Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8441141 | Predicting remission in juvenile rheumatoid arthritis with methotrexate treatment. | 1993 Jan | Forty-nine children with a polyarticular course of juvenile rheumatoid arthritis treated with methotrexate (MTX) for at least one year were analyzed to identify clinical characteristics that would predict remission of arthritis after MTX treatment. Twenty-two children (45%) had remission of arthritis after a mean of 13.6 months of treatment and did not differ from the 27 with persistently active arthritis regarding years of disease before starting MTX, age starting MTX, maximum MTX dose, disease onset type, presence of radiographic joint destruction, concomitant treatment with hydroxychloroquine, sulfasalazine or prednisone, or presence of rheumatoid factor or antinuclear antibodies. Higher dose MTX, earlier treatment, genetic markers, and a standardized route of therapy may yield important information in future studies. | |
| 8551408 | Liver biopsy findings in patients with juvenile rheumatoid arthritis receiving long-term, | 1996 Jan | We performed percutaneous liver biopsy in nine children who had received a weekly dose of methotrexate, 10 mg/m2 per week, for at least 3 years to address the concern about subclinical liver toxicity from single, weekly, low-dose methotrexate therapy for juvenile rheumatoid arthritis. No patient had clinical or biochemical evidence of liver injury. All biopsy results were interpreted as normal. These results suggest that the recommendations of the American College of Rheumatology for adults receiving single weekly methotrexate therapy for rheumatoid arthritis can be extended to children. | |
| 19077983 | More Aggressive Drug Treatment of Rheumatoid Arthritis in a University-based Practice. | 1995 Aug | We sought to assess the impact of recent observations and recommendations on the treatment of rheumatoid arthritis in a university-based rheumatology practice over a recent 6-year period. Data was collected from information recorded in a database by physicians treating patients in outpatient rheumatology clinics. The treatment regimens of all patients with rheumatoid arthritis seen during the first half of 1987 and 1993 were compared. The populations were similar in age, race, and sex distribution, disease duration, and seropositivity. Nonsteroidal anti-inflammatory drug use decreased from 85% to 74%, while corticosteroid use increased from 31% to 44% of patients. Second-line agent use increased from 46% to 65% of patients, all of which could be accounted for by the increase in methotrexate use from 11% to 32%. The use of other second-line agents remained stable (hydroxychloroquine, auranofin, azathioprine), declined (intramuscular gold, penicillamine), or increased slightly (sulfasalazine). An increase in combination second-line drug therapy from 2% to 6% was noted. This study shows that between 1987 and 1993, our drug therapy for rheumatoid arthritis has become more aggressive: we have increased steroid use, decreased nonsteroidal use, and more frequently used second-line agents, particularly methotrexate. | |
| 7768253 | Methotrexate in juvenile rheumatoid arthritis. Evidence of age dependent pharmacokinetics. | 1995 | Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5-16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg.kg-1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect. | |
| 7567188 | Drug treatment in children with juvenile rheumatoid arthritis. Past, present, and future. | 1995 Oct | Rheumatology made its debut as a legitimate subspecialty of pediatrics sometime in the 1940s in Europe, and in the 1970s in North America. Therapy of juvenile rheumatoid arthritis has evolved from salicylates and gold injections to newer, less toxic nonsteroidal anti-inflammatory drugs and methotrexate. Corticosteroids remain as important drugs when life-threatening complications or blinding iridocyclitis develop. Immune response modifiers and gene therapies offer considerable potential for eventually halting or curing the disease but have yet to make a substantial impact on therapy. Methods for the correct conduct and interpretation of data from clinical trials are discussed. | |
| 1419506 | Juvenile rheumatoid arthritis, juvenile chronic arthritis, and juvenile spondyloarthropath | 1992 Oct | Immunogenetics are supporting the marked heterogeneity of chronic arthritis in children. Thus DRw13-DRw18 and DQw6-DQw18 were associated with persistent pauciarticular disease in children with an early onset of disease. Several studies have shown DPw2 as an additional susceptibility factor in this subgroup. Standardization of diagnostic criteria for juvenile onset spondyloarthropathy and psoriatic arthritis is necessary; various studies are in progress, and although HLA-B27 provides the common marker, this may only apply to a small group of juvenile psoriatics who have spondyloarthropathy. In the management of juvenile rheumatoid arthritis, methotrexate in moderate doses has been shown to be superior to lower doses of methotrexate and placebo in controlling polyarthritis. Methotrexate may be of particular value in treating the polyarthritis that follows a pauciarticular onset. The possible value of sulfasalazine in a B27 group with persistent polyarthritis has been suggested. Highlights of corticosteroid therapy were intra-articular injections, particularly in pauciarticular disease, the suggestion that deflazacort has a calcium sparing effect, and the possible role of intravenous methylprednisone in the management of severe disease. | |
| 8216396 | Effects of methotrexate on radiologic progression in juvenile rheumatoid arthritis. | 1993 Oct | OBJECTIVE: To assess the effects of methotrexate (MTX) therapy on radiologic progression in juvenile rheumatoid arthritis (JRA). METHODS: We evaluated serial wrist radiographs for carpal length in 23 JRA patients with bilateral wrist involvement, before and during MTX treatment. These carpal length measurements were compared with established norms for carpal length in a healthy pediatric population. RESULTS: Both clinical responders to MTX (17 of 23 patients) and nonresponders (6 of 23) had decreasing carpal length prior to initiation of the treatment. Eleven of the 17 clinical responders had improved carpal length after a mean of 2.5 years of MTX treatment. All 6 clinical nonresponders had progressive loss of carpal length. CONCLUSION: MTX treatment resulted in radiologic improvement, as measured by carpal length, in the majority of children with JRA who had a clinical response to MTX. | |
| 19078078 | Open pilot study of the addition of sulfasalazine to methotrexate in patients with rheumat | 1996 Oct | The safety and efficacy of the sequential addition of sulfasalazine to baseline methotrexate was assessed in patients with active rheumatoid arthritis inadequately controlled by methotrexate alone. Nineteen patients were recruited in a pilot, prospective, open label, uncontrolled clinical trial. One patient was lost to follow-up, four dropped out due to toxicity, one dropped out due to inefficacy, and five violated the protocol. A modified intent-to-treat analysis was performed by carrying forward the clinical data before drop-out or protocol violation to the final visit for the 18 evaluable patients. Swollen and tender joint counts, physicians's and patient's global scores were significantly improved (p < 0.021 to 0.001). Forty-two percent of patients (8/19) demonstrated >/= 20% improvement and 26% (5/19) showed >/= 50% improvement in 4 or more clinical parameters at 6 month's follow-up. Rheumatoid factor negative patients were more likely (p < 0.025) to complete the trial. A controlled clinical trial will be necessary to determine the effectiveness of this combination and the value of sequential addition chemotherapy in patients with recalcitrant rheumatoid arthritis. | |
| 8932830 | Treatment of the neutropenia of Felty syndrome. | 1996 Sep | This review sets out to synthesize and critically evaluate the current reported data regarding therapeutic options for the neutropenia associated with Felty syndrome (Felty neutropenia). A MEDLINE search and bibliographies from recent reviews were used to identify trials and case reports that provided sufficient data to evaluate the effect of various interventions on both the neutropenia and the clinical course of patients with Felty syndrome. Data were obtained on baseline hematologic profiles, bone-marrow biopsies, and patient characteristics; length of follow-up; hematologic and clinical responses to the various interventions; and side-effect profiles. Treatment with hemopoietic growth factors or methotrexate can produce sustained hematologic and clinical responses with an acceptable side-effect profile. Splenectomy produces a long-term hematologic response in 80% of patients. Patients who do not respond hematologically have a higher incidence of non-fatal infections, but a significant minority (46%) do not experience any infections; the incidence of fatal infections is 12%, regardless of whether a hematologic response occurs. Of the patients who had infections prior to surgery, 55% did not experience further infections after splenectomy. Initial treatment of Felty neutropenia should consist of hemopoietic growth factors because of their rapid onset of action and relatively low incidence of side-effects. Splenectomy is a reasonable option if growth factors are ineffective and rapid amelioration of neutropenia is needed. Methotrexate offers a potentially promising alternative for the treatment of both the rheumatologic and the hematologic manifestations of Felty syndrome. | |
| 1280861 | [The use of interferon in the combined therapy of juvenile rheumatoid arthritis]. | 1992 | The efficacy of recombinant gene engineering alpha 2-interferon (reaferon) was studied and compared in 60 patients suffering from verified juvenile rheumatoid arthritis (JRA). Reaferon was shown to possess good tolerance and to produce an adequate therapeutic effect. The combined use of reaferon and methotrexate permits potentiating the therapeutic effect of interferon and avoiding side effects seen with methotrexate used alone. Besides, it makes it possible to reduce the incidence of respiratory infections which are often associated with exacerbation of the underlying disease when treated by conventional methods. | |
| 8295192 | Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumat | 1993 Oct | OBJECTIVE: To investigate the potential interaction of naproxen and methotrexate (MTX) in children with juvenile rheumatoid arthritis (JRA). METHODS: Nine children with JRA served as their own control taking their usual doses of MTX (0.22-1.02 mg/kg/week) and naproxen (14.6-18.8 mg/kg/day) separately and in combination. RESULTS: MTX affected a > or = 30% change in naproxen kinetics in 6/8 patients, while naproxen altered MTX kinetics by > or = 30% in 4/9 patients. CONCLUSION: MTX can alter nonsteroidal antiinflammatory drug (NSAID) kinetics in children with JRA and NSAID can alter MTX kinetics. NSAID toxicity should be considered when assessing adverse reactions in patients receiving the combination treatment of MTX and NSAID: | |
| 1464876 | Preliminary report of higher dose methotrexate treatment in juvenile rheumatoid arthritis. | 1992 Oct | Methotrexate (MTX) is widely used to treat juvenile rheumatoid arthritis (JRA). Although most patients respond to lower doses (0.15-0.5 mg/kg/wk), some patients have required higher doses of MTX to control their arthritis. Thirteen children were treated with MTX 0.82-1.1 mg/kg/wk for 2-26 months. Although all children initially responded (> 50% improvement in joint index, erythrocyte sedimentation rate, morning stiffness and global evaluation), 4 patients discontinued treatment because of side effects or lack of prolonged efficacy. Five patients have continued taking higher dose MTX for 4-26 months, while 4 other patients have been able to decrease their MTX dose and maintain improvement. Twenty-four hour MTX levels were done on all patients at initiation of higher dose MTX and all cleared MTX well. Our report suggests that MTX in doses of 0.82-1.1 mg/kg/wk can successfully treat active synovitis in some children with severe JRA with few short term toxicities. Longterm use at these doses has not been studied and thus its safety is not known. | |
| 8256630 | Non-steroidal anti-inflammatory drugs and slow-acting anti-rheumatic drugs in juvenile rhe | 1993 Oct | The preferred drugs for the initial treatment of juvenile rheumatoid arthritis (JRA) are salicylates or other non-steroidal anti-inflammatory drugs (NSAID) such as tolmetin or naproxen. If the disease activity does not respond adequately to the treatment, slow-acting anti-rheumatic drugs (SAARD) such as oral gold agents, low-dose D-penicillamine, or sulfasalazine should be given in addition to NSAID. If the systemic manifestations are severe, corticosteroid therapy may be commenced. Furthermore, if the joint destruction is progressive, immunosuppressants such as methotrexate would be selected as the third-line drugs of choice. The safety and efficacy of SAARD and immunosuppressants for the treatment of children with JRA, however, have not yet been confirmed, as the adverse effects such as bone marrow suppression, oncogenicity and mutagenicity are sometimes intense. Consequently, the strict indications for use and new therapeutic concepts for the management of JRA based on its pathogenesis are required. | |
| 19078020 | The use of methotrexate perioperatively in patients with rheumatoid arthritis undergoing m | 1996 Feb | Whether methotrexate can be safely administered during the perioperative period to rheumatoid arthritis patients undergoing arthroplasties is an issue that has not been resolved to date. We are describing our attempt to conduct a case-controlled, multicenter study addressing this issue. The estimated sample size of approximately 140 patients proved to be difficult to recruit. Complications were all mild, but there tended to be more perioperative complications in the methotrexate-treated than in the placebotreated patients. Possible explanations for the failure to complete the study are discussed. | |
| 1549149 | Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. do | 1992 Apr 16 | BACKGROUND: The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis. Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis, but the supporting data are from uncontrolled trials. METHODS: Centers in the United States and the Soviet Union participated in this randomized, controlled, double-blind trial designed to evaluate the effectiveness and safety of orally administered methotrexate. Patients received one of the following treatments each week for six months: 10 mg of methotrexate per square meter of body-surface area (low dose), 5 mg of methotrexate per square meter (very low dose), or placebo. The use of prednisone (less than or equal to 10 mg per day) and two nonsteroidal antiinflammatory drugs was also allowed. RESULTS: The 127 children (mean age, 10.1 years) had a mean duration of disease of 5.1 years; 114 qualified for the analysis of efficacy. According to a composite index of several response variables, 63 percent of the children who received low-dose methotrexate improved, as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group (P = 0.013). As compared with the placebo group, the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion (-11.0 vs. -7.1), the pain-severity score (-19 vs. -11.5), the number of joints with limited motion (-5.4 vs. -0.7), and the erythrocyte sedimentation rate (-19.0 vs. -6 mm per hour). In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects; none had severe toxicity. CONCLUSIONS: Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis, and at least in the short term this regimen is safe. | |
| 8636829 | Macrophage activation syndrome in systemic juvenile rheumatoid arthritis successfully trea | 1996 Feb | A macrophage activation syndrome, possibly related to methotrexate toxicity, developed in a boy with systemic juvenile rheumatoid arthritis. Corticosteroid administration was ineffective, whereas a prompt response to cyclosporine was observed. Two months later, Pneumocystis carinii pneumonia developed. | |
| 7473486 | Frequency of relapse after discontinuation of methotrexate therapy for clinical remission | 1995 Aug | OBJECTIVE: To investigate the outcome of children with juvenile rheumatoid arthritis (JRA) who discontinued taking methotrexate (MTX) therapy after the achievement of clinical remission. METHODS: We conducted a retrospective review of the clinical course of all consecutive patients with JRA treated with MTX at our department. RESULTS: Seventeen of the 30 patients who responded to treatment entered clinical remission 6 to 30 mo after beginning MTX therapy. All patients were discontinued from MTX within 2 to 5 mo. Five patients relapsed within 9 mo, whereas 12 patients had sustained remission for 12 mo or longer. Four of 5 children with extended pauciarticular JRA relapsed early after MTX discontinuation. These patients were less responsive to a further cycle of MTX, and 3 showed progression of radiographic joint lesions. CONCLUSION: These findings suggest that MTX should be continued in patients with extended pauciarticular JRA even after the achievement of clinical remission. | |
| 1379157 | Pharmacological management of juvenile rheumatoid arthritis. | 1992 Jun | The goals of pharmacotherapy in juvenile rheumatoid arthritis (JRA) are to suppress chronic synovitis which causes potential cartilage destruction and deformities, to control the systemic effects of inflammation (including growth retardation and nutritional deficits), relieve pain and limit psychological impact of disease. Currently available methods include nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, salicylates, naproxen, tolmetin, ibuprofen and indomethacin; disease modifying antirheumatic drugs (DMARDs) such as oral and injectable gold salts, hydroxychloroquine, penicillamine, oral and injectable methotrexate, and sulfasalazine; oral (daily or on alternate days), intravenous pulse or intra-articular corticosteroids; immunosuppresants, including cyclophosphamide, chlorambucil, cyclosporin, and azathioprine; and gammaglobulin and other experimental therapies. Over the past 10 years, rheumatologists have adopted more aggressive pharmacological treatment of JRA. As time progresses and the safety of certain drugs such as methotrexate and sulfasalazine becomes clearer, wider and earlier use of these agents can be expected. Still the approach to treatment is a 'step by step' one, starting with the classical NSAIDs and ending with the DMARDs as needed. | |
| 7774090 | High dose methotrexate in the treatment of refractory juvenile rheumatoid arthritis. | 1995 Jan | OBJECTIVE: To assess the response to and safety of long term, high dose (> or = 1 mg/kg/week or > or = 15 mg/m2/week) methotrexate (MTX) administration, in a cohort of 21 children with longstanding, severe juvenile rheumatoid arthritis (JRA). METHODS: Children received MTX at an average weekly dose of 27 mg for a mean of 15.2 months. Outcome was assessed using a disease activity score based on changes in concomitant therapy, laboratory parameters, physician's global assessment, and radiologic evaluation. RESULTS: Seven patients (33%) improved, including one child who achieved complete remission, while 14/21 children (67%) did not benefit from high dose MTX. Subsequently, 6/14 (43%) of the non-responders discontinued high dose MTX and began cyclosporine. Radiologic progression, regardless of clinical outcome, was documented in 10/15 (67%) of the patients. The drug was well tolerated despite mild gastrointestinal symptoms and transient liver enzyme elevation. CONCLUSION: The results of this open retrospective pilot trial suggest that high dose MTX is well tolerated, but that its role in the treatment of children with refractory JRA may be limited. Radiologic progression, despite improvement in the clinical status or in the laboratory parameters, supports the hypothesis that MTX acts as a potent antiinflammatory agent. | |
| 8068509 | Recent developments in psoriatic arthritis. | 1994 Jul | Psoriatic arthritis affects 5% to 7% of patients with psoriasis. Genetic, immunologic, and environmental factors play a role in its pathogenesis. The role of inflammatory cytokines has been better defined, and recent immunohistochemical studies of the synovial membranes have shown important differences and similarities between psoriatic arthritis and rheumatoid arthritis. The association of psoriatic arthritis with infection, particularly HIV, remains an interesting observation. The most common clinical presentation appears to be peripheral polyarticular, and extra-articular manifestations including the SAPHO (synovitis, acne, pustulosis, hypertosis, and osteitis) syndrome are not common. Methotrexate and sulfasalazine therapy are effective in patients who do not respond to nonsteroidal anti-inflammatory drugs. |