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ID PMID Title PublicationDate abstract
19369462 Less radiographic progression with adalimumab plus methotrexate versus methotrexate monoth 2009 Jul OBJECTIVE: To determine the relationship between radiographic progression and clinical response for adalimumab plus methotrexate (MTX) versus either monotherapy in patients with early rheumatoid arthritis (RA) in the PREMIER study. METHODS: Patients with early RA who received adalimumab plus MTX (n = 240), adalimumab (n = 222), or MTX (n = 216) were grouped by American College of Rheumatology (ACR) response, 28-joint Disease Activity Score (DAS28), or remission-like state [tender joint count (TJC) = 0; DAS28 < 2.6; swollen joint count = 0; ACR100] at 26 and 104 weeks. Radiographic progression was assessed by cumulative probability plots, mean changes in total Sharp score (DeltaTSS), and percentages of progressors (DeltaTSS > 0.5). RESULTS: Across the spectrum of clinical outcomes, including ACR20 nonresponses and remission-like responses, therapy with adalimumab plus MTX permitted less radiographic progression at Weeks 26 and 104 than MTX monotherapy. Adalimumab monotherapy was generally intermediate. A strong, proportional relationship was observed between clinical response and radiographic efficacy only for MTX monotherapy. The monotherapies approximated the radiographic efficacy of adalimumab plus MTX only among remission-like responders, although progression was significantly greater with MTX monotherapy versus adalimumab plus MTX for patients with TJC = 0. Concurrent clinical (DAS28 < 2.6) and radiographic (DeltaTSS
20859224 Oral tuberculosis in a patient with rheumatoid arthritis after long treatment with methotr 2010 Oct The treatment of rheumatoid arthritis (RA) with tumor necrosis factor α (TNF-α) inhibitors has been associated with an increased risk of tuberculosis (TB). Most patients have extrapulmonary disease. We describe a case of tonsil TB in an RA patient treated with methotrexate for 23 years and adalimumab (TNF-α inhibitor) for the last 3 years after an initial negative PPD (purified protein derivative of tuberculin) skin test. Our patient presented with a tonsil ulcer. PPD skin test was now positive; biopsy result of the lesion revealed Mycobacterium tuberculosis on culture, and a granuloma typical of TB on histologic assessment. The patient received antituberculous treatment with complete resolution of the lesion. This case illustrates that oral TB can occur after long treatment with TNF-α inhibitor and that tuberculous granulomas can be formed in such patients.
20536605 A case of emphysematous pyelonephritis in a patient with rheumatoid arthritis taking corti 2010 May Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by chronic synovial inflammation. Patients with RA have increased risk of infection; this is related to RA itself or the adverse effects of medication. In this report, we describe a case of emphysematous pyelonephritis in a patient with RA associated with AA amyloidosis and steroid-induced diabetes mellitus who was taking corticosteroid and low-dose methotrexate.
20186043 Viruses and arthritis: new challenges in diagnosis, therapy, and immunization. 2010 Jun BACKGROUND: Although many viruses produce musculoskeletal symptoms during an acute infection, a long-term inflammatory arthritis remains an unusual consequence. When evaluating arthritis in a patient with a chronic or latent viral infection, serologic testing and therapeutic options are significantly altered. RESULTS: The example of hepatitis C reveals how chronic infection can complicate the diagnosis of rheumatoid arthritis. Determination of rheumatoid factor is of limited utility, whereas the anticyclic citrullinated peptide has become a new test with improved specificity. Therapeutic options are severely constrained because of potential hepatotoxicity of oral agents such as methotrexate and leflunomide. Antitumor necrosis factor alpha biologics have demonstrated initial safety in the setting of hepatitis C virus but may be associated with reactivation of hepatitis B virus. Biologics such as abatacept and rituximab have been inadequately studied in this population to date. Prevention of viral infections by influenza and herpes zoster vaccines in rheumatoid arthritis patients needs improved administration rates and careful planning to maximize efficacy. CONCLUSIONS: Chronic viral infections complicate the diagnosis and therapy of inflammatory arthritis. The antitumor necrosis factor alpha biologics have become important therapeutic options for patients with hepatitis C. Vaccination against influenza and herpes zoster are underused in health maintenance of arthritis patients.
20678592 The effect of pharmacological therapy on the cardiovascular system of patients with system 2010 Oct The higher mortality rate among rheumatoid arthritis (RA) patients in comparison with the general population is largely attributable to cardiovascular (CV) disease, particularly coronary atherosclerosis, but also non-fatal myocardial infarction and heart failure. It may be due to RA-specific risk factors such as hyperhomocysteinemia, disease-related dyslipidemia or vascular inflammation, or morbidity related to high levels of cytokines such as tumour necrosis factor (TNF) and RA medications. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most important in rheumatology, but many are associated with CV disease. A number of randomised control trials have shown that, although exposure to low doses of corticosteroids for 1-3years does not significantly increase CV risk, longer exposure can increase CV events. The use of disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate, increases homocysteinemia, reduces inflammation and improves lipid profiles, thus reducing the development of atherosclerosis and clinically overt CVD. Although contraindicated in RA patients with severe heart failure, biological agents such as anti-TNF agents delay and even reverse the progression of endothelial dysfunction and atherosclerosis. Tocilizumab leads to changes in lipid profiles without increasing adverse vascular events. The effects on the CV system depend on the drug itself, the dose and the period of exposure, and so CV risk should be evaluated before starting treatment with any drug.
20514079 Polymorphisms C677T and A1298C in the MTHFR gene in Mexican patients with rheumatoid arthr 2011 Aug Rheumatoid arthritis (RA) is the prototype of the rheumatic diseases worldwide. Methotrexate (MTX) is the drug of first choice in the treatment of this disease due to its immunosuppressant effect. However, side events are present in 30% of the patients. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are involved in the metabolism of MTX. Earlier studies reported an association between these polymorphisms and elevation of hepatic enzymes. We analyzed the frequencies of both polymorphisms and the presence of transaminasemia in 70 Mexican patients with rheumatic arthritis treated with MTX. The 19% (13/70) of patients had an increase in the serum level of transaminases. The A1298C polymorphism was associated with elevation of transaminases (P=0.024). The identification of MTHFR genotypes for C677T and A1298C polymorphisms could lead clinicians to identify patients in risk of elevation of transaminases, and give them an individualized treatment, as is a goal of pharmacogenetics.
18801760 Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analy 2009 Jul OBJECTIVE: The effect of adalimumab on hand osteoporosis was examined and related to radiographic joint damage in the three treatment arms of the PREMIER study: adalimumab plus methotrexate, adalimumab and methotrexate monotherapy. Predictors of hand bone loss were also searched for. METHODS: 768 patients (537 fulfilled 2 years) with rheumatoid arthritis (RA) for less than 3 years, never treated with methotrexate, were included. Hand bone loss was assessed by digital x ray radiogrammetry (DXR) on the same hand radiographs scored with modified Sharp score at baseline, 26, 52 and 104 weeks. For DXR, metacarpal cortical index (MCI) was the primary bone measure. RESULTS: At all time points the rate of percentage DXR-MCI loss was lowest in the combination group (-1.15; -2.16; -3.03) and greatest in the methotrexate monotherapy group (-1.42; -2.87; -4.62), with figures in between for the adalimumab monotherapy group (-1.33; -2.45; -4.03). Significant differences between the combination group and the methotrexate group were seen at 52 (p = 0.009) and 104 weeks (p<0.001). The order of hand bone loss across the three treatment arms was similar to the order of radiographic progression. Older age, elevated C-reactive protein and non-use of adalimumab were predictors of hand bone loss. CONCLUSION: This study supports a similar pathogenic mechanism for hand bone loss and erosions in RA. The combination of adalimumab and methotrexate seems to arrest hand bone loss less effectively than radiographic joint damage. Quantitative measures of osteoporosis may thus be a more sensitive tool for assessment of inflammatory bone involvement in RA.
18957487 Progression of radiographic joint damage in rheumatoid arthritis: independence of erosions 2009 Oct OBJECTIVE: To compare the progression of erosions and joint space narrowing (JSN) in patients with early active rheumatoid arthritis (RA) using data obtained in the "Active-controlled Study of Patients receiving Infliximab for the treatment of Rheumatoid arthritis of Early onset" (ASPIRE) study. METHODS: This was a post hoc analysis of patients in ASPIRE who received placebo plus methotrexate (MTX) or infliximab (3 or 6 mg/kg) plus MTX. Radiographs of the hands (870 patients) and feet (871 patients) were obtained at baseline and week 54 and scored using the van der Heijde/Sharp method. In total, 7160 joints in the placebo plus MTX group and 18,908 joints in the combined infliximab plus MTX group were included in this analysis. RESULTS: At baseline, 83.4% of joints in the placebo plus MTX group had no radiographic damage, 8.5% had only erosions, 4.4% had only JSN and 3.7% had both. The distribution was similar in the infliximab plus MTX group. In the placebo plus MTX group, the majority of joints did not have development or progression of radiographic damage from baseline to week 54; among joints that did have development or progression of damage at week 54, erosions occurred more often than JSN. The same pattern was observed in the infliximab plus MTX group, although the proportions of joints with damage at week 54 were generally larger in the placebo plus MTX group. There was a tendency for joints with existing erosions or JSN to have progression of damage, rather than development of new damage. CONCLUSIONS: Erosions were the predominant type of damage observed in both treatment groups. Erosions and JSN are related but partly independent processes.
19707765 A systematic review and meta-analysis of the efficacy and safety of adalimumab for treatin 2010 Jun Adalimumab (ADA) is a monoclonal antibody. Published studies indicate that its use in patients with rheumatoid arthritis can be efficient in providing long-term benefits. The aim of this study is to evaluate the efficacy and safety of ADA for treating rheumatoid arthritis. A systematic review was performed to search for randomized clinical trials that compare subcutaneous doses of ADA 20 mg weekly or 40 mg every other week with placebo, with or without concomitant methotrexate. Only studies of moderate or high quality were included. A meta-analysis was conducted to assess the efficacy (based in changes of American College of Rheumatology ACR criteria) and the safety (based in serious adverse events, serious infections, malignancy and deaths) of ADA use. Withdrawals due to adverse events or lack of efficacy were also evaluated. Eight studies met the inclusion criteria, comprising 2,692 patients. In the efficacy meta-analysis, a greater number of ADA-treated patients relative to those in placebo group achieved ACR20, ACR50 and ACR70 values from 6 months to 2 years of treatment. For safety results, there were no statistically significant differences between the groups. Withdrawals due to adverse events were higher in ADA group relative to the placebo group, and withdrawals due to the lack of efficacy were higher in placebo group relative to the ADA-treated group. This meta-analysis shows a higher efficacy of ADA relative to placebo, but clinicians should be careful regarding adverse events in ADA-treated patients.
21044427 Increases in use of methotrexate since the 1980s. 2010 Sep In this chapter, we review the use of DMARDs in several clinical RA cohorts and databases between the 1970s and the 2000s. The DMARD profile in the QUEST-RA database provides an overview of clinical use of MTX in recent years in 25 countries. The data show that (I) MTX is currently the most frequently used DMARD in RA, and (II) that this development has taken about 20 years to emerge.
21044425 Methotrexate: from its introduction to non-oncologic therapeutics to anti-TNF-α. 2010 Sep The history of the rheumatologic use of methotrexate until the 1990s will be reviewed, beginning with its pharmacology, with the focus on rheumatoid arthritis (RA). The insufficient availability of cortisone in the 1950s as well as the early recognition of its potential toxicity stimulated searches for alternative anti-inflammatory drugs. Two related derivatives of folic acid, aminopterin and amethopterin (MTX,) were found to give rapid symptomatic relief in cases of psoriasis vulgaris and psoriatic arthritis. For several years MTX was used primarily to treat psoriasis, and the dermatologic treatment protocols came to be used by rheumatologists. Giving MTX weekly rather than daily was found to diminish the risk of toxic effects. MTX became favoured over cyclophosphamide because of its lack of carcinogenicity, and although azathioprine lacked the hepatotoxicity of MTX, its anti-rheumatic effects were considered to be somewhat weaker. Although trials of MTX for the treatment of severe RA began in the 1960s, the first placebo-controlled study of MTX in RA was reported in 1985 and a comparison with Myochrysine in 1987. MTX has replaced gold compounds because it has been found to be more rapidly effective and better tolerated. The mechanisms of its anti-rheumatic effects remain incompletely explained, as are explanations of instances of its failure. Its recent use in combination with anti-TNFα agents appears to be another therapeutic advance.
20576092 Early combination disease-modifying antirheumatic drug therapy and tight disease control i 2010 INTRODUCTION: Early treatment of rheumatoid arthritis (RA) has been shown to retard the development of joint damage for a period of up to 5 years. The aim of this study was to evaluate the radiologic progression beyond that time in patients with early RA initially treated with a combination of three disease-modifying antirheumatic drugs (DMARDs) or a single DMARD. METHODS: A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone (FIN-RACo), or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone (SINGLE). After 2 years, the drug-treatment strategy became unrestricted, but still targeted remission. The radiographs of hands and feet were analyzed by using the Larsen score at baseline, 2, 5, and 11 years, and the radiographs of large joints, at 11 years. RESULTS: Sixty-five patients in the FIN-RACo and 65 in the SINGLE group had radiographs of hands and feet available at baseline and at 11 years. The mean change from baseline to 11 years in Larsen score was 17 (95% CI, 12 to 26) in the FIN-RACo group and 27 (95% CI, 22 to 33) in the SINGLE group (P=0.037). In total, 87% (95% CI, 74 to 94) and 72% (95% CI, 58 to 84) of the patients in the FIN-RACo and the SINGLE treatment arms, respectively, had no erosive changes in large joints at 11 years. CONCLUSIONS: Targeting to remission with tight clinical controls results in low radiologic progression in most RA patients. Patients treated initially with a combination of DMARDs have less long-term radiologic damage than do those treated initially with DMARD monotherapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18445519.
20191522 Improvement in work place and household productivity for patients with early rheumatoid ar 2010 Feb OBJECTIVE: To evaluate household and work place outcomes for patients with rheumatoid arthritis (RA) who were homemakers or employed workers, respectively, and who were treated with adalimumab plus methotrexate versus methotrexate monotherapy. We also determined baseline predictors of household and work place outcomes. METHODS: Data were from a health economic companion study to PREMIER, a 2-year, randomized controlled trial of methotrexate-naive patients with early RA (<3 years) who received treatment with adalimumab plus methotrexate, adalimumab, or methotrexate. Absenteeism (number of days missed or unfit to work), presenteeism (self-judgment of the effects of RA on job or household performance), and employment status were collected from self-reports at baseline and varying time points during the study. RESULTS: Household and work place outcomes were generally similar for homemakers and employed workers. Over 2 years, patients who received combination therapy missed approximately half as many days as patients who received methotrexate (17.4 versus 36.9 days for employed workers; 7.9 versus 18.6 days for homemakers). Presenteeism was lower (reflecting better productivity) for combination therapy than methotrexate monotherapy. The likelihood of gaining/retaining employment over 2 years was greater for combination therapy than methotrexate monotherapy (odds ratio 1.530, 95% confidence interval 1.038-2.255; P = 0.0318). Baseline radiographic progression was an independent predictor for retaining/gaining employment at 2 years. CONCLUSION: Compared with methotrexate monotherapy, combination therapy was associated with more positive work outcomes: less absenteeism, less presenteeism, and greater likelihood of gaining/retaining employment. Radiographic progression at baseline was predictive of the ability to retain or gain employment.
20017457 Serum and synovial fluid concentrations of CCL2 (MCP-1) chemokine in patients suffering rh 2009 OBJECTIVE: To determine serum and synovial fluid (SF) concentrations of monocyte chemoattractant protein-1 (MCP-1) or CCL2 chemokine, in patients suffering (RA) and osteoarthritis (OA) and to correlate the values to disease activity, and other patient- and disease-related parameters. METHODS: The CCL-2/MCP-1 chemokine (CK) was measured in serum and SF of 30 RA and 15 OA patients using specific and very sensitive ELISA assay. RESULTS: The CCL2/MCP-1 CK was found in increased amounts in SF compared to serum (p < 0.001) and in RA compared to OA patients (p < 0.001). The values were significantly greater in RA patients with more active disease. Greater mean SF concentrations were observed in older RA patients, in patients with longer duration of RA disease and in those who had been treated with methotrexate. Also positive correlation was found between RA SF concentrations and SF leukocyte numbers (r = 0.497, p < 0.05). CONCLUSIONS: The SF and serum CCL2/MCP-1 concentrations are significantly greater in RA than in OA and in hda-RA than in mda-RA; increased SF over serum concentrations suggest that CCL2/MCP-1 is mainly produced locally by activated cells where it may exacerbate and sustain inflammation by attracting proinflammatory leukocytes, predominantly monocytes (Tab. 1, Fig. 2, Ref. 50). Full Text (Free, PDF) www.bmj.sk.
19417117 Anaphylactic reaction to anakinra in a rheumatoid arthritis patient intolerant to multiple 2009 May OBJECTIVE: To report a case of probable anaphylaxis due to anakinra in a patient with rheumatoid arthritis and multiple drug allergies. CASE SUMMARY: A 46-year-old Indian female with rheumatoid arthritis demonstrated distinct adverse reactions to all commercially available anti-tumor necrosis factor therapies, sulfasalazine, and hydroxychloroquine. Over a 4-year period her disease remained active during therapy with methotrexate and prednisone. Biologics were added sequentially, with development of intolerable reactions, first to infliximab (urticarial rash, infusion reactions) after 3 doses, and then to etanercept (autoantibodies, worsening Raynaud's phenomenon, digital microinfarcts) after 1 year. Following 2 months of daily injections of anakinra, she experienced an immediate immunoglobulin E-mediated anaphylactic reaction within 20 minutes of an injection, as evidenced by positive testing to both anakinra and histamine with the skin prick method. The patient subsequently started adalimumab therapy, which was discontinued after the fourth dose due to the development of generalized hives. DISCUSSION: The Naranjo probability scale demonstrated a probable relationship between anaphylaxis and anakinra in this patient. Although cases of anakinra-related hypersensitivity have been reported in patients in which therapy was interrupted and then reintroduced, to our knowledge, this is the first report of anaphylaxis with continuous therapy. CONCLUSIONS: This unusual case of a patient with multiple drug allergies presents a difficult clinical scenario, which was unsuccessfully managed with multiple biologic therapies on a trial-and-error basis. In the future, pharmacogenetics may help to better identify individuals at risk for multiple drug reactions and preclude unnecessary exposure to potentially harmful therapeutic options in similar patients.
19559690 Lymphocyte transformation test is not helpful for the diagnosis of methotrexate-induced pn 2009 Sep BACKGROUND: The pathophysiology underlying methotrexate (MTX)-induced pneumonitis has been considered as a hypersensitive reaction. The lymphocyte transformation test (LTT) is frequently used to detect hypersensitivity. Whereas previous reports have proposed that the LTT is not ideal to detect hypersensitivity to MTX, it has not been directly confirmed. METHODS: Forty rheumatoid arthritis (RA) patients (24 patients currently taking MTX and 16 patients with a past history of MTX administration) and 13 healthy subjects were recruited. LTT with MTX was used to assess thymidine incorporation. An MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay was also performed. The mitogenic activity was expressed as the Stimulatory Index (SI). The activity of RA was assessed by the disease activity score 28 (DAS28). RESULTS: In the presence of MTX, the SI measured by the LTT and by the MTS assay showed an inverse correlation. The presence of MTX significantly elevated the SI values measured by the LTT. However, the SI values were significantly lower in RA patients currently taking MTX than those of patients not currently taking MTX, although DAS28 was not different. Furthermore, a past history of MTX-induced pneumonitis did not affect the SI values. CONCLUSION: LTT with MTX in RA patients is not appropriate to detect MTX-induced pneumonitis.
19473570 Disability measured by the modified health assessment questionnaire in early rheumatoid ar 2009 Mar OBJECTIVE: To analyze the rate and baseline prognostic factors of disability measured by the modified HAQ (MHAQ), in a series of patients with early rheumatoid arthritis (RA) after two years of therapy with a structured algorithm using disease-modifying anti-rheumatic drugs (DMARDs). METHODS: One hundred and five patients (81% female) with early RA (disease duration <2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for two years. The outcome was the absence of disability (MHAQ=0) after two years of DMARD therapy. Clinical, biological, immunogenetic and radiographic data (Larsen score) were analyzed at study entry and at 12 and 24 months of follow-up. RESULTS: The MHAQ decreased significantly at 6 months after initiation of DMARD therapy and the reduction was maintained at 24 months (mean+/-SD: 0.97+/-0.56 at baseline, 0.51+/- 0.57 at month 6 and 0.45+/-0.5 at month 24). No disability (MHAQ=0) was observed in 26.6% of patients after two years of follow-up. Age, MHAQ>0.5, DAS28>5.1, VAS pain, positive rheumatoid factor and ESR at baseline were associated with disability in the univariate analysis. In the logistic regression analysis, only age (OR: 1.058, 95%CI 1.017; 1.101 p<0.006), rheumatoid factor status (OR: 3.772 95%CI 1.204; 11.813, p<0.02) and MHAQ>0.5 (OR:4.023, 95%CI 1.373; 11.783, p<0.02) were associated with disability (MHAQ>0) at two years. CONCLUSION: In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids, no disability was observed in a quarter of patients after two years. Age, rheumatoid factor positivity and MHAQ>0.5 were independent predictors of disability at two years.
20574649 Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with a 2010 Dec The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX-naïve patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6-8 mg/week (the E + M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E + M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E + M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E + M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX.
19823840 Compliance with methotrexate treatment in patients with rheumatoid arthritis: influence of 2010 Sep Objective of the study is to investigate how compliance during the first year of methotrexate (MTX) treatment in rheumatoid arthritis (RA) is influenced by the patients' perception of the necessity for and concern about MTX, the patients' functional disability, and the dose of MTX. A total of 126 RA patients completed a questionnaire at start of MTX treatment and after 9 months. The MTX compliance was measured by using the Compliance Questionnaire Rheumatology (CQR). The prevalence of having a CQR score in the bottom quartile was stratified according to age, gender, the duration of RA, MTX dose, years of school education, functional disability, use of folic acid, and co-morbidity. Crude and adjusted prevalence ratios (PR) with 95% confidence intervals (CI) were calculated by using log-binomial regression. The necessity and concern scales of the Beliefs about Medication Questionnaire were dichotomised into high perception of MTX necessity and low concern about MTX treatment, and the crude and adjusted PR of having a CQR score in the bottom quartile were estimated. The prevalence of having a CQR in the bottom quartile was 23%, both at baseline and after 9 months, and this finding was not associated with the MTX dose level or the patients' functional disability. Among patients with a CQR in the bottom quartile, the prevalence of having low perceptions of MTX necessity was 37.1 versus 14.0% for patients with high perceptions of necessity [adjusted PR: 0.3 (95% CI 0.2-0.8)]. The same tendency was seen after 9 months. The prevalence of having a CQR in the bottom quartile or not was almost equally distributed among patients who had high or low concerns about treatment at baseline. After 9 months, however, the prevalence of having a CQR in the bottom quartile was 18.9% for patients who had low concerns about the MTX treatment, versus 37.7% for patients who had higher concerns about the treatment [adjusted PR: 0.5 (95% CI 0.2-1.3)]. During the first year of treatment, compliance with MTX treatment among RA patients could be explained by strong perceptions of a personal need for the treatment. Compliance did not seem to be influenced by the patients' functional impairment or the MTX dose level.
20560138 Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic ag 2010 Oct OBJECTIVE: To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents. METHODS: Randomized controlled trials in RA patients, investigating the effects of drug treatment on the percentage of the annual radiographic progression rate (PARPR) were included in a meta-analysis performed with the use of Review Manager 5.0 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. RESULTS: Data from 70 trials (112 comparisons, 16 interventions) were summarized in 21 meta-analyses. Compared with placebo, the PARPR was 0.65% smaller in the single-DMARD group (P < 0.002) and 0.54% smaller in the glucocorticoid group (P < 0.00001). Compared with single-DMARD treatment, the PARPR was 0.62% smaller in the combination-DMARD group (P < 0.001) and 0.61% smaller in the biologic agent plus methotrexate (MTX) group (P < 0.00001). The effect of a combination of 2 DMARDs plus step-down glucocorticoids did not differ from the effect of a biologic agent plus MTX (percentage mean difference -0.07% [95% confidence interval -0.25, 0.11]) (P = 0.44). CONCLUSION: Treatment with DMARDs, glucocorticoids, biologic agents, and combination agents significantly reduced radiographic progression at 1 year, with a relative effect of 48-84%. A direct comparison between the combination of a biologic agent plus MTX and the combination of 2 DMARDs plus initial glucocorticoids revealed no difference. Consequently, biologic agents should still be reserved for patients whose RA is resistant to DMARD therapy. Future trials of the effects of biologic agents on RA should compare such agents with combination treatments involving DMARDs and glucocorticoids.