Background In most registration trials of antirheumatic agents co-medication with a stable low dose of glucocorticoids (GC; usually up to 10 mg/d of prednisolone equivalents) is allowed. GC are known inhibitors of damage progression in rheumatoid arthritis (RA), and yet in the analysis of trials their contribution has been mostly ignored.
Objectives Comparison of the 6-month radiographic progression rates of patients on or off GC in the control arms of biologics trials. Secondary objectives included analyses at 12 months and analyses of the active arms.
Methods Of the available trials, post-hoc analyses were obtained for 3 trials: the ATTRACT  and ASPIRE  trials studying infliximab in established and early RA, respectively, and the LITHE trial  studying tocilizumab in established RA. In ATTRACT, 428 patients were randomized to MTX background plus placebo (n=88) or one of 4 infliximab strategies plus MTX. At 6 months 50 placebo patients were available for analysis (30 on, 20 off GC). In ASPIRE, 1049 patients with disease duration of at most 3 years were randomized to de-novo MTX plus placebo (n=298) or one of two infliximab plus MTX strategies. At 6 months, 205 placebo patients were available for analysis (67 on, 138 off GC). Finally in the LITHE trial, 1196 patients were randomized to background MTX plus placebo (n=393) or one of two tocilizumab plus MTX strategies. At 6 months, 283 placebo patients were available for analysis (201 on, 82 off GC). Radiographic results were expressed in Sharp-van der Heijde units (reported in ATTRACT and ASPIRE; Sharp-Genant change scores from the LITHE trial were multiplied by 1,5).
Mean estimates were weighted by inverse variance to obtain pooled fixed effect estimates of the differences in radiographic progression rates. Because of major heterogeneity, results for the inflximab and tocilizumab trials are reported separately.
Results Mean (SD) disease duration was 11 (8), 0,9 (0,7) and 9 (range 0,5-44) years; 64%, 38%, and 62% of patients were on GC; and baseline mean (SD) damage scores were 82 (77), 11 (16), and 43 (range 0-286) for ATTRACT, ASPIRE and LITHE, respectively. Mean 6-month progression in the placebo groups was 4,8 (9,1), 2,4 (7,4) and 0,8 (2,0) respectively. Hetergeneity prevented overall pooling of the 3 studies (chisquare 6,7, p=0,04, I-square 70%). The two infliximab studies were homogeneous, GC treated patients had 2,6 (95%CI: 0,6; 4,5) points less progression at 6 months. In the LITHE study the advantage was absent (mean difference 0,1; 95%CI: –0,5; 0,6). The pattern was similar at 12 months (data not shown). Damage progression was greatly reduced in the active biologic treatment groups; here, no effect of GC on progression was seen (data not shown).
Conclusions GC treatment was favorable in placebo arms of infliximab, but not of tocilizumab trials. The effect is remarkable as GC treatment is preferentially given to patients with a poor prognosis, so more rapid progression could be expected in this observational study. We suggest that the lack of effect of GC in the LITHE trial may be due to the overall low progression rate. Nevertheless, stratification for GC use in analyses of future trials appears advisable.
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Acknowledgements We thank Janssen and Roche for providing the data and analyses.
Disclosure of Interest None declared