Rheumatoid Arthritis: Fatenejad S

van der Heijde D, Landewé R, Klareskog L, Rodríguez-Valverde V, Settas L, Pedersen R, Fatenejad S. · Rheumatology Department, University Hospital, Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #15641062 links to  free full text

Abstract: OBJECTIVE: To evaluate different methods of presentation and analysis of radiographic data in a rheumatoid arthritis (RA) randomized controlled trial. METHODS: A double-blind randomized controlled trial including 682 patients with active RA who were treated with methotrexate, etanercept, or a combination of the 2 drugs was used for this study. Probability plots of the change from baseline to year 1 were produced to visualize progression, and were compared with usual descriptive statistics. The primary analysis of the trial (based on annualized actual mean change from baseline in total Sharp score at 1 year, using linear imputation) was challenged using various ways of handling missing information with alternative imputation methods, and by various statistical analyses including analysis of covariance (ANCOVA) and mixed model analysis on both raw and log-transformed data. RESULTS: Probability plots provided detailed insight into the differentiated treatment effects between the 3 arms of this study. As adjuncts to formal hypothesis testing, these plots were more useful for presenting data than were summary descriptive statistics or use of preset cutoff points to define lack of progression. Additional analyses presented here support the results obtained with the per-protocol analysis that showed an advantage of the combination treatment compared with the monotherapy arms and for etanercept versus methotrexate alone. Various ways of handling missing information confirmed the robustness of the results. In addition, both ANCOVA and mixed model analyses on raw and on log-transformed data produced similar results. CONCLUSION: We suggest a panel of alternative analysis methods and alternative ways of handling missing information to verify that the radiographic results reported in an randomized controlled trial are not influenced by technical factors, such as interpolation, handling of missing data, and choice of statistical tests.

Zhou H, Mayer PR, Wajdula J, Fatenejad S. · Clinical Pharmacology, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA. · J Clin Pharmacol. · Pubmed #15496641 No free full text.

Abstract: The purpose of this study was to evaluate the potential impact of concurrent weekly oral methotrexate administration on the pharmacokinetics of etanercept in patients with rheumatoid arthritis (RA) in a phase 3B trial. As part of a double-blind randomized trial of 682 patients with rheumatoid arthritis who received etanercept (25 mg subcutaneously twice weekly), methotrexate (weekly oral dose, median weekly dose: 20 mg), or etanercept (25 mg subcutaneously twice weekly) plus methotrexate (weekly oral dose, median weekly dose: 20 mg), serum etanercept concentrations were measured in a subset of patients. Serum samples for 98 randomly selected patients (48 receiving etanercept-alone treatment, 50 receiving etanercept plus methotrexate combination treatment) were analyzed to assess the pharmacokinetics of etanercept. A single blood sample was drawn from each patient at baseline and at the week 24 visit. Given the variable sampling time for patients in both groups, a population pharmacokinetic analysis using NONMEM was conducted for etanercept. A final covariate population pharmacokinetic model was constructed based on previously obtained etanercept data from both healthy subjects (n = 53) and patients with RA (n = 212) in 10 prior clinical trials. The predictive performance of the final model was assessed by both bootstrap and data-splitting validation approaches. The final model was then used to estimate Bayesian pharmacokinetic parameters for the patients in both treatments in the current trial. The potential effect of the concurrent administration of methotrexate on the pharmacokinetics of etanercept was examined by comparing the clearance values between 2 treatments using statistical criteria. A population 2-compartment model with first-order elimination from the central compartment and with either zero-order (intravenous administration) or first-order (subcutaneous administration) input was selected based on the data from the prior 10 etanercept clinical studies. The following pharmacokinetic parameters (typical value +/- standard error) were estimated: clearance (CL: 0.072 +/- 0.005 L/h), volume of distribution in the central compartment (V(c): 5.97 +/- 0.45 L), volume of distribution in the peripheral compartment (V(p): 2.05 +/- 0.32 L), intercompartment clearance (Q: 0.0645 +/- 0.0093 L/h), first-order absorption rate constant (k(a): 0.0282 +/- 0.0039 1/h), and absolute bioavailability for subcutaneous administration (F: 0.626 +/- 0.056). Interindividual variability of the pharmacokinetic parameters was quantified for CL (25.1%), V(c) (41.7%), k(a) (53.1%), and F (24.2%). Residual variability consisted of combined additive (11.4 ng/mL) and proportional error (49.9%). Both age (< 17 years) and body weight (< 60 kg) were found to be important covariates on CL. The results of both validation tests indicated the adequate predictive performance of the population model. Based on the bioequivalence criteria, the Bayesian-estimated clearance for patients receiving etanercept alone (mean: 0.070 L/h) was comparable to that for patients receiving a combination of etanercept and methotrexate (mean = 0.066 L/h). The pharmacokinetics of etanercept were not altered by the concurrent administration of methotrexate in patients with rheumatoid arthritis. Thus, no etanercept dose adjustment is needed for patients taking concurrent methotrexate.

Zhou H, Buckwalter M, Boni J, Mayer P, Raible D, Wajdula J, Fatenejad S, Sanda M. · Clinical Pharmacology, Wyeth Research, Collegeville, PA 19426, USA. · Int J Clin Pharmacol Ther. · Pubmed #15176649 No free full text.

Abstract: OBJECTIVE: The purpose of this study was to evaluate the pharmacokinetics of etanercept in patients with ankylosing spondylitis (AS) in a phase 3 study. METHODS: Serum etanercept concentrations were analyzed from samples obtained at weeks 4 and 12 from 43 patients with AS (median age: 45 years; median body weight: 75 kg; white/non-white: 40/3; male/female: 34/9) receiving 25 mg subcutaneously twice weekly for 12 weeks. A population pharmacokinetics analysis using NONMEM was conducted to estimate individual etanercept pharmacokinetic parameters. Initially, appropriate base and covariate population pharmacokinetic models were built based on data from 10 prior clinical studies of etanercept administered subcutaneously or intravenously to healthy subjects (n = 53) and to patients with rheumatoid arthritis (RA) (n = 212). The influence of demographic characteristics on the pharmacokinetics of etanercept was thoroughly evaluated. The stability of the final model was evaluated using both internal (bootstrapping) and external (data splitting) validation approaches. Finally, the selected final population covariate model was used to estimate the Bayesian pharmacokinetic parameters for the patients with AS. RESULTS: The data from the 10 prior clinical studies were optimally fitted to a 2-compartment linear population covariate model. Both age (< 17 years) and body weight (< 60 kg) were found to be important covariates on clearance. Both bootstrapping and data splitting validated the population model. The mean Bayesian-predicted etanercept clearance and steady-state trough concentration were 0.072 l/h and 2,004 ng/ml, respectively. The pharmacokinetic parameters of etanercept in the patients with AS were similar to those observed in the patients with RA. CONCLUSIONS: The pharmacokinetics of etanercept in patients with AS were similar to those in patients with RA. The AS disease state does not appear to alter the disposition of etanercept.

Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Martín Mola E, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M, Anonymous00113. · Rheumatology Unit, Department of Medicine, Karolinska Institute/Karolinska Hospital, Stockholm 17176, Sweden. · Lancet. · Pubmed #15001324 No free full text.

Abstract: BACKGROUND: Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone. We aimed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis. METHODS: In a double-blind, randomised, clinical efficacy, safety, and radiographic study, 686 patients with active rheumatoid arthritis were randomly allocated to treatment with etanercept 25 mg (subcutaneously twice a week), oral methotrexate (up to 20 mg every week), or the combination. Clinical response was assessed by criteria of the American College of Rheumatology (ACR). The primary efficacy endpoint was the numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks. The primary radiographic endpoint was change from baseline to week 52 in total joint damage and was assessed with the modified Sharp score. Analysis was by intention to treat. FINDINGS: Four patients did not receive any drug; thus 682 were studied. ACR-N AUC at 24 weeks was greater for the combination group compared with etanercept alone and methotrexate alone (18.3%-years [95% CI 17.1-19.6] vs 14.7%-years [13.5-16.0], p<0.0001, and 12.2%-years [11.0-13.4], p<0.0001; respectively). The mean difference in ACR-N AUC between combination and methotrexate alone was 6.1 (95% CI 4.5-7.8, p<0.0001) and between etanercept and methotrexate was 2.5 (0.8-4.2, p=0.0034). The combination was more efficacious than methotrexate or etanercept alone in retardation of joint damage (mean total Sharp score -0.54 [95% CI -1.00 to -0.07] vs 2.80 [1.08 to 4.51], p<0.0001, and 0.52 [-0.10 to 1.15], p=0.0006; respectively). The mean difference in total Sharp score between combination and methotrexate alone was -3.34 (95% CI -4.86 to -1.81, p<0.0001) and between etanercept and methotrexate was -27 (-3.81 to -0.74, p=0.0469). The number of patients reporting infections or adverse events was similar in all groups. INTERPRETATION: The combination of etanercept and methotrexate was significantly better in reduction of disease activity, improvement of functional disability, and retardation of radiographic progression compared with methotrexate or etanercept alone. These findings bring us closer to achievement of remission and repair of structural damage in rheumatoid arthritis.

Combe B, Codreanu C, Fiocco U, Gaubitz M, Geusens PP, Kvien TK, Pavelka K, Sambrook PN, Smolen JS, Khandker R, Singh A, Wajdula J, Fatenejad S, Anonymous00051. · Service d'Immuno-Rhumatologie, Hopital Lapeyronie, Montpellier, France. · Ann Rheum Dis. · Pubmed #18794178 links to  free full text

Abstract: OBJECTIVE: To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy. METHODS: Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2-3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology criteria, disease activity scores (DAS) and patient-reported outcomes (PRO). RESULTS: Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS 5.1, 5.2 and 5.1 for etanercept (n = 103), etanercept plus sulfasalazine (n = 101) and sulfasalazine (n = 50), respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 (52%) vs 6 (6%) for either etanercept group, p<0.001). Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS 2.8, 2.5 versus 4.5, respectively (p<0.05); ACR 20 response was achieved by 67%, 77% versus 34% of patients, respectively (p<0.01) Overall, PRO followed a similar pattern; a clinically significant improvement in health assessment questionnaire was achieved by 76%, 78% versus 40% of patients, respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01). CONCLUSION: Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA. The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine.

van der Heijde D, Landewé R, van Vollenhoven R, Fatenejad S, Klareskog L. · Department of Rheumatology, Leiden University Medical Centre, PO Box 9600, 2300 CC Leiden, The Netherlands. · Ann Rheum Dis. · Pubmed #18203764 links to  free full text

Abstract: BACKGROUND: Many studies have examined the relationship between long-term radiographic damage and physical function. However, it is not known if short-term radiographic progression is also associated with physical function. Aim: To investigate the longitudinal relationship between physical function and both the level of radiographic damage and the radiographic progression rate in patients with early or advanced active rheumatoid arthritis. METHODS: The database for the 2-year Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) was used for this study. Physical function was measured by the Health Assessment Questionnaire (HAQ) score at baseline, 6 months and 1 and 2 years. Radiographs of the hands and feet, taken at the same time points, were scored by the van der Heijde-modified Total Sharp Score (TSS). The HAQ score was modelled using generalised mixed linear modelling by TSS or progression in TSS (interval 0-1 year and 1-2 years) adjusted for age, sex, treatment and disease activity. RESULTS: After adjustment for age, sex and disease activity, both TSS and the change in TSS (progression rate) were significant determinants of the HAQ score. When radiographic progression was divided into four categories (negative, zero, minor and greater progression), results showed that HAQ scores tended to be higher with a higher rate of progression. Patients with negative progression scores had lower HAQ scores than patients with positive progression scores. CONCLUSIONS: Patients with greater radiographic damage, and those with recent radiographic progression, have a higher degree of disability.

van der Heijde D, Klareskog L, Landewé R, Bruyn GA, Cantagrel A, Durez P, Herrero-Beaumont G, Molad Y, Codreanu C, Valentini G, Zahora R, Pedersen R, MacPeek D, Wajdula J, Fatenejad S. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. · Arthritis Rheum. · Pubmed #18050208 links to  free full text

Abstract: OBJECTIVE: The Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) is a 3-year, double-blind, multicenter study evaluating the efficacy and safety of etanercept, methotrexate, and the combination of etanercept plus methotrexate in patients with active rheumatoid arthritis (RA). The results after 1 and 2 years of the study have been previously reported. Here we provide the 3-year clinical and radiographic outcomes and safety of etanercept, methotrexate, and the combination in patients with RA. METHODS: In this randomized, double-blind, multicenter TEMPO study, 682 patients received etanercept 25 mg twice weekly, methotrexate < or =20 mg weekly, or the combination. Key efficacy assessments included the Disease Activity Score (DAS) and the DAS in 28 joints. RESULTS: Combination therapy resulted in significantly greater improvement in the DAS and in more patients with disease in remission than either monotherapy. This finding was confirmed by longitudinal analysis; patients receiving combination therapy were more than twice as likely to have disease in remission than those receiving either monotherapy. Independent predictors of remission included male sex, lower disease activity, lower level of joint destruction, and/or better physical function. Combination and etanercept therapy both resulted in significantly less radiographic progression than did methotrexate (P < 0.05). Etanercept and combination treatment were well tolerated, with no new safety findings. CONCLUSION: Etanercept plus methotrexate showed sustained efficacy through 3 years and remained more effective than either monotherapy, even after adjustment for patient withdrawal. Combination therapy for 3 years led to disease remission and inhibition of radiographic progression, 2 key goals for treatment of patients with RA.

Dias EM, Lukas C, Landewé R, Fatenejad S, van der Heijde D. · Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht, Maastricht, the Netherlands. · Ann Rheum Dis. · Pubmed #17644537 No free full text.

Abstract: OBJECTIVE: To compare the performance of a simplified scoring method for structural damage on radiographs of patients with rheumatoid arthritis (the Simple Erosion Narrowing Score or SENS) with the Sharp-van der Heijde Score (SHS) as reference. METHOD: We used the radiographic data from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO trial). The SENS was derived from the crude SHS data. Inter-observer reliability for status scores and change scores was determined by intraclass correlation coefficients and by the Smallest Detectable Change method. The ability to discriminate between treatment groups was assessed by the Mann-Whitney U test. Stratifying the sensitivity to change and discriminative ability for different levels of disease severity assessed a potential ceiling effect. RESULTS: Inter-observer reliability was similar for both methods. Intraclass correlation coefficients were higher for status scores than for change scores. The Smallest Detectable Change was 4.98 (1.1% of possible maximum score) for SHS and 2.28 (3.5%) for SENS. Sensitivity of SENS to detect progression above the Smallest Detectable Change, with reference SHS, ranged from 45.0 to 88.7%. Specificity ranged from 81.5 to 97.3%, and the kappa coefficient (between-method agreement) ranged from 0.58 to 0.66. Discriminative ability between treatment groups was good and similar for both methods. A ceiling effect could not be detected. CONCLUSIONS: With regard to most of the tested properties, the performance of SENS is as good as that of SHS. This confirms that SENS is a valuable method, which may be feasible in clinical practice.

Landewé R, van der Heijde D, Klareskog L, van Vollenhoven R, Fatenejad S. · University Hospital Maastricht, Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #17009230 links to  free full text

Abstract: OBJECTIVE: To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. METHODS: Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity x treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. RESULTS: GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. CONCLUSION: Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.

Combe B, Codreanu C, Fiocco U, Gaubitz M, Geusens PP, Kvien TK, Pavelka K, Sambrook PN, Smolen JS, Wajdula J, Fatenejad S, Anonymous00033. · Service d'Immuno-Rhumatologie, Hopital Lapeyronie, Montpellier, France. · Ann Rheum Dis. · Pubmed #16606651 No free full text.

Abstract: OBJECTIVE: To compare the efficacy and safety of etanercept and sulfasalazine, alone and in combination, in patients with active rheumatoid arthritis despite sulfasalazine treatment. METHODS: A double-blind, randomised study in adult patients with active rheumatoid arthritis despite stable sulfasalazine (2-3 g/day) treatment. The primary end point was a 20% response by the American College of Rheumatology (ACR) criteria at 24 weeks. RESULTS: At baseline, the three treatment groups (sulfasalazine, n = 50; etanercept, n = 103; etanercept and sulfasalazine, n = 101) were comparable for demographic variables and disease activity. Lack of efficacy was the primary reason for discontinuation (sulfasalazine, n = 12; etanercept, n = 1; etanercept and sulfasalazine, n = 4; p<0.001). Significantly more patients receiving etanercept, alone or in combination (74% for each), achieved ACR 20 responses at 24 weeks than those receiving sulfasalazine (28%; p<0.01). Similarly, more patients in the etanercept groups achieved ACR 50 and ACR 70 responses than those in the sulfasalazine group (p<0.01). In the groups receiving etanercept, significant differences in the ACR core components were observed by week 2 compared with those receiving sulfasalazine alone (p<0.01). The incidences of several common adverse events (headache, nausea, asthenia) were lower with etanercept alone than with the combination (p<0.05), but infections and injection site reactions were higher with etanercept alone (p<0.05). The safety profiles of both etanercept treatment groups were comparable with previous experience of etanercept. CONCLUSIONS: For all efficacy variables assessed, etanercept alone or in combination with sulfasalazine resulted in substantial and similar improvement in disease activity from baseline to week 24 compared with sulfasalazine alone in patients with active rheumatoid arthritis despite their sulfasalazine treatment. All three treatments were generally well tolerated.

van der Heijde D, Klareskog L, Rodriguez-Valverde V, Codreanu C, Bolosiu H, Melo-Gomes J, Tornero-Molina J, Wajdula J, Pedersen R, Fatenejad S, Anonymous00372. · Department of Rheumatology, University Hospital, Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #16572441 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. METHODS: Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. RESULTS: A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P<0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P<0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P<0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P<0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. CONCLUSION: Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.

van der Heijde D, Klareskog L, Singh A, Tornero J, Melo-Gomes J, Codreanu C, Pedersen R, Freundlich B, Fatenejad S. · Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands. · Ann Rheum Dis. · Pubmed #16079172 links to  free full text

Abstract: OBJECTIVE: To compare patient reported measures of function, health related quality of life (QoL), and satisfaction with medication among patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), etanercept, or both for up to 1 year. METHODS: In a 52 week, double blind, clinical trial, patients with active RA were randomised to receive etanercept 25 mg twice weekly, methotrexate up to 20 mg weekly, or combination therapy. The Health Assessment Questionnaire (HAQ) disability index, EuroQoL health status visual analogue scale (EQ-5D VAS), patient global assessment, and patient general health VAS were administered at baseline and weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52. Satisfaction with the medication was compared at 52 weeks. RESULTS: Of 682 enrolled patients, 522 completed 52 weeks of treatment. Mean improvement from baseline in HAQ score was 0.65, 0.70, and 1.0 for MTX, etanercept, and the combination, respectively. The mean percentage and absolute improvement in the HAQ was significantly higher (p<0.01) for combination therapy than for either of the monotherapies. Combination therapy produced significantly more rapid achievement of HAQ < or =0.5 sustained for 6 months than either of the monotherapies (p<0.01). Compared with patients receiving monotherapy, those receiving combination therapy achieved a significantly better (p<0.05) health state as measured by the EQ-5D VAS (mean (SD) 63.7 (3.2), 66.8 (3.2), 72.7 (3.1) for MTX, etanercept, and the combination, respectively). Results were similar for other assessments (p<0.01). Patients in combination and etanercept groups were significantly more likely (p<0.0001, p = 0.0009, respectively) to report satisfaction with the medication. CONCLUSIONS: Combination therapy with etanercept and methotrexate improved function, QoL, and satisfaction with the medication significantly more than monotherapy.

van der Heijde D, Klareskog L, Boers M, Landewé R, Codreanu C, Bolosiu HD, Pedersen R, Fatenejad S, Anonymous00064. · Rheumatology Department, University Hospital, Maastricht, PO Box 5800, 6202 AZ Maastricht, P Debyelaan 25, 6229 HX Maastricht, The Netherlands. · Ann Rheum Dis. · Pubmed #15860509 links to  free full text

Abstract: OBJECTIVE: To assess methods to calculate achieving and sustaining remission in a double blind randomised trial in patients with RA who received etanercept, methotrexate, or an etanercept/methotrexate combination. METHODS: Remission was defined as DAS <1.6, DAS28 <2.6, and ACR70 response. Sustaining remission was analysed in three ways: (a) analysis of sustained DAS remission, DAS28 remission, or ACR70 response continuously for 6 months; (b) analysis of sustained remission appraised through a continuity rewarded scoring system, which is the weighted sum of all intervals in the study in which patients are in DAS or DAS28 remission; or (c) longitudinal modelling of remission odds using generalised estimating equations. RESULTS: Significantly more patients treated with the etanercept/methotrexate combination reached DAS remission (37%) than those treated with either methotrexate (14%) or etanercept (18%) alone (p<0.01). Results for DAS28 and for the ACR70 response were similar. Agreement between DAS remission and DAS28 remission was good, but agreement between either of these and the ACR70 response was less. Patients in DAS or DAS28 remission had a lower level of disease activity (fewer active joints, lower ESR) than those achieving ACR70 response; the converse was seen using pain VAS. The three methods were comparable for sustainability of remission and showed significant advantage for combination therapy, which increased the number and durability of remission periods. CONCLUSIONS: DAS and DAS28 remission results were similar for assessing achieving and sustaining remission in RA, frequently differing from patients classified as ACR70 responders. The three methods of examining duration of remission produced comparable results.