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ID PMID Title PublicationDate abstract
9361161 Methotrexate pulmonary toxicity. 1997 Nov Drug-induced pulmonary disease is a well-recognized complication of MTX treatment of rheumatic diseases. Physicians involved in the management of patients receiving MTX should be aware of this potentially life-threatening complication. The prompt evaluation of new pulmonary symptoms in patients receiving MTX is important in the early recognition of this drug-induced complication. The characteristic symptoms are shortness of breath, nonproductive cough, fatigue, and fever. If an MTX-induced pulmonary reaction is suspected and abnormalities are noted on lung examination, chest radiography should be performed. In the presence of an abnormal chest radiograph, MTX should be discontinued, supportive measures instituted, and the diagnosis of the patient's pulmonary complaints investigated by specifically looking for features of the underlying rheumatic process, infection, and other medical conditions. Patients with severe pulmonary compromise should be hospitalized and given supplemental oxygen and high-dose corticosteroids. Most patients recover from their illness. No risk factors have been identified that consistently identify patients at the greatest risk for MTX-induced pulmonary toxicity. All patients receiving MTX should be educated concerning this potentially life-threatening drug toxicity and instructed to contact their physician immediately if significant pulmonary symptoms develop.
10622295 Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo 1999 Dec 4 BACKGROUND: Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate, a standard treatment for this disease. There is evidence that antitumour necrosis factor alpha (TNFalpha) is efficacious in relief of signs and symptoms. We therefore investigated whether infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate. METHODS: In an international double-blind placebo-controlled phase III clinical trial, 428 patients who had active rheumatoid arthritis, who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks, were randomised to placebo (n=88) or one of four regimens of infliximab at weeks 0, 2, and 6. Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate (median 15 mg/week for > or =6 months, range 10-35 mg/wk). Patients were assessed every 4 weeks for 30 weeks. FINDINGS: At 30 weeks, the American College of Rheumatology (20) response criteria, representing a 20% improvement from baseline, were achieved in 53, 50, 58, and 52% of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks, respectively, compared with 20% of patients receiving placebo plus methotrexate (p<0.001 for each of the four infliximab regimens vs placebo). A 50% improvement was achieved in 29, 27, 26, and 31% of infliximab plus methotrexate in the same treatment groups, compared with 5% of patients on placebo plus methotrexate (p<0.001). Infliximab was well-tolerated; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group. INTERPRETATION: During 30 weeks, treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate.
10589358 Combination DMARD therapy with hydroxychloroquine, sulfasalazine, and methotrexate. 1999 Nov Triple combination therapy with hydroxychloroquine, sulfasalazine, and methotrexate (MTX) has been shown in double-blind, placebo-controlled studies to be significantly superior to MTX alone (Paulus 50% responses of 77% versus 33%). In long-term follow-up studies, this therapy has now been shown to be well-tolerated with continued efficacy in the majority of patients.
11171681 Inappropriate medical management of spinal epidural abscess. 2001 Mar A 67 year old man with longstanding rheumatoid disease was referred to the regional spinal surgery unit with acute onset of paraparesis due to an extensive spinal epidural abscess of the lumbar spine. Ten months previously, he had started antibiotic treatment at another hospital for an epidural abscess arising at the level of the L2-3 disc space. Despite completing seven months of medical treatment with appropriate antibiotics, he had a recrudescence of acute back pain shortly after restarting methotrexate treatment. Urgent anterior spinal decompression with excision of the necrotic vertebral bodies of L1-3 was performed. The indications for the surgical management of spinal epidural abscess are reviewed.
10724046 The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy 2000 Mar 13 Many rheumatic diseases affect women of childbearing age, and the medications used to treat these diseases may affect conception, pregnancy, fetal development, and lactation. Physicians who care for these women need to be aware of the potential adverse effects of these medications, and which medications can be used safely prior to conception and during pregnancy and lactation. Although reviews of individual classes of medications are available, there is no practical and comprehensive review that summarizes all of this information, and includes anticoagulant drugs and 2 recently approved drugs for rheumatoid arthritis. Women who take cytotoxic drugs should be informed of the risks of impaired fertility and congenital malformations, and must use effective methods of contraception. During pregnancy, nonsteroidal anti-inflammatory agents may be used until the last 6 weeks, and low to moderate doses of corticosteroids are safe throughout pregnancy. Among the disease-modifying agents, sulfasalazine and hydroxychloroquine treatment may be maintained. Cytotoxic drugs may be used after the first trimester to treat life-threatening disease. During lactation, prednisone, sulfasalazine, and hydroxychloroquine may be used cautiously. Women using heparin for treatment of antiphospholipid antibody syndrome should take measures to prevent bone loss. Men taking methotrexate, sulfasalazine, cyclosporine, azathioprine, or leflunomide should be apprised of the possibilities of infertility and teratogenicity.
9552765 Leukocytoclastic vasculitis induced by low-dose methotrexate: in vitro evidence for an imm 1998 Jan The rare occurrence of methotrexate (MTX)-induced vasculitis has been associated mainly with high or intermediate MTX doses. We report herein a case of cutaneous leukocytoclastic vasculitis (LCV) following treatment with low-dose oral MTX (7.5 mg/week) for rheumatoid arthritis. The histological findings of a cutaneous lesion were consistent with drug-induced vasculitis. The clinical and histological findings, including the temporal relationship between MTX intake and the onset of vasculitis, and the results of withdrawal and rechallenge tests, suggest a causal relationship, and indicate a drug-induced LCV due to MTX. The role of MTX in the induction of the vasculitis was further supported by a positive mast cell degranulation (MCD) test.
10090160 Trends in the use of disease modifying antirheumatic medications in rheumatoid arthritis, 1999 Mar OBJECTIVE: Current treatment of rheumatoid arthritis (RA) emphasizes the early and consistent use of disease modifying antirheumatic drugs (DMARD). We studied how often these medications were used to treat patients with RA, and whether use of these medications has increased over time. METHODS: We used the National Ambulatory Medical Care Surveys to determine national probability estimates of the use of DMARD [hydroxychloroquine, intramuscular gold, auranofin, methotrexate (MTX), sulfasalazine, azathioprine, D-penicillamine, and cyclosporine] by patients with RA. The National Ambulatory Medical Care Surveys record information about treatments provided in outpatient settings by a nationally representative cross sectional sample of physicians. Estimates of the use of DMARD were based on the treatments reported on 502 visits by patients with RA in 1980-81, 339 visits by patients with RA in 1985, 386 visits by patients with RA in 1989-91, and 383 visits by patients with RA in 1993-95. RESULTS: DMARD were used in 30.3% of visits in 1980-81, 36.3% of visits in 1985, 24.9% of visits in 1989-91, and 43.6% of visits in 1993-95 (p for trend < 0.0001). Increased use of MTX accounted for most of the increased prevalence of DMARD use; MTX was used in 27.3% of visits in 1993-95. Use of DMARD increased in 1993-95 in all age, sex, and racial subgroups, and among visits reported by rheumatologists, but did not increase over time among visits reported by physicians other than rheumatologists. CONCLUSION: Use of DMARD in RA has increased in the recent past, but DMARD are currently used by fewer than 44% of patients with RA. Use of DMARD has not increased over time among patients of physicians other than rheumatologists.
9782754 [Combination therapy of rheumatoid arthritis]. 1998 Sep 28 The prevalence of rheumatoid arthritis (RA) is about 0.5-1%. The disease course is variable, but RA causes substantial morbidity and mortality. The effect of conventional therapy for RA, i.e. nonsteroidal antiinflammatory drugs (NSAID), glucocorticosteroids and Slow Acting Anti-Rheumatic Drugs (SAARD) including methotrexate, gold salts, anti-malarials, d-penicillamine and salazopyrine, is often suboptimal. Since the aim of treatment is a complete remission, combination therapy, i.e. treatment with two or more SAARDs, may be feasible since an additive/synergistic effect may be obtained. In this paper the literature about the effectiveness and toxicity of combination therapy is reviewed. Only a few randomized, clinically controlled trials have been published. None of them have documented that gold salts, d-penicillamine and azathioprine in combination with other SAARDs are better than monotherapy. However, recent trials have indicated that methotrexate in combination with salazopyrine and hydroxychloroquine or in combination with cyclosporine may cause a better therapeutic effect than methotrexate alone, without additional toxicity. Long term studies of the effect of combination therapy are not yet available.
11304108 Rational use of new and existing disease-modifying agents in rheumatoid arthritis. 2001 Apr 17 Because of radiographic evidence of progressive bone loss and the inability to eliminate synovial proliferation with methotrexate, it became apparent that therapy for rheumatoid arthritis needed further advancement. Methotrexate is not a remission-inducing drug and may have dose-limiting toxicity. In the past 2 years, three new disease-modifying antirheumatic drugs (DMARDs) have been approved: leflunomide, etanercept, and infliximab. Each of these agents has demonstrated efficacy compared with placebo in randomized, controlled studies. Because methotrexate had a dominant therapeutic role, the new drugs were also studied in combination with it. Other established DMARDs, such as sulfasalazine and hydroxychloroquine, have also demonstrated efficacy when used together with methotrexate. The results of these combination studies clearly demonstrate that clinical responses can be meaningfully improved when new and existing DMARDs are added to methotrexate. Although toxicity remains a serious concern when powerful immune modulators and antimetabolites are used in combination, relatively few serious adverse events have been reported during 2-year treatment periods. It has also become apparent that combinations of new DMARDs and methotrexate virtually halt radiographic progression over 2 years. The new agents are expensive, but annual costs must be weighed against the personal and societal expense of joint arthroplasty, hospitalizations, disability, and diminished quality of life that accompanies poorly controlled rheumatoid arthritis. The ultimate value of combination DMARD therapy with methotrexate will be determined by long-term data on safety, efficacy, and effects on radiographic deterioration of bone. Additional long-term observational data on the incidence of joint arthroplasty and disability will help to place the issue of societal costs in a better perspective. This will allow the value of aggressive treatment to be established with certainty.
11727846 Changes in plasma homocysteine in arthritis patients starting treatment with low-dose meth 2001 In 15 patients with rheumatoid arthritis (RA) (n = 13) or psoriatic arthritis (PsA) (n = 2) p-homocystcine and erythrocyte folate (erc-FA) were measured before start of methotrexate (MTX) treatment, after 4 weeks of MTX treatment (median 10 mg per week), and after further 4 weeks of treatment with MTX (median 12.5 mg per week) supplemented with folic acid (FA) (15 mg per week). Mean p-homocysteine were 12.3 +/- 3.4 micromol/l, 14.6+/-5.8 micromol/l (p<0.05) and 10.3+/-3.0 micromol/l (p<0.01) respectively. P-homocysteine concentrations were negative correlated to erc-FA after 4 weeks (rho -0.58; p<0.05). It is concluded that treatment with MTX induces a significant rise in p-homocysteine that is neutralised by FA supplementation. Supplementation with FA from the start of MTX treatment is recommended considering the increased risk of cardiovascular disease that is associated with elevated concentrations of p-homocysteine.
9739500 Epidemiology and optimal management of polymyalgia rheumatica. 1998 Aug Polymyalgia rheumatica (PMR) is a disease of unknown aetiology that occurs in elderly patients, predominantly affecting the Caucasian population. The disease has a slightly higher prevalence in women than in men. There is ongoing discussion regarding the relationship between PMR and giant cell arteritis; an increasing number of studies indicate that they are closely related. PMR has also been linked with rheumatoid arthritis, myopathy and malignant disease. Oral corticosteroids remain the mainstay of drug therapy for PMR. These drugs usually induce prompt relief of symptoms, and some authors consider this dramatic response to be diagnostic for PMR. However, the ideal initial dosage, the duration of treatment and the optimal tapering schedule are much debated. Other drugs, such as methotrexate and azathioprine, have been suggested as corticosteroid sparing agents. Nonsteroidal anti-inflammatory drugs are generally considered to be unsuitable for the long term treatment of PMR.
9133967 Comparison of intramuscular methotrexate and gold sodium thiomalate in the treatment of ea 1997 Mar The objective was to compare the safety and efficacy of methotrexate (MTX) and gold sodium thiomalate (GSTM) in patients with early erosive rheumatoid arthritis (RA). A total of 174 patients with active early erosive RA without deformities were enrolled in a 12 month, two-centre double-blind randomized trial. They received a weekly i.m. dose of 15 mg MTX (n = 87) or 50 mg GSTM (n = 87), respectively. Clinical and laboratory evaluations were carried out every 3 months in all patients, including the withdrawals. Ten patients (11.5%) in the MTX group and 21 patients (24.1%) in the GSTM group achieved a clinical remission of the disease [no swollen joints, erythrocyte sedimentation rate (ESR) < 20 mm, no steroids] within the study period (P < 0.05). An at least marked improvement (> 50% reduction of the number of swollen and tender joints and the ESR) was assessed in 59/87 (68%) and 66/87 (76%) patients treated with MTX or GSTM, respectively (P > 0.05). Significantly more patients in the GSTM group were withdrawn due to toxicity (six MTX/32 GSTM). A total of 126 patients (73 on MTX and 53 on GSTM) completed 12 months on their original medication. In the completers, a significant improvement of > 50% compared to baseline was noted in all six clinical variables [morning stiffness, joint count of swollen and tender joints, Lansbury index, grip strength and activities of daily living (ADL) score], the ESR and the C-reactive protein, without intergroup differences. The number of patients taking prednisone was reduced from 21 to 7% in the MTX group and from 15 to 4% in the GSTM group. While significantly more patients achieved a clinical remission with GSTM treatment, tolerability was significantly better with MTX.
10501685 [Ulcerative stomatitis as clinical clue to inadvertent methotrexate overdose]. 1999 Sep Gastrointestinal side effects and the development of toxic liver fibrosis are well-known side effects of low dose methotrexate therapy. A female patient receiving a long term low dose methotrexate therapy for a seronegative chronic polyarthritis developed an ulcerative stomatitis, as clinical clue to an inadvertently given methotrexate overdose. A summary of other side effects of methotrexate and of oral side effects of other cytostatic agents and immunosuppressive drugs is given.
11583481 Lack of pharmacokinetic interaction between rofecoxib and methotrexate in rheumatoid arthr 2001 Oct Rofecoxib is a highly selective and potent inhibitor of cyclooxgenase-2 (COX-2). Methotrexate is a disease-modifying agent with a narrow therapeutic index frequently prescribed for the management of rheumatoid arthritis. The objective of this study was to investigate the influence of clinical doses of rofecoxib on the pharmacokinetics of methotrexate in patients with rheumatoid arthritis. This was a randomized, double-blind, placebo-controlled study in 25 rheumatoid arthritis patients on stable doses of methotrexate. Patients received oral methotrexate (7.5 to 20 mg) on days -1, 7, 14, and 21. Nineteen patients received rofecoxib 12.5, 25, and 50 mg once daily on days 1 to 7, 8 to 14, and 15 to 21, respectively. Six patients received placebo on days 1 to 21 only to maintain a double-blinded design for assessment of adverse experiences. Plasma and urine samples were analyzed for methotrexate and its major although inactive metabolite, 7-hydroxymethotrexate. The AUC(0-infinity) geometric mean ratios (GMR) and their 90% confidence intervals (90% CI) (rofecoxib + methotrexate/methotrexate alone) for day 7/day -1, day 14/day -1, and day 21/day -1, for rofecoxib 12.5, 25, and 50 mg, were 1.03 (0.93, 1.14), 1.02 (0.92, 1.12), and 1.06 (0.96, 1.17), respectively (p > 0.2 for all comparisons to day -1). All AUC(0-infinity), GMR and Cmax GMR 90% CIs fell within the predefined comparability limits of (0.80, 1.25). Similar results were observed for renal clearance of methotrexate and 7-hydroxymethotrexate at the highest dose of rofecoxib tested (50 mg). It was concluded that rofecoxib at doses of 12.5, 25, and 50 mg once daily has no effect on the plasma concentrations or renal clearance (tested at the highest dose of rofecoxib) of methotrexate in rheumatoid arthritis patients.
10796393 Folic acid and folinic acid for reducing side effects in patients receiving methotrexate f 2000 OBJECTIVES: To assess the effects of folic acid and folinic acid in reducing the mucosal and gastrointestinal (GI) and haematologic side effects of low-dose of Methotrexate (MTX) in patients with Rheumatoid Arthritis (RA) and to determine whether or not folate supplementation alters MTX efficacy. SEARCH STRATEGY: We searched the Cochrane Controlled Clinical Trial's Register (CCTR), the Cochrane Musculoskeletal Group Specialized Register and Medline up to and including June 1999, using the search strategy developed by the Cochrane Collaboration (Dickersin 1994). We also handsearched the following: (i) bibliographic references; (ii) current contents of the last 6 months; (iii) abstracts of the rheumatology meetings; and (iv) all issues of four journals; Journal of Rheumatology, Arthritis & Rheumatism, Clinical and Experimental Rheumatology, and British Journal of Rheumatology. All languages were included. Principal investigators were also contacted in order to look for unpublished literature. SELECTION CRITERIA: We selected all double-blind, randomized, placebo-controlled, clinical trials (RCTs), in which adult RA patients were treated with a low dose of MTX (<20 mg / week) concurrently with folate supplementation. DATA COLLECTION AND ANALYSIS: Two observers extracted the data and assessed the quality of the trials. (BS, Z0) The overall treatment effect across trials was calculated using a fixed effect model. Disease activity was evaluated using standardized mean differences to ensure comparability across outcome measures. Results are presented with 95% Confidence Inervals (95% CI). Subgroup analyses were conducted evaluating different doses and sensitivity analysis looking at the quality of the trials. Publication bias was assessed with an inverted funnel plot technique. Heterogeneity of the trials was measured using a standard chi square test. Costs per month in different countries were compared. MAIN RESULTS: Of the 12 trials retrieved, 7 met the inclusion criteria. The total sample included 307 patients, of which 147 were treated with folate supplementation, 80 patients with folinic acid and 67 patients with folic acid. A 79% reduction in mucosal and GI side effects was observed for folic acid [OR = 0.21 (95% CI 0.10 to 0.44)]. For folinic acid, a clinically but non-statistically significant reduction of 43% was found [OR = 0. 57 (95% CI 0.28 to 1.15)]. No major differences were observed between low and high doses of folic or folinic acid. Haematologic side effects could not be analyzed, since details of each haematologic side effect by patients were not provided. No consistent differences in disease activity parameters were observed when comparing placebo and folic or folinic acid at low or high doses, although patients on high dose folinic acid had an increase in the number of tender joints, but not swollen joints. Large differences in costs across countries were found, but folinic acid was more expensive in all. REVIEWER'S CONCLUSIONS: The results support the protective effect of folate supplementation in reducing MTX side effects related to the oral and GI systems. We could not determine if folic was different from folinic acid. Therefore, for folinic acid to be considered cost-effective it must be found more effective than folic acid at reducing MTX side effects.
9150070 Lack of pharmacokinetic interaction of meloxicam with methotrexate in patients with rheuma 1997 May OBJECTIVE: To investigate the pharmacokinetic interaction of oral meloxicam with intravenous (i.v.) methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Thirteen patients with RA received MTX 15 mg i.v. in the absence of nonsteroidal antiinflammatory drugs (NSAID) and after one week in the presence of steady state levels of meloxicam. Plasma concentrations of MTX and meloxicam were determined using validated high performance liquid chromatography methods. One patient did not complete the study. The interaction of meloxicam and MTX was examined by equivalence testing. The endpoints AUCMTX, VssMTX, CltotMTX, and CmaxMTX were analyzed parametrically, whereas endpoints MRTMTX, CltotMTX, t1/2MTX, and tmaxMTX were analyzed nonparametrically. RESULTS: The MTX plasma concentrations over time, with and without meloxicam, did not differ significantly. The point estimator for the ratio of log transformed data of the primary endpoint AUCMTX was 108%; the lower 95% confidence limit was 100% and the upper 95% confidence limit was 117%. Clinical laboratory values and adverse events revealed no increased MTX toxicity during concomitant treatment with meloxicam. CONCLUSION: In this short term interaction study there was no statistically significantly effect of meloxicam on the pharmacokinetics of MTX. The combination of MTX and meloxicam did not lead to increased MTX toxicity.
9263140 Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid a 1997 Aug OBJECTIVE: To determine the effects of low dose methotrexate (MTX) on bone mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: We examined the relationship between BMD and disease modifying antirheumatic drug (DMARD) use with data from a prospective, randomized, placebo controlled trial assessing the effects of calcium and vitamin D3 supplementation on BMD of patients with RA. Measurements of BMD of the lumbar spine and femoral neck were performed at baseline and at yearly followup visits over 3 years. RESULTS: Information about DMARD use and BMD was available for 133 patients at baseline, and for 95 patients at Year 3. Lumbar spine and femoral neck BMD of MTX and non-MTX treated patients were similar at the start of the study. At the end of 3 years of followup, there was no significant differences in the change in BMD of the femoral neck and lumbar spine in MTX and non-MTX treated patients, in general. However, patients treated with prednisone > or = 5 mg/day plus MTX had greater loss of BMD in the lumbar spine than patients treated with a similar dose of prednisone without MTX (difference -8.08% over 3 years; p = 0.004). CONCLUSION: At the end of 3 years, low dose MTX use was not associated with change in femoral neck or lumbar spine BMD in patients who were not treated with corticosteroids. However, among patients treated with prednisone > or = 5 mg/day, combined treatment with MTX and prednisone was associated with greater bone loss in the lumbar spine than treatment with prednisone without MTX.
10406409 Insufficiency fractures of the tibia and fibula. 1999 Jun OBJECTIVE: Insufficiency fractures (IF) occur when normal or physiological muscular activity stresses a bone that is deficient in mineral or elastic resistance. IF of the tibia and fibula are probably less common than IF of the ribs, vertebrae, hip, pelvis, and distal ulna, and therefore they are frequently underrecognized and mistaken for other conditions. Our aim was to analyze the main features and outcome of IF of the tibia and fibula in patients attending our Rheumatology Service. METHODS: IF was considered when occurring spontaneously or with minimal trauma. Between January 1984 and July 1997, 25 patients were diagnosed as having IF of the tibia and fibula. The main predisposing factors, clinical features, therapy, and outcome were retrospectively reviewed. RESULTS: All the patients except four were women (mean age, 66+/-12 years). Three cases were diagnosed between 1984 and 1990 (0.42 cases/year) and 22 between 1991 and 1997 (three cases/year). Eighteen patients had an underlying condition: rheumatoid arthritis (RA, 13 cases), psoriatic arthritis (2), systemic lupus erythematosus (SLE) (1), kidney transplant (1), and Crohn's disease (1). Eleven patients had osteoporotic fractures in other locations. Risk factors for osteoporosis were corticosteroids (13 cases), prolonged immobilization (10), early menopause (2), and methotrexate therapy (10). All patients had pain on weight bearing and marked functional impairment, 16 had local inflammatory signs, and 10 had deformity. In only five patients the diagnosis of IF was considered at the first examination. The diagnostic delay was 76+/-117 days (median, 21). The initial radiograph was diagnostic in 20 patients, and in the remaining the diagnosis was made by computed tomography (CT) scan (three cases), magnetic resonance imaging (MRI) (1), and bone scan (1). IF were located as follows: tibia (10 cases), fibula (seven), tibia and fibula (eight). Nineteen patients were treated with conservative management, four received no specific treatment, and two required surgery. Sixteen patients were hospitalized for a mean period of 12+/-8 days. Most patients had complete recovery. The high frequency of IF seen in RA patients is probably due to the severe disease in patients treated by our Service and that such patients have a higher risk for osteoporosis and its complications. CONCLUSIONS: IF of the tibia and fibula are probably more common than previously thought. They usually occur in patients with underlying rheumatic diseases, mainly RA, and are frequently mistaken for other joint and bone conditions. Despite a frequent delay in diagnosis, they have a good prognosis with conservative management. Nonetheless, a higher index of suspicion may avoid unnecessary investigations and treatments.
11409155 How do the biologics fit into the current DMARD armamentarium? 2001 Jun Most disease modifying antirheumatic drugs (DMARD) are discontinued within 5 years because of loss of clinical efficacy or toxicity. As a result, there has been a concerted effort to develop new immunomodulatory agents, particularly biological agents, that block the putative proinflammatory cytokines. Among the agents developed thus far, inhibitors of tumor necrosis factor (TNF) have shown perhaps the greatest promise as therapeutic agents for rheumatoid arthritis (RA). Two TNF-blocking agents, etanercept (Enbrel) and infliximab (Remicade), have been approved in the US and more recently in Europe, for the treatment of patients with RA. The results of randomized placebo controlled trials have shown that both agents significantly decrease the intensity of synovitis and prevent or retard the progression of cartilage destruction, especially when combined with methotrexate. Their side effect profiles appear to be acceptable, although rare cases of lupus-like diseases and of severe infections have been reported. Although the early clinical experience with these agents has been encouraging, their longterm safety and continuing efficacy in the general population with RA, as well as in high risk patient subsets (i.e., patients with malignancies or chronic infections), remain to be determined. In addition, the costs of these newer agents must be justified on clinical grounds. Because of the questions still surrounding these new treatment principles, several consensus conferences have been held in Europe and the US to address the role of the new biologicals in the current RA armamentarium.
11409154 Conventional DMARD options for patients with a suboptimal response to methotrexate. 2001 Jun Methotrexate (MTX) is one of the disease modifying antirheumatic drugs (DMARD) commonly used to treat rheumatoid arthritis (RA). However, MTX therapy alone rarely results in remission and frequently does not even produce 50% improvement. Therefore, over the course of their disease, many patients will require additional therapy to manage their clinical symptoms. A number of treatment options have proven effective for such patients, most of which entail the continuation of MTX therapy and the addition of other DMARD. Although the combination of MTX and hydroxychloroquine (HCQ) is the one most commonly used in the US, many clinicians (particularly in Europe) prefer the combination of MTX and sulfasalazine. In addition, excellent data now exist for the triple combination of MTX, HCQ, and sulfasalazine in patients who have had a suboptimal response to MTX, as well as in those with early or well established disease. Other combinations, including MTX + cyclosporine or leflunomide, have also been helpful in some patients. Most recently, the tumor necrosis factor blockers, etanercept and infliximab, have successfully been used to treat a number of patients resistant to MTX. The combination of MTX with DMARD or biological agents with different mechanisms of action greatly expands the treatment options for patients with RA.
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