ABSTRACT
BACKGROUND: Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as approximately half of the patients do not respond adequately to TNFi. Thus, an unmet need exists to better predict therapeutic outcome of biologicals. OBJECTIVES: We investigated whether brain activity associated with arthritis measured by functional magnetic resonance imaging (fMRI) of the brain can serve as a predictor of response to TNFi in RA patients. METHODS: PreCePRA is a multi-center, randomized, double-blind, placebo-controlled fMRI trial on patients with RA [1] [2]. Active RA patients failing csDMARDs therapy with a DAS28 > 3.2 and at least three tender and/or swollen joints underwent a brain BOLD (blood-oxygen-level dependent) fMRI scan upon joint compression at screening. Patients were then randomized into a 12-week double-blinded treatment phase with 200 mg Certolizumab Pegol (CZP) every two weeks (arm 1: fMRI BOLD signal activated volume > 2000 voxel, i.e. 2 cm3; arm 2: fMRI BOLD signal activated volume <2000 voxel) or placebo (arm 3). DAS28 low disease activity at 12 weeks was assigned as primary endpoint. A 12-week follow-up phase in which patients were switched from the placebo to the treatment arm followed the blinded phase. fMRI was carried out at screening as well as after 12 and 24 weeks of receiving CZP or placebo. CONCLUSION: We hypothesize that high-level central nervous representation of pain in patients with rheumatoid arthritis predicts response to the TNFi CZP which we further investigate in the PreCePRA trial.
ABSTRACT
OBJECTIVE: To analyze the age-related changes of the physiological hand joint architecture. METHOD: To address this concept, healthy individuals (each 10 women and 10 men in six different age decades spanning from 21 to 80 years) were recruited through a field campaign, investigated for the absence of rheumatic diseases and other comorbidities and received high-resolution quantitative computed tomography (HR-pQCT) examination of the hand joints. Number and extent of erosions and osteophytes were quantified across the ages and different sexes. RESULTS: Bone erosions [median (Q1-Q3), 1 (0-2)] and osteophytes [2 (1-4)] were found in healthy women and men with no significant sex differences. Structural changes however accumulated with age: the overall incidence rate ratio (IRR) for the number of erosions and osteophytes per age were 1.04 (95% CI: erosions 1.03-1.06; osteophytes: 1.03-1.05). This means a 4% increase in the number of erosions and osteophytes per year. Using third decade as reference, healthy individuals in the age decades from 50 years had higher IRR for erosion numbers (sixth, seventh, eigth decade: 4.87 (2.20-11.75), 6.81 (3.08-16.46) and 6.92 (3.11-16.79)) compared to younger subjects (fourth, fifth decade: 1.80 (0.69-4.87), 1.53 (0.59-4.10)). The IRRs of osteophytes also indicate a gradual increase after the fifth decade, with IRRs of 2.32 (1.32-4.17), 4.17 (2.38-7.49) and 6.86 (3.97-12.20) for the sixth, seventh and eigth decades, respectively. CONCLUSIONS: Structural changes in the hand joints of healthy individuals are age dependent. While being rare under 50 years of age, erosions and osteophytes accumulate above the age of 50, suggesting that the threshold between "normal" and "pathological" is shifted with the increase of age.
