Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Tocilizumab (TCZ) Inhibits Progression of Joint Damage in Rheumatoid Arthritis (RA) Irrespective of Its Antiinflammatory Effects: Disassociation of the Link Between Inflammation and Destruction.
Smolen1, Josef, Martinez-Avila2, José, Aletaha3, Daniel
Joint damage in RA correlates with disease activity (DA) by composite scores, swollen joint counts or acute phase reactants during its natural course or during therapy with synthetic drugs like methotrexate (MTX). In contrast, treatment with TNF blockers (TNFi) plus MTX inhibits joint damage progression even in patients (pts) with higher DA, disassociating this link. Such disassociation implies a profound direct interference with the events eliciting joint damage beyond effects on disease activity and has not been shown for other biologics. Here we evaluated if IL-6 inhibition with TCZ interferes with joint destruction beyond its effects on DA.
We used a random 90% sample of data from the LITHE trial on active RA despite MTX1 with complete clinical and radiologic data at baseline (BL) and 1 year (yr) treated with placebo (PL; n=117), 4mg/kg TCZ (n=197) and 8mg/kg TCZ (n=217) every 4 weeks, pooling the TCZ groups because of similar radiographic effects1; all patients continued MTX. We calculated the SDAI, CDAI, DAS28 at BL and 1yr. We correlated BL and 1yr values of clinical and serologic variables with changes to 1yr of the Genant modified total Sharp score (TGSS) using Spearman test and also compared TGSS progression in low and high DA groups for PL and TCZ (Kruskal-Wallis).
BL DA variables were similar among the groups. In line with published results1, change of TGSS in this dataset was significantly lower in pts on TCZ than PL (TCZ:0.29±0.96; PL: 0.90±1.92; p=0.0007). In patients treated with PL, the correlation with TGSS change was low but significant for BL SDAI (r=0.18, p=0.047) and SJC28 (r=0.22, p=0.019) with similar trends for CRP (r=0.15, p=0.106) and CDAI (r=0.17, p=0.061), in line with previous notions mentioned above. Similar correlations were seen for SDAI, CDAI, DAS28 at 1yr with x-ray change during that year (r=0.260.28, p=0.002 p=0.006). In contrast, none of the BL or 1yr variables showed significant correlation with x-ray changes in pts on TCZ+MTX, suggesting a reduction or even abrogation of the link between DA and damage by TCZ.
Progression of TGSS was similar between treatment groups when remission or low DA was reached: PL: 0.4±1.1 (n=41); TCZ: 0.2±0.7 (n=217) (p=n.s). In contrast, when only moderate or high DA was reached after 1yr, PL treated patients had significantly higher TGSS change (1.2±2.2; n=76) than those treated with TCZ (0.4±1.2; p=0.0009).
IL-6 receptor inhibition with TCZ, in combination with MTX, appears to inhibit joint damage progression independent of its impact on disease activity. Similar effects have hitherto been reported only for TNF-i. These data indicate that the effects of IL-6 inhibition on progression of joint damage in RA are among the most profound currently attainable.
This study was supported by Roche and we thank Roche for providing us with the data for these analyses.
To cite this abstract, please use the following information:
Smolen, Josef, Martinez-Avila, José, Aletaha, Daniel; Tocilizumab (TCZ) Inhibits Progression of Joint Damage in Rheumatoid Arthritis (RA) Irrespective of Its Antiinflammatory Effects: Disassociation of the Link Between Inflammation and Destruction. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1614