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ID PMID Title PublicationDate abstract
11826747 [Use of glucocorticoids in rheumatoid arthritis. Inhibition of disease progression versus 2001 Dec This is a short overview of low dose oral treatment with 5-7.5 mg prednisolone/day in RA with emphasis on radiographic progression. Short-term studies over 1-2 weeks with 7.5-15 mg prednisolone/day demonstrate advantage over placebo and--less so--over NSAID in improving RA symptoms; over 6-12 months prednisolone seems to be less superior. Older studies were unable to demonstrate an inhibition of progression seen on radiographs. In the Kirwan study, there was a significant inhibition of x-ray progression with 7.5 mg prednisolone/day versus placebo. The German low-dose prednisolone treatment (LDPT) study demonstrated a significant retardation of radiographic progression with only 5 mg prednisolone/day in addition to DMARD treatment with parenteral gold or methotrexate versus DMARD + placebo in early RA during the first year of treatment while there was no difference between both groups during the second year. These data are in favor of a "bridging" treatment with low dose prednisolone. The risks of corticosteroid treatment are discussed, including an increased mortality rate as an independent risk factor. Two randomized studies and a metaanalysis indicate the development of steroid osteoporosis in RA already with low doses. As with every treatment, benefit and risk have to be considered carefully.
10878295 The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clini 2000 May Leflunomide, the newest disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA), acts by inhibiting dihydroorotate dehydrogenase, the rate-limiting enzyme in the pathway for pyrimidine production. The drug thus limits T-cell proliferation, a process thought to be a key step in the pathogenesis of RA. In placebo-controlled trials, leflunomide was superior to placebo and comparable to sulfasalazine and methotrexate for improving the signs and symptoms of RA; and superior to placebo, sulfasalazine, and methotrexate for improving health-related quality of life. In the same trials, leflunomide was also superior to methotrexate and comparable to sulfasalazine for slowing radiographically assessed progression of RA. When used in combination therapy in an open-label trial, leflunomide resulted in improvement for over half of a group of RA patients who had failed to respond to methotrexate alone. The most common adverse events associated with leflunomide treatment were gastrointestinal symptoms, allergic reactions, alopecia, and elevated liver enzyme levels. Adverse events were generally mild to moderate in severity and resolved without sequelae. Clinical trial results indicate that leflunomide is an efficacious and safe addition to the roster of therapeutic agents used to treat RA.
9471625 [Disturbed neutrophil activation in pneumonia during medicinal immunosuppression]. 1997 Nov BACKGROUND: In medically immunosuppressed patients with pneumonia, the BAL cell differential and neutrophils secretion products were determined and compared to patients with pneumonia without defined immunodeficiency in order to define a possibly deficient neutrophil function. PATIENTS AND METHODS: Forty-eight medically immunosuppressed patients were studied: 24 pts. after renal transplantation receiving threefold immunosuppression (cyclosporine, azathioprine, prednisolone), 14 pts. with non-Hodgkin-lymphoma receiving polychemotherapy and 10 pts. with rheumatologic disorders (rheumatoid arthritis n = 3, M. Wegener n = 5 und SLE n = 2) receiving cyclophosphamide or methotrexate. For comparison, 116 patients without defined immunodeficiency and pneumonia and 16 healthy adults were studied. In addition to the cell differential the BALF concentrations of the neutrophil degranulation products myeloperoxidase (MPO) and lactoferrin were determined using immunoluminometric assays. For identification of microorganisms semiquantitative cultures were used. RESULTS: Neutrophilia > 5% in BAL was present in only 36% of the immunosuppressed pts. in contrast to 91.3% of the immunocompetent pts. (p < 0.01). The same pathogen was found in 14 pts. of each group, so that a pathogen matched comparison was possible. The neutrophil percentage and the BALF concentration of lactoferrin was significantly lower in the immunosuppressed group. In blood there was no difference with regard to the neutrophil count between the groups. CONCLUSIONS: BAL characteristics of immunosuppressed pts. are different from those of immunocompetent pts. with pneumonia. The pathogen-matched comparison proved that this is not due to different pathogens. Medically immunosuppressed patients with pneumonia exhibit a disturbed neutrophil recruitment. A neutrophil percentage < 5% in BAL of medically immunosuppressed patients does not preclude a bacterial infection.
11263013 [Listeria arthritis in chronic polyarthritis during low dose prednisolone and methotrexate 2001 Feb We report about a patient with polyarticular rheumatoid arthritis taking methotrexat and 5 mg prednisolone who developed in the course of a RA flare a septic arthritis in the right shoulder. Listeria monocytogenes could be identified as the causative bacteria. Clinically, the Listeria-induced septic arthritis could not be differentiated from rheumatoid arthritis; fever was not present. The synovial analysis showed a granulocytic effusion with 19,000 cells/ml; there was no microbiological growth within the first 24 hours. Only the low glucose level indicated a possible septic arthritis. After 48 hours, gram-positive bacterial growth was evident and Listeria monocytogenes could be isolated after 72 hours. Therapy was initiated by antibiotic treatment and arthrotomy with synovectomy followed by extensive irrigation which proved effective in bacterial elimination but joint destruction resulted. During the whole course, Listeria antibodies were negative and proved to be too insensitive. The incidence of Listeria-induced arthritis is very low; a review of the literature revealed only 24 reported cases. It occurs primarily in patients with rheumatic diseases under immunosuppression and in prosthetic joints. The diagnosis is based on cultural detection. It is important to cultivate synovial effusions for longer than 24 hours in order to identify Listeria. This is of relevance since Listeria serology is not sensitive.
9417761 [Chronic polyarthritis and radiosynoviorthesis: a prospective, controlled study of injecti 1997 Jul The aim of this prospective study was to evaluate the efficiency of radiation synovectomy with rhenium-186 or erbium-169 in rheumatoid arthritis. In the control groups articulosynovitis was treated by injection of triamcinolonhexacetonid. Follow-up time was 3 years. Patients of the study had to fulfill the following criteria: rheumatoid arthritis (ARA criteria 1988), patient age above 40 years, standardized medical treatment with methotrexate, (started at least 6 month prior to injection therapy, given for the entiry study time), prednisolon < or = 7.5 mg/d and diclofenac < or = 150 mg/ d, and no previous surgery or injection therapy on this/these joint/s. Shoulder, elbow, wrist, and ankle joints were treated in group 1 by injection of rhenium-186 combined with triamcinolonhexacetonid, in group 2 by injection of triamcinolonhexacetonid alone. Each treatment group included 50 joints. Digital joints underwent injection of erbium-169 combined with triamcinolonhexacetonid (group 3 = 131 joints) or triamcinolonhexacetonid (group 4 = 86) alone. During the follow up period, the joints were assessed for pain, synovial swelling, joint motion, and stage of radiological destruction (Larsen-Dale-Eek). After 3 years follow-up, 228 joints met the above named criteria: group 1 = 41 joints, group 2 = 21 joints, group 3 = 131 joints, group 4 = 53 joints. Significantly better clinical results were achieved with the combined injection of rhenium-186 or erbium-169 and triamcinolonhexacetonid. Results for PIP joints were worse than for other joints, which is explained by better immobilization of the latter ones after injection. The progression in radiological joint destruction according to the stages of Larsen-Dale-Eek during the follow-up time of 3 years (= stage at 3 years minus stage prior to treatment) corresponded to the clinical results and was significantly slower in groups 1 and 3: group 1 = 0.62; group 2 = 1.7; group 3 = 0.75; group 4 = 1.43 Therefore, we recommend radiosynovectomy with erbium-169 or rhenium-168 in combination with triamcinolonhexacetonid and consequent immobilization after injection.
11200291 Atrial fibrillation occurring in a patient taking etanercept plus methotrexate for rheumat 2000 Dec A 57-year-old man with nodular rheumatoid arthritis was started on a combination of etanercept and methotrexate. After treatment for five months on this therapy, he presented with new-onset atrial fibrillation. While this report is anecdotal, any new drug warrants intense monitoring for unexpected toxicities in the post-marketing period. Etanercept is being tried in patients with congestive heart failure, where TNF-a seems to be increased. Further surveillance and caution are suggested in patients with known coronary artery disease or atrial dysrhythmia.
9613341 Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid 1998 Feb OBJECTIVES: To determine the effects of impaired renal function on the pharmacokinetics of methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: 77 RA patients were included in this study. MTX was administered intramuscularly (7.5 to 15 mg). Subjects were divided into four groups, according to their creatinine clearance (CLCR); group 1: CLCR lower than 45 ml/min; group 2: CLCR between 45 and 60 ml/min, group 3: CLCR between 61 and 80 ml/min and group 4: CLCR higher than 80 ml/min. Blood samples were collected from each subject before drug administration and at two and eight hours after administration. Individual pharmacokinetic parameters were estimated using a Bayesian approach. RESULTS: MTX concentrations (total and free) were 1.3 to 1.6-times higher in group 1 than in groups 2, 3, and 4. For total and free MTX, t1/2 eliminations were 22.7 hours in group 1, 13.5 hours in group 2, 12 hours in group 3, and 11 hours in group 4. Clearance of total MTX was 64, 92, 96, 115 ml/min in groups 1 to 4, respectively, it was 118, 163, 171, 206 ml/min in groups 1 to 4 for the free MTX, respectively. Volume of distribution averaged 2.16 l/kg in group 1, 1.92 l/kg in group 2, 1.61 l/kg in group 3, and 1.56 l/kg in group 4. Elimination half life was significantly increased and total clearance was significantly reduced with the degree of renal impairment. Linear regression revealed good correlations between clearance values of MTX and creatinine clearance. CONCLUSION: Individual testing is required rather than a general decrease of the MTX dose based only on CLCR.
10400407 Etanercept: a review of its use in rheumatoid arthritis. 1999 Jun Etanercept, a fusion protein consisting of the extracellular ligand-binding domain of the 75kD receptor for tumour necrosis factor-alpha and the constant portion of human IgG1, is administered by subcutaneous injection and is the first specific anti-cytokine therapy approved for rheumatoid arthritis. In patients with active rheumatoid arthritis [American College of Rheumatology (ACR) functional class I to III] who had failed to respond to previous treatment with > or = 1 disease-modifying antirheumatic drug (DMARD), etanercept, alone or in combination with methotrexate, produced improvements in all components included in the ACR core set of disease activity measures. A dose-response effect was apparent with etanercept 0.25 to 16 mg/m2 twice weekly in a randomised, double-blind study in 180 patients. The mean number of swollen or tender joints at the end of the 12-week study decreased by >50% in patients treated with etanercept 16 mg/m2 twice weekly and by <25% in patients treated with placebo. In a 24-week multicentre, randomised, double-blind study in 234 patients who were not allowed to use DMARDs, etanercept 10 or 25mg twice weekly had a rapid onset of effect. Significantly more patients treated with etanercept 25mg twice weekly than placebo experienced 20 (ACR 20), 50 (ACR 50) or 70% (ACR 70) improvement in ACR criteria after 3 and 6 months. Limited evidence suggests that the therapeutic effects of etanercept are maintained for up to 2 years. Etanercept 25mg twice weekly produced significant improvement in patients receiving oral or subcutaneous methotrexate 10 to 25 mg/week in a multicentre, randomised, double-blind, placebo-controlled study. A significantly greater proportion of patients treated with etanercept plus methotrexate (71%) than placebo plus methotrexate (27%) achieved the ACR 20 criteria after 6 months. Moreover, 39 and 15% of patients treated with etanercept plus methotrexate, but no placebo plus methotrexate recipients, had achieved the ACR 50 and ACR 70 criteria at this time. Etanercept 0.4 mg/kg twice weekly reduced disease activity in a preliminary, noncomparative study in 69 children aged > or =4 years with refractory juvenile rheumatoid arthritis. Although the overall frequency of infections was similar in patients treated with etanercept or placebo, upper respiratory tract infections were more common in patients treated with etanercept (29%) than placebo (16%). Injection site reactions occurred more frequently in etanercept- than placebo-treated patients, but did not bias the results of any study. CONCLUSIONS: When etanercept is administered alone or in combination with methotrexate in patients with refractory rheumatoid arthritis, significant reductions in disease activity occur within 2 weeks and are sustained for at least 6 months. Thus, etanercept appears to be particularly well suited for use in patients who fail to respond to treatment with DMARDs.
10955324 Treatment of rheumatoid arthritis with a DR4/1 peptide. 2000 Aug OBJECTIVE: To determine the safety and potential clinical efficacy of primary and booster injections of a DR4/1 peptide in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS. Subjects with active RA were enrolled in a randomized, placebo controlled, double blind, dose-escalating clinical trial of synthetic DR4/1 peptide containing the shared epitope. The primary injection of the DR4/1 peptide in alum adjuvant was administered at one of 3 doses, 1.3, 4.0, and 13 mg, followed by up to 3 or 4 booster injections every 6 or 8 weeks at the same dose. The primary outcomes were the occurrence of adverse effects and changes in measures of immune function. Clinical efficacy was assessed using the American College of Rheumatology 20% criteria for clinical improvement. RESULTS: Fifty-three patients were entered into the trial, including 44 who completed the study. In the absence of any observations of a dose response to the DR4/1 peptide injections, the 3 dosage groups were combined for subsequent analysis into 3 groups: patients receiving DR4/1 peptide injections every 6 weeks, patients receiving DR4/1 peptide injections every 8 weeks, and a placebo group. At all doses and each dosing interval the primary and booster injections of synthetic DR4/1 peptide were well tolerated and did not produce any significant changes in lymphocyte counts or evidence of generalized immunosuppression. Analysis of clinical efficacy showed that the 6 week group had trends toward improvement in disease measures. CONCLUSION: Primary and booster injections of the DR4/1 peptide containing the shared epitope were safe and did not broadly suppress immune function.
9022804 Analogues of methotrexate in rheumatoid arthritis. 1. Effects of 10-deazaaminopterin analo 1997 Jan 31 Carbonation of the dianions (LDA) of 5-methylthiophene-2-carboxylic, 2-methylpyridine-5-carboxylic, and 3-methylpyridine-6-carboxylic acids provided the respective carboxy heteroarylacetic acids. The crude diacids were directly esterified in MeOH-HCl to afford the diesters. Alkylation of the sodio anions with ethyl iodide yielded the appropriate alpha-ethyl diesters. The anions of the various diester substrates were then alkylated by 2,4-diamino-6-(bromomethyl)-pteridine followed by ester saponification at room temperature to afford the respective 2,4-diamino-4-deoxy-10-carboxy-10-deazapteroic acids. The 10-carboxyl group was readily decarboxylated by heating in DMSO at temperatures of 110-135 degrees C to give the diamino 10-deaza heteropteroic acid intermediates. Coupling with diethyl L-glutamate followed by ester hydrolysis afforded the target aminopterins. The analogues were evaluated for antiinflammatory effect in the mouse type II collagen model. The thiophene analogue of 10-ethyl-10-deazaaminopterin was found to be an effective inhibitor in terms of reduced visual evidence of inflammation and swelling as determined by caliper measurement.
10410272 Rheumatoid arthritis associated with methotrexate-induced pneumonitis: improvement with i. 1999 May Pneumonitis is one of the most serious adverse effects associated with low-dose weekly methotrexate (MTX) therapy. Immediate cessation of MTX, and the introduction of oxygen therapy and glucocorticoids usually results in a dramatic improvement in the pulmonary toxicity. We report here a case of MTX-induced pneumonitis in a patient with rheumatoid arthritis (RA). Severe hypoxemia and interstitial infiltration in both lung fields did not respond to the withdrawal of MTX and the administration of oxygen and steroid pulse therapy. When intravenous cyclophosphamide (CYC) pulse therapy was initiated, however, rapid physiologic and radiographic improvement was seen. Our case suggests that CYC treatment may have a beneficial effect on MTX-induced pneumonitis that is resistant to steroid therapy.
10364900 Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 1999 Apr OBJECTIVES: To investigate the potential clinical benefit of a combination therapy. METHODS: 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). RESULTS: The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). CONCLUSION: This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.
10743830 Reversible methotrexate associated lymphoproliferative disease evolving into Hodgkin's dis 2000 Mar We describe a case of nodular sclerosing Hodgkin's disease (NSHD) developing in a 61-year-old woman with seropositive rheumatoid arthritis treated with oral methotrexate (MTX) 5 to 15 mg/week for 5 years. Computed tomography (CT) of the abdomen revealed splenomegaly and marked abdominal and retroperitoneal lymphadenopathy. MTX was discontinued; several weeks later prednisone 10 mg/day was added to control worsening polyarthralgia. Repeat CT at 3 months showed almost complete regression of the splenomegaly and lymphadenopathy. However, CT studies at 10 months showed asymptomatic progression of lymphadenopathy, which on biopsy revealed NSHD. Patients with apparently reversible MTX associated lymphoproliferative disorder require periodic monitoring for asymptomatic development of malignant lymphoma.
9433869 Antiinflammatory and immunoregulatory action of methotrexate in the treatment of rheumatoi 1998 Jan OBJECTIVE: To look for in vitro modulation of the main immunoregulatory and antiinflammatory cytokines by methotrexate (MTX) during the course of rheumatoid arthritis (RA). METHODS: We quantified interleukin-2 (IL-2), IL-4, IL-10, and interferon-gamma (IFNgamma) gene expression by peripheral blood mononuclear cells ex vivo under basal conditions and in vitro after stimulation with phytohemagglutinin (PHA) or PHA plus MTX, by competitive reverse transcriptase-polymerase chain reaction (RT-PCR), in 12 patients with untreated active RA (group 1), 10 patients with MTX-treated disease in partial remission (group 2), and 11 healthy control subjects. Simultaneously, under the same experimental conditions, we quantified cytokine production by specific enzyme-linked immunosorbent assays (ELISAs). RESULTS: Under basal conditions, we found no differences in IL-2, IL-10, and IFNgamma gene expression in the 3 groups, while IL-4 gene expression was significantly decreased in RA patient group 1 compared with the control group. In vitro, under the action of MTX, IL-10 gene expression was significantly increased in the 3 groups, IL-4 gene expression was significantly increased in RA group 1 and in the control group, and IL-2 and IFNgamma gene expression was significantly decreased in RA group 1. Cytokine gene expression assessed by RT-PCR and cytokine production assessed by specific ELISAs were highly correlated. CONCLUSION: In vitro modulation of the cytokine network by MTX, increasing Th2 cytokines and decreasing Th1 cytokines, could explain its antiinflammatory and immunoregulatory actions in vivo during the treatment of RA.
11247319 Influence of cyclic intravenous pamidronate on proinflammatory monocytic cytokine profiles 2001 Jan OBJECTIVES: The aim of this work was to evaluate in a randomised double-blind prospective study the effect of pamidronate on intracellular monocytic cytokine profiles (IL-1, IL-6, TNF-alpha) and bone density in rheumatoid arthritis patients. METHODS: Twenty rheumatoid arthritis patients were treated for one year with methotrexate and a low dose of prednisolone. Double blind randomisation was performed for either i.v. pamidronate (at 3-month intervals) or placebo. The effect of pamidronate was evaluated on intracellular cytokine profiles (IL-1, IL-6, TNF-alpha), disease activity and bone mass measurements. The human monocytic cell line THP-1 was used to evaluate in vitro apoptosis by pamidronate. RESULTS: Spontaneous production of interleukin-1 beta by patient blood monocytes was lower in the pamidronate group and was associated with an increase in bone density of the spine after 12 months of therapy. In vitro a dose-related increase in pamidronate induced apoptosis was found in THP-1 cells. CONCLUSIONS: This prospective double-blind randomised study demonstrated that pamidronate therapy resulted in an increase of bone density despite treatment with steroids. This rise is associated with a suppression of interleukin-1 beta production in monocytes of patients treated with pamidronate. Our in vitro experiments suggest that this anti-inflammatory effect could be due to an increase in the apoptosis of monocytic cells.
9566103 [Basic therapeutic combination therapy in chronic polyarthritis: an overview]. 1998 Feb Therapy of rheumatoid arthritis with a combination of several disease-modifying drugs aims towards better control of the disease than achievable by monotherapy. Based on a broad variety of clinical studies, revealing more or less positive results, several combinations have been suggested: the inclusion of cyclosporin into combinations with methotrexate, the inclusion of sulfasalazine into combinations with methotrexate, the combined use of two chemotherapeutic substances, including methotrexate, azathioprine and cyclophosphamide, the inclusion of chloroquine derivatives into such or other combinations, and the combination of methotrexate with injectable gold. The validity of some of the studies is affected by high drop out rates and by the unknown influence of concomitant therapy with corticosteroids. Our own beneficial experience with the triple combination of methotrexate with azathioprine and chloroquine in 21 patients with refractory rheumatoid arthritis is summarized.
9330930 Total and free methotrexate pharmacokinetics in elderly patients with rheumatoid arthritis 1997 Oct OBJECTIVE: To determine the pharmacokinetics of methotrexate (MTX) in a group of patients 65 to 83 years of age and to compare the pharmacokinetic data to those in patients 21 to 45 years of age. METHODS: Thirty-eight elderly patients (8 men, 30 women) and 24 young patients (6 men, 18 women) underwent this pharmacokinetic study. They received intramuscular administration of MTX each week, at a dose varying from 7.5 to 15 mg depending on the patient. MTX concentrations in plasma and ultrafiltrate samples were assayed by a fluorescence polarization immunoassay. Pharmacokinetic variables were estimated using a Bayesian approach with population parameters as a priori information together with 2 plasma MTX concentrations (2 and 8 h after injection). RESULTS: The extent of unbound fraction and the volume of distribution were not statistically significantly different between the 2 age groups. The elimination half-life measures of the free and total MTX were greatest in the elderly group (p < 0.001). The total clearances of free and total MTX were inversely proportional to age (p < 0.001). CONCLUSION: MTX clearance decreases with decreasing creatinine clearance and smaller doses may be chosen in this group. Thus, a dosage regimen should be adjusted in elderly patients or in those with renal impairment.
11035130 Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg dail 2000 Oct BACKGROUND: It is postulated that some aspects of methotrexate toxicity may be related to its action as an anti-folate. Folic acid (FA) is often given as an adjunct to methotrexate therapy, but there is no conclusive proof that it decreases the toxicity of methotrexate and there is a theoretical risk that it may decrease the efficacy of methotrexate. OBJECTIVES: To look at the effect of stopping FA supplementation in UK rheumatoid arthritis (RA) patients established on methotrexate <20 mg weekly and FA 5 mg daily, to report all toxicity (including absolute changes in haematological and liver enzyme indices) and to report changes in the efficacy of methotrexate. METHODS: In a prospective, randomized, double-blind, placebo-controlled study, 75 patients who were established on methotrexate <20 mg weekly and FA 5 mg daily were asked to stop their FA and were randomized to one of two groups: placebo or FA 5 mg daily. Patients were evaluated for treatment toxicity and efficacy before entry and then at intervals of 3 months for 1 yr. RESULTS: Overall, 25 (33%) patients concluded the study early, eight (21%) in the group remaining on FA and 17 (46%) in the placebo group (P = 0.02). Two patients in the placebo group discontinued because of neutropenia. At 9 months there was an increased incidence of nausea in the placebo group (45 vs. 7%, P = 0.001). The placebo group had significantly lower disease activity on a few of the variables measured, but these were probably not of clinical significance. CONCLUSIONS: It is important to continue FA supplementation over the long term in patients on methotrexate and FA in order to prevent them discontinuing treatment because of mouth ulcers or nausea and vomiting. Our data suggest that FA supplementation is also helpful in preventing neutropenia, with very little loss of efficacy of methotrexate.
9184269 Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthr 1997 May Pneumonitis is emerging as one of the most unpredictable and potentially serious, adverse effects of treatment with MTX. Its prevalence in rheumatoid arthritis (RA) has been estimated from several retrospective and prospective studies to range from 0.3% to 18%. On the other hand, MTX-induced pneumonitis seems to be very rare in psoriatic arthritis (PsA). Our review of 194 RA patients and 38 PsA patients receiving MTX has identified four RA patients and one PsA patient with MTX-induced pneumonitis, giving a prevalence of 2.1% and 0.03%, respectively. Diagnosis was suggested by clinical history and radiographic findings, but the bronchoalveolar lavage plays an important role both in excluding infectious agents and in providing information for understanding the pathogenesis of lung injury. The presence of a lymphocyte alveolitis with a predominance of CD4+ T cells in 3 RA patients and CD8+ T cells with a concomitant increase in neutrophils in another case suggests that immunologically mediated reactions may be one damage mechanism in MTX-induced pneumonitis. Although risk factors for MTX-induced pulmonary toxicity are poorly understood, the presence in 3 out of 5 of our patients of pre-existing lung disease, represented by diffuse interstitial changes on chest X-ray, and mild bronchial asthma in two RA patients and by pulmonary silicosis in the patient with PsA may account for a predisposition to the development of MTX pneumonitis.
9433404 A retrospective study of treating RA patients with various combinations of slow-acting ant 1997 During the period 1/1990-9/1995 a total of 311 RA patients were challenged 458 times with 52 different COMBOs. As the first COMBO methotrexate (MTX), sulphasalazine (SSZ), im gold (GOLD), and hydroxychoroquine (HCQ) were combined with each other in 272/311 cases. The respective six and 12 months survivals of these COMBOs were 68.6% (95% CI 63.0% to 74.3%) and 53.6% (95% CI 47.4% to 59.9%). Inefficacy (27.9%), rather than adverse events (23.5%) or other causes (16.9%) was the leading reason for the discontinuations. Only in five cases (1.8%) these COMBOs were discontinued due to a remission. Not a single adverse event related to a COMBO treatment was judged as serious. The mean survival time for COMBOs including MTX (24.0 months; 95% CI 20.6 to 27.4) was statistically significantly longer than the respective time for COMBOs without MTX (14.5 months; 95% CI 11.2 to 17.7). We conclude that, when meticulously monitored, the treatment with COMBOs is safe. However, their efficacy on patients with advanced RA is modest. The survival time for COMBOs including MTX is longer than COMBOs without MTX.
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