Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 12083985 | Advances in the treatment of rheumatoid arthritis: old versus new therapies. | 2002 Jul | Rheumatoid arthritis (RA) is a common cause of disability in the western population, with an annual incidence of 0.05% and a prevalence of 1%. Although a small percentage of patients go into natural remission, the untreated disease progresses to cause disability, morbidity and early mortality. Unravelling of the cytokine network in the pathogenesis of RA has led to the development of drugs that target these cytokines and prevent joint damage. Three biological anticytokine agents, etanercept, infliximab and anakinra, are now available for use in RA. More experience will quantify their safety and benefits. The potency of the older disease-modifying antirheumatic drugs (DMARDs), such as methotrexate and sulfasalazine, is also being realised, especially when used early in the disease process and in combination. Leflunomide is a new DMARD with efficacy similar to methotrexate and sulfasalazine. Symptomatic treatment of RA with nonsteroidal anti-inflammatory drugs has also undergone a revolution with the availability of a new class of COX-2-specific inhibitors. These drugs control inflammation and provide pain relief with less GI toxicity. Management of comorbid conditions associated with RA and its treatment (i.e., osteoporosis, cardiovascular and lung disease) has also become a priority for the rheumatologist. It is hoped that more aggressive use of conventional DMARDs and biological agents will result in less disability and a higher proportion of patients achieving remission. | |
| 15248210 | Sulfasalazine is a potent inhibitor of the reduced folate carrier: implications for combin | 2004 Jul | OBJECTIVE: To investigate whether interactions of sulfasalazine (SSZ) with reduced folate carrier (RFC), the dominant cell membrane transporter for natural folates and methotrexate (MTX), may limit the efficacy of combination therapy with MTX and SSZ in patients with rheumatoid arthritis. METHODS: Human RFC-(over)expressing CEM cells of T cell origin were used to analyze the effect of SSZ on the RFC-mediated cellular uptake of radiolabeled MTX and the natural folate leucovorin. Moreover, both cells with and those without acquired resistance to SSZ were used to assess the antiproliferative effects of MTX in combination with SSZ. RESULTS: Transport kinetic analyses revealed that SSZ was a potent noncompetitive inhibitor of RFC-mediated cellular uptake of MTX and leucovorin, with mean +/- SD K(i) (50% inhibitory concentration) values of 36 +/- 6 microM and 74 +/- 7 microM, respectively. Consistent with the inhibitory interaction of SSZ with RFC, a marked loss of MTX efficacy was observed when MTX was coadministered with SSZ: up to 3.5-fold for CEM cells in the presence of 0.25 mM of SSZ, and >400-fold for SSZ-resistant cells in the presence of 2.5 mM of SSZ. Importantly, along with diminished efficacy of MTX, evidence for cellular folate depletion was obtained by the demonstration of an SSZ dose-dependent decrease in leucovorin accumulation. CONCLUSION: At clinically relevant plasma concentrations, interactions of SSZ with RFC provide a biochemical rationale for 2 important clinical observations: 1) the onset of (sub)clinical folate deficiency during SSZ treatment, and 2) the lack of additivity/synergism of the combination of SSZ and MTX when these disease-modifying antirheumatic drugs are administered simultaneously. Thus, when considering use of these drugs in combination therapies, the present results provide a rationale both for the use of folate supplementation and for spacing administration of these drugs over time. | |
| 12913927 | Toward a definition and method of assessment of treatment failure and treatment effectiven | 2003 Aug | OBJECTIVE: Time to treatment discontinuation (TTD) is an accepted method of assessing treatment effectiveness in the community, but is susceptible to channeling bias and secular and cohort effects. In addition, TTD does not consider the addition of new disease modifying antirheumatic drugs (DMARD) to insufficiently effective therapies. We expand the definition of treatment failure to include discontinuation or addition of a second DMARD (1) to examine leflunomide (LEF) versus methotrexate (MTX) effectiveness in clinical practice; (2) to obtain an estimate of overall clinical effectiveness; and (3) to identify factors associated with treatment successes and failure. In addition, (4) we test the feasibility of performing a clinical trial using a longitudinal data bank. METHODS: Using the National Data Bank for Rheumatic Diseases longitudinal data bank, 1431 patients with rheumatoid arthritis (RA) who began taking LEF or MTX as part of their routine medical care were followed from 1998 through 2001. None of the 1431 patients had received either treatment previously. Patients were assessed at 6 month intervals for periods up to 36 months by mailed questionnaires concerning DMARD therapy and demographic and RA severity factors. Kaplan-Meier survivor functions and Cox regression analyses were used to assess treatment failure, defined as time to discontinuation or to the addition of a second DMARD. RESULTS: For 756 patients taking LEF, the failure rate was 55.5 per 100 patient-years, and the median time to failure was 15 (95% CI 13, 17) months. For 675 patients taking MTX the failure rate was 57.3 per 100 patient-years, and the median failure time was 14 (95% CI 12, 18) months. These differences were not statistically significant. The overall rate of discontinuation was 68.7% of the failure rate. Discontinuation was predicted by adverse effects [hazard ratio 1.76 (95% CI 1.51, 2.04)] and by clinical status prior to starting DMARD, and these results were not affected by specific DMARD treatment. Discontinuation was more common with LEF, and addition of a second DMARD was more common with MTX. More than 77% of treatment failures, defined by use of additional therapy, resulted in starting anti-tumor necrosis factor treatment rather than a conventional DMARD. CONCLUSION: In an observational clinical trial using a contemporary longitudinal data bank, with time to treatment failure as the outcome, LEF and MTX had equal effectiveness as measured by time to treatment failure. Treatment failure rates were substantially greater than noted historically. Given the availability of many efficacious additional treatment options, this increase in failure rate appears to reflect a greater propensity to discontinue and/or add therapy. | |
| 15189743 | Leflunomide in the treatment of rheumatoid arthritis. | 2004 Apr | BACKGROUND: Current drug therapies for rheumatoid arthritis (RA), including nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs, help control inflammation but can cause significant toxicity. Drugs are needed that are able to suppress inflammation and modify the underlying immune response with improved tolerability. Leflunomide is an agent that affects the inflammatory process, particularly in RA. OBJECTIVE: This paper reviews the pharmacology of leflunomide, its approved use in RA, and the results of major clinical trials, including adverse events. METHODS: Relevant trials were identified through a search of the English-language literature indexed on EMBASE, MEDLINE, Current Contents, and the Cochrane Controlled Trials Register from January 1980 to November 2003. Search terms were limited to leflunomide. RESULTS: In 3 large Phase III clinical trials (US301, MN301, and MN302), leflunomide had equivalent clinical efficacy and tolerability to methotrexate and sulfasalazine and superior efficacy and tolerability compared with placebo. In US301 (N = 482), the ACR (American College of Rheumatology) 20 response rate (proportion of patients with > or =20% improvement from baseline in tender and swollen joint counts, patient's assessment of pain, patient's and physician's global assessment of disease activity, physical function, and acute-phase reactant value) at 1 year was similar with leflunomide and methotrexate and significantly greater with both active treatments than with placebo (52%, 46%, and 26%, respectively; both, P < 0.001). The efficacy of leflunomide was seen early (after 4 weeks of treatment) and was sustained throughout the study. There was less radiographic damage in both active-treatment groups compared with placebo (leflunomide, P < or = 0.001; methotrexate, P = 0.02). In MN301 (N = 358), the ACR20 response rate at 6 months was similar with leflunomide and sulfasalazine and significantly greater with both active treatments compared with placebo (55%, 56%, and 29%, respectively; both, P < 0.001). Radiographic progression was also similar with leflunomide and sulfasalazine, both of which were significantly superior to placebo (Larsen score, 0.42, 0.41, and 1.4; both, P < 0.001). An extension of this study revealed maintenance of efficacy at 12 and 24 months. In MN302 (intent-to-treat population, N = 999), 50.5% of patients in the leflunomide group were ACR20 responders at the end of 1 year, compared with 64.8% in the methotrexate group (P < 0.001 vs leflunomide). After 2 years, ACR20 response rates were similar with leflunomide and methotrexate (64.3% and 71.7%). The overall safety profile of leflunomide appears promising, although monitoring for elevations in liver enzymes and bone marrow suppression is recommended. The most common drug-related adverse events associated with leflunomide in these clinical trials were diarrhea, abnormalities in liver enzymes, rash, and hypertension. | |
| 12053152 | De novo CD5-positive diffuse large B cell lymphoma solely presenting as multiple subcutane | 2002 | Lymphomas may involve the subcutaneous tissue as a manifestation of generalized disease. However, they rarely present with multiple involvement of the subcutaneous fat tissue without other sites of the disease. We describe a patient with CD5+ diffuse large B cell lymphoma (DLBL) that was confined to the subcutaneous tissue. A 74-year-old woman with rheumatoid arthritis was admitted because of multiple subcutaneous nodules. The patient had not been treated with cytotoxic drugs or methotrexate. The biopsied specimen disclosed diffuse infiltration of large cells with a starry sky-like appearance. The cells were positive for CD5, CD19, CD20, CD25, IgM, lambda-chain, and negative for CD10, CD23 or cyclin D1. Thus a diagnosis of CD5+ DLBL was made. The patient was treated with a modified CHOP protocol and complete remission was achieved. | |
| 12794836 | Increased perivascular synovial membrane expression of myeloid-related proteins in psoriat | 2003 Jun | OBJECTIVE: To analyze S-100 protein expression, in the form of myeloid-related protein 8 (MRP8), MRP14, and the heterodimer MRP8/MRP14, in psoriatic arthritis (PsA) patients compared with rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients, and to determine the effect of methotrexate (MTX) on the MRP antigen expression in PsA patients. METHODS: Serum, synovial fluid (SF), and synovium (taken at arthroscopy) samples were obtained from PsA (before and after MTX treatment), RA, and SpA patients. Concentrations of MRP8/MRP14 in serum and SF were measured by enzyme-linked immunosorbent assay. Expression of MRP8, MRP14, and MRP8/MRP14 in synovium was determined by immunohistochemistry. RESULTS: MRP8, MRP14, and MRP8/MRP14 levels were increased in serum, SF, and synovium from PsA, RA, and SpA patients. In all 3 groups, paired samples of serum and SF showed significantly higher MRP8/MRP14 levels in SF (mean +/- SD 15310 +/- 16999 ng/ml [median 11400]) than in serum (908 +/- 679 ng/ml [median 695]) (P = 0.0001). MRP8/MRP14 levels in serum correlated with systemic parameters of disease activity (erythrocyte sedimentation rate [ESR] r = 0.55, P = 0.005; C-reactive protein [CRP] level r = 0.55, P = 0.005), whereas levels in SF correlated with local parameters of disease activity (white blood cell count r = 0.45, P = 0.01; acute-phase serum amyloid A level r = 0.32, P = 0.03). MRP expression was significantly higher in the synovial sublining layer (SLL) of PsA patients compared with RA and SpA patients. MRP antigens were predominantly expressed in perivascular areas of the SLL in PsA patients. Following MTX treatment, MRP expression in serum and synovium from PsA patients was significantly reduced. Serum levels of MRP were more sensitive to the effects of MTX than were the ESR, CRP, or clinical joint scores. CONCLUSION: MRP levels in serum and SF correlate with local and systemic inflammation and are equally increased in PsA, RA, and SpA patients. In contrast, MRP8, MRP14, and MRP8/MRP14 expression in the SLL of PsA patients is increased, particularly in perivascular regions, compared with that in RA and SpA patients, suggesting a central role of MRP proteins in transendothelial migration of leukocytes in PsA. Moreover, MRP expression is reduced following MTX treatment. MRP proteins may represent a novel therapeutic target in inflammatory arthritis. | |
| 14680509 | Etanercept versus etanercept plus methotrexate: a registry-based study suggesting that the | 2003 | Etanercept can be used both as monotherapy and in combination with methotrexate (MTX), but direct comparisons of these two options have not yet been reported. In order to compare the results seen in actual practice between these two options, clinical data on 97 patients followed in the Stockholm TNFalpha Follow-Up Registry were analysed. In 57 of these patients etanercept was added to previously started MTX while the others were treated with etanercept alone. The two groups had similar levels of disease activity at baseline. After 3 months, a significantly lower mean disease activity score (28-joint count-based disease activity score) was attained by the patients on etanercept plus MTX. In this group, the number of patients achieving European League Against Rheumatism-defined remission was also significantly greater. Other disease outcomes showed non-significant trends in the same direction. These data suggest that the combination of etanercept plus MTX is clinically more efficacious than etanercept alone. | |
| 12528101 | Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the tr | 2003 Jan | OBJECTIVE: To evaluate the efficacy and safety of adalimumab (D2E7), a fully human monoclonal tumor necrosis factor alpha antibody, in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite treatment with MTX. METHODS: In a 24-week, randomized, double-blind, placebo-controlled study, 271 patients with active RA were randomly assigned to receive injections of adalimumab (20 mg, 40 mg, or 80 mg subcutaneously) or placebo every other week while continuing to take their long-term stable dosage of MTX. The primary efficacy end point was the American College of Rheumatology criteria for 20% improvement (ACR20) at 24 weeks. RESULTS: An ACR20 response at week 24 was achieved by a significantly greater proportion of patients in the 20-mg, 40-mg, and 80-mg adalimumab plus MTX groups (47.8%, 67.2%, and 65.8%, respectively) than in the placebo plus MTX group (14.5%) (P < 0.001). ACR50 response rates with the 20-mg, 40-mg, and 80-mg adalimumab dosages (31.9%, 55.2%, and 42.5%, respectively) were significantly greater than that with placebo (8.1%) (P = 0.003, P < 0.001, and P < 0.001, respectively). The 40-mg and 80-mg doses of adalimumab were associated with an ACR70 response (26.9% and 19.2%, respectively) that was statistically significantly greater than that with placebo (4.8%) (P < 0.001 and P = 0.020). Responses were rapid, with the greatest proportion of adalimumab-treated patients achieving an ACR20 response at the first scheduled visit (week 1). Adalimumab was safe and well tolerated; comparable numbers of adalimumab-treated patients and placebo-treated patients reported adverse events. CONCLUSION: The addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously every other week to long-term MTX therapy in patients with active RA provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo. | |
| 12860493 | Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor n | 2003 Jun | BACKGROUND: Because traditional therapies for rheumatoid arthritis (RA) such as methotrexate (MTX) do not produce an adequate response in many patients, newer therapies that block the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) are increasingly being used in combination with MTX. OBJECTIVE: This study evaluated the efficacy, pharmacokinetics, and safety profile of adalimumab, a fully human anti-TNF alpha monoclonal antibody, when added to continuing MTX therapy. METHODS: This Phase I, randomized, dose-titration study consisted of a 4-week, double-blind, placebo-controlled treatment phase and a 26-month, open-label continuation phase. Patients with RA who had been taking stable doses of MTX (mean dose, 17 mg/wk) for > or =3 months before enrollment with an inadequate response were randomly assigned to receive 2 single doses of either adalimumab 0.25, 0.5, 1, 3, or 5 mg/kg i.v. or placebo in the double-blind phase. In the open-label phase, patients received treatment with 1 of the doses of adalimumab every other week or monthly for 18 months; patients were then switched to adalimumab 40 mg i.v. or SC every other week or monthly. The main efficacy end point was 20% improvement in American College of Rheumatology response criteria (ACR20). Other efficacy end points included 50% (ACR50) and 70% improvements in ACR response criteria. Pharmacokinetic parameters were analyzed for adalimumab and MTX during both phases of the study. Serum adalimumab concentrations were analyzed using a validated enzyme-linked immunosorbent assay relying on the double-antigen principle. Peak and trough concentrations were determined from observed concentration-time data, and a modeling approach was used to estimate total serum clearance, mean apparent terminal half-life, apparent volume of distribution at steady state, and area under the concentration-time curve. RESULTS: Sixty patients entered the double-blind phase, 45 receiving adalimumab and 15 receiving placebo; 1 placebo recipient chose not to continue into the open-label phase. Overall, the study population included 47 (78.3%) women and 13 (21.7%) men. The mean age was 52.9 years (range, 24-73 years), and the mean body weight was 69.7 kg (range, 43-98 kg). ACR20 and ACR50 responses were achieved on at least 1 assessment during the 4-week double-blind phase by a respective 29 (64.4%) and 11 (24.4%) of 45 patients receiving active treatment and by 4 (26.7%) and none of the 15 patients receiving placebo. Responses to adalimumab were rapid, with 10 (22.2%) of 45 patients achieving an ACR20 response within 24 hours of dosing. Of 29 adalimumab recipients who had an ACR20 response, 18 (62.1%) had a duration of response (time from first occurrence of a response to first occurrence of a nonresponse) of 1 to 2 weeks, and 11 (37.9%) had a duration of response of 3 to 13 weeks. The pharmacokinetic properties of adalimumab appeared to be linear. The mean apparent terminal half-life after a single intravenous dose of adalimumab ranged from 15 to 19 days in the 5 dose groups. Repeated administration of adalimumab had no statistically significant effect on the pharmacokinetics of MTX, indicating that dose adjustment of MTX is not necessary. Adalimumab was well tolerated, and there were no dose-related adverse events. CONCLUSIONS: Among patients with active RA who had not had an adequate response to MTX, addition of adalimumab to MTX achieved statistically significant, long-term improvement compared with placebo plus MTX (P < or = 0.05), as indicated by ACR responses at 26 months. The combination was well tolerated. Adalimumab exhibited linear pharmacokinetics. In this selected patient population, adalimumab's long half-life of 15 to 19 days supports every-other-week dosing. Coadministration of adalimumab did not alter serum levels of MTX. | |
| 15593184 | Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human o | 2004 Dec | OBJECTIVE: To demonstrate the effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through their effects on receptor activator of nuclear factor kappaB (RANK), osteoprotegerin (OPG), and RANK ligand (RANKL). METHODS: Peripheral blood mononuclear cells (PBMCs) and rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) were cocultured in the presence of macrophage colony-stimulating factor, 1,25-dihydroxyvitamin D(3), and various concentrations of methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine (HCQ), anti-tumor necrosis factor alpha monoclonal antibody (infliximab), interleukin-4 (IL-4), and IL-10. Osteoclast formation was assayed by counting cells after staining for tartrate-resistant acid phosphatase. RANKL expression in RA FLS and RANK expression in PBMCs were assayed by Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), and real-time PCR. OPG expression was measured by enzyme-linked immunosorbent assay, RT-PCR, and real-time PCR in cultures of RA FLS. RESULTS: MTX, SSZ, infliximab, and IL-4, but not IL-10 and HCQ, each inhibited osteoclast formation in a dose-dependent manner. We observed no evidence of synergistic inhibition of osteoclast formation by IL-4 and IL-10. High doses of infliximab suppressed the expression of RANK in PBMCs. MTX, SSZ, infliximab, and IL-4 each inhibited the expression of RANKL in RA FLS in a dose-dependent manner, and also increased the secretion of OPG in RA FLS supernatants. CONCLUSION: MTX, SSZ, infliximab, and IL-4 inhibit human osteoclastogenesis by modulating the interaction of RANKL, RANK, and OPG. These results are indicative of the underlying mechanisms of the antiresorptive effects of these 4 agents. | |
| 12436372 | [Gastrointestinal side effects in the therapy of rheumatologic diseases]. | 2002 Nov | Antirheumatic drugs may lead to a number of relevant gastrointestinal complications. Symptomatical treatments with glucocorticoids and non steroidal antirheumatic drugs (NSAD) are known to induce gastric or duodenal ulcers, above all under combination therapies. Side effects of DMARD's (methotrexate, leflunomide, hydroxy/chloroquine, sulfasalazine) include unspecifical gastrointestinal symptoms like nausea, vomiting and diarrhea as well as induction of ulcerative mucosal lesions (methotrexate) and occurrence of a hepatopathy. The latter may appear as an asymptomatical elevation of liver transaminases or cholestase parameters, but can also lead, in some cases of a monothera-py (hydroxy-/chloroqine, sulfasalazine) or combination therapy (methotrexate + leflunomide) to a fulminant hepatitis. TNF-alpha-inhibiting drugs (etanercept, infliximab) as a new generation of anti-inflammatory therapeutics don't have relevant gastrointestinal side effects according recently published data. | |
| 11815776 | Thalidomide therapy for recalcitrant systemic onset juvenile rheumatoid arthritis. | 2002 Jan | Systemic onset juvenile rheumatoid arthritis unresponsive to nonsteroidal anti-inflammatory drugs may be controlled with corticosteroids, but these drugs have significant side effects. We report 2 steroid-dependent children with systemic onset juvenile rheumatoid arthritis who did not respond to multiple nonsteroidal anti-inflammatory drugs, methotrexate, azathioprine, cyclosporine, and etanercept. Both children had significant improvement with thalidomide therapy. | |
| 14521561 | Harlequin ichthyosis in association with hypothyroidism and juvenile rheumatoid arthritis. | 2003 Sep | Harlequin ichthyosis is a rare and severe congenital erythrodermic ichthyosis characterized at birth by hyperkeratotic plates covering the entire body, ectropion, eclabium, poorly developed ears, and contractures of the hands and feet. Two Chinese children, a 2-year-old boy and an 11-year-old girl, presented with these classic features as well as alopecia and loss of eyebrows and eyelashes. The boy was small for his age and was found to have hypothyroidism at the age of 18 months; he is currently on thyroxine replacement therapy. At 6 years of age, the girl developed symmetrical polyarthritis associated with positive rheumatoid factor and radiologic evidence of erosive arthritis, suggestive of juvenile rheumatoid arthritis. She received prednisolone, nonsteroidal anti-inflammatory drugs (NSAIDs), and subsequently methotrexate for her arthritis, with clinical and radiologic improvement. Early therapy with oral retinoids in both children accelerated shedding of the hyperkeratotic plates as well as improved ectropion and eclabium. There was no major adverse reaction to oral retinoids. The development of juvenile rheumatoid arthritis in survivors with harlequin ichthyosis has not been previously described. The use of prednisolone and NSAIDs in the girl did not affect the skin condition, but the addition of methotrexate led to a decrease in erythema. The association with autoimmune disease is probably coincidental. The psychosocial impact of this severe lifelong disease on the two families was enormous. Early retinoid therapy may improve the disorder and help increase survival rates. A multidisciplinary approach, including psychosocial support of the affected families, is vital in the management of this lifelong disease. | |
| 17041465 | Cavitary necrobiotic nodule imitating malignant lung disease in a patient without articula | 2003 Aug | Pulmonary involvement is a serious complication of rheumatoid arthritis (RA) and may be seen as airway disease, rheumatoid nodules, interstitial lung disease, and pleurisy. However, cavitary rheumatoid nodules without articular manifestations are rare. We describe a male patient presenting with pleurisy and multiple rheumatoid necrobiotic nodules in the absence of arthritis or subcutaneous nodules. One of the nodules was quite large (5 x 8 cm in diameter) and cavitary, imitating bronchial carcinoma radiologically and bronchoscopically. Definite histopathologic diagnosis was obtained by open lung biopsy. The patient was given methylprednisolone and methotrexate, and significant regression was observed in clinical and radiologic findings. He has been followed for 14 months with no articular manifestations yet, receiving 4 mg/d methylprednisolone and 20 mg/wk methotrexate. The diagnosis of rheumatoid pulmonary involvement without articular manifestations can be difficult. Rheumatoid nodules may imitate bronchial carcinoma, or bronchial carcinoma may coexist in RA patients. Open lung biopsy may be necessary for differential diagnosis of pulmonary lesions in RA. | |
| 17143704 | A case of rheumatoid arthritis exhibiting accelerating rheumatoid pleurisy during low-dose | 2004 | A 75-year-old Japanese man suffering from rheumatoid arthritis (RA) had received methotrexate (MTX) treatment for 9 years and developed bilateral pleural thickening with exudative pleural effusions despite remission of the polyarthritis. A diagnosis of rheumatoid pleurisy, made by exclusion, was supported by the elevated rheumatoid factor level of the pleural fluid. The pleurisy developed concomitantly with MTX-induced leukocytopenia, and discontinuation of the MTX treatment partially improved the CRP level. These findings indicate a causal relation between the rheumatoid pleurisy and MTX and suggest that MTX therapy may be ineffective in the treatment of rheumatoid pleurisy. Treatment with 10 mg of prednisolone and 100 mg of cyclosporine A daily resulted in rapid resolution of the pleurisy. Although MTX-induced rheumatoid pleurisy is a rare condition, MTX therapy should be considered carefully in RA patients with concomitant rheumatoid pleurisy. | |
| 11773549 | Current treatment of juvenile rheumatoid arthritis. | 2002 Jan | Prognostic factors in juvenile rheumatoid arthritis (JRA) include polyarticular onset, polyarticular disease course, and rheumatoid factor positivity; in the systemic onset subtype, persistence of systemic features at 6 months after onset confers a worse prognosis. Timely diagnosis and appropriate aggressive treatment of patients with poor prognostic features improve quality of life and outcome. After nonsteroidal anti-inflammatory drugs, methotrexate is the most commonly used second-line agent. However, approximately one third of patients do not respond to methotrexate adequately. Randomized, placebo-controlled, clinical trials in patients with JRA are few, but one such trial with the tumor necrosis factor inhibitor etanercept shows that this drug is effective and well-tolerated. Other recently approved agents for rheumatoid arthritis, including infliximab, leflunomide, celecoxib, and rofecoxib, have not been adequately studied in pediatric patients, and the role of these agents in children with JRA remains to be determined. | |
| 12463452 | Disease-modifying antirheumatic drug therapy for psoriatic arthritis. | 2002 Nov | As erosive and deforming arthritis is present in 40% of patients with psoriatic arthritis (PsA), early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) may be as effective in controlling the progression of the disease as it is for rheumatoid arthritis (RA). Methotrexate (MTX), sulfasalazine (SSZ), and cyclosporine (CsA) are the most widely used DMARDs in the treatment of PsA and are safe and effective in patients with active peripheral arthritis, although they do not appear to be effective on axial manifestations. No controlled study has evaluated the efficacy of these drugs on the progression of radiological damage. It has recently been demonstrated that leflunomide and anti-tumor necrosis factor (TNF) agents are effective in PsA and psoriasis. The symptomatic improvement has been important and sustained and side effects minimal. In particular, inhibitors of TNF appear to have excellent potential to treat PsA. These agents are able to slow joint damage in rheumatoid arthritis and they are effective on spinal symptoms in ankylosing spondylitis. Hopefully, these findings will prove true in PsA as well. | |
| 14689077 | [44-year-old female patient with cutaneous rash, sore throat, fever and arthritis]. | 2003 Nov | We report on a 44 year old woman with fever, cutaneous rash, severe sore throat, arthritis, leukocytosis, splenomegaly and liver dysfunction. After exclusion of an infectious or malignant disease, adult onset Still's disease was diagnosed according to the Yamaguchi criteria. Reduction of the initial treatment with corticosteroids after 4 month caused a relapse of disease. Thus methotrexate treatment was started, which resulted in improvement of symptoms and inflammatory activity. | |
| 17043543 | Accelerated cutaneous nodulosis during infliximab therapy in a patient with rheumatoid art | 2004 Dec | Up to one fourth of patients with rheumatoid arthritis (RA) may have extraarticular findings such as subcutaneous nodules. These are discrete subcutaneous granulomatous nodules located on extensor surfaces, especially of the elbows. Over the past 10 to 15 years, there have been reports of accelerated cutaneous nodulosis in patients receiving methotrexate therapy. Recently, antitumor necrosis factor alpha (anti-TNFalpha) biologic therapy has become commonplace in the management of RA, especially in methotrexate-resistant or toxic patients. There have been recent reports of accelerated nodulosis in patients with RA on etanercept. We describe what we believe is the first case of accelerated cutaneous nodulosis resulting from infliximab anti-TNFalpha therapy in a patient with RA. One year after the initiation of infliximab, with RA in remission, our patient noted the rapid development of rheumatoid nodules of both hands. A biopsy was characteristic of a rheumatoid nodule, revealing palisading granulomas and fibrinoid necrosis. | |
| 12682624 | Steroid myopathy in a child with juvenile rheumatoid arthritis. Case report. | 2003 Mar | An 8-year-old boy who had been diagnosed as systemic-onset juvenile rheumatoid arthritis were on treatment for 8 months with methotrexate and additional steroids during activation. At the end of the 8th month when the corticosteroid dose was 12.5 mg/day, he began to suffer from numbness and weakness in his hands. Physical examination, laboratory findings and electromyography results demonstrated myopathy. Steroid myopathy was considered. Corticosteroids were tapered and stopped. At follow-up clinical findings remitted and electromyography became normal at the 4th month. We present here this case to direct attention to drug-induced myopathy besides myopathy due to primary disease in connective tissue disorders whenever myopathy exists. |