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9273826 Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A 1997 Sep 1 BACKGROUND: Toxicity limits the use of methotrexate. OBJECTIVE: To identify risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. DESIGN: Case-control study. SETTING: One private and five academic rheumatology practices. PARTICIPANTS: Methotrexate recipients with rheumatoid arthritis with and without lung injury. MEASUREMENTS: Potential risk factors examined were sociodemographic and lifestyle characteristics, medical history, clinical and ancillary features and treatment of rheumatoid arthritis before methotrexate therapy, and characteristics of methotrexate therapy. Cases of lung injury were defined according to the modified criteria of Searles and McKendry. RESULTS: Ninety-four percent of the study participants were white, and 67% were women. Case-patients (n = 29) were older than controls (n = 82) (61.5 compared with 54.5 years of age). The strongest predictors of lung injury, after adjustment for other variables, were older age (odds ratio [OR], 5.1 [95% CI, 1.2 to 21.1]), diabetes (OR, 35.6 [CI, 1.3 to infinity]), rheumatoid pleuropulmonary involvement (OR, 7.1 [CI, 1.1 to 45.4]), previous use of disease-modifying antirheumatic drugs (OR, 5.6 [CI, 1.2 to 27.0]), and hypoalbuminemia (OR, 19.5 [CI, 3.5 to 109.7]). Previous use of disease-modifying antirheumatic drugs and hypoalbuminemia had very large attributable risks. CONCLUSION: Knowledge of the risk factors that predispose patients with rheumatoid arthritis to the toxic effects of methotrexate on the lung may provide a rationale for monitoring high-risk patients and may facilitate their management.
10446880 Hodgkin's disease and B cell lymphoproliferation in rheumatoid arthritis patients treated 1999 Aug We describe 2 patients with seropositive rheumatoid arthritis treated with methotrexate (MTX) who developed Hodgkin's disease (HD) and non-Hodgkin's lymphoma. Followup allowed a lymph node biopsy at 4 different time points in 1 patient and at 2 in the other. In the first patient, the steps included a long history of benign follicle hyperplasia, a polymorphic diffuse B cell lymphoproliferation, and finally HD unassociated with Epstein-Barr virus (EBV). In the second patient, a polymorphic diffuse lymphoproliferation was followed by a monomorphic large B cell lymphoproliferation associated with EBV. The cytogenetic analysis showed a monoclonal proliferation associated with the same chromosomal abnormalities found in 1 of the clones observed in the initial biopsy. These 2 cases illustrate the complexity of the role of MTX in the outbreak of such manifestations.
11053088 Etanercept (Enbrel): update on therapeutic use. 2000 Nov Tumour necrosis factor (TNF) is an important inflammatory disease mediator in a wide spectrum of articular diseases, including adult and juvenile rheumatoid arthritis (RA, JRA). Etanercept (Enbrel), approved in the United States and in Europe for use in patients with RA and JRA, is an effective inhibitor of TNF that has been shown to provide rapid and sustained improvement in both of these diseases. Long term studies continue to show that etanercept controls signs and symptoms of RA and JRA with no change in rate or type of adverse event over time. To demonstrate that etanercept is effective as first line treatment for patients with early active RA who have not been previously treated with methotrexate, and to examine the effect of etanercept on radiographic progression, a double blind, placebo controlled study was recently conducted, comparing etanercept with methotrexate (median dose 20 mg per week). Both etanercept 25 mg twice weekly and rapidly escalated methotrexate were effective in reducing the signs and symptoms of RA, and etanercept was significantly better than methotrexate in slowing the rate of radiographic erosions. In patients with severe psoriatic arthritis (PsA), a double blind, placebo controlled study demonstrated that etanercept was also effective in reducing disease activity in PsA. Etanercept has been well tolerated in all of these clinical trials and offers an important new treatment option to patients with inflammatory articular diseases.
9710893 Methotrexate and emerging therapies. 1998 Aug It is likely that all new therapeutic interventions will be used with methotrexate in combination therapy. These combinations may yield real therapeutic advances. The potential for end organ toxicity, opportunistic infection, and malignancy will need to be carefully monitored with long-term, meticulously conducted observational studies. Expense, ease of use, and perceived benefit-to-risk ratio will determine which new agents become most commonly prescribed with methotrexate.
10589360 Methotrexate and leflunomide combination therapy for patients with active rheumatoid arthr 1999 Nov An open-label, one-year study was conducted to evaluate the safety and clinical response to leflunomide and methotrexate combination therapy for rheumatoid arthritis. Study results revealed tolerable safety, no significant pharmacokinetic interactions between methotrexate and leflunomide, and suggested improved clinical response with combination therapy.
10410264 Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate wit 1999 May OBJECTIVES: To measure MTX polyglutamates in circulating erythrocytes (E-MTX), mononuclear cells (MNC-MTX) and polymorphs (PMN-MTX) in rheumatoid arthritis (RA) patients and to see whether these correlated with clinical efficacy and side effects. METHODS: Sixty-five patients (40F, 25M; mean age 57 yrs.) with RA (ARA revised criteria) who had been on weekly pulse MTX (2.5-37.5 mg) for at least 2 months were entered into this study. The patients were classified as responders (R), partial responders (PR) or non-responders (NR) when blood was sampled for the MTX determination. Side effects since the initiation of MTX were also recorded. MTX-polyglutamates were measured (blinded to clinical details) using an enzymatic assay. RESULTS: E-MTX in responders and partial responders were significantly higher (p < 0.001) than in non-responders. Similarly, PMN-MTX were also higher, but the difference was only significant for the R group (p = 0.0019). The differences in concentrations could not be explained on the basis of the dose, which tended to be higher in NR than in R (p = 0.085). The concommitant prednisolone dose was significantly lower in R than in NR (p = 0.001), as were the ESR and CRP (p = 0.007, and p = 0.05 respectively), but the MCV was higher (p = 0.047). E-MTX tended to be higher in patients with side effects, but this difference did not reach statistical significance (p = 0.15). CONCLUSION: The results suggest that circulating intracellular levels of MTX polyglutamates in RBC and PMN correlate with clinical efficacy but not with toxicity in patients with RA.
10357121 Efficacy and safety of a combination therapy of methotrexate, chloroquine and cyclophospha 1999 The efficacy and safety of a combination of methotrexate (MTX), chloroquine (CQ) and cyclophosphamide (CYC) were studied in patients with refractory rheumatoid arthritis. A single-centre, matched-pair observational study with prospectively gathered data was performed. Fifty-six patients who had previously failed with MTX were treated with 15 mg MTX per week, 50 mg CYC three times a week and 250 mg CQ per day (group A). A 50% improvement of the swollen joint count was required to continue therapy. Data were compared with the results of the previous MTX therapy in the same group and with a matched-patient cohort receiving MTX monotherapy for the first time (group B). In group A, the combination therapy resulted in a significant decline of the swollen joint count after 1 year, in contrast to the previous MTX monotherapy in the same group. Complete remission of joint swelling was achieved in 13 patients (23%), compared with 26 patients in group B (47%). The median duration of effective combination treatment in group A was significantly longer than preceding therapies with MTX alone (19 vs 13 months, p<0.05). However, patients in group B could be treated for a median of 57.5 months (p<0.0001 compared with group A). Side-effects were comparable in both groups. The applied DMARD combination is safe and beneficial in a significant proportion of patients if MTX monotherapy is ineffective.
11192489 Efficacy of sulphasalazine plus methotrexate in rheumatoid arthritis. 2000 Apr Early intervention with slow acting anti-rheumatic drugs (SAARDs) has led to improvement in substantial proportion of rheumatoid arthritis (RA) patients. The present open, controlled study was designed to assess whether a combination of SAARDs offer any added benefit. Fifty-four adult RA patients were randomly allocated to methotrexate (MTX) (n = 27) and MTX plus sulphasalazine (SSZ) (n = 27) groups. The subjects were followed-up fortnightly for four weeks then monthly for six months. The disease activity was assessed with the help of 10 clinical and four laboratory indices. The improvement was graded as: minor, mild decreases in indices, non-steroidal anti-inflammatory drugs (NSAIDs) continued, physician's global assessment (PGA) decreased by one; marked, acceptable decreases in indices, NSAIDs being taken sparingly, PGA decreased by at least 2, and complete, all indices normalised and patients discontinued NSAIDs completely. The improvement was considered clinically important when marked or complete improvement occurred. Adverse drug reactions resulted in withdrawal of 4 subjects from the MTX + SSZ group and 1 from the control groups. Four and three subjects in the combined and MTX groups respectively were lost to follow-up. Subjects in both groups showed significant decline in all indices except hemoglobin and neutrophil count. The differences between the two groups in the pre-treatment and post-treatment values were insignificant. Complete, marked, minor and no improvement occurred in 4 (21%), 12 (63%), 3 (16%) & 0 in the MTX and in 11 (48%), 7 (30%), 4 (17%) & 1 (4%) in MTX + SSZ groups respectively. The differences in the rates of complete and clinically important improvement between the two groups were insignificant (P 0.1398 and 0.7092). The incidence of side effects was insignificantly higher in the MTX + SSZ group. Most of them were mild and transient. The combination of SAARDs offered little added advantage in RA. However, the higher rate of complete improvement in the combination group justifies trials including larger samples.
10606360 Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacok 1999 Dec OBJECTIVE: To determine the effects of celecoxib, a specific inhibitor of cyclooxygenase 2 (COX-2) on the renal clearance and plasma pharmacokinetic profile of stable methotrexate (MTX) doses in patients with rheumatoid arthritis (RA). METHODS: Fourteen adult female patients with RA taking a stable weekly dose of MTX (5 to 15 mg/wk) for a minimum of 3 months were randomized to receive concomitantly either celecoxib (200 mg BID) or placebo for a period of 7 days in a single blind, 2 period crossover study of MTX pharmacokinetics and renal clearance. RESULTS: The plasma pharmacokinetic profile of MTX did not change significantly when celecoxib or a placebo was coadministered. The mean renal clearance of MTX alone, 7.98+/-2.18 l/h, was virtually unchanged by coadministration of celecoxib (7.94+/-1.61 l/h) or placebo (7.97+/-1.19 l/h). CONCLUSION: Celecoxib has no significant effect on the pharmacokinetics or renal clearance of MTX in patients with RA, although these results should be confirmed in prospective studies of elderly and renally impaired patients.
9101493 Variations and trends in the prescription of initial second line therapy for patients with 1997 Apr OBJECTIVE: To evaluate practice variation and time trends in the initial prescription of second line drugs for the treatment of rheumatoid arthritis (RA) by a group of selected rheumatologists. METHODS: We retrospectively reviewed medical charts of all patients with a diagnosis of RA, initially seen between January 1, 1985, and June 30, 1994, by rheumatologists from a tertiary center and a rheumatology referral clinic in Edmonton. RESULTS: 1427 patients initially seen between 1985 and 1994 were included in the study. Of these, 1244 (87%) received a second line drug, 71% within 1.5 years after the disease onset. Overall, antimalarials and parenteral gold were the most frequently prescribed. Statistically significant trends were observed for the years under study. From 1985 to 1987, the most frequently prescribed initial second line drug was parenteral gold, between 1988 to 1990, sulfasalazine, and after 1991, antimalarials. Methotrexate was rarely used as a first choice. Marked variability was observed among rheumatologists in the use of initial second line drugs. In general, year of prescription and prescribing rheumatologist were significantly associated with the selection of all second line drugs but methotrexate. In addition, disease duration and residence (urban or rural) were associated with the selection of antimalarials and parenteral gold. CONCLUSION: Most patients were treated early with second line drugs. Initial prescription patterns varied among rheumatologists. These patterns have changed over the last 10 years. An increasing trend in the use of antimalarials was noted, and unlike prescription patterns in the US, methotrexate was rarely used as the first second line drug.
10813283 Rheumatoid arthritis in Sweden. Drug prescriptions, costs, and adverse drug reactions. 2000 May OBJECTIVE: Many patients with rheumatoid arthritis (RA) need continuous medication, bringing considerable costs for drugs and a need for monitoring adverse drug reactions. We studied drug exposure, drug costs, and adverse drug reactions in patients with RA in Sweden from 1987 to 1997. METHODS: Prescription patterns, drug costs, and adverse drug reactions, and their distributions and trends were analyzed by cross sectional annual data. Drug exposures and costs were assessed from the National Diagnosis and Therapy Survey. All costs were recalculated to the 1997 level using the drug price index. Information on adverse drug reactions was obtained from the national pharmacovigilance system. RESULTS: The drug prescription level was, on average, 2 defined daily doses (DDD) throughout the study period. Nonsteroidal antiinflammatory drugs (NSAID) accounted for > 40% of the drugs prescribed, methotrexate (MTX) 10%, corticosteroids 10%, and sulfasalazine 5%. Analgesics and opioids made up 14% of prescriptions - a low estimate considering the availability of over-the-counter preparations. Disease modifying antirheumatic drugs (DMARD) increased their proportion from 28.5 to 39.3%. Total costs were stable at $16 million US annually. NSAID costs decreased, while those of sulfasalazine, MTX, and cyclosporine increased. On average, 91 adverse drug reactions were reported annually. Hematological reactions (agranulocytosis, thrombocytopenia, leukopenia, pancytopenia) predominated, constituting 21% of reported reactions. Skin and gastrointestinal reactions, mainly mild, accounted for 15 and 14%, respectively. Deaths from adverse drug reactions were uncommon, about 3 per year, and were mainly attributed to hematological reactions. CONCLUSION: The total volume as well as the total cost of drug consumption for RA in Sweden was relatively constant during our 11 year observation period, despite a notable increase in the use of DMARD. This was mainly due to a decrease in costs per DDD of NSAID, and an increased use of cyclosporine. Drug related adverse reactions were dominated by hematological reactions, and fatal events were few. This emphasizes the need for an extended evaluation of which safety procedures are most cost effective for monitoring the drugs used for RA.
11876141 [Leflunomide--a new disease modifying anti-rheumatic agent]. 2001 Nov 10 BACKGROUND: Leflunomide is a novel disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis. The agent has been developed for the treatment of rheumatoid arthritis, but its multiple immunomodulatory properties may in the future be of interest in the treatment of other rheumatic and immunological diseases. MATERIAL AND METHODS: Review of the literature in order to present the current relevant clinical documentation of the drug. RESULTS: The clinical documentation is mainly based on three large, prospective, randomized trials of six months "to two years" duration comparing leflunomide with placebo, sulphasalazine or methotrexate. The efficacy of leflunomide in all trials was superior to placebo and comparable to sulphasalazine and methotrexate. The frequency of adverse events was also comparable to the comparators. INTERPRETATION: Leflunomide is a safe and efficacious addition to the roster of antirheumatic drugs, but further clinical trials and experience from clinical practice are needed in the evaluation of its place as a disease-modifying agent.
10631383 Additive triple DMARD combination therapy of a low dose of sulfhydryl compounds, sulfasala 1999 Dec To evaluate the efficacy and safety of additive triple disease modifying anti-rheumatic drug (DMARD) combination therapy of a low dose of sulfhydryl compounds ¿D-penicillamine, bucillamine or tiopronin¿, sulfasalazine (SSZ) and methotrexate (MTX) as a treatment for rheumatoid arthritis (RA) patients, we studied a total of 33 Japanese RA patients (6 males, 27 females). At 1 or 2 months after simultaneous administration of the 3 above-mentioned DMARDs was begun, significant improvements were seen in markers of joint inflammation, i.e., erythrocyte sedimentation rate and C-reactive protein in sera. At 6 months, clinical improvement judged by the physicians' overall assessment of joint symptoms and laboratory data was observed in 29 (88%) of the 33 RA patients. No marked effect was observed in the other 4 (12%) patients, however. We observed no significant adverse reaction to this therapy. This suggests that additive triple DMARD combination therapy of a low dose of sulfhydryl compounds, SSZ and MTX could be a useful drug therapy for the treatment of RA patients, even those who are refractory.
11229464 Development of fulminant hepatitis B (precore variant mutant type) after the discontinuati 2001 Feb A 75-year-old female rheumatoid arthritis patient who was positive for hepatitis B surface antigen and for antibodies to hepatitis Be antigen showed liver dysfunction, and therefore methotrexate (MTX) therapy was discontinued. Her drug lymphocyte stimulation test indicated positivity for MTX. Her liver dysfunction improved briefly, but she developed fulminant hepatitis with elevated levels of hepatitis B virus (HBV)/DNA polymerase and subsequently died. HBV/DNA analysis performed with polymerase chain reaction-mutation site-specific assay revealed that the fulminant hepatitis was caused by a precore mutant virus. Sudden reactivation of the immune system by discontinuation of MTX may have led to the attack on infected cells. Even when hepatitis Be antibodies are present, MTX should not be used in patients who have chronic infection with HBV.
11391029 Adverse reactions to disease-modifying anti-rheumatic drugs in clinical practice. 2001 Jun We analysed computerized records of disease-modifying anti-rheumatic drug (DMARD) monotherapy to determine how long rheumatoid arthritis (RA) patients continued on five commonly prescribed DMARDs, and the incidence and time-course of adverse drug reactions (ADRs) they experienced. We studied the records for 3923 courses of DMARDs given to a cohort of 2170 patients monitored for a total of 9378 treatment-years. Methotrexate (MTX) was the DMARD most likely to be continued long-term; <45% of patients had discontinued the drug after 96 months. For the other DMARDs, the time until 50% discontinued due to ADRs or inefficacy was 43.3 months for sulphasalazine (SAS), 33.9 months for D-penicillamine (DPN) and 26 months for myocrisin. Most monitored ADRs requiring drug discontinuation were seen early in therapy, with a median time to onset of <6 months; the important exceptions to this were haematological ADRs to MTX, where the median delay to neutropenia was 16.9 months, and that to thrombocytopenia was 9.4 months. Monitored ADRs (identified by blood or urine tests) were seen least frequently with SAS (one ADR in every 35 patient-years of monitoring) but this apparent advantage was offset by a high incidence of gastrointestinal ADRs and inefficacy. Overall, one toxicity reaction requiring drug discontinuation was identified for every 15.9 patient-years of monitoring.
9444414 Methotrexate as the initial second-line disease modifying agent in the treatment of rheuma 1997 Nov OBJECTIVE: To assess the efficacy and toxicity profile of methotrexate (MTX) as the initial second-line disease modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA). METHODS: This was an observational retrospective cohort study comparing 28 patients who were treated with MTX as the first DMARD (MTX cases) and 55 matched patients treated with MTX after other DMARDs (MTX controls). RESULTS: The follow-up time was identical in the two groups: 19.4 +/- 14 months (2-56) for the MTX cases and 21.8 +/- 15.3 months (3-87) for MTX controls (NS). MTX efficacy was the same in the two groups, except for a higher incidence of remission in the MTX cases (8/28, 28.6% versus 5/55, 9.1%, p = 0.028). The toxicity profiles, frequencies, and reasons for MTX withdrawals were similar in the two groups. CONCLUSION: The results obtained in this study suggest a benefit from MTX prescribed as an initial second-line agent in the treatment of RA, but studies involving a larger number of patients are needed.
10882166 Infliximab: a review of its use in the management of rheumatoid arthritis. 2000 Jun Infliximab is a chimaeric monoclonal antibody to human tumour necrosis factor-alpha (TNFalpha). It binds to both soluble and transmembrane forms of TNFalpha at picomolar concentrations in vitro. Secondary to inhibition of TNFalpha, infliximab reduces serum levels of inflammatory mediators and vascular endothelial growth factor, decreases the expression of chemokines in the synovial tissue and reduces lymphocyte migration into the joints of patients with rheumatoid arthritis. In 2 multicentre randomised double-blind trials conducted over 26 and 30 weeks, infliximab plus methotrexate was significantly more effective than placebo plus methotrexate according to American College of Rheumatology response criteria in patients with active rheumatoid arthritis. A substantial response to infliximab-containing regimens was evident within 2 weeks. Extension phases of these studies indicate sustained clinical efficacy for up to 54 weeks. Of considerable importance are preliminary 1-year radiographic findings that show zero median progression of joint damage in infliximab plus methotrexate recipients compared with a 7 to 8% deterioration in placebo plus methotrexate recipients. Headache, nausea, upper respiratory tract infection and infusion-related reactions are the most commonly reported adverse events with infliximab. Serious events occurred in 4.4% of infliximab versus 1.8% of placebo recipients. In the largest clinical trial, 2 patients died from disseminated infection and 3 developed new or recurrent malignancies, although the exact relationship between infliximab and these events is unknown. To date, 2 patients with rheumatoid arthritis have developed drug-induced lupus. About 10% of patients may develop antibodies to infliximab, although the clinical significance of these is presently unknown. CONCLUSION: Infliximab represents an important advance in the treatment of rheumatoid arthritis, with tolerability concerns raised by early studies having been eased somewhat by more recent data in larger patient numbers. If preliminary results indicating that infliximab is able to arrest joint destruction in patients with rheumatoid arthritis are corroborated, the drug will likely become an integral component of future management strategies for this difficult-to-treat condition.
11831013 [Cytopenia associated with low dose pulse methotrexate in the treatment of rheumatoid arth 2001 Dec OBJECTIVES: To assess the associated risk factors of methotrexate (MTX)-induced cytopenia in rheumatoid arthritis (RA). METHODS: We followed 420 patients started on MTX for RA. We evaluated the frequency and clinical significance of patients with cytopenia related to MTX therapy. RESULTS: The prevalence of patients remaining in the follow-up in the MTX treatment was 21% at 60 months. eighty-seven patients (21%) continued treatment. The treatment termination in MTX was 28% for toxicity, 78 (19%) for no effect, 70 (17%) for relapse and 116 (28%) for toxicity and 69 (16%) for other reasons. A total of 10 patients with cytopenia related to MTX therapy were identified among them. The prevalence of cytopenia, including leukopenia (n = 6), thrombocytopenia (n = 3) and pancytopenia (n = 1), estimated to be 2.4% in MTX treated RA patients. Patients with cytopenia received 2.5-8 mg/w over a mean duration of 60.0 months (10-119 months). nine of 10 patients received NSAIDs with MTX therapy. The presence of renal abnormality (Cr > 1.2 mg/d) was in 3 cases, age over 70 years old in 4 patients, body weight under 50 kg in 8 patients, mean corpuscular volume (MCV) over 100 fl in 2 patients. High MCV value (over 94 fl) was in 7 patients, 6 of whom had some symptoms including fever (n = 3) and oral mucosa/lip abnormalities (n = 3). Low MCV value (under 84 fl) was in 3 patients, who had no symptom but arthralgia and no renal abnormality. And they were younger and received MTX in shorter period than high MCV group. CONCLUSIONS: In patients with high MCV (over 94 fl), most hematological toxicities seen during the course of MTX therapy can be predictable. But, some patients may develop unpredictable hematological reaction. We need to monitor hematological examination frequently and observe patients closely for the appearance of hematological toxicity throughout the presctiption period of MTX irrespective of the duration of treatment.
10589364 Combination DMARD treatment with parenteral gold and methotrexate. 1999 Nov INTRODUCTION: Both methotrexate (MTX) and gold sodium thiomalate (GSTM) have been shown to be very effective in the treatment of rheumatoid arthritis (RA) and to slow x-ray progression. The combination of both drugs could be useful because of their different and complimentary mechanisms of action. However, there is only one long-term study comparing this combination with MTX monotherapy. METHODS: In this prospective long-term observational study, all patients who started MTX treatment from 1980 to 1987 in one center were followed for 12-108 (mean 34.1) months. Ninety-seven patients were treated with MTX, while 126 patients received the combination MTX/GSTM, both drugs being given at the full dose. All patients had active disease, most of them long-lasting destructive RA not responsive to previous disease-modifying antirheumatic drug (DMARD) treatment. RESULTS: There were no significant differences in the demographic and baseline data between the two groups, with the exception of higher swollen joint counts (SJC) and C-reactive protein (CRP) in the combination group. In both groups the parameters of disease activity (erythrocyte sedimentation rate [ESR], CRP, SJC) improved significantly. A > 50% improvement in the SJC after 1 and 3 years was seen in 62% and 70% of patients in the MTX group, and in 55% and 85% of the patients in the combination group, respectively. A > 50% improvement in the ESR occurred in 54%/63% (MTX group) and in 49%/68% (combination group) for the same timepoints. There was no difference between the groups regarding the nature, frequency, or severity of side effects. A total of 20.6% (MTX) and 15.1% (combination) of patients were withdrawn for side effects. After 5 years, 54% of the patients in both groups were still being treated. CONCLUSION: This long-term observational study shows that the combination MTX/GSTM is well tolerated and is at least as effective as MTX single treatment. Taking into account the higher disease activity at baseline and the greater x-ray progression before baseline among the patients in the combination group, one may conclude that combination treatment is superior to monotherapy.
10643696 Factors predicting response to treatment in rheumatoid arthritis: the importance of diseas 2000 Jan OBJECTIVE: To use individual patient data from rheumatoid arthritis (RA) clinical trials to identify factors that affect the response to treatment as defined by the American College of Rheumatology (ACR) criteria for improvement (the "ACR response"). METHODS: Primary trial data from 14 diverse, randomized, controlled trials of second-line drugs or devices in RA were analyzed. The trials included 11 methotrexate (MTX) trials (5 placebo controlled and 6 comparative, of which 2 were unpublished), 1 combination trial of cyclosporine plus MTX, 1 induction trial of a combination treatment in early RA (the COBRA trial), and 1 placebo-controlled trial of a new device (Prosorba). Both patient factors and disease activity measures (primarily, items from the ACR core criteria set) were available. RESULTS: A total of 1,435 patients (549 in placebo-controlled trials, 886 in comparative trials) were studied. In both active treatment and placebo groups, disease duration had a strong effect on the likelihood of patient response (e.g., with any active treatment, the response rate was 53% for patients with < or =1 year of disease, 43% for 1-2 years' disease duration, 44% for 2-5 years, 38% for 5-10 years, and 35% for > 10 years; P = 0.001). Decreasing response with greater disease duration was seen during treatment with most of the individual active drugs, as well as with placebo. Other factors decreasing the rate of response to treatment included any prior use of a disease-modifying antirheumatic drug (DMARD), higher disease functional class (according to the Steinbrocker criteria), low disease activity (according to patient's global assessment), and female sex. Each ACR core set variable exhibited a diminished response to treatment in patients with long-standing disease. The difference between active treatment and placebo response rates was not affected by disease duration nor by other factors associated with the ACR response. CONCLUSION: RA patients with longer disease duration do not respond as well to treatment compared with patients with early disease, and female sex, prior DMARD use, disease functional class, and disease activity also have effects on the likelihood of patient response to treatment. This has implications for trial interpretation and for the clinical expectations of RA patients.
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