total of 1190 pts were randomly assigned (1:1:1) to receive TCZ (4 mg/kg [TCZ4] or 8 mg/kg [TCZ8]) or placebo (control) every 4 wks plus MTX (10–25 mg/wk). After wk 52, pts switched to open-label treatment with TCZ8, an option chosen by the majority of pts (62%-68% across all 3 treatment groups). Radiographs of hands and feet were analyzed by Genant-modified Total Sharp Score (GmTSS) for any pt who had a baseline, wk 52, wk 104, and at least 1 post-wk 104 assessment. If a patient had a post-wk 104 but not a wk 152 value, linear extrapolation was used to impute up to wk 152. Signs and symptoms data and safety data are reported as pooled data (All TCZ) in all pts who received at least 1 dose of TCZ; data are presented from the first dose of TCZ to August 28, 2009 (mean duration, 2.43 yrs). LOCF was used for missing tender and swollen joint counts; no imputation was used for missing HAQ score, CRP, ESR, and VAS assessments.

Results:

The radiographic population consisted of 704 pts, accounting for approximately 80% of the pts who ultimately would have a post-wk 104 assessments: 244, 241, and 219 pts had been initially assigned to TCZ8, TCZ4, and control, respectively. The majority of pts had received open-label TCZ8 for at least 2 of 3 yrs of the study; 9% of placebo and 19% of TCZ4 pts had remained on original blinded treatment at 1 yr. The mean change in GmTSS from baseline to yr 3 was 60% lower in pts who were randomly assigned to TCZ compared with those initially receiving control, demonstrating inhibition of joint damage by TCZ (Table). The majority of radiographic progression in pts randomly assigned to control was observed in the first yr before switching to TCZ. By yr 3, no radiographic progression was observed in a greater proportion of pts initially assigned to TCZ8 and TCZ4 than to control.

The All TCZ group included 1149 pts with 2790 pt-yrs (PY) of exposure. ACR response and DAS28 remission rates were high, demonstrating continued clinical benefit (Table). At wk 104, 34% (257/768) of pts had HAQ scores <0.5; the proportion of pts with HAQ scores <0.5 was maintained through wk 152.

Overall rates/100 PY of serious adverse events and serious infections were 11.0 and 3.2; overall rates/100 PY of deaths and deaths from infections were 0.39 and 0.14. Malignancies occurred at an overall rate of 0.7/100 PY, including solid cancers (0.6/100 PY) and nonmelanoma skin cancer (n = 1; 0.0/100 PY).

Table. Outcomes at Week 152

GmTSSTCZ8 n=244TCZ4 n=241Control n=219
Mean (SD) change from baseline0.72 (2.56)a,b0.71 (2.14)b,c1.78 (3.64)
Pts with no progression (GmTSS change from baseline <=0), % (n)69 (169)a,d67 (162)d,c51 (111)
Signs and Symptoms All TCZ 
ACR20, % (n/n) 80 (472/591) 
ACR50, % (n/n) 59 (346/591) 
ACR70, % (n/n) 36 (212/591) 
DAS28 remission, % (n/n) 57 (325/572) 
TJC and SJC= 0, % (n/n) 21 (137/656) 
HAQ <0.5, % (n/n) 37 (202/552) 
n/n=no, patients achieving end point/no. patients reaching time point with valid assessments.
ap <0.0001 vs control.
bp calculated by Van Elteren test stratified by region.
cp=0.0002 vs control.
dp calculated by logistic regression analysis adjusted for region.
ep=0.0008 vs control.

Conclusions:

During long-term treatment, TCZ + MTX continued to inhibit radiographic progression. Improvements in physical function and other clinical benefits were maintained at high levels. The safety profile did not change compared with the 2-yr analysis.

To cite this abstract, please use the following information:
Kremer, Joel M., Furst, Daniel E., Burgos-Vargas, Ruben, Dudler, Jean, Mela, Christopher M., Vernon, Emma, et al; LITHE: Tocilizumab (TCZ) Inhibits Radiographic Progression and Improves Physical Function in Rheumatoid Arthritis (RA) Patients (pts) at 3 Years with Maintenance of Clinical Efficacy over Time. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1819
DOI: 10.1002/art.29584

Abstract Supplement

Meeting Menu

2010 ACR/ARHP