Disease-related brain activation forecasts TNF inhibitor response in RA

In patients with rheumatoid arthritis (RA), high disease-associated central nervous system (CNS) pain activation on functional MRI (fMRI) brain scan may help predict clinical response to TNF inhibitor treatment, as shown in a phase III study.

The study included 139 adult patients with active RA despite the use of at least one conventional synthetic disease-modifying antirheumatic drug, enrolled at rheumatology centres across Germany, Portugal, and Serbia. CNS pain activation was measured for all patients at baseline. The results were used to categorize patients according to the results of the fMRI brain scan (high volume [>700 voxel per 5·9 cm³] or low volume [≤700 voxel per 5.9 cm³]).

The patients were randomly assigned to receive treatment with the TNF inhibitor certolizumab pegol (400 mg subcutaneously on weeks 0, 2, and 4, followed by 200 mg thereafter, administered once every 2 weeks for a maximum of 24 weeks) or placebo. Patients with high CNS-activated volume and who received certolizumab pegol comprised the high-volume certolizumab pegol group, whereas those with low CNS-activated volume and who received certolizumab comprised the low-volume certolizumab pegol group. The placebo group involved patients with all baseline activated volumes.

At week 12, the primary outcome of low disease activity (defined as Disease Activity Score in 28 joints of ≤3.2) occurred in 57 percent of patients in the high-volume certolizumab pegol group, 44 percent in the low-volume certolizumab pegol group, and 26 percent in the placebo group at week 12.

Response in the high-volume certolizumab pegol group was significantly higher than those in the placebo group (p=0.0017), but it did not differ between the low-volume certolizumab pegol group and the placebo group (p=0.063).

In terms of safety, 25 treatment-related adverse events were documented overall, including 22 in the combined certolizumab pegol groups and three in the placebo group.