IL-6 Inhibitor Outperforms Anti-TNF Agents in Effectiveness, Drug Survival in Patients With RA

A new study comparing the clinical effectiveness of anti—tumor necrosis factor (TNF) agents and the interleukin-6 (IL-6) inhibitor tocilizumab (Acterma) in patients with rheumatoid arthritis (RA) found that tocilizumab outperformed anti-TNFs in terms of effectiveness and drug survival.

In the global, comparative, observational study, ACT-iON, funded by Roche and published in Arthritis Care and Research, patients with moderate to severe rheumatoid arthritis (n = 1216) who initiated biologic therapy after responding inadequately to conventional disease-modifying anti-rheumatic drugs (DMARDs) were observed in routine clinical practice for 52 weeks after starting treatment with intravenous tocilizumab or an anti-TNF agent.

Data were collected between February 2012 and February 2015. The primary observation was the mean change from baseline in the Disease Activity Score 28 scale using erythrocyte sedimentation rate values (DAS28-ESR) at week 24. Secondary outcome measures included mean change from baseline in DAS28-ESR at week 52, swollen joint count (SJC), tender joint count (TJC), remission rates according to DAS28-ESR and the Clinical Disease Activity Index (CDAI), and patient-reported outcomes (PROs). Safety was assessed by monitoring adverse events (AEs), abnormalities in laboratory assessments, and vital signs.

Tocilizumab was initiated in 35% of patients (n = 423), and anti-TNF agents were initiated in 65% (n = 793).

In the anti-TNF arm, patients received the following biologics:

• Etanercept, 39.7%
• Adalimumab, 25.6%
• Certolizumab pegol, 19.5%
• Infliximab, 8.2%
• Golimumab, 6.9%

Patients initiating tocilizumab had a shorter mean disease duration than those initiating anti-TNF agents , as well as a slightly higher mean DAS28-ESR and SJC, and more frequent oral corticosteroid use. In the tocilizumab arm, 73.8% of patients received conventional synthetic DMARDs together with biologic therapy, as did 85.6% of patients receiving anti-TNF agents. Methotrexate was the most common concomitant DMARD.

The researchers found, with a 95% confidence interval (CI), the following:

• Patients receiving tocilizumab had significantly more change from baseline in DAS28-ESR than did those who initiated anti-TNFs at week 24 (—1.086, –0.576) and week 52 (–1.204, –0.617)
• There were significant decreases from baseline to week 24 for patients in the tocilizumab arm compared with patients in the anti-TNF arm in terms of SJC (−1.08, −0.08, P&thinsp;<&thinsp;.05)
• No statistically significant difference in TJC was observed at week 24
• At week 52, the treatment difference was significant in terms of SJC (−1.24, −0.27, P&thinsp;=&thinsp;.002)
• There was a statistically significant difference in improvement of PROs between the tocilizumab arm and the anti-TNF arm as measured by the Health Assessment Questionnaire Disability Index (—0.15) and Functional Assessment of Chronic Illness Therapy Fatigue scores (—3.89) at week 24

In terms of drug survival, 14.9% of patients who initiated tocilizumab and 27.4% of those who started treatment with anti-TNF agents terminated biologic therapy

• Of this group, 38.1% and 40.1%, respectively, terminated because of AEs
• 23.8% and 48.8%, respectively, terminated because of a lack of efficacy
• Probability of a patient discontinuing tocilizumab was 9% at week 24 and 15% at week 52
• Probability of a patient discontinuing anti-TNF therapy was 15% at week 24 and 27% at week 52

AEs and serious AEs were reported in similar proportions and rates between the 2 groups. The most common AEs were infections and infestations. Serious infections were reported in 8 (1.9%) of those receiving tocilizumab and 26 (3.3%) of those receiving anti-TNF agents. Three patients in the tocilizumab group died (2 of pneumonia, 1 of cardiac failure), and 6 patients in the anti-TNF group died (causes of death included sepsis, pneumonia, and pericardial effusion).

The researchers concluded that patients who initiated biologic treatment with tocilizumab experienced better drug survival and better clinical improvements than did those who initiated biologic treatment with anti-TNF agents.