Early stage RA treated with tocilizumab or tocilizumab and methotrexate realized clinical benefits with no safety concerns at two years.
Researchers reporting in the April 7 online issue of the Annals of the Rheumatic Diseases report that after two years on tocilizumab monotherapy or tocilizumab plus methotrexate combination therapy, patients with early rheumatoid arthritis maintained clinical benefits in the second year of treatment with no new safety concerns.
The trial - a multicenter, 2-year, double-blind, double-dummy, randomized, parallel-group, phase III trial - investigated the efficacy and safety of tocilizumab in combination with methotrexate as compared to methotrexate monotherapy in patients with early, active, progressive rheumatoid arthritis who were methotrexate naive. The trial, called FUNCTION, is the first to look at the IL-6 receptor-alpha inhibitor tocilizumab in early rheumatoid arthritis.
FUNCTION previously showed that after 52 weeks, tocilizumab in combination with methotrexate or as monotherapy, as compared to tocilizumab alone, significantly improved remission rates and inhibited joint damage progression in patients with early, active, progressive rheumatoid arthritis who were methotrexate naive.
“The week 52 analysis showed that compared with methotrexate, tocilizumab and methotrexate or tocilizumab significantly improved rates of remission according to Disease Activity Score based on 28 joint counts and erythrocyte sedimentation rate (DAS28-ESR <2.6). Tocilizumab and methotrexate also inhibited joint damage progression and improved physical function at 52 weeks compared with methotrexate,” researchers wrote.
The follow-up analysis reported in the Annals of the Rheumatic Diseases focused on outcomes at 104 weeks.
1,157 methotrexate-naÃ¯ve patients with early progressive rheumatoid arthritis patients were included in the intention to treat group and 1,153 in the safety group. They were randomized to receive 8mg/kg tocilizumab and methotrexate, 4mg/kg tocilizumab with methotrexate, 8mg/kg tocilizumab with placebo or placebo with methotrexate.
Patients who did not receive 8 mg/kg tocilizumab and not achieving DAS28 of less than 3.2 at 52 weeks were switched to 8 mg/kg tocilizumab and methotrexate).
Utilizing disease activity scores based on 28 joint counts and erythrocyte sedimentation rate remission was achieved in 49.3% of patients taking 8mg/kg tocilizumab with methotrexate at 52 weeks and 47.6% at 104 weeks and when low disease activity was included, 57.9% and 55.5% of patients met criteria at those intervals.
Significant adverse events occurred in 83 patients in the 8mg/kg tocilizumab plus methotrexate group compared to 67 in the 8mg/kg tocilizumab plus placebo, 58 in the 4mg/kg tocilizumab plus methotrexate group and 31 in the placebo plus methotrexate group. Adverse events were mild and mostly consisted of infections.
Patients treated with 8mg/kg tocilizumab with methotrexate or tocilizumab alone saw sustained improvement in disease activity and inhibition of joint damage through their second year of treatment. This group also saw the best response with regards to radiographic endpoints.
Treatment with tocilizumab alone after dual therapy with methotrexate can maintain initial response to both and is particularly useful in those not tolerating methotrexate.
Some patients improved after week 52 implying that longer therapy may be of benefit.
Escape therapy was effective, raising the dose of tocilizumab from 4mg/kg to 8mg/kg however response rates were lower and joint damage greater in those patients. This highlights the need for early and appropriate therapy (8mg/kg tocilizumab with or without methotrexate).
Implications for physicians
Intensive early treatment for rheumatoid arthritis which may include the addition of a biologic to conventional synthetic disease-modifying anti-rheumatic drug (DMARD), is recommended when disease features point to a poor prognosis to prevent permanent joint damage and disability.
Roche provided financial support.
Gerd R Burmester, William F Rigby, Ronald F van Vollenhoven, et al. “Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial” Annals of the Rheumatic Diseases. 2017;0:1–6. doi:10.1136/annrheumdis-2016-210561