Dynamics of body mass index and visceral adiposity index in patients with rheumatoid arthritis treated with tofacitinib.

The increase in cardiovascular risk in patients with rheumatoid arthritis (RA) compared with the general population is due to the combined effect of traditional risk factors for cardiovascular diseases, metabolic disorders, systemic inflammation, and side effects of antirheumatic drugs. Tofacitinib (TOFA) is an oral reversible inhibitor of janus kinases for the treatment of RA with proven efficacy and good tolerability, but its effects on body weight and metabolic profile need to be clarified. We investigated the effects of TOFA on body mass index (BMI) and visceral adiposity index (VAI) in RA patients. Thirty-one consecutive patients with active RA and starting new treatment with TOFA were included in a prospective 1 year follow-up observational study of cardiovascular effects of TOFA treatment. Weight, height, waist circumference, BMI, blood pressure, lipid profile, fasting glucose and VAI were measured at baseline and 12 months of treatment. Median weight gain was 3 kg (4.2%) after 1 year of TOFA. 23 (74%) patients suffered from a weight gain, and 6 (26%) out of them from a weight increment of 10% or more. Patients with lower BMI (p = 0.024) and higher baseline DAS28 [ESR] (p = 0.017) have the risk of an increase in BMI > 5% during TOFA treatment in a multivariate analysis. A decrease in VAI after 12 months was recorded. Weight increment and improvement of VAI are frequent on TOFA treatment. BMI dynamics associated with higher disease activity at baseline and lower baseline BMI.

Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients are associated with improved clinical response to methotrexate therapy.

OBJECTIVE: To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. METHODS: Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction. The protein concentrations in peripheral blood mononuclear cells were quantified using enzyme-linked immunosorbent assay. Receiver operating characteristic curve analyses were used to suggest thresholds that were associated with the prediction of the response. RESULTS: Decreases in the disease activity at the end of the study were accompanied by significant increases in joint space narrowing score (JSN). Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1) and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen joint count were noted at baseline. The baseline tumor necrosis factor (TNF)α gene expression was positively correlated with JSN at the end of the follow-up, whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were correlated with the ΔDAS28 values. CONCLUSIONS: Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity. Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to MTX therapy.

Rheumatoid factor positivity is associated with increased joint destruction and upregulation of matrix metalloproteinase 9 and cathepsin k gene expression in the peripheral blood in rheumatoid arthritic patients treated with methotrexate.

We evaluated changes in gene expression of mTOR, p21, caspase-3, ULK1, TNF α , matrix metalloproteinase (MMP)-9, and cathepsin K in the whole blood of rheumatoid arthritic (RA) patients treated with methotrexate (MTX) in relation to their rheumatoid factor status, clinical, immunological, and radiological parameters, and therapeutic response after a 24-month follow-up. The study group consisted of 35 control subjects and 33 RA patients without previous history of MTX treatment. Gene expression was measured using real-time RT-PCR. Decreased disease activity in patients at the end of the study was associated with significant downregulation of TNF α expression. Downregulation of mTOR was observed in seronegative patients, while no significant changes in the expression of p21, ULK1, or caspase-3 were noted in any RA patients at the end of the study. The increase in erosion numbers observed in the seropositive patients at the end of the follow-up was accompanied by upregulation of MMP-9 and cathepsin K, while seronegative patients demonstrated an absence of significant changes in MMP-9 and cathepsin K expression and no increase in the erosion score. Our results suggest that increased expression of MMP-9 and cathepsin K genes in the peripheral blood might indicate higher bone tissue destruction activity in RA patients treated with methotrexate. The clinical study registration number is 0120.0810610.