The efficacy of tocilizumab in combination with methotrexate and as monotherapy was maintained for 2 years in patients with early rheumatoid arthritis (RA), according to an analysis of the results of the FUNCTION trial (Burmester G, et al. Ann Rheum Dis. 2017. Epub ahead of print). No new safety signals associated with tocilizumab were reported with longer- term follow-up of this trial.
“FUNCTION is the first study of tocilizumab [interleukin (IL)-6 inhibitor] initiated in patients with early RA. Year 2 results show that the efficacy of tocilizumab was maintained for extended treatment periods: patients with early RA who received tocilizumab plus methotrexate or tocilizumab monotherapy exhibited sustained improvement in disease activity and maintained inhibition of joint damage during their second year of treatment,” said lead investigator Gerd R. Burmester, MD, Chairman, Center of Internal Medicine and Dermatology, Clinic for Rheumatology and Clinical Immunology, Charite University of Medicine, Berlin, Germany, in an interview with Value-Based Care in Rheumatology.
“It is important to note that in both tocilizumab-treated groups, week 52 improvements were maintained through 2 years for all clinical parameters, including those for remission, low disease activity, and radiographic progression,” he continued.
Dr Burmester emphasized that the best responses were consistently observed in the combination therapy group, particularly for radiographic end points. “Maintenance of response with tocilizumab monotherapy suggests that early tocilizumab therapy is a viable option for patients intolerant of methotrexate,” he noted.
“These findings may open the possibility of early treatment with tocilizumab, very much in-line with the recent U-ACT-early trial. Currently, we still start with methotrexate, but with more data very early treatment [with tocilizumab] might be considered in the future,” Dr Burmester said.Study Details
Tocilizumab is an IL-6 receptor inhibitor approved for the treatment of adult patients with moderate-to-severe RA. FUNCTION was a multicenter, 2-year, double-blind, double-dummy, randomized, parallel-group, phase 3 trial evaluating the efficacy and safety of tocilizumab combined with methotrexate and tocilizumab monotherapy versus methotrexate alone in patients with early, active, progressive RA who were naïve to methotrexate at study entry. Patients were randomized to tocilizumab 4 mg/kg plus methotrexate, tocilizumab 8 mg/kg plus methotrexate, tocilizumab 8 mg/kg, or placebo.
The week 52 analysis of study results showed that, compared with methotrexate, the combination treatment and monotherapy significantly improved remission rates as reflected by Disease Activity Score based on 28 joint counts and erythrocyte sedimentation rate <2.6 (DAS28-ESR).
The combination of tocilizumab plus methotrexate inhibited joint damage progression and improved physical function at 52 weeks versus methotrexate alone. The study randomized 1162 patients; 1157 were included in the intent-to-treat analysis of efficacy, and 1153 in the safety analysis.
The present study looked at the efficacy and safety of tocilizumab use in 809 patients who completed 104 weeks of treatment. At week 52, 33% of patients in the combination therapy arm of tocilizumab 4 mg/kg plus methotrexate and 49% in the methotrexate monotherapy arm, switched to “escape” treatment with a higher dose of tocilizumab—8 mg/kg plus methotrexate. Demographics and disease characteristics were similar at baseline across treatment arms in the intent-to-treat population and escape patients.
In both tocilizumab 8-mg/kg arms, week 52 improvements were maintained through week 104 for DAS28-ESR remission and low disease activity, American College of Rheumatology (ACR) 20/50/70 responses, and radiographic progression.
DAS28-ESR remission was achieved by 49.3% and 47.6% of patients in the tocilizumab 8-mg/kg plus methotrexate group at weeks 52 and 104, respectively. In the same group, DAS28-ESR low disease activity was reached by 57.9% and 55.5% of patients at weeks 52 and 104, respectively.
The proportions of patients who achieved an ACR20, ACR50, and ACR70 response were similar at weeks 52 and 104 in the tocilizumab plus methotrexate and the tocilizumab monotherapy cohorts.
Following 52 weeks of escape therapy, DAS28-ESR was achieved by 30.5% of patients originally assigned to tocilizumab 4 mg/kg plus methotrexate and 51.4% of patients assigned to methotrexate monotherapy. ACR20, ACR50, and ACR70 response rates were 43.0%, 30.3%, and 16.2%, respectively, in the methotrexate monotherapy group, and 29.5%, 16.8%, and 6.3%, respectively, in the tocilizumab 4-mg/kg plus methotrexate group.
Between weeks 52 and 104, radiographic progression inhibition was maintained in both 8-mg/kg tocilizumab groups, but was numerically greater in the group receiving tocilizumab plus methotrexate.
In a post-hoc analysis, certain patients who received tocilizumab and did not respond by week 52 achieved remission at week 104. This suggests that lengthier treatment may be necessary to observe efficacy in certain patients, according to Dr Burmester and colleagues.
The safety profile of tocilizumab was consistent with that of previous reports. Most events were mild to moderate.
“The rate of serious infections was numerically higher with TCZ [tocilizumab]....Rates of infection and serious infection did not appear to increase over time,” Dr Burmester and colleagues reported.