The 48-week phase 4 study showed that tocilizumab was more effective than rituximab in patients with rheumatoid arthritis with low B cell levels in synovial tissue.
Tocilizumab is more effective than rituximab in achieving low disease activity in patients with rheumatoid arthritis (RA) whose synovial tissue show a low level of B cell infiltration and who did not respond to conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor inhibitors (TNFis) first, according to a new study.
The study findings were presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting.
RA is the most common type of autoimmune arthritis that causes joint pain, stiffness, swelling, and decreased movement of the joints.
“Approximately half of patients [with RA] lack treatment responses to expensive biologic therapies that also carry the risk of [adverse events]. Predictive markers of response could help stratify RA,” lead study author Constantino Pitzalis MD, PhD, FRCP, director of the Center for Experimental Medicine and Rheumatology at Barts and the London School of Medicine and Dentistry, said in a press release. “This leaves a major unmet clinical need and an urgent necessity to identify markers of treatment response to avoid delays in disease control, unnecessary exposure to potentially toxic drugs and considerable waste of resources.”
B cells are pivotal to RA pathogenesis, validated by the efficacy of the B cell-depleting agent rituximab, which is approved for use in patients with RA after inadequate response to conventional synthetic DMARDs and TNFis. However, only 30% of these difficult-to-treat patients show a 50% improvement (ACR50 response) in disease activity at 6 months after starting rituximab.
In a previous trial, the study’s researchers found that, in patients with early RA, more than 50% had low levels or an absence of B-cell infiltration in their synovial tissue. For this study, the researchers hypothesized that alternative B-cell independent pathways drive inflammation in this subgroup, and that alternative biologic agents to rituximab should work more effectively in these patients.
The 48-week, phase 4, open-label randomized controlled trial evaluated whether or not stratifying patients with RA according to synovial B-cell rich or poor status would help predict response to rituximab. Patients who did not respond, or who were intolerant, to conventional synthetic DMARD therapy and at least 1 TNFi were recruited from 19 European medical centers. Researchers obtained synovial tissue samples at the beginning of the trial, and histologically classified them as either B-cell rich or B-cell poor to balance the randomization of 164 patients in equal groups to receive either rituximab or tocilizumab.
Researchers tested the superiority of tocilizumab over rituximab at 16 weeks in the B-cell poor patient population. The study’s primary endpoint was a Clinical Disease Activity Index (CDAI) improvement of 50% or higher from baseline. The co-primary endpoint was the Major Treatment Response, which was equal to CDAI improvement of 50% or higher along with a CDAI of 10.1 or lower. The secondary outcomes included an assessment of CDAI response in the B-cell rich patient cohort, where they evaluated the non-inferiority of rituximab compared with tocilizumab. They also reported safety data for the therapies up to week 48 of the trial.
Eighty-one of the 83 patients who received rituximab and 73 of 81 patients who received tocilizumab completed treatment to week 16 of the trial. Baseline characteristics among the 2 treatment groups were similar. In the B-cell poor cohort, a numerically higher proportion of patients responded to tocilizumab (56.1%) compared with rituximab (44.7%) considering the primary outcome. A significantly greater proportion of patients responded to tocilizumab (46.3%) compared with rituximab (23.7%) considering the co-primary outcome as well as several additional secondary endpoints including the proportion of patients in remission at 36.6% versus 15.8%. The number of patients reaching moderate or good EULAR response was 87.8% versus 65.8%, respectively.
In the B-cell rich cohort, the researchers found no significant difference in the majority of endpoints. Patients treated with tocilizumab also had a higher number of adverse and serious adverse events, such as infections, compared with those treated with rituximab.
Overall, tocilizumab was more effective than rituximab at achieving both low levels and significant falls in disease activity in patients with RA who are classified as B-cell poor who have failed conventional synthetic DMARDs and TNFi therapy, according to the study.