In patients with rheumatoid arthritis and suboptimal response to conventional synthetic disease-modifying antirheumatic drugs, the initiation of tocilizumab appears to yield greater effectiveness and drug survival vs. the introduction of tumour necrosis factor inhibitors, according to findings from the ACT-ion study.
In the prospective, large-scale, global, multicenter comparative study, researchers evaluated 1,216 patients with RA who were prescribed IV tocilizumab (Actemra, Genentech) or tumor necrosis factor inhibitors (TNFi). The patients were followed in routine clinical practice for 52 weeks across 158 sites in 26 countries. The study’s primary endpoint was the change from baseline to week 24 in DAS28-ESR, using analysis of covariance for between-groups comparison. Clinical Disease Activity Index (CDAI) and patient-reported outcomes at weeks 24 and 52 were designated as secondary endpoints
Of the patients in the overall population, 423 (35%) began treatment with tocilizumab and 793 (65%) initiated TNFi. The tocilizumab group had a shorter duration of RA, but higher disease activity and corticosteroid use.
At weeks 24 and 52, tocilizumab patients had more significant improvement in DAS28-ESR (week 24 difference in adjusted means: –0.831; 95% CI, –1.086 to –0.576)
Significantly greater reductions in CDAI and Simplified Disease Activity Index (SDAI) from baseline to weeks 24 and 52 were also demonstrated by the tocilizumab group vs. the TNFi group (CDAI week 24 treatment differences: –3.48; 95% CI, –5.48 to –1.47; CDAI week 52 treatment differences: –4.60; 95% CI, –6.72 to 2.49; SDAI week 24 treatment differences: –3.23; 95% CI, –5.81 to –0.65; SDAI week 52 treatment differences: –3.25; 95% CI, –5.12 to –0.37).
Greater improvements in the Health Assessment Questionnaire (HAQ) disability index were seen in tocilizumab-treated patients vs. TNFi-treated patients (P < .05).
The researchers also found that tocilizumab-treated patients had significantly greater reductions from baseline to week 24 vs. TNFi patients in erythrocyte sedimentation rate (treatment difference: –13.23; 95% CI, –15.51 to –10.95), C-reactive protein (–6.67; 95% CI, –10.27 to –3.07) and swollen joint count (–0.58; 95% CI, –1.08 to –0.08).
In the primary models, no statistically significant difference in tender joint count was seen between the two groups at week 24. There were significant treatment differences at week 52 for ESR (–12.65; 95% CI, –15.42 to –9.88) swollen joint count (–0.75; 95% CI, –1.24 to –0.27) and tender joint count (–1.22; 95% CI, –2.04 to –0.39). No significance was seen for CRP at week 52.
In tocilizumab patients, the probability of drug discontinuation was 9% (95% CI, 6-12) at week 24 and 15% (95% CI, 12-19) by week 52. TNFi-treated patients had a cumulative probability of drug continuation of 15% (95% CI, 13-18) at week 24 and 27% (95% CI, 24-30) at week 52.
Unadjusted frequencies (events per 100 patient-years) for serious adverse events were 6.44 in the tocilizumab group vs. 11.99 in the TNFi group. The unadjusted frequencies for serious infections were 1.98 for tocilizumab vs. 5.03 for TNFi, whereas for deaths, it was 0.74 for tocilizumab vs. 0.77 for TNFi.
“Patients in the ACT-iON observational study who initiated tocilizumab as their first biologic agent therapy after failure of csDMARDs experienced better drug survival and better improvements in DAS28-ESR, SJC, CDAI and physical function than those treated with TNFi,” the researchers wrote. “Additional prospective randomized controlled trials may be required to confirm these findings.”