Cerebral Pain Processing Following TNFalpha Inhibitor Treatment in Rheumatoid Arthritis: A Randomized Double-Blind Placebo-Controlled fMRI Study

ACR Open Rheumatol. 2026 May;8(5):e90069. doi: 10.1002/acr2.90069.

ABSTRACT

OBJECTIVE: This study investigated the effects of tumor necrosis factor α (TNFα) blockade treatment, adalimumab (ADA), on cerebral pain processing in relevant brain regions in patients with rheumatoid arthritis (RA). Its secondary aim was to identify pretreatment markers in cerebral pain processing that might predict treatment response.

METHODS: A total of 25 patients with RA were randomly allocated treatment with 40 mg ADA (n = 14) or placebo (PBO) (n = 11) injected subcutaneously. During functional magnetic resonance imaging (fMRI), patients underwent individually calibrated pressure-pain stimulation on the most inflamed interphalangeal joint and on an unaffected control site before and after four weeks of treatment.

RESULTS: The ADA but not the PBO group showed significant changes in subjective, clinician-rated, and objective measures. Both groups exhibited significant activations in pain-relevant brain regions during the fMRI task. Cerebral activations did not change following treatment nor did they correlate pre- or post-treatment with changes in systemic inflammation (measured as the change in erythrocyte sedimentation rate [ΔESR]). Baseline cerebral activations did not correlate with treatment response in terms of ΔESR nor with pain or fatigue outcomes. However, in an exploratory analysis, five baseline activation clusters in the ADA group, and one in the PBO group, correlated positively with changes in swollen joint count (P < 0.001).

CONCLUSIONS: Our study did not observe any associations between treatment with TNFα inhibitors and changes in cerebral pain processing, indicating that this treatment may not have a clear central effect.

PMID:42157681 | DOI:10.1002/acr2.90069