Two-year tocilizumab regimen shows potential in early RA
The interleukin-6 receptor-alpha inhibitor tocilizumab alone or in combination with methotrexate demonstrated clinical benefit after 2 years of treatment in methotrexate-naïve patients with early rheumatoid arthritis (RA), according to the FUNCTION* trial.
A total of 1,157 methotrexate-naive patients with early (≤2 years) active and progressive RA were randomized 1:1 to receive intravenous tocilizumab at doses of 4 mg/kg or 8 mg/kg every 4 weeks in combination with oral methotrexate or as monotherapy (8 mg/kg only), or methotrexate monotherapy (initial dose of 7.5 mg/week to a maximum of 20 mg/week at week 8 if joints were tender or swollen) for 104 weeks, about 70 percent of whom (n=809) completed treatment.
At week 52, 33 percent of patients in the 4 mg/kg tocilizumab + methotrexate group and 49 percent of patients on methotrexate monotherapy switched to escape therapy using 8 mg/kg tocilizumab + methotrexate. [Ann Rheum Dis 2017;76:1279-1284]
DAS28-ESR** remission rates were achieved by nearly half of the participants in the 8 mg/kg tocilizumab + methotrexate group (49.3 percent and 47.6 percent at weeks 52 and 104, respectively) vs those in the 4 mg/kg tocilizumab + methotrexate (36.1 percent and 28.1 percent, respectively) and methotrexate monotherapy groups (20.2 percent and 16.0 percent, respectively).
These results suggest that patients in the 8 mg/kg tocilizumab + methotrexate arm exhibited the best response, said the researchers. “Year 2 results show that the efficacy of [tocilizumab] was maintained for extended treatment periods.”
After 52 weeks of escape therapy, DAS28-ESR remission was achieved by 30.5 percent and 51.4 percent of escape subjects (4 mg/kg tocilizumab + methotrexate and methotrexate monotherapy, respectively), which underlines the significance of longer treatment periods to establish efficacy in some patient groups, said the researchers.
Despite improved remission rates, participants in the escape group had lower ACR*** response rates and a greater degree of joint damage, said the researchers, noting the importance of early treatment.
The comparable improvements between the original 8 mg/kg tocilizumab + methotrexate and methotrexate escape arms suggest that serum tocilizumab concentrations between the tocilizumab monotherapy and 8 mg/kg tocilizumab + methotrexate arms were maintained at similar levels, which could indicate the lack of additive effect of methotrexate on serum drug levels. [Ann Rheum Dis 2015;74:1037-1044]
Overall, tocilizumab monotherapy or the 8 mg/kg tocilizumab + methotrexate combination resulted in sustained improvement and inhibited joint damage at year 2, said the researchers. “Maintenance of response with 8 mg/kg [tocilizumab] monotherapy suggests that early [tocilizumab] therapy is a viable option for patients intolerant of methotrexate.”
Given the large number of patients who shifted to escape therapy, the researchers recommended exercising caution when interpreting the findings of this group.