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PMID	Title	PublicationDate	abstract
15201938	[Correlation between radiographic, echographic and MRI changes and rheumatoid arthritis pr	2004 Jan	OBJECTIVES: To review the imaging methods used for the evaluation of disease progression in rheumatoid arthritis (RA) and to evaluate the results of their application in pharmacological trials. METHODS: Literature articles dealing with radiology, echography, and magnetic resonance imaging (MRI) of patients with RA were evaluated in a non-systematic fashion. RESULTS: Conventional radiology is the gold standard for the evaluation of disease progression in RA because of its diffusion, economy, and standardization. Different techniques have been proposed to evaluate radiological damage of the joints, with the Larsen's and Sharp's methods being most widely used. These methods are commonly used for the evaluation of the ability of DMARDs to slow RA progression. Among traditional DMARDs, gold salts, sulphasalazine, methotrexate, cyclosporin, and leflunomide have shown efficacy in slowing the appearance of new erosions. The same effect has been recently demonstrated for infliximab plus methotrexate, anakinra and etanercept. However, conventional radiology has several disadvantages, because it is monoplanar and has a low sensitivity to change. Newer imaging techniques, such as echography and MRI are extensively studied and have been used occasionally in the mediumterm evaluation of DMARDs, with promising results. CONCLUSIONS: Although conventional radiology is still the gold standard for the evaluation of disease progression in RA, newer techniques are increasingly studied. In particular, standardization of echographic and MRI imaging of the joints is in progress.
12827063	A longitudinal study of rheumatoid arthritis in South Africans.	2003 Feb 5	Little is known about the functional outcome of rheumatoid arthritis (RA) in Africans treated with disease-modifying antirheumatic drugs (DMARDs). We describe our experience with 182 RA patients seen at a tertiary hospital in South Africa. During the median follow-up period of 3.3 years, the proportion of patients with severe functional disability (American College of Rheumatology [ACR] functional classes [FCs] 3 and 4) declined significantly from 48.9% at presentation to 30.8% at last visit (P =.0006). There was a significant fall in the median Westergren erythrocyte sedimentation rate (ESR) (46-28 mm/hour, P <.00001) and C-reactive protein (CRP) (19-15.5 mg/L, P =.006) over this period. Logistic regression analysis showed that the factors that negatively affected functional outcome at last visit were severe functional disability at presentation (odds ratio [OR] = 4.1, P =.0004), delay in referral for specialist care > 2 years (OR = 3.1, P =.02), and ESR at last visit > 28 mm/hour (OR = 3.2, P =.002). DMARDs and oral corticosteroids were prescribed in 93.1% of patients at presentation and 60.4% of patients at last visit. Life-table analysis showed that the survival time with methotrexate (MTX) use was significantly longer compared with the other DMARDs (P =.0002). A total of only 37 surgical procedures were performed on 21 patients. This retrospective study shows that despite the late presentation and severe disease, patients do improve on DMARD therapy in the medium term. The study highlights the need for prospective studies to assess the efficacy and safety of DMARDs, particularly in early disease, in the developing countries where biologics are unlikely to be affordable in the foreseeable future.
15459811	Atlanto-odontoid osteoarthritis in rheumatoid arthritis: dynamic CT findings.	2004 Oct	We analyzed the CT appearances of degenerative change in the atlanto-odontoid joint (AOJ) in patients with rheumatoid arthritis (RA) and evaluated the effect of these changes on atlanto-axial joint (AAJ) rotation by dynamic CT. This revealed that 9 patients (24%) treated with methotrexate had degenerative features in the AOJ. The ratio of AAJ rotation to the total rotation of the cervical spine was significantly higher in normal subjects (54 +/- 3%) than in patients (38 +/- 12%). The degree of AAJ rotation was significantly lower in the patient group with degenerative features in the AOJ (20.9 +/- 8.4 degrees ) than in patients without degenerative features (28.5 +/- 7.4 degrees ). RA patients with a history of longstanding disease and treatment with antirheumatic drugs may develop AO OA. Although secondary OA was described as healing phenomena in the joints of RA patients, it can limit rotation in the AAJ and cause suboccipital neck pain. A regular check-up of the AAJ and AOJ by means of dynamic CT in all RA patients is proposed to avoid possible antirheumatic drug complications.
12079906	Practical progress in realisation of early diagnosis and treatment of patients with suspec	2002 Jul	BACKGROUND: Early diagnosis and treatment with disease modifying antirheumatic drugs (DMARDs) have been advocated for patients with rheumatoid arthritis (RA). This survey focuses on the individual definitions and treatment modalities of rheumatologists, and aims at determining the practical realisation of these concepts. METHODS: A questionnaire to be self completed was handed out at the EULAR Symposium 1997. The main issues dealt with were definition, referral time, diagnosis, follow up, and treatment of early RA. Of the 111 participants, who were from all continents and all age groups, 85 (77%) gave their name and address. In 2000, the same questionnaire was sent to these 85 primary respondents. Forty four questionnaires (52%) were returned, and their results were matched and further evaluated. RESULTS: The definition of early RA was heterogeneous, but two of three rheumatologists use the term "early" for symptoms shorter than three months. There was a drift towards acceptance of involvement of fewer affected joints. Serological tests obtained for early diagnosis were mostly rheumatoid factor and antinuclear antibodies, usually in combination (approximately 70%), while other tests (antikeratin antibodies, antiperinuclear factor, anti-RA33) were used rarely, but increasingly (21-25% all together). No significant change in the lag time of referral to the specialist of patients with suspected early RA was seen within these three years (<3 months for 50%, >6 months for 20%), while the proportion followed up during the first three months increased. At both times, every second rheumatologist started DMARD treatment only when the 1987 American College of Rheumatology (ACR) criteria were fulfilled. However, in 1997 about 10% were willing to wait for erosions before starting DMARDs, while none did so in 2000. Methotrexate, sulfasalazine, and antimalarial drugs were the most commonly prescribed DMARDs in early RA, with the first two of these still being in increasing use. CONCLUSION: The understanding of "early" rheumatoid arthritis is heterogeneous, but the vast majority of the rheumatologists surveyed regard symptom duration of <3 months as early. Rheumatoid factor was the most useful laboratory support in early diagnosis. Because there has been no shortening of referral time of patients with new RA within the past three years, and many rheumatologists start DMARDs only when the ACR criteria are fulfilled, it is concluded that guidelines for early referral, as well as for early (rheumatoid) arthritis, are needed.
12050946	Long-term observation study of Austrian patients with rheumatoid arthritis.	2002	We examined retrospectively in a long-term observation study the outcome of patients with RA in Austria. Eighty-one inpatients with definite rheumatoid arthritis (RA) completed a standardized clinical and laboratory examination 3-8 times between 1978 and 1999. The course of the disease was assessed by determining the disease activity score (DAS), 28-joint count (28 JC), 30 swollen joint count (30 SJC), proximal interphalangeal joint score (PIP), Ritchie index, Stoke index, Steinbrocker stage, and Larsen score. In a mean duration of follow-up of 10 years, we observed a statistically significant improvement in PIP, Ritchie index, Stoke index, and DAS. Steinbrocker stage and Larsen score increased significantly. A high percentage of the patients did not receive any disease-modifying antirheumatic drug (DMARD) within the first 2 years of disease. Of all drugs used, methotrexate (MTX) was continued longer than other DMARDs. The most frequent extra-articular manifestation was sicca syndrome. In our long-term follow-up, a change in treatment from the onset of the disease in the 1980s to a more aggressive treatment within the last decade could be observed. However, with respect to the significant increase in Steinbrocker stage and Larsen score as well, an early aggressive therapy is required. With respect to the association of ANA and extra-articular manifestations, elevated ANA should give rise to an exact organ screening. For the development of predictive factors for the outcome in patients with RA, it would be helpful to refer patients at risk to specialist care as soon as possible.
12563672	Interleukin 1 receptor antagonist anakinra improves functional status in patients with rhe	2003 Feb	OBJECTIVE: This study evaluated the benefit of anakinra, a human recombinant form of interleukin 1 receptor antagonist, on the functional status of patients with active rheumatoid arthritis (RA) despite taking maximally tolerated doses of methotrexate (MTX). METHODS: Patients (n = 419) were randomized to receive, in addition to MTX (15 to 25 mg/wk), placebo or anakinra doses of 0.04, 0.1, 0.4, 1, or 2 mg/kg once daily for 24 weeks. Functional status measured on 8 scales (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities) was evaluated at baseline and every 4 weeks with the Health Assessment Questionnaire (HAQ). A weighted sum of the scale scores is the HAQ disability index (HAQ-DI). Primary analysis of the HAQ-DI was based on an omnibus test for a positive dose-response relationship between anakinra treatment and change in HAQ-DI from baseline to week 24. RESULTS: Patients receiving anakinra experienced rapid and sizeable improvements in their HAQ-DI scores in a dose-related fashion. For patients receiving either of the 2 highest doses of anakinra, improvements in the HAQ-DI occurred by week 4 that were of a magnitude considered clinically important and statistically significantly superior to placebo. CONCLUSION: In patients with persistence of RA despite MTX therapy, treatment with anakinra results in a rapid improvement in functional status as measured by the HAQ-DI.
12366812	Relationship between histological findings and clinical findings in rheumatoid arthritis.	2002 Aug	The aim of the present study was to compare histological findings and clinical symptoms of patients with advanced stages of rheumatoid arthritis (RA). Synovial tissue specimens were obtained during reconstructive knee surgery from 93 RA patients (18 men; 75 women). The histological assessments of specimens were evaluated using two histological scoring systems reported by Rooney and Koizumi. Clinical symptoms (duration of morning stiffness, joint score, grip strength), laboratory data (erythrocyte sedimentation ratio, C-reactive protein (CRP), rheumatoid factor), X-ray findings (Larsen score) and drug usage were assessed before surgery. Significant statistical correlations between both histological scoring systems were observed; however, there was no significant correlation between the clinical findings and the histological scoring systems. A statistically significant correlation was found between the levels of CRP and Koizumi's scoring system. In addition, Koizumi score correlated significantly to X-ray findings. Rooney's scoring system had an inverse correlation to methotrexate history. Histological findings do not correlate to simultaneous clinical symptoms in advanced RA patients. However, our data indicate that observed histological changes reflect X-ray damage.
12540080	The influence of rheumatoid chemotherapy, age, and presence of rheumatoid nodules on posto	2003 Jan	The records of 104 patients who underwent reconstructive foot and ankle surgery for deformities secondary to rheumatoid arthritis were reviewed. The use of rheumatoid chemotherapeutic agents, age, sex, rheumatoid nodule status, and the number of concurrent surgical procedures performed was analyzed to determine any association with the postoperative outcome for wound healing and infectious complications. The 104 patients, ranging in age from 23 to 83 years, underwent 725 operative procedures. An overall 32% complication rate was recorded. Analysis of five specific rheumatoid chemotherapeutic agents (NSAIDs, steroids, methotrexate, hydroxychloroquine, gold), age, sex, number of operative procedures performed, and presence of rheumatoid nodules, either alone or in combination, failed to prove a statistical association with either a healing or infectious postoperative complication.
12737326	Reumacon (CPH82) showed similar x-ray progression and clinical effects as methotrexate in	2003	OBJECTIVES: To study x-ray development and clinical effects, tolerability and safety after 2 years treatment of RA patients with Reumacon (CPH82) or methotrexate (MTX). PATIENTS AND METHODS: This study is a 74 week open continuation of a 24 week double blind comparison of 100 patients with early RA (disease duration less than 2 years) treated either with Reumacon or MTX. RESULTS: The mean Larsen scores and the mean number of erosions increased significantly from baseline to 24 weeks and from 24 weeks to endpoint in both groups with no significant difference between them. Both groups had improved significantly in all clinical variables after 24 weeks and this improvement was sustained after two years. CONCLUSIONS: Radiological progression in patients treated with CPH82 was similar to that in patients treated with MTX. The clinical effect of the two drugs was sustained over the two year trial in both treatment groups.
15338190	Acute erythroleukemia in a rheumatoid arthritis patient during low-dose methotrexate thera	2005 May	Acute leukemia is uncommonly seen with rheumatoid arthritis during or following treatment with low-dose methotrexate, a safe and effective treatment for the arthritic condition. We describe here a 68-year-old woman with rheumatoid arthritis who developed acute erythroleukemia during low-dose methotrexate therapy (total dose 1702.5 mg). This may be the first such case reported in the literature.
15144126	Survey of practices regarding management of early rheumatoid arthritis by rheumatologists	2004 May	OBJECTIVE: To describe the practices of rheumatologists in France regarding the initial management of early rheumatoid arthritis (RA) and to estimate the associated costs. METHODS: A questionnaire on the diagnosis and treatment of early RA was sent to the 2485 practicing rheumatologists in France. The results of the 917 completed questionnaires (37% response rate) were analyzed, and initial investigation and treatment costs, including the first month of treatment, were calculated from a socio-economic perspective. RESULTS: For the RA diagnosis, more than 80% of the respondents recommended the erythrocyte sedimentation rate, C-reactive protein, complete blood count, rheumatoid factor, antinuclear antibody and wrist radiographs. In 40% and 60% of the cases, antikeratin antibody, liver enzymes, serum creatine, serum protein electrophoresis and radiographs (chest, foot and knee) were advocated. Initial drugs administered were non-steroidal antiinflammatory agents (88%), analgesics (76%), disease modifying anti-rheutmatic drugs (74% with methotrexate in 46% of cases, followed by hydroxychloroquine [13%], sulfasalazine [8%], leflunomide [7%], intramuscular gold therapy [6%]), and glucocorticoids (21%). Rehabilitation was recommended by 51% of the respondents. The median cost for this initial management was 273 euros (mean 301 euros, range 49-1,336 euros). CONCLUSION: Marked variations occur among French rheumatologists in the initial management of early RA. These data may be helpful in identifying obstacles to physician compliance with recommendations regarding everyday clinical practice and to set up more a specific evaluative study.
14608733	[Radiologic progression of rheumatoid arthritis lesions treated with methotrexate].	2003 Aug	Methotrexate is the treatment of reference in rheumatoid arthritis (RA) because it has proved effective in this pathology. Its clinical efficacy is largely admitted but its radiological efficacy is still in certain. The other aim is to look for other clinical and radiological indices that influence these score evolution in patients treated by Methotrexate. Our study is an open prospective study about thirty RA defined about ACR criterions that don't receive other treatment followed up for 6 months. The methotrexate is administered at least 12 months (12 to 72 months) we evaluate its efficacy by Larsen score and Cohin indices. Remission has been reported in 80% of patients according to Larsen score and in 63.3% of patients according to Cohin indices. Its more efficace if admitted as a first treatment and for at least 12 months in young patients (under 40 years) with an arthritis evolution below 10 years and is at stage 0 or 1 of steinbroker but these data are not statistically significant first for patient age and ancientness of RA.
12509606	The effect of treatment on radiological progression in rheumatoid arthritis: a systematic	2003 Jan	OBJECTIVE: To undertake a systematic review of randomized placebo-controlled trials to assess and rank the efficacy of pharmacological interventions in preventing radiological progression of rheumatoid arthritis. METHODS: The two outcome measures were the weighted standardized mean difference and the odds of progression of X-ray scores pooled as close to 12 months as possible to minimize heterogeneity. RESULTS: A total of 38 trials were identified. Of these, 13 were excluded, leaving data on 3907 subjects. Infliximab, cyclosporin, sulphasalazine, leflunomide, methotrexate, parenteral gold, corticosteroids, auranofin and interleukin 1 receptor antagonist were statistically better than placebo in terms of change in erosion scores. All agents were equivalent statistically, with the exception of infliximab (which was superior to the last five agents). There were similar findings for the odds of progression, with the exception of auranofin (P=0.06) and the infliximab-methotrexate comparison (P=0.07). Other agents did not reach statistical significance in either outcome measure. With the exception of the antimalarials, the magnitude of the effect was consistent with the effect seen in short-term disease activity trials. CONCLUSION: There is published evidence which supports the efficacy of nine agents in decreasing radiological progression in rheumatoid arthritis.
15194582	Relationship between inflammation and joint destruction in early rheumatoid arthritis: a m	2004 Jul	BACKGROUND: The relationship between inflammation and joint destruction in rheumatoid arthritis (RA) has not been unequivocally characterised. Joint destruction may result from the cumulative inflammatory burden over time, modified by an individual constant factor. OBJECTIVE: To test the hypothesis that the relationship between radiological progression and inflammation can mathematically be expressed as: [equation: see text] where Re is a factor that varies from person to person. METHODS: Clinical data and radiographs of 76 patients with early RA receiving different disease modifying antirheumatic drugs were analysed. Radiographs were quantified using the modified Larsen score and the "X-Ray RheumaCoach" software. The cumulative inflammatory burden was estimated by the time integrated 28 joint Disease Activity Score (DAS28), calculated as the area under the curve. RESULTS: 76 patients with early RA who started treatment with methotrexate (n = 20), sulfasalazine (n = 37), or oral gold (n = 19) monotherapy were evaluated. The mean (SEM) DAS28 decreased from 4.6 (0.1) at baseline to 2.3 (0.1) after 2 years. The mean (SEM) DeltaLarsen score from baseline to year 2 was 10.3 (1.5). Correlation between cumulative inflammation and radiographic change was poor. In contrast, when calculating a person's factor Re in year 1 ( Re 1) and year 2 ( Re 2), a strong and significant correlation (r = 0.58, p<0.000001) was seen between Re 1 and Re 2. CONCLUSIONS: Joint destruction is the result of the cumulative burden of inflammation over time, modified by an individual factor Re that remains relatively constant over the first 2 years of observation. The data support a mathematical model that expresses the interrelationship between inflammation and joint destruction.
15201942	[IL-1Ra (recombinant human IL-1 receptor antagonist) in the treatment of rheumatoid arthri	2004 Jan	Interleukin 1 receptor antagonist (IL-1Ra) is a naturally occurring IL-1 inhibitor, acting as a "receptor antagonist", which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of rheumatoid arthritis (RA). In 1991, almost 8 years after the initial isolation of IL-1, recombinant IL-1Ra (IL-1ra, Kineret) was introduced in clinical trials involving patients with RA. Between 2001 and 2002 IL-1ra was approved by the US Food and Drug Administration and by the European Agency for the Evaluation of the Medicinal Products and in 2003 it was registered in Italy, too. In RA recombinant IL-1ra has been evaluated in 5 randomized, placebo-controlled clinical trials involving more than 2900 patients. Two of the trials involved the use of IL-1ra as monotherapy versus placebo and two trials in combination with methotrexate (MTX); the last trial explored the use of a fixed 100 mg/day IL-1ra dosage in a RA patient population including a wide array of co-morbid conditions as well as concomitant medications. The studies confirmed both the efficacy and the safety of IL-1ra in patients with active and severe RA. 43% of patients receiving 150 mg/day IL-1ra achieved a 20% response according to the American College of Rheumatology criteria (ACR20), compared to 27% in the placebo group. In the MTX combination therapy study, 42% of the patients receiving 1 mg/Kg/day of IL-1ra achieved an ACR20, 24% an ACR50 and 10% an ACR70. In each study, significant improvements in the Health Assessment Questionnaire scores (HAQ) were observed. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose related. At early 24 weeks, there was significant reduction of both the score for progression of joint space narrowing (JSN) and the Total modified Sharp-Genant score (a combination of erosion and JSN) in all treatment groups (30,75 and 150mg/day). The clinical benefits of treatment with daily subcutaneous injections of IL-1ra in active RA patients were maintained for up to 48 weeks. IL-1ra, a selective inhibitor of the IL-1 pathway, represents an important new biologic approach to treating patients with RA, that significantly reduces clinical signs and symptoms of the disease and joint destruction and has proved safe and well tolerated also in combination with other DMARDs and concomitant medications.
15361376	Methotrexate related adverse effects in patients with rheumatoid arthritis are associated	2004 Oct	BACKGROUND: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. OBJECTIVE: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. DESIGN: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. RESULTS: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. CONCLUSIONS: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.
11961317	Successful treatment of progressive rheumatoid interstitial lung disease with cyclosporine	2002 Apr	Treatment of interstitial lung disease (ILD) in rheumatoid arthritis (RA) has been controversial. Although there have been several anecdotal reports on the efficacies of corticosteroids or cytotoxic agents such as methotrexate, cyclophosphamide, azathioprine, and D-penicillamine for the treatment of ILD associated with RA, no controlled studies have been performed. To date, corticosteroids have been a central agent for the treatment of this disease, but their effects are partial and temporary in most cases. In addition, the adverse effects of these agents are considerable. On the other hand, limited information is available on the cyclosporine use in ILD associated with RA. We describe a 49-yr old female patient with RA and ILD that had initially responded to high dose prednisolone and cyclophosphamide intravenous pulse therapy, and the lung disease was aggravated with the tapering of prednisolone. After 10 months of follow-up loss, the patient was successfully treated with low dose cyclosporine without high dose corticosteroids.
14530867	An open, randomized comparison study of cyclosporine A, cyclosporine A + methotrexate and	2005 Jan	PURPOSE: To determine whether a regimen of cyclosporine (CSA) and methotrexate (MTX), or CSA and hydroxychloroquine (HCQ) introduced in early rheumatoid arthritis (RA) can produce a significant improvement in clinical outcome and/or retard radiographic damage in comparison with standard monotherapy with CSA alone. METHODS: One hundred five patients with active RA of less than 36 months duration, who had never previously been treated with immunosuppressive agents, were included in a 12-month, multi-center, open, randomized trial. Patients who fulfilled the criteria for early severe RA were randomized to receive either combination therapy (CSA + MTX n = 34, CSA + HCQ n = 35) or CSA alone (n = 36). RESULTS: CSA + MTX was more effective than the other two treatment groups in controlling RA symptoms. CSA+MTX did not show a significant radiographic progression according to Larsen-Dale (0.90 +/- 3.89 compared to baseline values, P > 0.05); moreover, patients treated with CSA alone or CSA+HCQ showed a significant worsening of Larsen-Dale score (2.91 +/- 5.99 and 2.97 +/- 4.28 respectively vs baseline values, P < 0.05), although not significant when compared with the CSA + HCQ group (P = 0.56 and 0.39, respectively). CONCLUSIONS: This trial indicated that CSA+MTX was more effective than the other two treatments in improving clinical data and inhibiting radiographic progression, although the differences were not significant in this relatively small study. However, the difference was significant in favor of CSA + MTX regarding ACR 50% response.
15610214	Tumour necrosis factor inhibitors: risks and benefits in patients with rheumatoid arthriti	2004 Dec	Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis and can, if left untreated, result in significant disability and early death. It is also associated with large direct and indirect costs to the individual and to society. Early and aggressive disease modifying anti-rheumatic drug (DMARD) treatment of patients at risk of erosive disease has improved the outcome in the majority, but not all, RA patients. Tumour necrosis factor (TNF) appears to be a key mediator of the inflammatory and destructive process in RA, and consequently inhibitors of TNF action have been tested in randomized controlled trials in patients with RA. The results of these studies have suggested that TNF inhibitors are potent DMARD particularly when combined with methotrexate. They appear well tolerated with the commonest adverse events related to their parenteral route of administration, and the serious but rare side-effects being various infections, notably tuberculosis, multiple sclerosis, and worsening of cardiac failure. Treatment costs are high and range from $15 000 to $25 000 per patient per year. Etanercept, adalimumab and infliximab have recently been subsidised under the Pharmaceutical Benefits Scheme in Australia for patients with severe DMARD-resistant RA. The availability of TNF inhibitors in RA represents a significant advance in the treatment of patients with severe RA.
12510360	[Clinical implication of cyclosporin for rheumatoid arthritis].	2002 Dec	Cyclosporin is a non-cytotoxic immunomodulating drug which inhibits NF-AT-dependent IL-2 transcription in lymphocytes. Cyclosporin is, therefore, beneficial as a monotherapy or as a combined therapy with methotrexate for refractory rheumatoid arthritis (RA). We also document that cyclosporin recovers the low concentration of intracellular multidrugs in lymphocytes by competitively binding to P-glycoprotein, a product of multidrug resistance gene-1, in vitro. Thus, cyclosporin could be used for the reversal of multidrug resistance, experienced in patients with longterm treated RA.