Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 15560380 | [Legionella pneumonia which occurred in a private whirlpool bath user]. | 2004 Oct | A 88 year old female with active rheumatoid arthritis treated by low dose of prednisolone and methotrexate was admitted to our hospital because of severe bilateral pulmonary infiltration and acute respiratory distress syndrome. On admission, she had consciousness disturbance and was intubated because of severe respiratory failure. We heard from her family of her habit she had taking a private whirlpool bath 2 or 3 times everyday. So, we suspected a Legionella pneumophila infection. We started intravenous erythromycin (EM) (1,500mg/day) and methylprednisolone pulse therapy (1,000mg x 3days) and full controlled mechanical ventilation supported with PEEP. Her respiratory failure was gradually improved and she was discharged on the 44 the hospital day. Legionella pneumophila (serogroup 6) was isolated in her sputum by B-CYE alpha culture. Legionella pneumophila (serogroup 6) was isolated in her private whirlpool bath too. Both samples revealed the same by genetic analysis with pulse field gel electrophoresis (PFGE). This is the first adult case of Legionella pneumophila pneumonia infected from a private whirlpool bath confirmed by genetic analysis. We should always suspect Legionella pneumonia as one of the severe community-acquired pneumonia, because Legionella pneumophila were frequently detected among various water sources including the private whirlpool bath. | |
| 15148945 | Anakinra: new preparation. Weakly effective in rheumatoid arthritis. | 2004 Apr | (1) There is no consensus on the best treatment option for rheumatoid arthritis when a first-line agent fails (most often methotrexate). Among the recent immunosuppressants, etanercept should be used before infliximab. (2) Anakinra, an interleukin-1 type 1 receptor antagonist, was recently authorised in the European Union as a second-line treatment for rheumatoid arthritis in combination with methotrexate. (3) There are no published trials comparing anakinra with other slow-acting antirheumatic drugs (especially infliximab and etanercept). In one clinical trial in patients who did not respond adequately to methotrexate, the combination anakinra + methotrexate was more effective than methotrexate + placebo on ACR 20%, ACR 50% and ACR 70% criteria, but the clinical relevance of these results is doubtful. (4) An indirect comparison suggests that etanercept is more effective than anakinra + methotrexate. (5) In a placebo-controlled trial of anakinra, 75% of patients had reactions at the injection site. Serious infections, neutropenia and anti-anakinra antibodies were also reported. There is no evidence that anakinra is any safer than etanercept. (6) Anakinra + etanercept offers no gains in efficacy, just an increased risk of severe infections. (7) Subcutaneous injections of anakinra are required daily (twice-weekly subcutaneous injections for etanercept). (8) In short, there is no argument for using anakinra as a second-line treatment for rheumatoid arthritis; it does not improve disease management. | |
| 11838843 | Disease modifying antirheumatic drugs in early rheumatoid arthritis: a longterm observatio | 2002 Feb | OBJECTIVE: To investigate the effectiveness, toxicity, and drug survival in an observational longterm study of patients with early rheumatoid arthritis (RA). METHODS: Four hundred twenty-eight patients with early RA were investigated between January 1987 and December 1995. All patients had a disease duration of less than one year and had not been previously treated with any disease modifying antirheumatic drug (DMARD). The following drugs were introduced at the doses specified: hydroxychloroquine (HCQ) (200-400 mg/day), D-penicillamine (D-Pen) (500 mg/day), sulfasalazine (SSZ) (2-3 g/day), auranofin (6 mg/day), intramuscular gold (IM gold, 50 mg/week), methotrexate (MTX) (0.15 mg/kg/week, per os), cyclosporin A (CSA) (3 mg/kg/day), azathioprine (AZA) (2-3 mg/kg/day), cyclophosphamide (CYC) (1-2 mg/kg/day). RESULTS: Three hundred eighty-three patients were treated with one DMARD for at least 6 months. Sixty-five percent of patients were seropositive. The disease duration was 9.2 (3.1) months and the followup period of 12.7 (4.8) years, ranging from 7 months to 13 years. The drugs of first choice were: D-Pen (32%), HCQ (30%), MTX (21%), CSA (8%), and IM gold (7%). After the 2nd, 3rd, and 4th prescriptions, MTX was the most popular drug (27%), while D-Pen and HCQ were prescribed less frequently. The longest drug survival was seen in MTX treated patients, followed by CSA, without significant differences between them. D-Pen, HCQ, and IM gold had the largest dropout rate. The main causes for drug discontinuation were drug inefficacy (HCQ), followed by adverse drug reactions (D-Pen). CONCLUSION: It appears that MTX has the longest survival time, with CSA following in second place. The main reasons for discontinuation of treatment were drug inefficacy, followed by adverse drug reactions. | |
| 15645660 | Rheumatoid arthritis complicated with acute interstitial pneumonia induced by leflunomide | 2004 Dec | A 49-year-old Japanese man with rheumatoid arthritis acutely developed a skin eruption and severe non-productive cough seventeen days after the administration of leflunomide. Because all bacteriology findings were negative, steroid pulse-therapy was initiated promptly due to the rapidity of chest X-ray progression and the deterioration of arterial blood oxygen pressure. Although cough was induced by methotrexate, interstitial pneumonia was not detected clinically before leflunomide administration. He finally died of respiratory failure 128 days after the onset of acute interstitial pneumonia. According to the post-market surveillance, as high as approximately 1.1% of the patients on,leflunomide have developed interstitial pneumonia in Japan. It is important to emphasize that acute interstitial pneumonia due to leflunomide is a very severe and potentially fatal side effect. | |
| 12572373 | [Clinical observation on treatment of rheumatoid arthritis by combined therapy with methot | 2002 Aug | OBJECTIVE: To observe the effect of Fengshi No. 1 (FS1) in treating patients with active stage of rheumatoid arthritis (RA). METHODS: Patients with RA were randomly divided into two groups, the 40 patients in the treated group were treated with combined therapy of methotrexate (MTX), sulfasalazine (SSZ) and FS1, and the 20 in the control groups were treated with MTX and SSZ alone. RESULTS: In the treated group, the total effective rate was 97.5%, the clinical controlled and markedly effective rate 95.0% and the occurrence rate of side-toxic reaction 10.0%, as compared with those in the control group, 60.0%, 20.0% and 45.0% respectively, the difference was significant (chi 2 = 11.91, 32.23 and 7.67 respectively, all P < 0.01). The effect in the treated group was superior to that in the control group in abating joint swelling and pain, improving function of joint, reducing immune indices and ameliorating iconographic features (P < 0.01 or P < 0.05). CONCLUSION: FS1 not only has the effects of anti-inflammation, analgesis, regulating immune reaction, but also could retard the occurring of bone destruction, reduce the toxic-side effects of MTX and SSZ. | |
| 14501231 | Acute secondary gastrointestinal amyloidosis in a patient with rheumatoid arthritis. | 2003 Sep | Secondary amyloidosis is well recognized as a severe complication in the late stages of rheumatoid arthritis (RA). However, there have been few reported cases of secondary amyloidosis developing early during the course of RA. We here report the case of a 35-year-old woman, in whom RA who had been diagnosed 1 year before, with intractable watery diarrhea as a symptom of RA-induced secondary intestinal amyloidosis. Combination treatment with intravenous hyperalimentation, corticosteroids, and methotrexate (MTX) resulted in a dramatic improvement of her symptoms and objective findings of serological abnormalities. Subsequent administration of corticosteroids and MTX resulted in long-term survival without recurrence. This case indicates that we should be alert for the development of secondary amyloidosis, even in patients with a short history of RA, when the disease is active. Furthermore, combination therapy with intravenous hyperalimentation and strong immunosuppressive agents seems to be very efficacious in the treatment of RA-associated secondary intestinal amyloidosis. | |
| 11920396 | Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 recepto | 2002 Mar | OBJECTIVE: To evaluate the efficacy and safety of anakinra in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: Patients with moderate-to-severe active RA who were receiving MTX for 6 consecutive months, with stable doses for > or = 3 months (those with disease duration of >6 months but <12 years) were randomized into 6 groups: placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of anakinra administered in a single, daily, subcutaneous injection. The primary efficacy end point was the proportion of subjects who met the American College of Rheumatology 20% improvement criteria (attained an ACR20 response) at week 12. RESULTS: A total of 419 patients were randomized in the study. Patient demographics and disease status were similar in the 6 treatment groups. The ACR20 responses at week 12 in the 5 active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR20 response in the placebo plus MTX group. The ACR20 response rate in the anakinra 1.0-mg/kg (46%; P = 0.001) and 2.0-mg/kg (38%; P = 0.007) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. Similar improvements in anakinra-treated subjects were noted in individual ACR components, erythrocyte sedimentation rate, onset of ACR20 response, sustainability of ACR20 response, and magnitude of ACR response. Anakinra was safe and well tolerated. Injection site reaction was the most frequently noted adverse event, and this led to premature study withdrawal in 7% (1.0-mg/kg group) to 10% (2.0-mg/kg group) of patients receiving higher doses. CONCLUSION: In patients with persistently active RA, the combination of anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone. | |
| 12405893 | Remission of lymphoma after drug withdrawal in rheumatoid arthritis. | 2002 Nov 4 | A 63-year-old man with rheumatoid arthritis presented with pain and swelling of his right buttock. Imaging and tissue biopsy revealed a diffuse large B-cell, non-Hodgkin's lymphoma. The disease-modifying drugs he was taking, cyclosporin and methotrexate, were stopped, and the lymphoma resolved spontaneously without the use of chemotherapy. | |
| 12195320 | [Tubulointerstitial nephritis and uveitis (TINU syndrome) - comorbidity and complications | 2002 Jul | BACKGROUND: TINU syndrome probably is a frequently overlooked disease where uveitis occurs in association with acute tubulointerstitial nephritis. Diagnostic criteria have been published recently. PATIENTS AND METHODS: In this retrospective case series the charts of four consecutive patients with TINU syndrome (follow-up 36, 23, 17, and 12 months, respectively) were analysed, including comorbidity and complications, and the literature was reviewed. RESULTS: Two patients were treated with methotrexate or ciclosporin A and mycophenolate mofetil. In one patient autoimmune thyroiditis was known. During the follow-up, symptoms indicative of rheumatoid arthritis were observed. Because of her uveitis she required methotrexate therapy. Three patients were obese (mean BMI 32.2 kg/m (2)). Ocular complications were posterior synechiae (two patients) and papillary and macular oedema (three patients). One patient developed cerebrospinal hypertension under ciclosporin A treatment which resolved after discontinuation of therapy. CONCLUSIONS: Patients with definite TINU syndrome frequently suffer from other diseases and associated immune phenomena. The course of the disease can vary considerably. Complications do occur, despite overall good prognosis. Regional and systemic steroids may be sufficient; frequently steroid sparing immunosuppressives are necessary at least temporarily. Patients with this multiorgan disease do need to be followed by a paediatrician or a medical specialist. | |
| 15497523 | Noncardiogenic pulmonary edema in low-dose oral methotrexate therapy. | 2004 Sep | In the past two decades, low-dose methotrexate (MTX) has been widely used in the treatment of rheumatoid arthritis (RA). As adverse effects, various types of pulmonary toxicity have been reported with this therapy. We report a case of MTX-induced noncardiogenic pulmonary edema in a 35-year-old woman. MTX used in high dose for anti-cancer therapy is known to cause non-cardiogenic pulmonary edema. However, there are no previous reports of noncardiogenic pulmonary edema caused by low-dose MTX therapy. This report suggests that patients receiving oral weekly, low-dose MTX may be at risk for the development of noncardiogenic pulmonary edema. | |
| 15550533 | Cost effectiveness of adalimumab in the treatment of patients with moderate to severe rheu | 2005 Jul | BACKGROUND: Societal decision makers increasingly emphasise their need for evidence based economic analyses to make reimbursement decisions. OBJECTIVE: To analyse the cost utility of adalimumab, on both incremental cost and incremental quality adjusted life years (QALYs), versus traditional disease modifying antirheumatic drugs and the other tumour necrosis factor (TNF) antagonists suitable for submission to the Swedish LFN (Pharmaceutical Benefit Board). METHODS: Swedish unit costs and treatment guidelines from a lifetime perspective were implemented. A mathematical model, incorporating data from seven trials, simulated the experiences of 10 000 hypothetical patients with moderate to severe rheumatoid arthritis (RA). The primary outcome measure-QALYs-was derived from utility values calculated from a relationship between the Health Assessment Questionnaire (HAQ) Disability Index (DI) and Health Utility Index-III (HUI-3) from adalimumab trial results. The model followed the progression of HAQ-DI through a number of treatments in a sequence accounting for mortality, drug and monitoring costs, and other direct costs. RESULTS: When using ACR50 as a response threshold for determining successful treatment, adalimumab plus methotrexate showed the greatest number of QALYs gained (2.3 from one study and 2.1 from the pooled results of two trials). The etanercept plus methotrexate strategy yielded QALY gains similar to the pooled adalimumab results. Except for the infliximab strategy, the costs results were between 35 000 and 42 000, a range normally considered cost effective in other European countries. CONCLUSION: Adalimumab appears to be cost effective for the treatment of moderate to severe RA. The results suggest that adalimumab is at least as cost effective as other TNF antagonists. | |
| 15187208 | Leflunomide-associated pancytopenia with or without methotrexate. | 2004 Jul | OBJECTIVE: To report 18 cases of pancytopenia associated with leflunomide use in Australia, 5 of which were treated at Princess Alexandra Hospital, Brisbane. case summaries: Leflunomide was used in the treatment of rheumatoid arthritis in 17 of 18 patients; the other patient was diagnosed with systemic lupus erythematosus. Median age was 65.5 years (range 18-79), and 15 of the patients were female. Fourteen patients were on combined treatment with methotrexate. Pancytopenia was typically severe, requiring hospital admission, withdrawal of the immunosuppressant(s), intensive supportive therapy, and treatment of neutropenic sepsis. Five patients died, 4 of whom were receiving concomitant methotrexate. Time to onset of pancytopenia ranged from 11 days to 4 years (median 4 mo). In one case in which the patient had been stable while receiving leflunomide, methotrexate, and hydroxychloroquine for 4 years, fatal pancytopenia was triggered by acute renal failure secondary to dehydration and use of nonsteroidal antiinflammatory drugs. The Naranjo probability scale suggested a probable causal association in 5 cases and possible association in the remainder. DISCUSSION: Leflunomide, indicated for treatment of active rheumatoid arthritis, inhibits pyrimidine synthesis in lymphocytes and other rapidly dividing cells and may rarely be associated with life-threatening pancytopenia. Combination therapy with methotrexate may increase the risk. Time to onset is variable, and clinicians should remain vigilant, particularly when there is a change in the patient's baseline health status. CONCLUSIONS: The risk of pancytopenia during leflunomide therapy appears to be increased when the drug is combined with methotrexate and in older patients. Onset may be delayed, and ongoing monitoring of blood counts is essential. | |
| 15361377 | Better efficacy of methotrexate given by intramuscular injection than orally in patients w | 2004 Oct | OBJECTIVE: To compare the clinical efficacy of methotrexate and tolerance to the drug in patients with rheumatoid arthritis who were switched from intramuscular to oral administration because of a shortage of the intramuscular preparation. METHODS: 143 patients were switched from intramuscular to oral methotrexate. Of these, 47 were switched back to the intramuscular form. A multiple choice questionnaire was sent by mail to evaluate clinical and biological criteria of efficacy and tolerance. RESULTS: When methotrexate was first switched from intramuscular to oral administration, increased disease activity, exacerbation of morning pain and hand stiffness, duration of morning stiffness, increased joint pain, and increased joint swelling were observed. There was a greater frequency of gastrointestinal symptoms, but without a significant increase in liver abnormalities. When intramuscular methotrexate became available again, 47 of the 143 patients were switched back and were followed for at least three months. On average, disease manifestations were improved and side effects reduced by the switch. CONCLUSIONS: Methotrexate given intramuscularly had improved clinical efficacy with fewer side effects than given orally. Intramuscular methotrexate administration should be considered when rheumatoid arthritis remains active in spite of high dose oral methotrexate. | |
| 12475006 | Drug-induced lupus following treatment with infliximab in rheumatoid arthritis. | 2002 | After introduction of infliximab for the treatment of rheumatoid arthritis (RA), there have been many reports of patients developing asymptomatic higher rate of antinuclear antibodies and anti-dsDNA antibodies than in non-infliximab-treated patients. However, only five clinical drug-induced lupus (DIL) cases have been documented following treatment with infliximab, in RA and in Crohn's diseases. We report a case of a 69-year-old female with a 5 year history of RA, whowas successfully treated with low-dose methotrexate (MTX) and infliximab (initially 3 mg/kg and from the fourth infusion 5 mg/kg) for 23 weeks. Before the sixth infusion, she was diagnosed with DIL by both clinical features (fever > 38 degrees C, recurrence of active synovitis, myalgia, erythematous rash and general malaise) and laboratory findings (antinuclear antibodies 1:160, anti-double-stranded DNA positive by ELISA assay, decreased serum complement C3 andC4, hypergammaglobulinaemia, increased erythrocyte sedimentation rate). After discontinuation of treatment and therapy with oral prednisone, lupus resolved within 8 weeks. | |
| 14668929 | Role of adalimumab, a novel TNF antagonist in advancing rheumatoid arthritis control. | 2003 | Adalimumab was approved by the U.S. Food and Drug Administration in 2002 for the treatment of moderate to severe rheumatoid arthritis and was granted approval from the European Medicines Evaluation Agency (EMEA) in September 2003. The standard dose is 40 mg given subcutaneously every other week, and the drug can be used alone or in combination with disease-modifying antirheumatic drugs such as methotrexate. The efficacy of adalimumab has been demonstrated in clinical trials with more than 2400 patients. In these trials, adalimumab has acted rapidly to reduce the signs and symptoms of disease, with responses sustained over the long term. The significant inhibition of disease progression seen with adalimumab has led to significant improvements in physical function and health-related quality of life. Data from the clinical safety database in nearly 2500 patients have also shown that the drug is generally safe and well-tolerated. | |
| 11817593 | Association of baseline levels of urinary glucosyl-galactosyl-pyridinoline and type II col | 2002 Jan | OBJECTIVE: To evaluate whether measurements of urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II), 2 new markers of destruction of the synovium and cartilage collagen breakdown, respectively, are associated with the progression of joint damage in patients with early rheumatoid arthritis (RA), and to compare this association with that with serum matrix metalloproteinase 3 (MMP-3), a proteinase expressed by synovial tissue and chondrocytes, and that with serum C-reactive protein (CRP), an index of systemic inflammation. METHODS: The prospective study cohort comprised 116 patients with early RA who were part of a large, double-blind, randomized study comparing the efficacy of etanercept and methotrexate. The relationship between baseline levels of urinary Glc-Gal-PYD, urinary CTX-II, and serum MMP-3 and the progression of joint destruction, as measured by changes in the modified Sharp score (average findings of 2 independent readers) over 1 year, was investigated. RESULTS: Levels of urinary Glc-Gal-PYD (+70%), urinary CTX-II (+104%), and serum MMP-3 (+219%) were elevated compared with the levels in 76 healthy controls. The baseline levels of Glc-Gal-PYD (r = 0.30), CTX-II (r = 0.25), and MMP-3 (r = 0.29) correlated with the changes over 1 year in the total Sharp score (joint space narrowing and bone erosion). Patients with baseline levels of Glc-Gal-PYD, CTX-II, and MMP-3 that were higher than the mean + 2 SD in healthy controls had a significantly greater progression of joint damage, with an increase in the total Sharp score over 1 year that was from 3- to 8-fold higher than that in patients with low baseline levels of these markers. Moreover, patients with these higher levels of Glc-Gal-PYD, CTX-II, and MMP-3 had a higher risk of progression of the disease (increase in total Sharp score > or =0.5 units) than did the other patients (relative risks and 95% confidence intervals [95% CI] 3.3 [95% CI 1.5-7.4], 2.5 [95% CI 1.1-5.7], and 2.5 [95% CI 1.1-5.6], respectively). The baseline serum level of CRP was not significantly associated with the progression of joint damage. Adjustment of the levels of Glc-Gal-PYD, CTX-II, and MMP-3 according to radiologic damage at baseline did not alter their association with progression. After adjustment for serum CRP, the relative risk slightly decreased, but remained significant, for Glc-Gal-PYD (2.6 [95% CI 1.1-6.3]). Patients with both increased levels of the molecular markers and radiologic damage at baseline had a higher risk of progression of joint damage than did those with either high molecular marker levels or radiologic damage. CONCLUSION: High baseline levels of Glc-Gal-PYD, CTX-II, and MMP-3 are associated with increased risk of progression of joint destruction over 1 year in early RA. The association between baseline levels of urinary Glc-Gal-PYD and progression of joint erosion was independent of the severity of radiologic damage and inflammation at baseline. Combining the measurements of these molecular markers with radiologic assessment of joint damage may be useful for identifying patients with RA who are at high risk of rapid progression and for whom early aggressive treatment would be beneficial. | |
| 12137712 | Infliximab for the treatment of rheumatoid arthritis. | 2002 | BACKGROUND: Infliximab is a human murine chimeric anti-tumour necrosis factor alpha monoclonal antibody recently approved for the treatment of refractory RA. OBJECTIVES: To assess the efficacy and safety of infliximab for the treatment of rheumatoid arthritis. SEARCH STRATEGY: Electronic databases including Biological Abstracts, CINAHL, Current Contents, Dissertation Abstracts, EBM Reviews, HealthSTAR and MEDLINE were searched from 1966 to March 2002. Rheumatoid arthritis was searched as an exploded MESH heading. Infliximab was searched as a text word as it is not currently indexed. The search was not limited by language, year of publication or type of publication. The specific search strategy is shown below. SELECTION CRITERIA: All randomized controlled trials comparing infliximab 1, 3, 5 or 10 mg/kg with methotrexate(MTX) to MTX alone, or without MTX to placebo, with a minimum duration of 6 months and at least 2 infusions were eligible. DATA COLLECTION AND ANALYSIS: Data was extracted by 2 independent reviewers and the methodological quality of the trials was assessed using a validated assessment tool scale. Outcome variables included the ACR core set of disease activity measures for RA clinical trials and radiographic outcome data. Withdrawals and toxicity were also included. End of trial results were pooled. Continuous data were pooled using weighted mean differences and dichotomous data using relative risks. MAIN RESULTS: Two trials with a total of 529 patients met the inclusion criteria. Patients fulfilling the American Rheumatism Association 1987 RA diagnostic criteria were randomized to receive either infliximab 1mg/kg (with and without MTX), 3mg/kg(with and without MTX), 10mg/kg of infliximab (with and without MTX) or placebo infusion plus MTX. Infusions were given every 4 or 8 weeks. After 6 months ACR 20, ACR 50 and ACR 70 response rates were significantly improved in all infliximab doses compared to control. The number needed to treat with infliximab to achieve an ACR 20, 50 or 70 response in patients with refractory RA under specialist care ranged from 2.9 to 3.3 for ACR 20, 3.6 to 4.8 for ACR 50 and 5.9 to 12.5 for ACR 70 depending on the dose (3mg/kg or 10mg/kg given either every 4 or 8 weeks). Total withdrawals and withdrawals due to lack of efficacy were lower for all doses of infliximab versus controls. Withdrawals for adverse events and withdrawals for other reasons were not statistically significantly different for those receiving infliximab from control. REVIEWER'S CONCLUSIONS: Treatment with infliximab for 6 and 12 months significantly reduces RA disease activity and appeared to have an acceptable safety profile in these trials. Total radiographic scores improved, fewer patients showed radiographic progression, and more patients showed radiographic improvement with infliximab treatment at 12 months compared to controls. However, only 2 trials met the inclusion criteria, and these results are largely driven by the largest trial. The available efficacy and toxicity data is relatively short-term (6-12 months). In order to detect rare events that may be associated with infliximab, larger and longer term studies are required. | |
| 15228617 | Does route of administration affect the outcome of TNF antagonist therapy? | 2004 | The tumor necrosis factor (TNF) antagonists are parenterally administered biologic response modifiers indicated for the management of rheumatoid arthritis. Although infliximab, etanercept, and adalimumab are all members of this class, they differ in route of administration and dosing regimen. In the USA and in Europe, infliximab, in combination with oral methotrexate, is administered intravenously, initially at a dose of 3 mg/kg at weeks 0, 2, and 6, then every 8 weeks thereafter. The US Food and Drug Administration (FDA) has further approved that the dosage can be increased to 10 mg/kg and the doses can be given as often as every 4 weeks to optimize patient outcome (information based on the US package insert dated June 2002). Etanercept and adalimumab are given subcutaneously and can be self-injected. The FDA-approved dose of etanercept is 25 mg twice weekly, and of adalimumab is 40 mg every 2 weeks with methotrexate, or 40 mg alone. Medication adherence, possibly the most important factor in maintaining the benefits of anti-TNF therapy, is influenced by the interaction between the patient and his or her healthcare team, the patient's attitude toward the disease and medication regimen, and the choice of therapy. | |
| 14657632 | Erythema multiforme-like drug eruption with oral involvement after intake of leflunomide. | 2003 | Leflunomide is an antirheumatic agent of the type of a 'disease-modifying antirheumatic drug'. In rare cases, severe skin reactions up to the extreme expression of toxic epidermal necrolysis have been observed. A female patient with rheumatoid arthritis had been treated with systemic steroids and methotrexate for 2 years. Five weeks prior to admission to our hospital methotrexate was replaced by leflunomide. Three weeks after initiation of leflunomide therapy a progressive generalized erythema with blistering formation occurred accompanied by increase of body temperature, chills and erosive lesions on the lips and oral mucosa. The palmar and plantar surfaces revealed edema, erythema and pulpitis with epidermolysis. On histologic examination necrotic keratinocytes and epidermal spongiosis were observed. After administration of high-dose prednisolone and topical treatment the patient recovered within 14 days. This is one of the few cases of severe drug reaction after intake of leflunomide. Therefore, the indication of this relatively new drug should be considered carefully. | |
| 15121040 | An economic approach to health care. | 2004 Apr | Economic analyses have the potential to put all of the positive and negative outcomes of an intervention into perspective to aid decision making. The quality of the data upon which the analysis is based has an impact on the resulting quality of the analysis itself. Analysis of cost-effectiveness requires the input of many types of data, and where data are not available, assumptions must be made. There are many instances where the analysis may go wrong, and it is important to remain cognizant of these. The critical parts of the analysis, which have also been identified in quality assessment tools, include the following: design of the study question, sources of probability estimates and cost data, sensitivity analysis, and the interpretation of results. If the readers are able to identify the assumptions of the analysis they are better equipped to judge the validity. We have reviewed economic analyses relating to two hot economic topics in rheumatology. These are the cost-effectiveness of cyclooxygenase-2 (COX-2) inhibitors for 'arthritis' and cost-effectiveness of anti-tumor necrosis factor alpha (anti-TNF) agents for rheumatoid arthritis (RA). The results of the COX-2 analyses vary by review. Some show cost savings, while others calculate a significant cost in order to achieve any change in quality of life. Given the unanswered questions that still exist, it seems reasonable to conclude that COX-2 inhibitors may be cost effective when used in patients at a high risk of GI complications. Unanswered questions remain regarding the concomitant use of low-dose ASA and proton pump inhibitors and how they may affect the results of these economic analyses. The cost-effectiveness of anti-TNF agents has not been explored in as much detail as that of the COX-2 agents. Two studies have presented cost-effectiveness models that include a hypothetical biologic agent. Two economic analyses report on the cost-effectiveness of etanercept compared with traditional disease-modifying anti-rheumatic drugs (DMARDs) in methotrexate-resistant and methotrexate-naïve patients with RA. Both the analyses show that etanercept has a cost-effectiveness ratio of around 40,000 US dollars for every patient who achieves an American College of Rheumatology 20% improvement score (ACR 20) within a 6-month period. A cost-utility analysis was published regarding the use of infliximab in methotrexate resistant RA. It showed a cost-utility ratio of 3400:34,000 Euro per quality adjusted life year (QALY) gained, depending on the country evaluated (Sweden and the UK, respectively). An important finding in all three studies was that indirect costs dominate costs in RA; therefore, they should be included in all future analyses of this disease. |