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ID PMID Title PublicationDate abstract
19033290 Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a syst 2009 Jul OBJECTIVES: To review systematically the available literature on the optimal dosage and route of administration of methotrexate in patients with rheumatoid arthritis (RA), as an evidence base for generating clinical practice recommendations. METHODS: A systematic literature search was carried out in MEDLINE, EMBASE, Cochrane Library and American College of Rheumatology/European League Against Rheumatism meeting abstracts, searching for randomised controlled trials evaluating various dosages or routes of administration of methotrexate in RA. Articles that fulfilled predefined inclusion criteria were systematically reviewed and the quality was appraised. Effect sizes and odds ratios for clinical, radiological and toxicity outcomes were calculated and directly or indirectly compared between study groups using methotrexate in different dosages or by different routes. RESULTS: A total of 38 publications out of 1748 identified references was included in the review. Start doses of 25 mg/week or fast escalation with 5 mg/month to 25-30 mg/week were associated with higher clinical effect sizes and more (gastrointestinal) adverse events in comparison with doses of 5-15 mg/week or slow escalation. Starting with 15 mg/week subcutaneous versus oral methotrexate was associated with higher clinical efficacy but more withdrawal due to toxicity in early RA. In longstanding RA, after failure on 15-20 mg/week orally, a switch to 15 mg/week intramuscularly with subsequent dose escalation did not result in increased efficacy. CONCLUSIONS: Starting on methotrexate 15 mg/week orally, escalating with 5 mg/month to 25-30 mg/week, or the highest tolerable dose, with a subsequent switch to subcutaneous administration in the case of an insufficient response, seems to be the optimal evidence-based dosing and routing recommendation for methotrexate in RA.
18377141 Effect of couple illness perception congruence on psychological adjustment in women with r 2008 Mar OBJECTIVE: To characterize similarities and differences in illness perceptions between women with rheumatoid arthritis (RA) and their husbands, and examine whether illness perception congruence predicted wives' subsequent psychological adjustment. DESIGN: Women with RA and their husbands (N=190 couples) recruited from community and clinical settings completed mailed surveys at baseline and 4-month follow-up. MAIN OUTCOME MEASURES: Data for this investigation included illness perceptions in partners and illness severity, marital variables, and psychological adjustment in wives. RESULTS: In general, wives and husbands had similar views of RA. Couple congruence concerning women's personal control over RA and its cyclic nature predicted better psychological adjustment in women 4 months later. Post hoc tests showed better psychological adjustment in wives from couples with similar optimistic beliefs about personal control, illness coherence, and RA consequences, when compared to those in couples with similar pessimistic beliefs. Furthermore, when partners disagreed about RA's consequences, wives fared better when husbands overestimated rather than underestimated their beliefs. In contrast, couple congruence about the emotions and timeline of RA was unrelated to adjustment. CONCLUSION: It may be important for husbands to understand wives' views on their control over RA and its cyclic nature. Furthermore, wives may benefit when they share optimistic views with their husbands about RA, and when their husbands avoid underestimating RA's consequences. Developing interventions to enhance partners' illness understanding may be beneficial.
17339437 Targeting of the transcription factor STAT4 by antisense phosphorothioate oligonucleotides 2007 Mar 15 The transcription factor STAT4 mediates signals of various proinflammatory cytokines, such as IL-12, IL-15, and IL-23, that initiate and stabilize Th1 cytokine production. Although Th1 cytokine production has been suggested to play a major pathogenic role in rheumatoid arthritis, the role of STAT4 in this disease is poorly understood. In this study, we demonstrate a key functional role of STAT4 in murine collagen-induced arthritis (CIA). In initial studies we found that STAT4 expression is strongly induced in CD4(+) T cells and to a lesser extent in CD11b(+) APCs during CIA. To analyze the role of STAT4 for arthritis manifestation, we next investigated the outcome of interfering with STAT4 gene expression in CIA by using STAT4-deficient mice. Interestingly, STAT4-deficient mice developed significantly less severe arthritis than wild-type control mice and the T cells from such mice produced less IL-6, TNF, and IL-17. In addition, the targeting of STAT4 expression by a specific antisense phosphorothioate oligonucleotide directed at the translation start site suppressed STAT4 levels and signs of CIA even when applied during the onset of disease manifestation. These data suggest a key regulatory role of STAT4 in the pathogenesis and manifestation of murine collagen-induced arthritis. Furthermore, the targeting of STAT4 emerges as a novel approach to therapy for chronic arthritis.
16689008 [Clinical observation on effects of leflunomid and total glucosides of paeony on rheumatoi 2006 Apr OBJECTIVE: The observe the clinical effect of leflunomide (LEF) and total glucosides of Paeony (TGP) on rheumatoid arthritis (RA) and their influences on laboratory findings. METHODS: Eighty patients with RA were randomly divided into 2 groups, 40 in each group: the treated group treated with TGP and leflunomide, and the control group treated with LEF alone, the therapeutic course for both groups was 12 weeks. Clinical effect after treatment, changes of symptoms and physical signs before and after treatment were observed and the relative laboratory indexes were detected as well. RESULTS: The total effective rate in the treated group was higher than that in the control group (97.5% vs 85.0%, P < 0.05). The clinical and laboratory indexes in the treated group were improved significantly after treatment (P < 0.05, P < 0.01), with the improvement superior to those in the control group (P < 0.05, P < 0.01) respectively. There was no significant difference in adverse reaction between the two groups. CONCLUSION: Combined application of TGP and LEF is superior to using of LEF alone in treating RA, owing to its quicker initiating action and less adverse reaction.
18709606 Quantification of colour Doppler activity in the wrist in patients with rheumatoid arthrit 2008 Aug PURPOSE: The amount of colour Doppler activity in the inflamed synovium is used to quantify inflammatory activity. The measurements may vary due to image selection, quantification method, and point in cardiac cycle. This study investigated the test-retest reliability of ultrasound colour Doppler measurements in the wrist of patients with rheumatoid arthritis (RA) using different selection and quantification methods. MATERIALS AND METHODS: 14 patients with RA had their wrist scanned twice by the same investigator with an interval of 30 minutes. The images for analysis were selected either by the anatomical position only or by the anatomical position with maximum colour Doppler activity. Subsequently, the amount of colour Doppler was measured in an area defined by either the synovial tissue or by specific anatomical structures surrounding the synovial tissue. RESULTS: The best test-retest reliability was obtained when the images were selected guided by colour Doppler and the subsequent quantification was done in an area defined by anatomical structures. With this method, the intra-class coefficient ICC (2.1) was 0.95 and the within-subject SD (SW) was 0.017, indicating good reliability. In contrast, poor test-retest reliability was found if the images were selected by anatomical position only and the quantification was done in an area defined by the synovial tissue (ICC [2.1] = 0.48 and SW = 0.049). CONCLUSION: The study showed that colour Doppler measurements are reliable if the images for analysis are selected by anatomical position in combination with colour Doppler activity and the subsequent analysis is performed in an area defined by anatomical structures.
16507142 CXCL12 is displayed by rheumatoid endothelial cells through its basic amino-terminal motif 2006 The chemokine CXCL12 (also known as stromal cell-derived factor, SDF-1) is constitutively expressed by stromal resident cells and is involved in the homeostatic and inflammatory traffic of leukocytes. Binding of CXCL12 to glycosaminoglycans on endothelial cells (ECs) is supposed to be relevant to the regulation of leukocyte diapedesis and neoangiogenesis during inflammatory responses. To improve our understanding of the relevance of this process to rheumatoid arthritis (RA), we have studied the mechanisms of presentation of exogenous CXCL12 by cultured RA ECs. RA synovial tissues had higher levels of CXCL12 on the endothelium than osteoarthritis (OA) tissues; in both, CXCL12 colocalized to heparan sulfate proteoglycans (HSPGs) and high endothelial venules. In cultured RA ECs, exogenous CXCL12alpha was able to bind in a CXCR4-independent manner to surface HSPGs. Desulfation of RA EC HSPGs by pretreatment with sodium chlorate, or by replacing in a synthetic CXCL12alpha the residues Lys24 and Lys27 by Ser (CXCL12alpha-K2427S), decreased or abrogated the ability of the chemokine to bind to RA ECs. Ex vivo, synovial ECs from patients with either OA or RA displayed a higher CXCL12-binding capacity than human umbilical vein ECs (HUVECs), and in HUVECs the binding of CXCL12 was increased on exposure to tumor necrosis factor-alpha or lymphotoxin-alpha1beta2. Our findings indicate that CXCL12 binds to HSPGs on ECs of RA synovium. The phenomenon relates to the interaction of HSPGs with a CXCL12 domain with net positive surface charge located in the first beta strand, which encompasses a canonical BXBB HSPG-binding motif. Furthermore, we show that the attachment of CXCL12 to HSPGs is upregulated by inflammatory cytokines. Both the upregulation of a constitutive chemokine during chronic inflammation and the HSPG-dependent immobilization of CXCL12 in EC surfaces are potential sites for therapeutic intervention.
17522454 Continuing to work after the onset of rheumatoid arthritis. 2007 The aim of this qualitative study was to explore and describe what have made it possible for a group of people with rheumatoid arthritis to remain in work. There were ten participants, six women and four men, aged from 32 to 59. They were working either full time or part-time, at the time the study was conducted. Data was gathered using focus group interviews. The transcribed interviews were analysed in accordance with the constant comparative method. The result showed that the assets the individuals possessed and the character of the environment in which they worked were important reasons why they were able to remain in employment. Four main categories were identified: the constructive value of work, the characteristics of work, physical health and well-being and the understanding and support of colleagues. The findings support a client-centred occupational therapy and rehabilitation, where the experiences of the person provide the reason for the intervention.
17334047 [Erosive enteropathy in a patient with polyarthritis]. 2006 Oct Anaemia is a common clinical feature in patients with rheumatoid arthritis and the coexistence of blood loss may not show an obvious iron deficiency anaemia. The cause may be a cancer or other reason for gastrointestinal bleeding that could be underestimated for being explained as associated with the chronic rheumatic disease. Although less described than gastroduodenal lesions, small bowel damage of non-steroidal anti-inflammatory drugs, used in the treatment of rheumatic diseases, are more common than previously thought. The authors describe a clinical case paradigmatic of the difficulties that may appear in the approach of anaemia in a patient with a chronic rheumatic disease and discuss some features of intestinal toxicity of nonsteroidal anti-inflammatory drugs.
16395755 Healthcare and burden of disease in psoriatic arthritis. A comparison with rheumatoid arth 2006 Jan OBJECTIVE: To compare quality of life and treatment among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) treated by German rheumatologists. METHODS: Data for outpatients with PsA (n = 1863), RA (n = 9627), or AS (n = 1378) enrolled in the national database of the German collaborative arthritis centers in the year 2002 were analyzed. Among those with PsA, 2 subgroups with predominantly peripheral arthritis (n = 1612) and predominantly axial disease (n = 251) were distinguished. RESULTS: We found a high burden of illness in patients with PsA treated by rheumatologists. Among the 2 subgroups, those with axial PsA had worse outcomes (pain, function) than those with peripheral PsA. However, compared with RA and AS, physician ratings of disease activity and severity were lower in PsA. Concerning access to rheumatology care, there were similarities between AS and axial PsA, with very long disease duration at first visit (mean of about 6 yrs), versus RA and peripheral PsA, with shorter duration (1.6 and 2.5 yrs, respectively). A majority (84%) of patients with PsA were treated with disease modifying antirheumatic drugs. Thirty percent of the patients with PsA currently were under therapy with glucocorticoids, mainly (89%) with a dose < 7.5 mg. CONCLUSION: Patients with PsA seen in rheumatologic care have a burden of illness comparable to that of patients with RA or AS.
18361235 [Prevention and treatment of perioperative period complication of total ankle replacement] 2008 Jan OBJECTIVE: To explore the cause of the perioprative period complication of scandinavian total ankle replacement (STAR) and to summarize the experience in the treatment and prevention. METHODS: From March 1999 to November 2006, 35 patients were given total ankle replacement (TAR) with STAR system. There were 19 males and 16 females with an average age of 50.5 years (27 to 68 years), including 12 cases of posttraumatic arthritis, 8 cases of osteoarthritis and 15 cases of rheumatoid arthritis. All patients had pain of ankle joint, swelling and limitation of joint motion. The disease course was 9-64 months. The curative effect was estimated by Kofoed total ankle scoring system. The mean preoperative ankle score was 29 (6-48); the mean pain score was 18.3 (0-35); the mean function score was 11.7 (6-18); and the mean activity score was 9.2 (3-12). The type of all complications were record, and its cause, prevetion and treatment were analyszed. RESULTS: Thirty-three patients achieved healing by first intention, 2 achieved delayed union because of infection. Twenty-eight patients were followed up 3-80 months (mean 43.5 months). Medial malleolus fracture occurred in 2 cases, unstable ankle joint introversion in 2 cases, limitation of ankle dorsiextension in 1 case and 1 case had hypoesthesia at intermediate dorsal skin of foot and 3rd-5th metatarsal skin without obvious dysfunction; all were treated with symptomatic medication. The postoperative mean ankle score was 85.5 (58-95); the mean pain score was 48.3 (35-50); the mean function score was 20.7 (18-30); the mean activity score was 17.2 (16-20). There were statistically significant differences when compared with preoperative score (P<0.01). The clinical results were excellent in 16 patients, good in 9 patients and fair in 3 patients. The X-ray films showed no loosening and subsidence of prosthesis. CONCLUSION: Although STAR can retain the functions of the operated joint, it has its special complications. It is important to obey operation principle with proficient operative technique, to strictly control surgical indication and to intensify perioperative period treatment so as to decrease the complications.
18627338 Is tocilizumab an option for the treatment of arthritis? 2008 Aug BACKGROUND: Some patients with rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis are resistant to inhibitors of interleukin-1 and tumour necrosis factor. Raised levels of interleukin-6 are associated with both these conditions. Tocilizumab is a humanised monoclonal antibody that binds to both forms of interleukin-6 receptor that has recently been used in Phase III trials in rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis. METHODS: The study conducted an evaluation of Phase III trials with tocilizumab. RESULTS: In the Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders the primary efficacy end-point was the proportion of subjects with a 20% improvement in their rheumatoid arthritis signs and symptoms according to the American College of Rheumatology criteria and, at 24 weeks, this value was 26% with placebo and was increased to 48 and 59% with tocilizumab at 4 and 8 mg respectively. In the trial of tocilizumab in systemic-onset juvenile idiopathic arthritis, the primary end-point in the open-label lead-in was the proportion of subjects achieving an American College of Rheumatology Pediatric 30 response and 91% of subjects had achieved this at 6 weeks. This response was maintained by the majority of subjects being treated with tocilizumab during a 12-week double-blind trial and 48 weeks of open trial follow-up. Small numbers of subjects developed infections in both studies. CONCLUSIONS: Provided long-term safety can be established, tocilizumab will probably become part of the treatment for rheumatoid arthritis and may become a major breakthrough for the treatment of systemic-onset juvenile idiopathic arthritis.
17500615 Sleep and the affective response to stress and pain. 2007 May OBJECTIVE: The current study examined sleep disturbance (i.e., sleep duration, sleep quality) as a correlate of stress reactivity and pain reactivity. DESIGN AND OUTCOME MEASURES: An ecological momentary assessment design was used to evaluate the psychosocial functioning of men and women with fibromyalgia or rheumatoid arthritis (N=49). Participants recorded numeric ratings of pain, the occurrence of a stressful event, as well as positive and negative affect 7 times throughout the day for 2 consecutive days. In addition, participants reported on their sleep duration and sleep quality each morning. RESULTS: Sleep disruption was not found to be an independent predictor of affect. However, sleep was found to buffer the relationship between stress and negative affect and the relationship between pain and both positive and negative affect. CONCLUSION: These results are consistent with a model in which good-quality sleep acts as a biobehavioral resource that minimizes allostatic load.
17133577 Association of citrullinated proteins with synovial exosomes. 2006 Dec OBJECTIVE: In addition to releasing proteins and mediators, cells also release membrane vesicles (exosomes and apoptotic blebs) into the extracellular environment. Apoptotic blebs contain multiple autoantigens, but few data are available concerning the protein content of exosomes. Exosomes are formed during an immune response and can directly stimulate T cells or bind to dendritic cells. The aim of this study was to identify the nature of synovial exosomes from patients with different rheumatic diseases and to examine their potential autoantigenic content, which may be involved in the induction of an autoimmune response. METHODS: Synovial exosomes from patients with rheumatoid arthritis (RA), patients with reactive arthritis, and patients with osteoarthritis were purified, analyzed by electron microscopy, and labeled with immunogold to detect IgG and IgM molecules. Autoantigen content was identified by 2-dimensional electrophoresis-immunoblotting and subsequent mass spectrometry. In order to investigate the presence of citrullinated proteins, immunoblotting with anticitrulline antibodies was performed. RESULTS: Citrullinated proteins were observed in all exosome preparations, in contrast to other autoantigenic proteins (e.g., BiP and heterogeneous nuclear RNP A2) that were previously observed in RA and other autoimmune diseases. These citrullinated proteins included the fibrin alpha-chain fragment, fibrin beta-chain, fibrinogen beta-chain precursor, fibrinogen D fragment, and the Sp alpha (CD5 antigen-like protein) receptor. Purification of synovial exosomes led to the detection of citrullinated fibrinogen and citrullinated Sp alpha associated with IgM and IgG. CONCLUSION: Synovial exosomes contain citrullinated proteins, which are known to be autoantigens in RA. Although immune mechanisms in which exosomes carry citrullinated peptides could play an important role in the induction and distribution of citrullinated proteins, there must be a specific recognition of these proteins that is unique to the RA immune system.
16613612 The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via 2006 S100A8 and S100A9, two Ca2+-binding proteins of the S100 family, are secreted as a heterodimeric complex (S100A8/A9) from neutrophils and monocytes/macrophages. Serum and synovial fluid levels of S100A8, S100A9, and S100A8/A9 were all higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA), with the S100A8/A9 heterodimer being prevalent. By two-color immunofluorescence labeling, S100A8/A9 antigens were found to be expressed mainly by infiltrating CD68+ macrophages in RA synovial tissue (ST). Isolated ST cells from patients with RA spontaneously released larger amounts of S100A8/A9 protein than did the cells from patients with OA. S100A8/A9 complexes, as well as S100A9 homodimers, stimulated the production of proinflammatory cytokines, such as tumor necrosis factor alpha, by purified monocytes and in vitro-differentiated macrophages. S100A8/A9-mediated cytokine production was suppressed significantly by p38 mitogen-activated protein kinase (MAPK) inhibitors and almost completely by nuclear factor kappa B (NF-kappaB) inhibitors. NF-kappaB activation was induced in S100A8/A9-stimulated monocytes, but this activity was not inhibited by p38 MAPK inhibitors. These results indicate that the S100A8/A9 heterodimer, secreted extracellularly from activated tissue macrophages, may amplify proinflammatory cytokine responses through activation of NF-kappaB and p38 MAPK pathways in RA.
18664547 Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumat 2009 Aug OBJECTIVES: The use of biologicals such as infliximab has dramatically improved the treatment of rheumatoid arthritis (RA). However, factors predictive of therapeutic response need to be identified. A proteomic study was performed prior to infliximab therapy to identify a panel of candidate protein biomarkers of RA predictive of treatment response. METHODS: Plasma profiles of 60 patients with RA (28 non-responders (as defined by the American College of Rheumatology 20% improvement criteria (ACR20)) negative and 32 responders (ACR70 positive) to infliximab) were studied by surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS) technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterisation was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by matrix assisted laser desorption/ionisation time-of-flight (MALDI-TOF) MS analysis. RESULTS: Two distinct protein profiles were observed on both arrays and several proteins were differentially expressed in both patient populations. Five proteins at 3.86, 7.77, 7.97, 8.14 and 74.07 kDa were overexpressed in the non-responder group, whereas one at 28 kDa was increased in the responder population (sensitivity>56%, specificity>77.5%). Moreover, combination of several biomarkers improved the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterised as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4. CONCLUSIONS: Six plasma biomarkers are characterised, enabling the detection of patient response to infliximab with high sensitivity and specificity. Apolipoprotein A-1 was predictive of a good response to infliximab, whereas platelet factor 4 was associated with non-responders.
17959074 [Expression of high mobility group box chromosomal protein 1 in peripheral blood of patien 2007 Jul OBJECTIVE: To investigate the mRNA and protein expression of high mobility group box chromosomal protein 1 (HMGB1) in peripheral blood mononuclear cells (PBMCs) and serum. METHODS: Levels of HMGB1mRNA were detected with reverse transcription polymerase chain reaction (RT-PCR) in PBMC and levels of HMGB1 protein in PBMC and plasm were measured with Western blot in 38 patients with active rheumatoid arthritis (RA), 24 with inactive RA and 20 healthy controls. Ficoll density gradient centrifugation was used to separate PBMCs from peripheral blood. The correlation between the levels of HMGB1 in serum and the index of disease activity in RA was analyzed. RESULTS: There was no statistically significant difference of the mRNA expression of HMGB1 in PBMCs from active RA patients as compared with those from inactive RA group and healthy controls (F = 1.23, P > 0.05). The protein expression of HMGB1 was significantly lower in PBMCs from active RA patients (F = 70.91, P < 0.01), while the protein expression of HMGB1 was higher in plasma from active RA patients (P < 0.001) as compared with that from inactive RA patients and healthy controls. However, there was no statistically significant difference between inactive RA patients and healthy controls (P > 0.05). The level of HMGB1 protein in plasma of RA patients was correlated with erythrocyte sedimentation rate (ESR) (r(s) = 0.478, P < 0.001) and C- reactive protein (CRP) (r(s) = 0.574, P < 0.05). It was not correlated with age, the number of tender joints and swollen joints, radiographic scores and therapeutic effect. CONCLUSION: The protein expression of HMGB1 was significantly decreased in PBMCs from active RA patients, while it was increased in serum from active RA patients. HMGB1 plays a pivotal role in the pathogenesis of RA and may be a target of therapy as a novel cytokine.
17717914 [Effect of strengthening Pi and activating blood circulation therapy on serum levels of ad 2007 Jul OBJECTIVE: To observe the effect of strengthening Pi and activating blood circulation therapy (SPAB) on serum levels of adrenocorticotrophic hormone (ACTH) and vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA) patients. METHODS: Seventy RA patients were randomly assigned to 3 groups. The 30 in the Chinese medicine (CM) group were treated with SPAB; the 20 in the Western medicine (WM) group were treated with indomethacin and methopterin; and the 20 in the CM-WM group were treated with the combination of the therapy in the above two groups, and the course of treatment was 3 months for all. Serum levels of ACTH and VEGF were determined before and after treatment. RESULTS: The total effective rate in the CM group was 80.0%, WM group 85.0% and CM-WM group 95.0%, the last one showed the best efficacy (P<0.05). Serum level of ACTH increased and level of VEGF decreased after treatment in all groups (P<0.05 or P<0.01), but the increment/decrement in the CM-WM group was higher than that in the other two groups (P<0.01), while comparison between that in the CW group and WM group showed insignificant difference. CONCLUSION: SPAB therapy has the effect in alleviating the condition of RA, similar to that of Western medicine, it can increase the serum level of ACTH and decrease the serum level of VEGF remarkably in RA patients.
17278017 Scientific basis for the efficacy of combined use of antirheumatic drugs against bone dest 2007 Finding a means to ameliorate and prevent bone destruction is one of the urgent issues in the treatment of rheumatoid arthritis. Recent studies revealed bone-resorbing osteoclasts to be essential for arthritic bone destruction, but to date there has been scarce experimental evidence for the underlying mechanism of the bone-protective effect of antirheumatic drugs. Here we examined the effects of one or a combination of disease-modifying antirheumatic drugs (DMARDs) on osteoclast differentiation to provide a cellular and molecular basis for their efficacy against bone destruction. The effects on osteoclast precursor cells and osteoclastogenesis-supporting cells were distinguished by two in vitro osteoclast culture systems. Methotrexate (MTX), bucillamine (Buc) and salazosulphapyridine (SASP) inhibited osteoclastogenesis by acting on osteoclast precursor cells and interfering with receptor activator of NF-kappaB ligand (RANKL)-mediated induction of the nuclear factor of activated T cells (NFAT) c1. MTX and SASP also suppressed RANKL expression on osteoclastogenesis-supporting mesenchymal cells. Interestingly, the combination of three antirheumatic drugs exerted a marked inhibitory effect on osteoclastogenesis even at a low dose at which there was much less of an effect when administered individually. These results are consistent with the reported efficacy of combined DMARDs therapy in humans and suggest that osteoclast culture systems are useful tools to provide an experimental basis for the bone-protective effects of antirheumatic drugs.
18688917 Safety of anti-tumor necrosis factor-alpha therapy in patients with rheumatoid arthritis a 2008 Oct OBJECTIVE: The prevalence of concurrent rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection is probably underestimated because of the increasing spread of this virus worldwide, especially in developing countries. In these patients, anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy may aggravate hepatitis and increase viremia. We evaluated the safety of these treatments, which remain controversial. METHODS: Thirty-one HCV-positive patients (23 women, 8 men, mean age 59+/-13 yrs, mean disease duration 13+/-11.5 SD yrs) with active RA [Disease Activity Score 28 (DAS28)>3.2] unresponsive to conventional therapies were treated with TNF-alpha blockers (infliximab 11, etanercept 17, adalimumab 3) at standard dosages. Safety and efficacy were evaluated at the third month of treatment and at the patient's last observation. RESULTS: A significant clinical-serological improvement was recorded at the 3-month reevaluation. Mean values of patients assessment of general health on visual analog scale (range 0.100) decreased from 69+/-29 (SD) to 35+/-27 (p<0.0001), Ritchie index from 21.6+/-13.9 to 10.1+/-3.7 (p<0.0001), erythrocyte sedimentation rate from 36+/-25 to 28+/-22 mm/h (p=0.04), and DAS28 from 5.2+/-1.6 to 2.78+/-1.3 (p<0.0001); a DAS28<2.6 was recorded in 15/31 (48%) patients. At the last observation 19 patients (61%) continued TNF-alpha blockers, and the observed benefits persisted after 22+/-11 months of followup. Mean values of transaminases (ALT) and HCV viral load showed no significant variations; TNF-alpha blockers were discontinued in only one patient because of persistently elevated ALT not correlated to the variations of HCV viremia; this latter increased significantly (>or=2 log10) in 4 cases. CONCLUSION: Previous observations had suggested the safety of TNF-alpha blockers for treatment of RA in patients with concurrent HCV infection. Given the clinical-therapeutic implications, our results support the safety of TNF-alpha blockers in patients with HCV, provided there is close monitoring of clinical and virological data (mainly ALT and HCV viremia).
16552464 Effectiveness of anakinra in rheumatic disease in patients naive to biological drugs or pr 2006 Nov The aim of this study was to evaluate the effectiveness of IL-1 inhibition in rheumatic disease using real-life, observational methods. We analyzed data from 47 patients collected from the national ROB-FIN for rheumatic disease. Commonly used, validated measures of efficacy and adverse effects were documented and analyzed. The series contains 47/1,135 patients (mean age 47+/-11 years, range 25-73, females 83%) on anakinra of whom 39 patients suffered from rheumatoid arthritis (RA), two presented with psoriatic arthritis, and four with juvenile RA. At 3 months (26/40), 46% reached American College of Rheumatology (ACR) 20 and 27% ACR 50. In patients naive to biological drugs, the response rate at 3 months was 60% for ACR 20 and 20% for ACR 50. At follow-up of the total series, ACR responses at 6 and 12 months were 69/56% for ACR 20 and 23/22% for ACR 50. These data give room for IL-1 suppression when treating patient with rheumatic disease. Careful selection of patients, together with combining anakinra with disease-modifying antirheumatic drugs, perhaps adds effectiveness. For treating clinicians in Finland, these results are encouraging, as reimbursed treatment alternatives for patients refractory to all other therapies are still few.