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ID PMID Title PublicationDate abstract
19898488 Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. 2009 Dec Active rheumatoid arthritis originates from few joints but subsequently affects the majority of joints. Thus far, the pathways of the progression of the disease are largely unknown. As rheumatoid arthritis synovial fibroblasts (RASFs) which can be found in RA synovium are key players in joint destruction and are able to migrate in vitro, we evaluated the potential of RASFs to spread the disease in vivo. To simulate the primary joint of origin, we implanted healthy human cartilage together with RASFs subcutaneously into severe combined immunodeficient (SCID) mice. At the contralateral flank, we implanted healthy cartilage without cells. RASFs showed an active movement to the naive cartilage via the vasculature independent of the site of application of RASFs into the SCID mouse, leading to a marked destruction of the target cartilage. These findings support the hypothesis that the characteristic clinical phenomenon of destructive arthritis spreading between joints is mediated, at least in part, by the transmigration of activated RASFs.
19436841 The clinical efficacy of tocilizumab in rheumatoid arthritis. 2009 Mar Interleukin-6 (IL-6) has emerged as a potential therapeutic target in rheumatoid arthritis (RA). This is based on the greater understanding of the role this cytokine can play in various aspects of the immunopathphysiology of RA. Recently, theory has been put into practice with the assessment of IL-6 inhibitors in clinical trials. The largest amount of data to date comes from trials of the humanized anti-IL-6 receptor antibody tocilizumab. Studies worldwide have demonstrated the clinical efficacy of this agent in patients with RA.
19758195 Genetic susceptibility loci in rheumatoid arthritis establish transcriptional regulatory n 2009 Sep Linkage studies have identified the human leukocyte antigen (HLA)-DRB1 as a putative rheumatoid arthritis (RA) susceptibility locus (SL). Nevertheless, it was estimated that its contribution was partial, suggesting that other non-HLA genes may play a role in RA susceptibility. To test this hypothesis, we conducted microarray transcription profiling of peripheral blood mononuclear cells in 15 RA patients and analyzed the data, using bioinformatics programs (significance analysis of microarrays method and GeneNetwork), which allowed us to determine the differentially expressed genes and to reconstruct transcriptional networks. The patients were grouped according to disease features or treatment with tumor necrosis factor blocker. Transcriptional networks that were reconstructed allowed us to identify the interactions occurring between RA SL and other genes, for example, HLA-DRB1 interacting with FNDC3A (fibronectin type III domain containing 3A). Given that fibronectin fragments can stimulate mediators of matrix and cartilage destruction in RA, this interaction is of special interest and may contribute to a clearer understanding of the functional role of HLA-DRB1 in RA pathogenesis.
20565921 Reduced trabecular bone mineral density and cortical thickness accompanied by increased ou 2010 INTRODUCTION: The objective of this study was to assess three-dimensional bone geometry and density at the epiphysis and shaft of the third meta-carpal bone of rheumatoid arthritis (RA) patients in comparison to healthy controls with the novel method of peripheral quantitative computed tomography (pQCT). METHODS: PQCT scans were performed in 50 female RA patients and 100 healthy female controls at the distal epiphyses and shafts of the third metacarpal bone, the radius and the tibia. Reproducibility was determined by coefficient of variation. Bone densitometric and geometric parameters were compared between the two groups and correlated to disease characteristics. RESULTS: Reproducibility of different pQCT parameters was between 0.7% and 2.5%. RA patients had 12% to 19% lower trabecular bone mineral density (BMD) (P
20566736 The effectiveness of anti-TNF-alpha therapies when used sequentially in rheumatoid arthrit 2010 Dec OBJECTIVES: To systematically review and meta-analyse evidence on the effectiveness of the TNF-α inhibitors when used sequentially. METHODS: Systematic review of comparative and single-arm observational studies. Data were synthesized using random-effects meta-analysis. Treatment effects were estimated using four outcome measures from the included studies: European League Against Rheumatism (EULAR) and ACR20 response rates and mean improvement in disease activity score-28 (DAS-20) and HAQ. The effect of other factors was explored via meta-regression and sub-group analyses. RESULTS: Twenty studies comprising 2705 patients were included in the analysis. All studies were observational and most had no control group. Therefore, our primary analysis considered patient changes from baseline. The mean percentage of ACR20 responders was 60.8% (95% CI 53.8, 67.4), EULAR responders 70.5% (95% CI 63.7, 76.6), mean overall improvement in DAS-28 scores was 1.53 (95% CI 1.25, 1.80) and in HAQ scores was 0.25 (95% CI 0.11, 0.40). Four studies made comparisons with patients who received TNF-α inhibitors for the first time. Response rates associated with sequential TNF-α inhibitor treatment were lower than for first-time use. CONCLUSIONS: Sequential TNF-α inhibitor use is likely to lead to treatment benefit in terms of the signs and symptoms of disease and physical function. There is also some evidence to suggest that the probability of achieving a response is lower, and the average magnitude of response is lower than the first use. Further evidence from randomized controlled trials is required to confirm and further quantify the role specific anti-TNF-α agents have when used sequentially.
20621538 Outcome and safety of TNFα antagonist therapy in 475 consecutive outpatients (with rheuma 2010 Dec OBJECTIVE: To investigate the effectiveness and safety of TNFα antagonists in patients with rheumatoid arthritis (RA) or spondyloarthropathies (SpA) treated by a single physician, according to the presence of the inclusion and non-inclusion criteria used to select patients for pivotal clinical trials. METHODS: Effectiveness was evaluated based on four categories defined by the DAS28-ESR and BASDAI values, from a very good response (mean DAS-28-ESR less than 3.2 and mean BASDAI less than 2.0) to failure (DAS28-ESR unchanged or greater than 5.1 and BASDAI unchanged). Serious adverse events were defined as events that required permanent TNFα antagonist discontinuation or that led to sequelae, hospital admission, or death. RESULTS: The study included 475 patients, 230 with RA, 226 with SpA, 10 with juvenile-onset arthritis, and nine with unclassifiable arthritis. Mean number of TNFα antagonists used per patient was 1.3 and mean duration of TNFα antagonist treatment was 28±23 months. Overall, 41% of patients met the inclusion and non-inclusion criteria used in pivotal trials; the proportion was 43% in the RA group and 40% in the SpA group. These patients had a 3-fold higher rate of very good responses (54 versus 19%) and a 5-fold lower rate of failures (5 versus 25%) compared to the other patients. Of the 15 (3%) patients who died, none met pivotal trial criteria. The group that met pivotal trial criteria had a significantly lower rate of serious adverse events (11 versus 16%; Chi(2), p=0.0001), although age was similar in the two groups (53±16 years versus 57±14 years). CONCLUSION: Patients meeting the selection criteria used in pivotal trials had a higher response rate and significantly fewer serious adverse events.
19255226 Acetabular revision with impacted morselized cancellous bone graft and a cemented cup in p 2009 Mar 1 We previously reported our results at a minimum of three years after thirty-five revisions of total hip arthroplasty acetabular components in twenty-eight patients with rheumatoid arthritis. The revisions were performed with use of impacted morselized bone graft and a cemented cup. This update report presents the results at eight to nineteen years after the surgery, which, to our knowledge, is the longest follow-up available in the literature. No patient was lost to follow-up. Since our previous report, there were two additional cup failures due to aseptic loosening, at ten and sixteen years postoperatively. Kaplan-Meier analysis showed the probability of survival of the acetabular component at twelve years to be 80% (95% confidence interval, 65% to 95%) with removal of the cup for any reason as the end point and 85% (95% confidence interval, 71% to 99%) with aseptic loosening as the end point. Cup revisions performed with cement and use of impaction bone-grafting in patients with rheumatoid arthritis led to acceptable long-term prosthetic survival rates. This technique is attractive from a biological standpoint because of the possibility of maintaining acetabular bone stock.
19879280 Differing patterns of peripheral blood leukocyte telomere length in rheumatologic diseases 2010 Jan 5 Telomeres progressively shorten with repeated somatic tissue cell division, their length being an indicator of cellular ageing. Telomeric dysfunction may be implicated in a variety of diseases. We measured mean telomere length in peripheral blood leukocytes (PBL) from patients with various rheumatologic diseases. Mean PBL telomere length was measured using real-time quantitative polymerase chain reaction (Q-PCR) assay in a control population (n=130; age range: 3-94 years) and in subjects diagnosed with rheumatoid arthritis (RA; n=86; age range: 31-82 years), psoriatic arthritis (PA; n=56; age range: 26-79 years) and ankylosing spondylitis (AS; n=59; age range: 21-75 years). These diseases are associated with chronic systemic inflammatory activity. Telomere length was also quantified in subjects with osteoarthritis (OA; n=34; age range: 43-82 years) and osteoporosis (OP; n=35; age range: 59-95 years), diseases without a chronic systemic inflammatory component. Telomere length in OA showed no differences from age-matched controls (p=0.234), but was significantly shorter in OP (p=0.001). Telomere length was significantly longer than controls in RA (p=0.015), PA (p<0.001) and AS (p<0.001). Different patterns in telomere length from PBL are evidenced in rheumatologic pathologies, possibly dependent on the presence or absence of chronic systemic inflammation.
19280933 [Diagnostic imaging of systemic rheumatic diseases]. 2009 Mar In patients with systemic rheumatic diseases, imaging often plays an important role in diagnosis. Erosions of cartilage and bone are among the cardinal features of RA. Plain radiography is used most often to assess for the presence of joint damage, however, other imaging techniques such as contrast-enhanced magnetic resonance imaging (MRI) and ultrasonography are valuable to detect early inflammatory change of joint. In addition, chest CT is essential to detect pulmonary involvement which sometimes can be a main prognostic factor. Finally, arteriograms are helpful in identifying and characterizing a vasculitis of large and medium-sized arteries, in whom an obvious area for biopsy is absent. The present article reviews these imaging techniques.
20133510 Efficacy and safety of ketoprofen patch in patients with rheumatoid arthritis: a randomize 2010 Oct This study assessed the efficacy and safety of ketoprofen patch compared with placebo in patients who had rheumatoid arthritis and persistent wrist pain. Patients (N = 676)who had achieved systemic disease control with a disease-modifying antirheumatic drug and/or systemic corticosteroid, but still had persistent wrist pain, were randomized to a 2-week course of once-daily treatment with application of a 20-mg ketoprofen patch or a placebo patch to the wrist. The primary efficacy end point was the percent change from baseline to the end of treatment in the intensity of wrist pain scored by each patient on a 100-mm visual analog scale. The mean ± SD percent change on the pain intensity scale was significantly larger in patients treated with ketoprofen than in those receiving placebo (31.2% ± 30.3% [95% confidence interval: 28.0-34.4] vs 25.5% ± 31.2% [95% confidence interval: 22.1-28.8]; P = .020). However, the actual difference of the mean pain intensity scale between the 2 groups was small at the end of treatment. The frequency of adverse events was similar in both groups. The ketoprofen patch was more effective than placebo for relieving persistent local joint pain in patients with rheumatoid arthritis. The patch was also safe and well tolerated during the 2-week treatment period.
19565542 Multicenter, randomized, double-blind, controlled trial of treatment of active rheumatoid 2009 Jul 15 OBJECTIVE: To assess the efficacy and safety of T-614 versus methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: In this multicenter, double-blind trial, 489 patients randomly received either T-614 25 mg/day for the first 4 weeks and 50 mg/day for the subsequent 20 weeks (group 1, n = 163), T-614 50 mg/day for 24 weeks (group 2, n = 163), or MTX 10 mg/week for the first 4 weeks and 15 mg/week for the subsequent 20 weeks (n = 163). Clinical and laboratory parameters were analyzed at baseline and at 4, 10, 17, and 24 weeks. RESULTS: After 24 weeks of treatment, the American College of Rheumatology 20% improvement criteria response rate for patients in T-614 group 2 (63.8%) was not statistically significantly different from that for patients receiving MTX treatment (62.0%), and was superior to that for patients in T-614 group 1 (50.9%). The result of the noninferiority analysis indicated that the efficacy of T-614 (50 mg/day) was not lower than that of MTX by <10%. Rheumatoid factor and IgA, IgG, and IgM demonstrated a statistically significant decrease in all groups. Frequently reported adverse events included hematologic disorder, skin reactions, gastrointestinal symptoms, and transient liver enzyme elevations in the T-614 therapy groups. Side effects in the T-614 groups were generally fewer and milder than in the MTX group, except for skin reactions. There were no prominent cardiovascular adverse events and gastrointestinal ulcers found in the T-614 groups. CONCLUSION: Results indicate that T-614 therapy 50 mg/day is effective and well tolerated, and represents a new option for the treatment of patients with active RA.
20192994 IRF4 and its regulators: evolving insights into the pathogenesis of inflammatory arthritis 2010 Jan Accumulating evidence from murine and human studies supports a key role for interleukin-17 (IL-17) and IL-21 in the pathogenesis of inflammatory arthritis. The pathways and molecular mechanisms that underlie the production of IL-17 and IL-21 are being rapidly elucidated. This review focuses on interferon regulatory factor 4 (IRF4), a member of the IRF family of transcription factors, which has emerged as a crucial controller of both IL-17 and IL-21 production. We first outline the complex role of IRF4 in the function of CD4(+) T cells and then discuss recent studies from our laboratory that have revealed a surprising role for components of Rho GTPase-mediated pathways in controlling the activity of IRF4. A better understanding of these novel pathways will hopefully provide new insights into mechanisms responsible for the development of inflammatory arthritis and potentially guide the design of novel therapeutic approaches.
21081527 Increased cartilage turnover and circulating autoantibodies in different subsets before th 2011 Mar BACKGROUND: Previous studies have indicated that autoantibodies may be detected years before the clinical onset of rheumatoid arthritis (RA). Cartilage biomarkers, such as cartilage oligomeric matrix protein (COMP), have not been studied previously in samples collected before the diagnosis of RA. METHODS: Between 1991 and 1996, 30 447 subjects were included in the Malmö Diet Cancer Study (MDCS). People who developed RA after inclusion were identified by linking the MDCS database to different Swedish registers. One matched control for each validated case was selected from the MDCS. IgG antibodies against cyclic citrullinated peptide (anti-CCP) and mutated citrullinated vimentin (anti-MCV) and IgM rheumatoid factor (IgM RF) were determined by ELISA. Serum COMP was measured with a sandwich ELISA. RESULTS: 172 incident cases of RA (median time from inclusion to diagnosis 5 years; range 1-13) were identified. Pre-RA cases were significantly more likely than controls to be positive for anti-CCP (21.9% vs 0.6%), anti-MCV (29.6% vs 3.0%) and IgM RF (18.9% vs 2.4%) (all p<0.001). Overall, mean serum COMP levels did not differ between cases and controls. Among pre-RA cases included 1-3 years before diagnosis, raised COMP (>12 U/l) was seen in a greater proportion of anti-CCP-negative than anti-CCP-positive subjects (50% vs 15%; p=0.04). CONCLUSIONS: Increased cartilage turnover, measured by COMP, and circulating RA-specific antibodies may be distinct processes in the preclinical phase of RA.
18812394 Homozygosity for DNASE2 single nucleotide polymorphisms in the 5'-regulatory region is ass 2009 Sep OBJECTIVES: To analyse the distribution of single nucleotide polymorphisms (SNPs) in the 5'-regulatory region of the DNASE2 gene, in patients with rheumatoid arthritis (RA) and healthy controls. METHODS: A total of 906 patients with RA and 878 healthy controls were genotyped. All subjects were of German Caucasian origin. Genotyping was performed by real-time polymerase chain reaction technology, using a TaqMan 5'-allele discrimination assay. RESULTS: In the initial analysis of unrelated case-control samples, three DNASE2 SNP alleles in the 5'-regulatory region were significantly more frequent in patients with RA than in healthy controls. The strongest association was found for the -1066G allele (33.5% vs 27.2%, p = 0.007, odds ratio (OR) = 1.34). Homozygosity for this allele (genotype GG) resulted in an additional increase in disease susceptibility (12.5% vs 6.2%, OR = 2.17). The association was replicated in a second case-control series of 483 patients with RA from two German multicentre studies and 474 controls. The association of DNASE2 -1066 GG homozygosity with RA was limited to rheumatoid factor-positive disease, but was not influenced by the presence of anti-cyclic citrullinated peptide or antinuclear antibodies. Similarly, the presence or absence of the HLA-DRB1 shared epitope or the RA-associated PTPN22 allele had no influence on this association. CONCLUSIONS: The association of SNPs in the 5'-regulatory region of the DNA degrading enzyme DNASE2 with RA implies a role for this enzyme in the pathogenesis of this autoimmune disease.
21298986 [Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy in Po 2010 Dec Results of a multicenter, non-interventional, observational study assessing efficacy and safety of 1st course rituximab treatment with methotrexate in patients with rheumatoid arthritis and a history of inadequate response to anti-TNF-therapies, in the routine clinical settings in Poland (MIRACLE-POL 1). The aim of the study was to determine the efficacy and safety of treatment with rituximab and methotrexate in patients with active rheumatoid arthritis (RA) who had inadequate response to anti-TNF-therapies in routine clinical settings in Poland. MATERIAL AND METHODS: We evaluated effectiveness and safety of RTX and MTX therapy in 73 patients enrolled in the multicenter, non-interventional, observational study. Patients with active RA had a history of an inadequate response to 1 or more anti-TNF-alpha agents received 1st course of rituximab consisting of 2 intravenous infusions of 1000 mg each. The end points were: EULAR response criteria at 180 days, changes of Disease Activity Scores in 28 joints (DAS28) from the original baseline at 180 days, rate of remission, rate of low disease activity according to EULAR criteria and rate of adverse events (AEs) during treatment. RESULTS: At 180 days 22% of treated patients demonstrated good-to-moderate EULAR response and 12% of patients demonstrated moderate response. In 77% of cases DAS28 decreased > 1.2. 16% of patients achieved remission according to EULAR criteria and 23% of patients achieved low disease activity. After 180 days mean DAS28 score decreased from 6.33 to 4.06. In 16% of patients AEs occurred with the first rituximab infusion, in 12% of patients with the second rituximab one, and in 43% of patients afterwards. All AEs were mild or moderate in severity. There were no serious AEs including serious infections. Infusion-associated AEs occurred in a higher proportion during the first infusion. CONCLUSIONS: Results of this multicenter, non-interventional, observational study confirm efficacy and safety of 1st course rituximab treatment with concomitant methotrexate in patients with rheumatoid arthritis who had inadequate response to anti-TNF-therapies in the routine clinical settings in Poland.
20208070 Rheumatoid arthritis is an independent risk factor for increased carotid intima-media thic 2010 Jun OBJECTIVES: To evaluate the extent of subclinical atherosclerosis in patients with RA and low cardiovascular risk by measuring intima-media thickness (IMT) of the carotid arteries and to determine factors associated with increased IMT. METHODS: IMT was measured by ultrasonography in 42 non-diabetic, normotensive, female RA patients and 32 matched healthy controls [age 45.3 (10.0) vs 45.2 (9.8) years] at common carotid arteries (CCAs), carotid bifurcation (BF) and internal carotid arteries (ICAs), bilaterally. Mean and maximal (max) IMTs were calculated from three measurements at each site. Clinical work-up included laboratory analyses, determination of the disease activity and evaluation of treatment. RESULTS: RA patients had increased IMT (mm) in comparison with controls [CCA(max): 0.764 (0.148) vs 0.703 (0.100); CCA(mean): 0.671 (0.119) vs 0.621 (0.085); BF(max): 1.055 (0.184) vs 0.941 (0.161); BF(mean): 0.889 (0.168) vs 0.804 (0.124); ICA(max): 0.683 (0.108) vs 0.613 (0.093); ICA(mean): 0.577 (0.101) vs 0.535 (0.076)]. Parameters associated with IMT in RA patients were (correlation at x/6 measurement sites): age (6/6), BMI (2/6), smoking (2/6), RF concentration (2/6), sedimentation rate (1/6) and duration of MTX + chloroquine therapy (4/6; inverse correlation). Multivariate regression analysis revealed that RA is an independent risk factor for increased IMT. Factors correlating with IMT in the controls were: age (6/6), BMI (3/6), total cholesterol (5/6), low-density lipoprotein cholesterol (3/6), total/high-density lipoprotein cholesterol (2/6), triglycerides (1/6) and glycaemia (4/6). CONCLUSION: Despite a favourable risk profile, our female RA patients had significantly enlarged carotid IMT than controls. RA itself was an independent risk factor for increased IMT. Impact of chronic inflammation on atherosclerosis was confirmed by negative correlation of IMT and duration of anti-inflammatory treatment.
20592283 Junctional adhesion molecule-C is a soluble mediator of angiogenesis. 2010 Aug 1 Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed by endothelial cells (ECs) that plays a role in tight junction formation, leukocyte adhesion, and transendothelial migration. In the current study, we investigated whether JAM-C is found in soluble form and whether soluble JAM-C (sJAM-C) mediates angiogenesis. We found that JAM-C is present in soluble form in normal serum and elevated in rheumatoid arthritis (RA) serum. The concentration of sJAM-C is also elevated locally in RA synovial fluid compared with RA serum or osteoarthritis synovial fluid. sJAM-C was also present in the culture supernatant of human microvascular ECs (HMVECs) and immortalized human dermal microvascular ECs, and its concentration was increased following cytokine stimulation. In addition, sJAM-C cleavage from the cell surface was mediated in part by a disintegrin and metalloproteinases 10 and 17. In functional assays, sJAM-C was both chemotactic and chemokinetic for HMVECs and induced HMVEC tube formation on Matrigel in vitro. Neutralizing anti-JAM-C Abs inhibited RA synovial fluid-induced HMVEC chemotaxis and sJAM-C-induced HMVEC tube formation on Matrigel. sJAM-C also induced angiogenesis in vivo in the Matrigel plug and sponge granuloma models. Moreover, sJAM-C-mediated HMVEC chemotaxis was dependent on Src, p38, and PI3K. Our results show that JAM-C exists in soluble form and suggest that modulation of sJAM-C may provide a novel route for controlling pathological angiogenesis.
20615918 Patient-reported 28 swollen and tender joint counts accurately represent RA disease activi 2010 Nov OBJECTIVE: Formal joint assessments are critically important to improve rheumatological care of patients with RA. The aim of this study was to determine the usefulness of patient-recorded 28 tender joint counts (TJCs) and swollen joint counts (SJCs) using a tablet personal computer and to explore the possibility of using patient-recorded data to calculate 28-joint DAS (DAS-28) and EULAR response. METHODS: Forty-seven patients were included before initiation of adalimumab therapy and assessed at baseline and after 3 months. SJC and TJC were registered by the patients and thereafter by an experienced rheumatology specialist. Changes were correlated using Spearman's rank correlation test. RESULTS: The correlations between SJC and TJC derived by the physician and the patient at baseline were excellent (r = 0.78 and 0.87, respectively P < 0.01 for both). After 3 months, the correlations were less strong (0.645 and 0.745, respectively, P < 0.001 for both). When using the patient-derived SJC/TJC for calculation of the DAS-28 (patDAS-28), similar values were obtained, and correlations between DAS-28 and patDAS-28 were excellent (r = 0.91 at baseline, r = 0.90 at 3 months). According to the EULAR response criteria, the percentage of responders at the group level was nearly identical, although there was some disagreement at the individual level when DAS-28 and patDAS-28 were used to determine response to therapy. CONCLUSION: Patient-reported SJC and TJC can in research settings be used instead of physician-reported ones. Patient-derived SJC and TJC may also make it possible for rheumatologists to obtain quantitative joint count recordings much more frequently than is feasible for traditional joint counts.
21190991 How I treat LGL leukemia. 2011 Mar 10 Large granular lymphocyte (LGL) leukemia is characterized by a clonal expansion of either CD3(+) cytotoxic T or CD3(-) NK cells. Prominent clinical features of T-LGL leukemia include neutropenia, anemia and rheumatoid arthritis (RA). The terminal effector memory phenotype (CD3(+)/CD45RA(+)/CD62L(-)CD57(+)) of T-LGL suggests a pivotal chronic antigen-driven immune response. LGL survival is then promoted by platelet-derived growth factor and interleukin-15, resulting in global dysregulation of apoptosis and resistance to normal pathways of activation-induced cell death. These pathogenic features explain why treatment of T-LGL leukemia is based on immunosuppressive therapy. The majority of these patients eventually need treatment because of severe or symptomatic neutropenia, anemia, or RA. No standard therapy has been established because of the absence of large prospective trials. The authors use low-dose methotrexate initially for T-LGL leukemia patients with neutropenia and/or RA. We recommend either methotrexate or oral cyclophosphamide as initial therapy for anemia. If treatment is not successful, patients are switched to either the other agent or cyclosporine. The majority of patients experience an indolent clinical course. Deaths infrequently occur because of infections related to severe neutropenia. As there are no curative therapeutic modalities for T-LGL leukemia, new treatment options are needed.
19565512 Disease remission state in patients treated with the combination of tumor necrosis factor 2009 Jul OBJECTIVE: For patients with rheumatoid arthritis (RA) in remission who are receiving disease-modifying antirheumatic drugs (DMARDs), radiographic progression correlates with imaging-detected synovitis as measured by power Doppler activity. In contrast, patients with disease in remission who are receiving the combination of tumor necrosis factor (TNF) blockade with methotrexate (MTX) (combination treatment) have reduced radiographic damage for the equivalent clinical state. We undertook this study to determine whether the difference in radiographic outcome is a result of more complete suppression of imaging-detected synovitis. METHODS: One hundred patients with RA in remission (Disease Activity Score in 28 joints [DAS28] <2.6) for at least 6 months while receiving either combination treatment (n = 50) or DMARDs (n = 50) were matched for clinical variables. Ultrasound of metacarpophalangeal joints 1-5 and the wrist joints was performed. Remission according to imaging results was defined as a score of 0 for both grey scale synovitis and power Doppler activity. RESULTS: In patients receiving combination treatment or DMARDs (median DAS28 1.65 versus 1.78, median disease duration 120 months versus 90 months, and median duration of remission 13 months versus 18 months), the proportion with remission according to imaging results was not significantly different (10% versus 16%, respectively). The combination treatment group had more grey scale synovitis (P < 0.001) but similar power Doppler activity (48% versus 60%, respectively; P = 0.229) in any joint as compared with the DMARD group. Results were not affected by stratification for duration of disease or remission. CONCLUSION: In RA patients with disease in remission, imaging-detected synovitis persists, with power Doppler activity seen in >or=48% of the patients regardless of therapy. These results suggest that superior radiographic outcomes in patients treated with the combination of TNF blockade and MTX may not be due to complete suppression of imaging-detected synovitis.