MTX-treated Patients Research Articles

Hepatic ultrastructure after methotrexate therapy for rheumatoid arthritis.

Twenty-six patients receiving long-term oral methotrexate (MTX) therapy for rheumatoid arthritis (24 patients) or psoriasis (2 patients) were prospectively evaluated for alterations in liver morphology by light microscopy, electron microscopy, and immunofluorescence microscopy. Although only 4 MTX-treated patients had light microscopic evidence of mild fibrosis, all had evidence of collagen deposition in the space of Disse near Ito cells and changes in hepatocyte lysosomes on electron microscopy. These findings were absent from control livers. Fibrinogen, fibronectin, and type IV collagen were identified by immunofluorescence in both MTX-treated patients and controls. We conclude that long-term MTX therapy for rheumatoid arthritis is associated with alterations in hepatic ultrastructure, including collagen deposition in the space of Disse and changes in hepatocyte lysosomes.

Neuropsychological Rehabilitation

<h3>Background</h3> For long, rheumatoid arthritis (RA) was thought not to associate with central nervous system (CNS) involvement. In recent years some studies suggest that cognitive function is impaired in RA patients. Accelerated atherosclerosis and reduced function of intracranial vessels in RA can be associated with vascular dementia. <h3>Objectives</h3> We assessed RA patients and healthy controls by neuropsychological tests, cognitive function such as attention, intelligence, memory tests and also by anxiety and depression tests. We wished to explore the prevalence of neuropsychiatric manifestations and cognitive impairment in patients with RA. Intracerebral vascular lesions were investigated by brain MRI. <h3>Methods</h3> Sixty RA female patients were included. Among them, 20 were MTX-treated, biologic-free, 40 patients received biologics. The controls included 39 non-RA healthy women. The following standardised tests were used: the Montreal Cognitive Assesment (MoCa) Test, the Victoria Stroop Test (VST), the Spielberger State-Trait Anxiety Inventory (STAI), the Benton Visual Retention Test (BVRT), the Beck Depression Inventory (BDI), the Brigg’s and Nebe’s Test, the Trail Making Test (TMT) A and B, the Word fluency with the letter (WF-L) and with category naming tests (WF-C), the Rey-Osterreich Auditory Verbal Learning Test (RAVLT), the Weschler Adult Intelligence Scale (WAIS). We also performed brain MRI in all patients in order to associate cognitive function with MRI changes. <h3>Results</h3> The MoCa total score was significantly lower in RA patients (23.3±3.8) especially in biologic-treated group (22.6±4.3) compared to controls (25.6±2.4) (p=0,002; 0,001). The attention MoCa test score was significantly lower in biologic- (4.5±1.6) compared to MTX-treated patients (5.7±0.6)(p=0.001). The STAI scores were significantly higher in RA (STAIS: 45.5±8.5; STAIT: 48.0±11.0) compared to controls (STAIS: 36.9±9.1; STAIT: 41.1±9.0)(p&lt;0.001; 0.002). The BDI score was significantly higher in RA (13.2±8.8) and in biologic-treated patients (13.7±8.7) than in controls (8.9±6.5)(p&lt;0.05). The TMT scores were significantly higher in RA (TMT-A: 69.0±26.3; TMT-B:100.2±48.5) compared to controls (TMT-A: 53.1±14.3; TMT-B: 53.1±22.7)(p&lt;0,05). The VST scores were also significantly higher in RA vs controls. The WAIS and Benton scores were significantly lower in RA and in biologic-treated patients than in controls (p=0.005). On brain MRI scans, there were significantly more vascular lesions both in the left and the right side in RA patients (55,1%&gt;53,1%) than in controls (23,5%&gt;20,1%) (p&lt;0,05), the cerebral atrophy is much more common in RA (0,26 vs. 0,03;p=0,005). <h3>Conclusions</h3> These findings suggest that the presence of neuropsychiatric manifestations and cognitive impairment in RA patients is significant. Biologic-treated patients may represent a more severe RA subset thus having cognitive dysfunction more commonly. Brain atrophy, emollition and vascular lesions are more often in RA patients than controls. <h3>Disclosure of Interest</h3> None declared

Immunologic studies of rheumatoid arthritis patients treated with methotrexate.

Immunologic functions of peripheral blood mononuclear cells were studied in rheumatoid arthritis (RA) patients treated with methotrexate (MTX). Spontaneous IgM rheumatoid factor (IgM-RF) synthesis by unstimulated cultured blood mononuclear cells was seen in only 3 of 18 MTX-treated patients, compared with 31 of 54 RA patients who were not receiving long-acting drugs. Total IgM production by unstimulated cultured mononuclear cells, pokeweed mitogen-induced antibody synthesis, and plasma levels of IgM-RF were also lower in MTX-treated patients than in other RA patients. The numbers of circulating B cells, T4 and T8 cells, the T4:T8 cell ratio, and mitogen-induced proliferation indices were similar in MTX-treated and non-MTX-treated patients. Eleven additional patients were studied prospectively after initiation of MTX therapy. All showed significant decreases in spontaneous IgM-RF synthesis, with declining IgM-RF:IgM ratios, including all of the 9 who were studied during the first 24 hours of treatment. The results indicate that MTX has rapid effects on IgM-RF synthesis, and this action might be associated with its therapeutic efficacy in RA.

Enzymatic assay for methotrexate in erythrocytes.

Methotrexate (MTX) accumulates in erythrocytes in MTX-treated patients. We present a modified enzymatic assay measuring MTX concentrations between 10 and 60 nmol/l in erythrocytes, adapted for a centrifugal analyser (Cobas Bio). About 40 patient's samples could be analysed within 1 h. The detection limit was 3 nmol/l. Within run and between-run precision was 7.4% and 13.5% for control 10 nmol/l and 1.2% and 3.2% for control 50 nmol/l. Recovery was 85-115% of MTX added to haemolysed erythrocytes. We found the method useful for pharmacokinetic studies of MTX in erythrocytes in MTX-treated patients.