Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7911664 | Treatment of refractory rheumatoid arthritis with a chimeric anti-CD4 monoclonal antibody. | 1994 Jun | OBJECTIVE: To evaluate CD4+ T cell counts of rheumatoid arthritis (RA) patients at 18 and 30 months after treatment with a chimeric anti-CD4 monoclonal antibody (MAb), cM-T412, in a phase I trial. METHODS: Of the 25 RA patients who received the MAb, 23 were available for followup at 18 and 30 months. Levels of circulating CD4+ T cells were measured by flow cytometry. RESULTS: Circulating CD4+ T cell levels in these 23 RA patients remained below normal at 18 and 30 months posttreatment. More profound CD4+ T cell depletion was noted in the higher-dose groups (300 and 700 mg). CONCLUSION: Prolonged suppression of circulating CD4+ T cells was noted both in single-infusion and multiple-infusion groups 18 and 30 months after cM-T412 treatment. The depression was more pronounced in patients who received multiple infusions of cM-T412. The prolonged decrease in CD4+ T cell numbers suggests that the capacity to reconstitute CD4+ T cells in this patient population (treated with methotrexate) is limited. One patient, who was also receiving methotrexate and prednisone, died 18 months after receiving 100 mg of cM-T412. No other significant adverse effects, in particular, no opportunistic infections, were reported in these 23 RA patients at 18 and 30 months of followup. | |
| 7966066 | Osteocalcin in patients with rheumatoid arthritis. A one-year followup study. | 1994 Jul | OBJECTIVE: To analyze clinical, radiological, and drug (disease modifying antirheumatic drug, DMARD) dependent factors influencing bone turnover in patients with rheumatoid arthritis (RA). METHODS: We investigated in a one-year double blind randomized study comparing intramuscular (im) gold with im methotrexate (MTX), whether the variation of inflammatory activity or functional capacity, the ascending anatomic stage, or DMARD treatments have an influence on bone formation (osteocalcin) in patients with RA. RESULTS: Patients (n = 48) enrolled at the beginning of our study had significantly increased osteocalcin levels (3.45 +/- 0.93-->4.42 +/- 1.39 ng/ml p < 0.02) after one year if inflammatory activity decreased (> or = 1 SD: erythrocyte sedimentation rate (ESR) 26.4 mm/h, C-reactive protein (CRP) 3.8 mg/dl). We found a significant negative correlation of the one-year CRP- (r = -0.44, p < 0.001) or ESR differences (r = -0.45, p < 0.001) with the corresponding osteocalcin differences. This was also evident if these patients were pooled with 15 patients excluded from the double blind study as already receiving DMARD treatment (n = 63; p < 0.01). Patients with impaired functional capacity also had significantly reduced osteocalcin levels (p < 0.01). In both cases, alkaline phosphatase showed no significant differences. CONCLUSIONS: Our data suggest that osteocalcin, a useful followup variable of bone turnover, is changed significantly (p < 0.02) in patients with RA regarding inflammatory activity and functional capacity. In contrast to alkaline phosphatase, a fall in inflammatory activity stimulated and impairment of functional capacity significantly decreased osteocalcin levels in patients with RA. | |
| 8296082 | [Rheumatoid arthritis. Therapeutic efficacy of methotrexate and its hepatotoxic effects]. | 1993 Jul | The efficacy and toxicity (specially hepatic) of methotrexate in low doses (7.5 mg/week) was prospectively assessed in 21 patients with rheumatoid arthritis refractory to treatment with gold or penicillamine, during two years. Three patients were prematurely withdrawn from the protocol. A fast and significant improvement of RA was observed during the first six months, which tapered thereafter. Erythrocyte sedimentation rate decreased from 51.5 +/- 20.1 to 27.7 +/- 11.5 mm/h (p < 0.05). A rise in serum transaminases, always raising to less than twice the normal value, was observed in 75% of patients in some moment of the follow up. Hepatic scintigraphy did not show significant changes. Hepatic histological alterations were mild and no changes were observed after two years of treatment. The main secondary effects were moderate and transitory gastrointestinal and hematological disturbances. The prednisone dose was decreased from 6.8 +/- 2.6 to 4.8 +/- 1.9 mg/day at twelve months. There were no withdrawals due to drug toxicity. It is concluded that methotrexate proved to be efficacious in the treatment of rheumatoid arthritis refractory to conventional treatments. Its secondary effects, although frequent, were discrete and transitory and there were no changes in liver histology. | |
| 9091886 | [Complicated course of rheumatoid arthritis with pulmonary involvement, myocardial fibrosi | 1996 Dec | We report on a 67 year old man in whom the chest x-ray revealed marked interstitial opacities in both lungs. The diagnosis of Rheumatoid Arthritis (RA) was established by the presence of five criteria of the American College of Rheumatology for diagnosing RA. High resolution computertomography of the chest confirmed the abnormalities seen in the conventional chest x-ray. A biopsy, taken by open lung surgery, showed the typical pattern of pulmonary involvement in RA and confirmed the association of RA and interstitial lung fibrosis. The histologic examination pointed out lymphocytic infiltration of the bronchies, thickened alveolar walls with lymphoplasmarcellular infiltration and an increase in fibrous connective tissue. A congestive heart failure with severe arrhythmias and an obstructive sleep apnea syndrome (OSAS) were diagnosed in addition. The rhythm disturbances were attributed to the participation of the myocardium in RA and/or by the OSAS. By the treatment with prednisolone, methotrexate, mexiletine and continuous positive airway pressure (CPAP) the rhythm disturbances were alleviated and the patient's condition improved. | |
| 8216395 | Radiographic assessment of disease progression in rheumatoid arthritis patients enrolled i | 1993 Oct | OBJECTIVE: To determine the radiographic progression of disease in rheumatoid arthritis (RA) patients from the Cooperative Systematic Studies of the Rheumatic Diseases clinical trial of auranofin (AUR) versus methotrexate (MTX) versus a combination of the two. METHODS: Baseline (week-0) and study-end (week-48) hand/wrist radiographs in 200 of the 211 patients who completed this multicenter trial (95%) were scored blindly by 2 readers for the presence of erosions and joint space narrowing (JSN). Both intraobserver reliability and interobserver reliability were 0.80 for erosions (P < or = 0.001); intraobserver reliability and interobserver reliability were both 0.75 for JSN (P < or = 0.001). RESULTS: Worsening erosion and JSN scores occurred in all 3 treatment groups, but the difference from baseline reached significance only in the AUR group. CONCLUSION: Clinical improvement has been clearly documented in all 3 treatment groups in this trial. Radiographic deterioration occurs in RA even when clinical features improve, but progression of disease as determined radiographically may be slowed by treatment with MTX. | |
| 8013988 | Immunotherapy in rheumatoid arthritis: a review. | 1993 Dec | The starting mode of the pathological process in rheumatoid arthritis (RA) is the presentation of an unknown 'rheumatoid' antigen by an antigen presenting cell to the receptor on the CD4+ T cell. The activation of the CD4+ T cell, and consequently of the cytokine network, is the second step in the inflammatory process. Immunosuppression in RA, obtained using either immunosuppressive drugs (azathioprine, cyclophosphamide, methotrexate), or physical procedures (lymphoapheresis, total lymphoid irradiation) acts specifically on all lymphocyte populations, and can induce a number of side effects, such as myelotoxicity and opportunistic infections. Two promising new therapeutic approaches are being developed, one aimed at specifically reducing the proliferation of activated T cell clones, and the second designed to modulate the activity of the cytokines involved in the inflammatory process. Encouraging results have been so far obtained with: a) cyclosporine A, a somewhat more specific immunosuppressive agent; b) monoclonal antibodies against surface antigens (CD4, CD5, CD7, CD25, CD54) expressed on activated T cells; c) T cell vaccination; and finally (i.v.) recombinant cytokines, their agonists or antagonists. Besides their utility in the treatment of the disease, these new therapeutical procedures should also lead to a better understanding of pathological processes in RA. | |
| 8003056 | Chloroquine reduces the bioavailability of methotrexate in patients with rheumatoid arthri | 1994 Jun | OBJECTIVE: To evaluate the effects of a single dose of chloroquine (CQ) on the pharmacokinetics of methotrexate (MTX) in patients with rheumatoid arthritis. METHODS: Eleven patients (ages 41-75 years) who were taking oral doses of MTX (15 mg/week) were studied after a dose of MTX alone and after a dose of MTX plus CQ (250 mg). Plasma and urine samples were collected for 24 hours after dose intake, and the concentrations of MTX and its major metabolite 7-hydroxymethotrexate were determined by high-performance liquid chromatography. RESULTS: Administration of CQ together with MTX caused a reduction in the area under the plasma MTX concentration versus time curve (AUC). The median value of individual AUC ratios (MTX/MTX + CQ) was 1.6 (95% confidence interval 1.2-3.6). CONCLUSION: The most likely mechanism for the interaction is that CQ reduces the bioavailability of MTX. This gives a possible explanation for a suggested reduction in MTX-associated liver toxicity by coadministration of CQ. The significance of the interaction for the therapeutic effect remains to be elucidated. | |
| 8216418 | Reduction of leukocyte and interleukin-1 beta concentrations in the synovial fluid of rheu | 1993 Sep | OBJECTIVE: To examine the effect of methotrexate (MTX) on the numbers of leukocytes in the peripheral blood (PB) and synovial fluid (SF) of patients with active rheumatoid arthritis (RA). METHODS: Twelve patients were treated with MTX; 5 patients not taking MTX served as controls. Samples of PB and SF were collected at 0, 1, 4, and 8 weeks of the study. Disease activity was scored, and total leukocytes, neutrophils, lymphocytes, and CD4+, CD8+, DR+, and CD25+ lymphocyte subsets were analyzed in PB and SF. Interleukin-1 beta (IL-1 beta) concentrations in SF were determined. RESULTS: Patients treated with MTX showed significant clinical improvement. No change in PB leukocytes or lymphocyte subsets was observed in either patient group over the 8-week study period. In contrast, the number of leukocytes, the number and proportion of neutrophils, and the concentration of IL-1 beta in the SF of patients treated with MTX were reduced. In addition, in MTX-treated patients, there was an appreciable decrease in SF CD8+ lymphocytes, but not CD4+, DR+, or CD25+ lymphocytes. CONCLUSION: These findings suggest that in RA, MTX acts, at least in part, by reducing the migration of leukocytes into the inflamed synovium. Local reduction of IL-1 beta secretion may contribute to this effect. | |
| 8535645 | Possible mechanisms of action of methotrexate in patients with rheumatoid arthritis. | 1995 Nov | Methotrexate has been reported to be effective in various animal models of arthritis as well as a variety of human disorders without a shared pathogenesis. Reports have emerged of the effect of the drug on lymphocytes, cytokines, leukotrienes, neutrophils, as well as a large variety of intracellular biochemical pathways. At present, it is not possible to identify which of the many possible mechanisms of action are relevant to its action when used in patients with rheumatoid arthritis (RA). More definitive insights may have to await a better understanding of the immunopathogenesis of RA. | |
| 8064737 | Accelerated nodulosis, pleural effusion, and pericardial tamponade during methotrexate the | 1994 May | We describe a patient with seropositive erosive rheumatoid arthritis (RA) who developed accelerated nodulosis, pleural effusion, and pericardial tamponade during methotrexate (MTX) therapy while her arthritis remained inactive. MTX is an effective therapy for the articular manifestations of RA. However, on occasion it may result in triggering the development of extraarticular manifestations of RA. | |
| 7740304 | Pulmonary involvement in rheumatoid arthritis. | 1995 Feb | Pulmonary involvement is one of the extra-articular manifestations of rheumatoid arthritis (RA) and includes pleurisy, parenchymal nodules, interstitial involvement, and airway disease. Rheumatoid pulmonary vasculitis is rare. Pulmonary disease also may be observed as a toxic event consequent to treatment for RA. Although RA is more common in women, rheumatoid lung disease occurs more frequently in men who have long-standing rheumatoid disease, positive rheumatoid factor and subcutaneous nodules. Pleural involvement, usually asymptomatic, is the most common manifestation of lung disease in RA and may occur concurrently with pulmonary nodulosis or interstitial disease. The clinical features and course of pulmonary fibrosis in RA are similar to those of idiopathic pulmonary fibrosis. Bronchiolitis obliterans organizing pneumonia (BOOP), which has been recently described in RA patients, has nonspecific clinical features. The histological patterns correspond to proliferative bronchiolitis in the airway and organizing pneumonia in the alveoli. Obstructive lung disease in RA includes obliterative bronchiolitis (OB) and bronchiectasis. OB is an acute illness characterized histologically by a constrictive bronchiolitis. It may be idiopathic or induced by D-penicillamine or intramuscular gold compounds. Methotrexate (MTX)-pneumonitis is an uncommon complication of MTX treatment. Its clinical presentation is not specific, and diagnosis must be made after exclusion of other causes of pulmonary diseases. It is uncertain if preexisting lung disease predisposes RA patients to MTX-pneumonitis. Treatment of lung disease in RA is empirical. Corticosteroids are usually administered and immunosuppressive drugs are often added when pulmonary disease progresses and/or steroid side-effects appear. | |
| 1609236 | [Therapeutic maintenance dose with methotrexate in rheumatoid polyarthritis. Prospective s | 1992 Mar | One hundred and ninety one patients with rheumatoid arthritis were included in an open prospective trial with the aim of evaluating the acceptability, efficacy and therapeutic maintenance levels of methotrexate. The mean treatment duration was 19 +/- 13.2 (3-58) months and the mean weekly dose of methotrexate 10.2 +/- 0.2 mg. Analysis of the 191 patients by intention to treat showed a statistically significant improvement in all clinical parameters as well as a significant fall in sedimentation rate with a corticosteroid-sparing effect. The therapeutic maintenance level of methotrexate was 73% at one year, 65% at 2 years and 46% at 5 years. Adverse reactions occurred in 71 patients (37.1%) including 30 who stopped methotrexate permanently as a result. With cautious and strict patient selection, methotrexate could be used in RA as basic treatment of first choice. | |
| 8967184 | [Radiologic healing phenomena in chronic polyarthritis treated with methotrexate or sodium | 1996 Jul | PROBLEM: Do radiographs of hands and forefeet obtained from patients with rheumatoid arthritis present with healing phenomena? What is their importance relative to progressive changes? METHODS: Dorsopalmar/-plantar radiographs of hands and forefeet of 43 patients with early rheumatoid arthritis (median disease duration 1.7 years, anatomical Steinbrocker's age < or = 2, patients selected from a prospective study, treatment with methotrexate vs gold-sodiumthiomalate) were obtained at months 0, 6, 12, 24 and 36. Radiographs were evaluated without knowing the mode of treatment at 34 sites according to their time sequence for the following variables: a modified Larsen index, numbers of erosive and of radiologically active joints, and the numbers of joints being improved vs. deteriorated in relation to the preceding x-ray. RESULTS: The radiologic progression could be measured by both a score derived from the modified Larsen index as well as by the numbers of erosive joints with the result of an increasingly crescent, but flattening curve. The number of erosive joints was more sensitive to progression than the score derived from Larsen index. The number of joints deteriorating, compared with the preceding x-ray, decreased from month 6 to month 36 from 16.1% to 7.1% resp. At the same time, 90% of patients increasingly developed radiologic improvement in 2.9% zu 9.3% of joints, including diminution in size and recortication of erosions and particular cysts with a "filling in" by trabecular bone and recovery of a bony outline. There were no relevant differences between therapy groups. CONCLUSIONS: Progression in early rheumatoid arthritis is best measured by the number of joints with erosions. Reparative signs show up with increasing frequency during the course of the disease. After 3 years of treatment the numbers of joints exhibiting improvement predominate those with deterioration. The data support the concept of early aggressive therapy of rheumatoid arthritis and suggest the inclusion of reparative phenomena into the criteria for improvement of this disease. | |
| 1345138 | Radiographic evidence of disease progression in methotrexate treated and nonmethotrexate d | 1992 Dec | Methotrexate (MTX) has proven to be efficacious in the treatment of rheumatoid (RA), but it remains to be proven whether it can slow disease progression, as determined radiographically, in comparison with other disease modifying antirheumatic drugs (DMARD). We performed a meta-analysis of the available data to answer this question. A literature search, including abstracts, was conducted and inclusion criteria developed (description of patients, accountability of patients, inclusion of a control group of patients, specified radiographic endpoint, and appropriate reading of the radiographs). Publications were scored on a scale of 0 to 5 with a score > or = 3 required for inclusion in the study. For abstracts selected, additional data were obtained directly from the investigators. Data for 353 MTX treated and 205 non-MTX-DMARD treated patients with RA were gathered. Not all publications used the same scoring system, so some assumptions were required to analyze the combined data. Only the erosion score was included since not all publications included a reading of the joint space. All scores were transformed into Sharp scores (Arthritis Rheum 1985;28:1449), including the important contributions of 3 Larsen scored publications. Finally a monthly rate of disease progression was computed. Several comparisons were made. Overall, the rates of disease progression were similar for MTX and non-MTX-DMARD treated patients with RA. The non-MTX-DMARD treated patients with RA were separated into a group treated with gold salts (oral or parenteral) and a group treated with azathioprine with each group compared to the MTX treated patients. MTX had slower rates of disease progression than azathioprine, (rates 0.004 vs 0.012) but not slower rates than gold salts (0.008 vs 0.008). Despite its efficacy, the possible role of MTX in slowing disease progression more than other DMARD, as determined radiographically, appears to be evident only when compared to azathioprine. | |
| 7495340 | Survival and drug discontinuation analyses in a large cohort of methotrexate treated rheum | 1995 Sep | OBJECTIVES: To determine the probability of drug continuation in a large cohort of methotrexate treated rheumatoid arthritis (RA) patients, the reasons for discontinuation of methotrexate, the overall survival of the members of this cohort, and the causes of death in these patients. METHODS: Yearly follow up was conducted in methotrexate treated RA patients who formed a cohort between 1981 and 1986 at a tertiary care centre. The probability of drug continuation and the patients' survival were calculated using standard statistical procedures; standardised mortality ratios were calculated using death certificate data and USA general population and mortality tables. RESULTS: The probability of methotrexate continuation at 10 years from the time the first members entered the cohort was 30%. Toxicity (and its severity) was the most frequent cause of discontinuing methotrexate. The cumulative probability of survival was 85% for women and 45% for men. A greater than expected number of deaths from infections was observed, but the number of deaths from cancer and cardiovascular diseases were within the range expected. CONCLUSIONS: Toxicity remains the most common cause for methotrexate discontinuation. Survival was comparable to that of other RA cohorts. Methotrexate may be implicated as an associated factor in the deaths from infections. | |
| 8991980 | Risk factors for early wound complications after orthopedic surgery for rheumatoid arthrit | 1995 Oct | OBJECTIVE: To identify risk factors for the occurrence of early wound complications following orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: We reviewed records of patients with RA undergoing joint surgery to identify predictors of the following early postoperative surgical outcomes: (1) prolonged drainage; (2) wound cellulitis; (3) wound dehiscence; (4) suture abscess; and (5) superficial or deep wound infection. RESULTS: During the study, 204 patients with RA underwent 119 total knee replacements, 105 total hip replacements and 143 procedures of other joints, for a total of 367 orthopedic surgeries. A total of 57 complications were observed (15.9%) of which 26 were considered major (7%). Of the 230 total arthroplasties of the hip, knee, shoulder or elbow, 3 were followed by early deep wound infections (1.3%). In univariate analysis, factors significantly related to the occurrence of complications included Hispanic ethnicity [relative risk (RR) 1.43, 95% confidence interval (CI) 1.16 to 1.78]. and preoperative use of azathioprine (RR 2.13, 95% CI 1.04 to 4.37). Complications were less frequent among patients given methotrexate, but the differences was not significant. Operative blood loss was inversely related to the occurrence of complications. In the multivariate model, the only significant predictors of complications were Hispanic ethnicity (RR 2.86, 95% CI 1.43 to 5.56) and operative blood loss (RR 0.50/liter lost, 95% CI 0.29 to 0.86). CONCLUSIONS: We were unable to demonstrate an independent effect of antirheumatic therapy at the time of surgery on the occurrence of postoperative wound complications. Our study suggests that patients with RA of Hispanic ethnicity may be at increased risk of developing postoperative wound complications following orthopedic surgery. Further study is necessary to explain the mechanism of increased complications in this population. | |
| 1494322 | Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. | 1992 Dec | One of the features of inflammation is increased oxygenation of arachidonic acid which is metabolized by two enzymic pathways--the cyclooxygenase (CO) and the 5-lipoxygenase (5-LO)--leading to the production of prostaglandins and leukotrienes respectively. Amongst the CO products, PGE2 and amongst the 5-LO products, LTB4 are considered important mediators of inflammation. More than 200 potential drugs ranging from non-steroidal anti-inflammatory drugs, corticosteroids, gold salts, disease modifying anti-rheumatic drugs, methotrexate, cyclosporine are being tested. None of the drugs has been found safe; all are known to produce from mild to serious side-effects. Ginger is described in Ayurvedic and Tibb systems of medicine to be useful in inflammation and rheumatism. In all 56 patients (28 with rheumatoid arthritis, 18 with osteoarthritis and 10 with muscular discomfort) used powdered ginger against their afflictions. Amongst the arthritis patients more than three-quarters experienced, to varying degrees, relief in pain and swelling. All the patients with muscular discomfort experienced relief in pain. None of the patients reported adverse effects during the period of ginger consumption which ranged from 3 months to 2.5 years. It is suggested that at least one of the mechanisms by which ginger shows its ameliorative effects could be related to inhibition of prostaglandin and leukotriene biosynthesis, i.e. it works as a dual inhibitor of eicosanoid biosynthesis. | |
| 8129764 | Interleukin-2 receptor levels in the sera of rheumatoid arthritis patients treated with me | 1994 Jan | OBJECTIVE: To evaluate the association of the level of soluble serum interleukin-2 receptor (sIL-2R) with disease activity and response to therapy in patients with rheumatoid arthritis (RA). METHODS: The sIL-2R levels of 148 patients with refractory RA were determined by enzyme-linked immunosorbent assay. This parameter was correlated with other clinical observations obtained during a prospective, randomized, placebo-controlled trial of methotrexate, sponsored by the Cooperative Systematic Studies of Rheumatic Diseases consortium. Using statistical modeling, the usefulness of sIL-2R as a measure of disease activity and a predictor of outcome was evaluated. RESULTS: The mean sIL-2R level in all RA patients was markedly elevated compared with that in normal control subjects, and decreased significantly during the trial. There was no correlation of the sIL-2R level and the joint pain/tenderness count either at study entry or study end. There was a significant correlation of the sIL-2R level and the erythrocyte sedimentation rate, both at study entry and study end. A multiple linear regression model showed that treatment with methotrexate, but not the sIL-2R level or the change in sIL-2R level, predicted a change in joint count. A stepwise multiple logistic regression model defined no significant predictive information for outcome for the level of sIL-2R at study entry. CONCLUSION: After controlling for the simultaneous effects of other important clinical variables, the level of sIL-2R does not appear to predict the response to methotrexate in patients with refractory RA. Further analysis of cohorts of patients with earlier RA needs to be performed. | |
| 8222842 | Pneumonitis complicating low-dose methotrexate therapy for rheumatoid arthritis. Discrepan | 1993 Nov | Two very similar cases of drug-induced pneumonitis complicating treatment of rheumatoid arthritis with low-dose methotrexate are presented. Diagnosis was suggested by clinical history and findings, but the bronchoalveolar lavage showed a high percentage of neutrophils, an unusual feature in methotrexate-induced pneumonitis. Transbronchial lung biopsies (TBB) confirmed the diagnosis by showing interstitial lymphocytic infiltrate with microgranulomas. Although histologic findings are not strictly pathognomonic, when a differential diagnosis has to be made with infectious and rheumatoid lung disease, TBB appears to be of great promise. | |
| 7575712 | Light and electron microscopic analysis of sequential liver biopsy samples from rheumatoid | 1995 Sep | OBJECTIVE: To describe liver histopathologic features and ultrastructural changes in a prospectively studied cohort of rheumatoid arthritis (RA) patients receiving long-term methotrexate (MTX) therapy, and to seek correlations between these changes and simultaneously measured laboratory indices of liver function. METHODS: This was a long-term, prospective, open observational study. Twenty-seven outpatients with RA who began therapy with MTX and continued treatment for extended periods underwent baseline and followup liver biopsies. One hundred seventy liver biopsy specimens were analyzed by light microscopy (LM) and assessed according to a modified Roenigk score and a newly devised numerical grading system. Ninety-three biopsy specimens were also analyzed by electron microscopy (EM). Blood samples were obtained at 4-6-week intervals for determination of bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), and albumin levels, and the weekly dosage of MTX was adjusted if there were abnormalities in the AST or albumin level. A mean of 6.3 liver biopsies per patient were obtained over a mean followup period of 8.2 years (range 2-13 years). RESULTS: The modified Roenigk score was significantly different from baseline at year 3, when it increased from a mean of 1.8 to 2.3 (P = 0.05) and at year 6, when it increased to 2.4 (P = 0.04), but this was not considered clinically meaningful. No other significant changes from baseline were observed by either LM grading system. No significant progression was observed by EM over the course of the investigation. Increases in serial measurements of AST correlated with both the modified Roenigk score (r = 0.21, P = 0.016) and the numerical rating score (r = 0.19, P = 0.027). CONCLUSION: Patients with RA who are receiving weekly single-dose oral MTX therapy exhibit little deterioration in hepatic architecture by LM or EM when the dosage of the drug is adjusted for abnormalities in AST and serum albumin, monitored at frequent intervals. |