Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16650588 Positive affect as a factor of resilience in the pain-negative affect relationship in pati 2006 May OBJECTIVE: The purpose of this study is to examine positive affect (PA) as a factor of resilience in the relationships between pain and negative affect (NA) in a sample of patients with rheumatoid arthritis. METHODS: Forty-three patients (30 women; mean age, 57 years) were interviewed weekly by telephone for 8 weeks. Multilevel modeling was applied to study the within-week relationships among the variables. RESULTS: There was a Pain x PA interaction effect on NA (beta=-0.05, P<.01) indicating a weaker relationship between pain and NA in weeks with more PA. Pain (beta=0.37, P<.002), interpersonal stress (beta=2.42, P<.001), depression (beta=0.26, P<.01), average perceived stress (beta=10.80, P<.001), and also weekly PA (beta=-0.1, P<.01) had a main effect upon NA. CONCLUSION: Positive affect is most influential in reducing NA during weeks of higher pain and may be a factor of resilience, helping patients experiencing pain fluctuations as less distressful than at lower levels of PA.
16393763 Is interleukin-18 useful for monitoring rheumatoid arthritis? 2005 Nov OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory regulator of immune responses. Its similarities to IL-1beta and ability to induce tumour necrosis factor-alpha (TNF-alpha) make it potentially important in the pathogenesis of rheumatoid arthritis (RA). METHODS: The level of IL-18 was assessed in matched pairs of blood and synovial fluid samples from 90 RA patients (47 erosive, 43 non-erosive) by an enzyme-linked immunosorbent assay (ELISA), and the results compared to 40 healthy controls. RESULTS: In RA patients with erosive joint disease, the IL-18 level was higher than that in non-erosive RA [(median+/-QR) blood: 385+/-200 vs. 235+/-183 pg/mL, p = 0.02; synovial fluid: 392+/-392 vs. 224+/-324 pg/mL, p = 0.05]. IL-18 levels in blood of RA patients were similar and closely related to the local, intra-articular level (r = 0.96). The IL-18 level was not related to other markers of inflammation, to the duration of RA, or to the treatment modality. The IL-18 level in RA patients was similar to that of the controls (278+/-234 vs. 344+/-179 pg/mL, not significant). CONCLUSIONS: An increased IL-18 level is associated with erosive joint disease, but the measurement of IL-18 does not help to distinguish between RA patients and healthy controls.
16371802 Infliximab-induced scleredema in a patient with rheumatoid arthritis. 2005 Dec A 52-year-old patient with rheumatoid arthritis (RA) developed scleredema-like skin induration after treatment with the tumor necrosis factor alpha (TNFalpha) blocking agent, infliximab. Skin induration occurred within a few weeks of initiation of infliximab, resolved with discontinuation of the drug, and recurred with rechallenge with the drug, implicating infliximab as the offending agent. Laboratory evaluation revealed a high titer of human antichimeric antibodies (HACA). The skin induration improved within a few weeks of discontinuation of infliximab and did not recur with the use of etanercept. Scleredema has been reported in association with bacterial and viral infections, diabetes mellitus, and monoclonal gammopathies. Infliximab use should be added to the list of potential associations with scleredema. This effect appears possibly specific to infliximab and may be related to the development of HACA because it did not occur with the use of etanercept in this patient. In addition, there appears to be a complex relationship between TNFalpha and tumor growth factor beta (TGF-beta), a cytokine which promotes collagen synthesis and deposition. TNFalpha blockade with infliximab may affect TNFalpha-TGF-beta interactions and may be implicated in the development of scleredema in this case.
17122966 Superoxide production and NADPH oxidase expression in human rheumatoid synovial cells: reg 2006 Nov OBJECTIVES: to evaluate the rheumatoid synovial cell capacity to produce superoxide anion in response to interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha), and to study the NADPH oxidase involvement in this production. MATERIAL AND METHODS: Synovial cells obtained from 7 rheumatoid arthritis (RA), 5 osteoarthritic (OA) patients, and dermal fibroblasts, were stimulated (i) with IL-1beta and TNF-alpha, or (ii) with specific oxidase activators and inhibitors, before studying superoxide production; we also studied NADPH oxidase mRNAs and protein expression, and p47-phox phosphorylation. RESULTS: Constitutive superoxide production by RA cells was increased in comparison to OA cells and dermal fibroblasts, and was stimulated by PMA and ionomycin. This production was increased after cytokine treatment of RA synovial cells. Cytokine-induced superoxide production by RA cells was inhibited by iodonium diphenyl or apocynin, suggesting the involvement of NADPH oxidase. RT-PCR and western blot analysis revealed the presence of p47-phox, gp91-phox and Nox4 in RA and OA cells, and in dermal fibroblasts. P47-phox phosphorylation was enhanced after cytokine-treatment in RA and OA cells, suggesting a PKC-mediated up-regulation of NADPH oxidase. CONCLUSIONS: NADPH oxidase is involved in the superoxide release by RA synovial cells, constitutively and after cytokine up-regulation. These cells express two different homologues (gp91-phox and Nox4).
16508942 Hypermethylated promoter region of DR3, the death receptor 3 gene, in rheumatoid arthritis 2006 Mar OBJECTIVE: To examine the promoter activity and protein expression of the death receptor 3 gene DR3, a member of the apoptosis-inducing Fas gene family, with particular reference to the methylation status of its promoter region in rheumatoid arthritis (RA). METHODS: Genomic DNA was prepared from peripheral blood mononuclear cells obtained from healthy individuals and from patients with RA and synovial cells obtained from patients with RA and osteoarthritis. The methylation status of the DR3 promoter was analyzed by bisulfite genomic sequencing and methylation-specific polymerase chain reaction techniques. Gene promoter activity and protein expression were examined using the luciferase reporter and Western blotting techniques. RESULTS: The promoter region of the DR3 gene contained many CpG motifs, including one CpG island that was specifically hypermethylated in synovial cells from patients with RA. Promoter assays showed that the promoter CpG island was essential for the transactivation of the DR3 gene and that forced hypermethylation of the CpG island with the bacterial methylase Sss I in vitro resulted in inhibition of the DR3 gene expression. Furthermore, the expression of DR-3 protein was down-modulated in association with methylation of the promoter CpG island in RA synovial cells. CONCLUSION: The CpG island in the DR3 gene promoter was specifically methylated to down-modulate the expression of DR-3 protein in rheumatoid synovial cells, which may provide resistance to apoptosis in RA synovial cells.
16309927 Raised chondroitin sulfate epitopes and hyaluronan in serum from rheumatoid arthritis and 2006 Mar OBJECTIVES: Serum hyaluronan (HA) and chondroitin sulfate (CS) epitopes WF6 and 3B3 (+) were determined to investigate disease association in patients with osteoarthritis (OA), rheumatoid arthritis (RA) and healthy controls. METHODS: Specific assays for HA and CS epitopes WF6 and 3B3 (+) were established and applied to a cross-sectional study of serum samples from patients (96 OA, 57 RA and 50 healthy controls). RESULTS: Both CS epitopes were increased in serum of many OA and RA patients and average levels were significantly above in healthy controls. In contrast serum HA was increased in RA, but only in few OA patients. CONCLUSIONS: CS epitopes WF6 and 3B3 (+) are raised in serum of patients with both OA and RA and were thus distinct from serum HA. The results suggest that OA may be detected systemically as well as RA. The range of levels of CS epitopes detected in OA and RA was wide and correlation with any aspect of disease activity is yet to be determined.
16313342 Role of nuclear factor-kappaB in the immune system and bone. 2005 Dec Bone metabolism is regulated by hormonal or local factors in the bone microenvironment, and recent studies have revealed that bone homeostasis is also influenced by immune system. The term 'osteoimmunology' has been proposed to explain the cross-talk between bone and the immune system. A critical element in this cross-talk is the inducible transcription factor nuclear factor-kappaB (NF-kappaB), which regulates gene expression during inflammatory and immune responses. However, NF-kappaB-signaling pathways are also important for bone homeostasis, in particular for osteoclast differentiation. By bridging inflammation and bone homeostasis, NF-kappaB also contributes to the onset and progression of arthritis. Several natural compounds, synthetic drugs, and gene-transfer technologies that lead to inhibition of the inhibitor of NF-kappaB kinase (IKK)/NF-kappaB activation pathway can prevent arthritis in animal models. In this review, we discuss the signaling pathway that leads to NF-kappaB activation and the role of NF-kappaB on osteoclast differentiation. Furthermore, we discuss the possibility that inhibition of NF-kappaB might provide novel therapeutic approach for inhibiting bone destruction in rheumatoid arthritis.
15818663 New classification of HLA-DRB1 alleles supports the shared epitope hypothesis of rheumatoi 2005 Apr OBJECTIVE: The shared epitope hypothesis was formulated to explain the involvement of HLA-DRB1 in rheumatoid arthritis (RA). However, several studies, which considered only the HLA-DRB1 alleles shown to be associated with RA risk, rejected this hypothesis. In this report, we propose that a different classification of HLA-DRB1 alleles be considered, based on the amino acid sequence at position 70-74. METHODS: The fit of both HLA-DRB1 classifications was tested in 2 groups of RA patients. All subjects were recruited through the European Consortium on Rheumatoid Arthritis Families, and included 100 patients with isolated RA and 132 patients with at least 1 affected sibling. RESULTS: The new classification produced risk estimates that fit all of the observed data, i.e., the distribution of the HLA-DRB1 genotype in the 2 patient groups, and the distribution of parental alleles shared by affected sibpairs. The risk of developing RA under this new classification depends on whether the RAA sequence occupies position 72-74 but is modulated by the amino acid at position 71 (K confers the highest risk, R an intermediate risk, A and E a lower risk) and by the amino acid at position 70 (Q or R confers a higher risk than D). CONCLUSION: A new classification based on amino acid sequence allows us to show that the shared epitope RAA sequence at position 72-74 explains the data, with the risk of developing RA modulated by the amino acids at positions 70 and 71.
16368734 Limited VH gene usage in B-cell clones established with nurse-like cells from patients wit 2006 May OBJECTIVES: Nurse-like stromal cells (NLC) in synovia and bone marrow of patients with rheumatoid arthritis (RA) can support pseudoemperipolesis, protect from apoptosis and enhance immunoglobulin production of peripheral blood B cells isolated from healthy individuals, suggesting the profound contribution of hyperactivation of B cells in RA. In the course of establishing RA-NLC from RA patients, we observed the growth of B cells in the presence of RA-NLC. METHODS: We cloned B cells from the synovium or bone marrow of RA patients using the limiting dilution technique. For established clones, nucleotide sequences of immunoglobulin and surface antigens were investigated. To investigate the dependence of these clones on NLC, differences in the proliferation and the amount of immunoglobulin produced in the presence or absence of NLC were compared. Immunocytochemical staining of various cells was performed using the antibody these clones produced. RESULTS: Nine B-cell clones established from RA patients showed RA-NLC-dependent growth. These B-cell clones expressed CD19, CD20, CD38, CD39 and CD40, suggesting that the cloned cells were mature and activated. All clones secreted immunoglobulins in culture media, which were specific for intracellular components of various cell lines, including RA-NLC. Interestingly, we found limited usage of immunoglobulin heavy-chain variable regions (VH) among B-cell clones from RA patients. These repertoires were reported to be detected preferentially in fetal livers. CONCLUSION: The present study provides a novel insight into the involvement of RA-NLC in the immunopathogenesis of RA via an autoreactive B cell development and/or activation mechanism.
15864873 Early and late effect of infliximab on circulating dendritic cells phenotype in rheumatoid 2005 The aim of this study was to analyze the phenotype of circulating dendritic cells (DCc) in rheumatoid arthritis (RA) patients before and after treatment with infliximab (at 24 h and 6 months) and the correlation between these changes and the clinical response to treatment. Sixteen patients with RA were recruited and clinical status was determined using the Disease Activity Score 28 (DAS28). All patients had active disease (mean DAS28 = 5.96) and were suitable for treatment with infliximab. Samples of peripheral venous blood were obtained before administration of the first dose of infliximab and again at 24 h and 6 months after treatment. DCc populations were analyzed by flow cytometry. At 24 h, there were no differences in the clinical status of the patients. However, we found a decrease in CD11c+ and, to a lesser extent, CD123+ DCc percentages. The expression of CD83, the most important activation marker for DC, was also shown to be decreased 24 h after infliximab therapy. After 6 months of treatment, all patients showed significant clinical improvement (mean DAS28 = 3.64, p < 0.001) and expression of the activation marker on DCc remained low. In conclusion, this study supports the role of tumor necrosis factor (TNF)-alpha blockade in preventing the maturation of DCc and in reducing the expression of their activation markers. Although the clinical response to infliximab was not observed after 24 h, DCc activation was strongly reduced by anti-TNF-alpha therapy. After 6 months of treatment, current data show a less active phenotype of DCc associated with clinical improvement in all patients in the study.
16271901 Injectable corticosteroids in treatment of arthritis of the knee. 2005 Nov Injection of corticosteroid preparations for the local treatment of musculoskeletal disorders affecting the knee, such as osteoarthritis and rheumatoid arthritis, has been used widely since the 1950s. This local therapy minimizes systemic toxicity and can result in rapid improvement in symptoms, most often as an adjunctive therapy for acute or severe symptom flares. The evidence assessing safety and efficacy is reviewed and analyzed. Intra-articular knee injection technique is described and is a procedure that is easy to learn and can be performed quickly in an office or hospital setting.
15730403 Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein- 2005 Mar Associations of Epstein-Barr virus (EBV) and autoimmune diseases have been hypothesized. We have analysed IgG antibodies to EBV nuclear antigen (EBNA)-2 in sera from Japanese patients with autoimmune systemic connective tissue diseases (CTD), exemplified by systemic lupus erythematosus (SLE), primary Sjogren's syndrome (SS), rheumatoid arthritis (RA), systemic sclerosis (SSc) and secondary SS (classical CTDs complicated with SS). An enzyme-linked immunosorbent assay (ELISA) which uses glutathione-S-transferase polypeptides fused to EBV nuclear antigen (EBNA)-2 and EBNA-1 was developed. Ratios of IgG antibody reactivity to whole IgG concentrations of sera were calculated to normalize EBNA-2 and EBNA-1 antibody levels to the hypergammaglobulinaemia that occurs in CTD. The ELISA optical density OD(450) readings of IgG antibodies to both the amino-terminal aa 1-116 of EBNA-2 and carboxyl-terminal aa 451-641 of EBNA-1 were elevated significantly in patients with SLE, primary SS, RA, SSc and secondary SS when compared to EBNA-1. The OD readings were divided by serum IgG concentrations to normalize for the hypergammaglobulinaemia. The specific levels of IgG antibodies to the amino-terminal region of EBNA-2 were elevated in patients with SLE, primary SS or RA, as well as those with secondary SS complicated with SLE or RA. The EBNA-2 amino-terminal region contains a polyproline tract and a proline-rich sequence and has considerable amino acid sequence homology with many cellular proline-rich proteins. High ratios of EBNA-2 aa 1-116 to EBNA-1 aa 451-641 IgG antibody levels which probably suggest reactivation of EBV latent infection were associated significantly with pulmonary involvement in SS patients. These results are consistent with the hypothesis that the sequence similarity between the amino-terminal region of EBNA-2 and proline-rich cellular proteins is associated with pathogenesis in a subpopulation of CTD patients, possibly by the molecular mimicry-epitope shift mechanism.
16414972 Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfati 2006 Sep BACKGROUND: Rheumatoid arthritis is a chronic autoimmune inflammatory condition characterised by polyarthritis and severe change in body mass and neuroendocrine environment. OBJECTIVES: To investigate plasma levels of adipocytokines (leptin, adiponectin, visfatin and resistin) in patients with rheumatoid arthritis and to compare them with levels in healthy controls. METHODS: Adiponectin, resistin, visfatin and leptin concentrations were measured in 31 patients with rheumatoid arthritis and 18 healthy controls by using specific enzyme-linked immunosorbent assays. RESULTS: Patients with rheumatoid arthritis showed considerably higher plasma levels of leptin, adiponectin and visfatin than healthy controls. No marked difference was observed in resistin levels between patients and controls. CONCLUSION: A marked increase in plasma levels of leptin, adiponectin and visfatin was noted in patients with rheumatoid arthritis, whereas resistin levels were similar to those observed in healthy controls. Coordinated roles for adiponectin, leptin and visfatin are suggested in the modulation of the inflammatory environment in patients with rheumatoid arthritis, whereas the lack of modulation in resistin levels is predictive of an irrelevant role for this peptide, suggesting that resistin level is probably not one of the main signals associated with the pathogenesis of this disease.
16001180 Comparison of modern marker proteins in serum and synovial fluid in patients with advanced 2006 Mar Numerous studies have focused on the significance of modern marker proteins in the synovial fluid of the knee joint and in the serum both, for osteoarthritis (OA) and rheumatoid arthritis (RA). The relationship between the serum concentrations and the concentrations in the synovial fluid is still unclear. Synovial fluid and serum samples were obtained from 13 patients with advanced OA and from 8 patients with severe RA and concentrations of MMP-1, MMP-3, MMP-13, TIMP-1, COMP and MIA/CD-RAP were determined. All values were normalized against the total protein concentrations. Serum concentrations of MMP-13 in the RA-group were statistically higher than the synovial values (P<0.05). MMP-13 was the only marker protein that revealed distinct higher levels in the serum than in the synovial fluid. The study design allows only conclusions about advanced stages of RA and OA. Longitudinal investigations may provide further information about the value of MMP-13 as a potential marker to monitor the course of RA and OA.
15811060 Periodontal infection as a possible severity factor for rheumatoid arthritis. 2005 Apr OBJECTIVE: Clinical effects of periodontal treatment on biochemical and clinical markers of disease severity in rheumatoid arthritis (RA) patients with periodontal disease were evaluated. METHODS: Forty-two patients were assigned to two groups, G1 (n=16) and G2 (n=26). G1 patients were submitted to oral hygiene instruction and professional tooth cleaning and G2 patients additionally had full-mouth scaling and root planing (SRP). Clinical periodontal measurements were obtained at baseline and 3 months after periodontal treatment. A Health Assessment Questionnaire (HAQ) was used to evaluate their performance on daily living. Rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and drug therapy were assessed. RESULTS: Both groups presented a full-mouth improvement in all periodontal clinical parameters (p<0.05), with the exception of clinical attachment level (CAL) and probing pocket depth (PPD) >6 mm for G1. G2 showed greater mean reductions on PPD >4 mm than G1 (p<0.001). HAQ analyses showed a reduction on the degree of disability of G2, but not statistically significant. ESR was significantly reduced for G2 after SRP although RF did not show statistical reductions. CONCLUSION: The data suggest that periodontal treatment with SRP might have an effect on the ESR reduction.
16134385 [The role of Salmonella and Yersinia in the pathogenesis of spondyloarthropathies and rheu 2005 To investigate the role of Salmonella and Yersinia in the pathogenesis of spondyloarthropathies and rheumatoid arthritis synovial specimens from 92 patients were analysed for the presence of bacterial DNA with the use of polymerase chain reaction and for the presence of lipopolysaccharide and enterobacterial common antigen (ECA) with the use of Dot-ELISA. In addition, peripheral blood samples were available for PCR analysis from 68 patients. Salmonella and Yersinia chromosomal DNA was not found in any of the synovial specimens and blood samples from the patients. All of the synovial fluids were also culture-negative. Salmonella LPS antigens were observed in 8 (8.6%), Yersinia in 20 (21.7%) and ECA antigens in 32 (34.9%) synovial specimens. Our findings revealed the presence of bacterial degradation products, but not bacteria from the genus Salmonella and Yersinia or their DNA in the synovial fluid or blood of patients with spondyloarthropathies and rheumatoid arthritis.
17065120 Osteolysis after Sutter metacarpophalangeal arthroplasty: a prospective study of 282 impla 2006 Our aim was to evaluate the incidence and degree of osteolysis in a prospective series of patients with rheumatoid arthritis operated on with Sutter implants. Eighty-seven of the 110 operated hands (104 patients) with 282 implants were evaluated after a mean of 5.7 years (2.1-7.4). Osteolytic changes were present in 142 (50%) of the metacarpal and 152 (54%) of the phalangeal bones. Twenty-six of the metacarpal (9%) and 36 of the proximal phalangeal (13%) bones had osteolytic changes that did not affect the cortical bone. Cortical invasion was recorded in 100 (35%) of the metacarpal and 103 (37%) of the proximal phalangeal bones. The cortex was perforated in both bones in 14 (5%). Osteolytic changes were related to fractures of implants and to the dominant hand, but not to pain. Surgeons who operate on patients with rheumatoid diseases should note that silicone rubber implants often cause osteolytic changes.
16119657 The evaluation of the functioning and of the quality of life of patients with rheumatoid a 2005 PURPOSE: It has been reported that Rheumatoid Arthritis (RA) affects 0.5-1% of the adult population in Poland. The condition is two or three times more common among women than among men. The majority of the onsets of disease occur between the ages of 40 and 60. The aim of this study was to assess the functioning and quality of life of patients with Rheumatoid Arthritis treated in Rheumatoid Special Clinic in Poznań, Poland. The specific question was: does the functioning and the quality of life of RA patients depend on demographic variables (gender and age) and duration of the disease? MATERIAL AND METHODS: The study sample consisted of 168 RA patients, including 123 women (73.2%) and 45 men (26.8%). To assess the functioning and the quality of life the Polish version of the Arthritis Impact Measurement Scales 2 (AIMS 2) was applied. The Arthritis Impact Measurement Scales 2 was translated into Polish according to standardized approach (internal consistency reliability for the global score, alpha = 0.78). AIMS 2 scores range from 0-10, with 0 representing high functioning and quality of life, 10 representing poor functioning and quality of life. RESULTS: The results showed that the mean scores on the AIMS 2 for physical state and mobility was 3.53, which is within the medium section of the average measurement of the quality of life. The quality of life depended on the sex of the patients. Women scored significantly lower in the emotional area than men. Youngest patients demonstrated higher evaluation of quality of life in the area of bending and walking (4.4). Life satisfaction of people with RA is higher among the patients suffering longer than 5 years.
16826439 Single-factor scoring validation for the Health Assessment Questionnaire-Disability Index 2006 Oct OBJECTIVE: Structural validity for the Health Assessment Questionnaire-Disability Index (HAQ-DI) has recently been provided for patients with rheumatoid arthritis (RA). The goal of the current study was to examine the structural validity of the HAQ-DI in patients with systemic sclerosis (SSc, scleroderma) and to compare its performance with that in patients with RA. METHODS: The HAQ-DI structural validity was first assessed in a sample of 100 scleroderma patients using confirmatory factor analysis. Second, the similarity of factor structures between SSc patients (n = 291) and RA patients (n = 278) was tested using a multigroup structural validity model to assure that comparison of scores between these two diagnostic groups is appropriate. RESULTS: Results yielded a single-factor HAQ-DI score which favored the current scoring system of the HAQ-DI (model fit was CFI = 0.99 and RMSEA = 0.04). Moreover, even the most stringent model of multigroup structural validity affirmed the similarity between SSc and RA patients on the HAQ-DI (model fit was CFI = 0.99 and RMSEA = 0.04) nor was it different from a model without any demands on group similarity: CFI difference = 0.007; chi(2) = 4.29, df = 26, p=0.99. CONCLUSION: The current results indicate that a single-factor HAQ-DI is appropriate for future clinical trials in scleroderma and, in addition, HAQ-DI scores among patients with SSc and early RA can be compared legitimately with one another.
16463408 Retrospective analysis of utilization patterns and cost implications of coxibs among senio 2006 Feb 15 OBJECTIVE: In September 2004, the manufacturer of rofecoxib announced a voluntary worldwide withdrawal of the drug. The impact of this withdrawal on drug budgets is unclear. This study evaluated average daily doses and costs of rofecoxib and celecoxib and concomitant use of gastroprotective agents (GPAs) in elderly patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in Quebec, prior to the rofecoxib withdrawal. METHODS: This retrospective cohort study used prescription drug and medical service data from the Quebec government health agency administrative database and included coxib users > or =66 years of age with OA or RA who filled > or =3 consecutive rofecoxib or celecoxib prescriptions in 2001-2002. Results were adjusted for gastrointestinal risk factors and other patient baseline characteristics. RESULTS: Data were analyzed for 11,975 rofecoxib and 12,480 celecoxib users. Mean daily dosages were 20.7 mg for rofecoxib and 231.3 mg for celecoxib. Rofecoxib users consumed a mean +/- SD of 0.95 +/- 0.43 pills per day, and celecoxib users took 1.34 +/- 0.65 pills per day. Mean +/- SD unadjusted daily acquisition costs were $1.18 +/- $0.53 (Canadian) for rofecoxib and $1.45 +/- $0.74 for celecoxib. After adjusting for patient baseline characteristics, the mean daily acquisition cost for rofecoxib was $0.25 lower than for celecoxib. Rofecoxib users were less likely than celecoxib users to fill a GPA coprescription (odds ratio 0.88; 95% confidence interval 0.81, 0.95). Subgroup analyses yielded comparable results. CONCLUSION: Celecoxib appears to be a more expensive therapeutic option than rofecoxib due to a relatively higher daily dose and tablet consumption.