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ID PMID Title PublicationDate abstract
21259184 Ultrasound Doppler score correlates with OMERACT RAMRIS bone marrow oedema and synovitis s 2012 Dec PURPOSE: MRI is considered the standard of reference for advanced imaging in rheumatoid arthritis (RA). However, in daily clinical practice ultrasound (US) imaging with Doppler information is more versatile and often used for fast and dynamic assessment of joint inflammation. The aim was to compare low-field MRI scores with the US Doppler measurements in the wrist joint of patients with RA. MATERIAL AND METHODS: Fifty consecutive patients with RA (46 women & 4 men) completed both low-field dedicated extremity MRI (E-scan®, Esaote) and a high-end US (Sequioa®, Siemens) imaging of the wrist before initiating either biological treatment (n = 26) or intraarticular injection of Depomedrole® (n = 24). Mean age was 56 years (range 21 - 83 years); mean disease duration 87.2 months (range 4 - 349 months), mean DAS 28 4,8 (range 2 - 7). MRI was scored according to the OMERACT RAMRIS recommendations and US Doppler colour-fractions were determined. RESULTS: Using Spearman's rho, we found a relatively good to moderate correlation between the US colour-fraction and the total OMERACT bone marrow oedema and synovitis scores on MRI (r = 0.6; p < 0.001 and r = 0.4; p < 0.006 respectively). There was a trend but no significant correlation with the total OMERACT erosion score (r = 0.3; p = 0.06). CONCLUSION: Within limits, the OMERACT RAMRIS scores of inflammation in RA patients (bone marrow oedema and synovial enhancement) are comparable to the US colour-fraction measurements using a high-end US scanner. Both imaging modalities detect inflammation although showing different aspects of the inflammatory process in the wrist joint. The higher correlation between US colour-fractions and MRI bone marrow oedema indicates a potential importance of US Doppler in monitoring inflammatory disease changes in RA.
22803817 Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis in sexually intact g 2012 Aug OBJECTIVES: To investigate the frequency of Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis in the genital tract of sexually intact girls with arthritides, and to search for optimal means of their elucidation. METHOD: Sixty girls with rheumatic arthritides and 61 girls who had applied to a children's gynaecologist because of genital complaints (control group), aged 2-16 years, were examined. First-catch urine and swabs were taken from the vaginal arc and the surface of the external orifice of the urethra. C. trachomatis was elucidated by ligase chain reaction (LCR). U. urealyticum and M. hominis were detected with the Mycoplasma Duo diagnostic kit. RESULTS: One of the investigated microorganisms was found in nine (15%) girls with arthritis: C. trachomatis in one (1.7%), U. urealyticum in six (10%), and M. hominis in two (3.3%). In patients without arthritis, only U. urealyticum was detected in two (3.3%) girls. Nine (15%) girls with arthritis had genital symptoms (actively revealed only through a questionnaire), and in seven of them the investigated microorganisms were elucidated. Taking smears from the external orifice of the urethra failed to elucidate the microorganisms studied in only 1/11 positive cases from both patient groups. CONCLUSIONS: C. trachomatis was found in 1.7%, U. urealyticum in 10%, and M. hominis in 3.3% of 60 sexually intact girls with rheumatic arthritides. Actively detected genital symptoms may serve as a guide for examining girls with arthritis for these rare infections. The external orifice of the urethra may be an alternative easily accessible site for taking material for examination.
21078625 Long-term effectiveness and safety of TNF-blocking agents in daily clinical practice: resu 2011 Jan OBJECTIVES: Experience with anti-TNF agents for a decade can be used to research the safety and effectiveness of anti-TNF agents in the long term. The objective of this article is to describe drug survival, disease activity, daily functioning, quality of life and adverse events of TNF-blocking agents in daily clinical practice after 5 years of follow-up. METHODS: Data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register of 1560 RA patients were used for analyses (5-year follow-up, n=174). Drug survival and time to first serious infection or malignancy were analysed by Kaplan-Meier analysis. Several outcome measures at several follow-up moments were analysed per intention to treat and per protocol. RESULTS: The 5-year drug survival of the first anti-TNF was 45%, and 60% for total use of TNF-blocking agents. Baseline 28-joint DAS (DAS-28) was 5.1 (s.d. 1.3). After 5 years, the mean DAS-28 was 3.2 (s.d. 1.3) in all patients who had started with TNF-blocking agents and 2.9 (s.d. 1.1) in patients who were still on TNF-blocking agents. In the latter group, the HAQ score was 0.88 (s.d. 0.7) and the EuroQol five dimensions (EQ-5D) utility score was 0.7 (s.d. 0.2). Incidence rates of serious infections and malignancies were 2.9 and 0.6 per 100 patient-years, respectively. CONCLUSION: Five-year follow-up of RA patients treated with TNF-blocking agents showed a 60% drug survival accompanied by sustained low disease activity, normalized function and quality of life similar to that in the general population. The benefit to risk ratio for long-term TNF-blocking therapy remains favourable.
22460416 Possible role of adipokines in systemic lupus erythematosus and rheumatoid arthritis. 2012 Mar In recent years, mediators synthesized in the adipose tissue, the so-called adipokines, have been described. They have a hormonal action, regulating appetite and glucose metabolism, but also act as cytokines with effects on the immune system, including effects on autoimmunity. The most important adipokines are leptin, adiponectin, resistin and visfatin, and some of them have been assessed in autoimmune rheumatic diseases, especially systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Studies have shown high levels of leptin and adiponectin in SLE, but correlation with disease activity is questionable. In RA, studies have also reported increased levels of leptin and adiponectin, and correlation with disease activity and joint erosion, but the results are conflicting. This review describes the role of leptin and adiponectin on the immune system, as well as on SLE and RA.
22333381 Hypogammaglobulinemic patient with polyarthritis mimicking rheumatoid arthritis finally di 2012 Hypogammaglobulinemia is a reduction or absence of immunoglobulin, which may be congenital or associated with immunosuppressive therapy. In addition to infectious diseases, autoimmune diseases have also been reported in patients with hypogammaglobulinemia. A 26-year-old man with hypogammaglobulinemia had multiple joint pain and swelling with erosive changes in the proximal interphalangeal joint of the right middle finger on X-ray film, mimicking rheumatoid arthritis (RA). As polyarthritis remained after immunoglobulin replacement therapy and there was no finding indicating any infection at that time, a diagnosis of RA was made. Prednisolone and etanercept were started. However, his polyarthritis did not improve and he developed meningitis and massive brain ischemia. Finally, a diagnosis of disseminated Mycoplasma hominis infection was made. The differential diagnosis of polyarthritis in patients with hypogammaglobulinemia should strictly exclude Mycoplasma infection by culture with special media or longer anaerobic culture, and molecular methods for mycoplasma.
22048455 A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of th 2012 Apr The etiology of systemic lupus erythematosus (SLE) involves a complex interaction of genetic and environmental factors. Investigations have shown that environmentally driven epigenetic changes contribute to the etiology of SLE. Here, we hypothesize that aberrant DNA methylation may contribute to the activation of the immune machinery and trigger lupus disease activity. A whole genome methylation array was applied to investigate the DNA methylation changes between 12 pairs of active SLE patients and healthy controls. The results were further confirmed in 66 SLE patients, 102 healthy controls. The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (age-adjusted odds ratios, 64.2 and 16.9, respectively, P<0.0001). There was a trend toward SLE patients having hypomethylated IL10 and IL1R2 genes accompanied by greater disease activity. We observed that the methylation degree of IL10 and IL1R2 genes were reduced in the rheumatoid arthritis (RA) patients as well but the hypomethylation change was more significant in IL1R2 genes than in the IL10 genes in RA patients. This study demonstrated that DNA hypomethylation might be associated with SLE. Hypomethylated IL10 and IL1R2 genes may provide potential epigenetic markers as clinical predictors for autoimmune diseases.
23594898 [Elbow replacement]. 2012 Sep Elbow replacement or arthroplasty is a good therapeutic option for a large percentage of patients with significant joint destruction. However, many orthopaedic surgeons are no familiar with the surgical approaches or techniques associated with elbow replacement implants. Furthermore, the incidence of complications is higher than in other joint replacements, the most important being infections, mechanical failure, cubital neuropathy, and problems with the triceps. For these reasons, the use of bone arthroplasty in Spain may be less than ideal. Although, inflammatory arthritic diseases, such as rheumatoid arthritis, are the most frequent indication for this operation, distal humerus fractures and post-traumatic disease are a growing indication. This work attempts to summarise the most important current concepts associated with elbow replacement.
22200807 PAI-1 mRNA expression and plasma level in rheumatoid arthritis: relationship with 4G/5G PA 2012 Dec Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, cartilage and bone. PAI-1 is a key regulator of the fibrinolytic system through which plasminogen is converted to plasmin. The plasmin activates the matrix metalloproteinase system, which is closely related with the joint damage and bone destruction in RA. The aim of this study was to investigate the relationship between 4G/5G PAI-1 polymorphism with mRNA expression and PAI-1 plasma protein levels in RA patients. 113 RA patients and 123 healthy subjects (HS) were included in the study. The 4G/5G PAI-1 polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism method; the PAI-1 mRNA expression was determined by real-time PCR; and the soluble PAI-1 (sPAI-1) levels were quantified using an ELISA kit. No significant differences in the genotype and allele frequencies of 4G/5G PAI-1 polymorphism were found between RA patients and HS. However, the 5G/5G genotype was the most frequent in both studied groups: RA (42%) and HS (44%). PAI-1 mRNA expression was slightly increased (0.67 fold) in RA patients with respect to HS (P = 0.0001). In addition, in RA patients, the 4G/4G genotype carriers showed increased PAI-1 mRNA expression (3.82 fold) versus 4G/5G and 5G/5G genotypes (P = 0.0001), whereas the sPAI-1 plasma levels did not show significant differences. Our results indicate that the 4G/5G PAI-1 polymorphism is not a marker of susceptibility in the Western Mexico. However, the 4G/4G genotype is associated with high PAI-1 mRNA expression but not with the sPAI-1 levels in RA patients.
21811993 CXCL10 and its receptor CXCR3 regulate synovial fibroblast invasion in rheumatoid arthriti 2011 Nov OBJECTIVE: CXCL10 is expressed in increased levels in highly invasive fibroblast-like synoviocytes (FLS) from arthritic DA rats and from patients with rheumatoid arthritis (RA). This study was undertaken to analyze the role of CXCL10 and its receptor CXCR3 in regulation of the invasive properties of FLS. METHODS: FLS were isolated from synovial tissue of RA patients and from DA rats and arthritis-resistant DA.F344(Cia5d) rats with pristane-induced arthritis. We used an in vitro model of invasion through Matrigel, which has been shown to correlate with articular damage in RA and in rat arthritis. FLS were cultured in the presence or absence of CXCL10, anti-CXCR3 antibody, or the CXCR3 inhibitor AMG487 and then studied for invasion, matrix metalloproteinase (MMP) production (MMPs 1-3), intracellular calcium influx, and cell morphology. RESULTS: DA rat FLS produced higher levels of CXCL10 compared with minimally invasive FLS from DA.F344(Cia5d) rats. CXCL10 treatment increased the invasiveness of FLS from DA.F344(Cia5d) rats by 2-fold, and this increase was blocked by anti-CXCR3. Both anti-CXCR3 and AMG487 reduced invasiveness of FLS from DA rats, by as much as 77%. AMG487 significantly reduced invasiveness of RA FLS (by 58%). CXCR3 blockade reduced levels of MMP-1 by 65%, inhibited receptor signaling (64-100% reduction in intracellular calcium influx), and interfered with actin cytoskeleton reorganization and lamellipodia formation in FLS from rats and RA patients. CONCLUSION: We describe and characterize a new autocrine/paracrine role of CXCL10/CXCR3 in the regulation of FLS invasion in rats with arthritis and in RA patients. These observations suggest that the CXCL10/CXCR3 axis is a potential new target for therapies aimed at reducing FLS invasion and its associated joint damage and pannus invasion and destruction in RA.
21923740 Expression of G protein αq Subunit is Decreased in Lymphocytes from Patients with Rheumat 2012 Feb Gαq, the alpha subunit of Gq, a member of the Gq/11 sub-family, was reported to inhibit phosphatidylinositol-3-Kinase (PI3K) activation and prevent the activation of Akt. Previous studies demonstrated that mice losing Gαq in their immune system could spontaneously develop inflammatory arthritis. In this study, we showed that the Gαq expressions at mRNA and protein levels in the peripheral blood lymphocytes (PBLs) from patients with rheumatoid arthritis (RA) were significantly decreased in comparison of which in healthy individuals. The expression levels of Gαq mRNA in PBLs from patients with RA were correlated with RA disease activity (DAS28), anti-cyclic citrullinated protein antibodies, C-reactive protein and rheumatoid factor. We also demonstrated that Gαq controlled the apoptosis of RA PBLs through regulating the activity of Mcl-1 and caspase-3. These data suggested that Gαq might be involved in the pathogenesis of RA by regulating PBLs apoptosis.
22485125 Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patie 2012 BACKGROUND: T-helper (Th) 22 is involved in the pathogenesis of inflammatory diseases. The roles of Th22 cells in the pathophysiological of ankylosing spondylitis (AS) and rheumatoid arthritis (RA) remain unsettled. So we examined the frequencies of Th22 cells, Th17 cells and Th1 cells in peripheral blood (PB) from patients with AS and patients with RA compared with both healthy controls as well as patients with osteoarthritis. DESIGN AND METHODS: We studied 32 AS patients, 20 RA patients, 10 OA patients and 20 healthy controls. The expression of IL-22, IL-17 and IFN-γ were examined in AS, RA, OA patients and healthy controls by flow cytometry. Plasma IL-22 and IL-17 levels were examined by enzyme-linked immunosorbent assay. RESULTS: Th22 cells, Th17 cells and interleukin-22 were significantly elevated in AS and RA patients compared with OA patients and healthy controls. Moreover, Th22 cells showed positive correlation with Th17 cells as well as interleukin-22 in AS and RA patients. However, positive correlation between IL-22 and Th17 cells was only found in AS patients not in RA patients. In addition, the percentages of both Th22 cells and Th17 cells correlated positively with disease activity only in RA patients not in AS patients. CONCLUSIONS: The frequencies of both Th22 cells and Th17 cells were elevated in PB from patients with AS and patients with RA. These findings suggest that Th22 cells and Th17 cells may be implicated in the pathogenesis of AS and RA, and Th22 cells and Th17 cells may be reasonable cellular targets for therapeutic intervention.
23126056 [Secondary (AA) renal/bone amyloidosis complicating rheumatoid arthritis]. 2011 Sep Amyloidosis is a clinical entity that results from deposition of an extracellular protein material that causes disruption in normal architecture and impairs function of multiple organs and tissues. Secondary amyloidosis (AA) is a rare but serious complication that appears in the context of cancer, chronic inflammation, and chronic infectious disease, including rheumatoid arthritis. Renal failure is the most common clinical presentation of AA, ranging from nephrotic syndrome and impaired renal function to renal failure, with a potential for high morbidity. We present a case of a 52-year-old female patient diagnosed with rheumatoid arthritis at age 27. She was hospitalized due to worsening clinical condition. Physical examination revealed marked peripheral edema in both lower extremities. Laboratory tests showed an increase of inflammatory reactants, anemia, electrolyte disbalance, and severe hypoalbuminemia and hypoproteinemia. She had proteinuria 15.4 g/24 h and renal function estimated by creatinine clearance was 78 mL/min, within the second degree of chronic kidney disease. Renal biopsy was performed for evaluation of renal insufficiency with nephrotic range proteinuria. Congo red staining showed the presence of characteristic amyloid deposits that immunoreacted with the antibody against amyloid A protein, thus confirming the diagnosis of secondary amyloidosis.
21272164 Tocilizumab: is there life beyond anti-TNF blockade? 2011 Apr Anti-TNF-α therapy has become the most effective biological treatment for rheumatoid arthritis. Despite having changed the prognosis of the disease establishing new targets for treatment strategy, there are several aspects that still remain unmatched. About 30% of the patients with rheumatoid arthritis have a less than satisfactory response to anti-TNF therapy, which has led the way for the pursuit of new targets and approaches to treatment. IL-6 is one of these alternative targets and data from the more recent clinical trials involving tocilizumab (an anti-IL-6 soluble receptor antibody) suggest advantages in relation to some clinical aspects which are not addressed by anti-TNF-α treatment.
22526478 Effect of exercise on cardiac autonomic function in females with rheumatoid arthritis. 2012 Aug The objective of this study is to evaluate the effect of exercise on cardiac autonomic function as measured by short-term heart rate variability (HRV) in females suffering from rheumatoid arthritis (RA). Females with confirmed RA were randomly assigned to an exercise group (RAE) and a sedentary group (RAC). RAE was required to train under supervision two to three times per week, for 3 months. Three techniques (time domain, frequency domain and Poincaré plot analyses) were used to measure HRV at baseline and study completion. At baseline, RAC (n = 18) had a significantly higher variability compared to RAE (n = 19) for most HRV indicators. At study completion, the variables showing significant changes (p = 0.01 to 0.05) favoured RAE in all instances. Wilcoxon signed rank tests were performed to assess changes within groups from start to end. RAE showed significant improvement for most of the standing variables, including measurements of combined autonomic influence, e.g. SDRR (p = 0.002) and variables indicating only vagal influence, e.g. pNN50 (p = 0.014). RAC mostly deteriorated with emphasis on variables measuring vagal influence (RMSSD, pNN50, SD1 and HF (ms(2)). Study results indicated that 12 weeks of exercise intervention had a positive effect on cardiac autonomic function as measured by short-term HRV, in females with RA. Several of the standing variables indicated improved vagal influence on the heart rate. Exercise can thus potentially be used as an instrument to improve cardiac health in a patient group known for increased cardiac morbidity.
22942261 Risk of failure of a clinical drug trial in patients with moderate to severe rheumatoid ar 2012 Nov OBJECTIVE: We conducted a systematic review to determine the risk of drug failure in clinical testing with patients with moderate to severe rheumatoid arthritis (RA). METHODS: Therapies for RA were investigated by reviewing phase I to phase III studies conducted from December 1998 to March 2011. Clinical trial success rates were calculated and compared to industry standards. Trial failures were classified as either commercial or clinical failures. The exclusion criteria for drugs in this study: drugs that were started in phase I studies prior to January 1998 for this indication; or studies that enrolled patients who were methotrexate-naive and/or had failed biologic therapy. RESULTS: A search in clinicaltrials.gov and approved drugs for the indication yielded a total of 69 drugs that met the study criteria. The cumulative success rate was determined to be 16%, which is equivalent to the industry standard of 16%. For each phase, the frequency of clinical failures exceeded commercial failures. Clinical studies equally comprised investigations of small molecules and biological agents, but biologics seemed to exhibit a higher success rate overall. CONCLUSION: Clinical trial risk in RA with the 84% failure rate reported here is at par with industry performance and phase II success rate seems to be highly predictive of phase III success.
22605835 Complication of etanercept treatment for rheumatoid arthritis--purulent pericarditis cause 2012 May 8 The patient presented with increasing fatigue and dyspnoea. The patient had medical history of rheumatoid arthritis for which she had been taking methotrexate for the past 15 years and etanercept for the past 6 years. Initial diagnosis was cardiac failure but further investigation by echocardiogram revealed a large pericardial effusion. Empirical piperacillin-tazobactam was started due to moderately raised inflammatory markers. Four hundred millilitre of frank pus was aspirated from the pericardial sac and antimicrobial treatment was changed to meropenem. Gram positive cocci were seen in the initial Gram stain, but conventional cultures remained negative. However, 16S ribosomal RNA gene sequencing of the pus sample detected the presence of Parvimonas micra genome. Reaccumulation of the effusion required further drainage where again P micra was detected by 16S ribosomal RNA gene sequencing. Two weeks of meropenem was completed followed by treatment with benzylpenicillin and metronidazole.
22144400 Enrichment of circulating interleukin-17-secreting interleukin-23 receptor-positive γ/δ 2012 May OBJECTIVE: Ankylosing spondylitis (AS) is a common inflammatory arthritis affecting primarily the axial skeleton. IL23R is genetically associated with AS. This study was undertaken to investigate and characterize the role of interleukin-23 (IL-23) signaling in AS pathogenesis. METHODS: The study population consisted of patients with active AS (n = 17), patients with psoriatic arthritis (n = 8), patients with rheumatoid arthritis, (n = 9), and healthy subjects (n = 20). IL-23 receptor (IL-23R) expression in T cells was determined in each subject group, and expression levels were compared. RESULTS: The proportion of IL-23R-expressing T cells in the periphery was 2-fold higher in AS patients than in healthy controls, specifically driven by a 3-fold increase in IL-23R-positive γ/δ T cells in AS patients. The proportions of CD4+ and CD8+ cells that were positive for IL-17 were unchanged. This increased IL-23R expression on γ/δ T cells was also associated with enhanced IL-17 secretion, with no observable IL-17 production from IL-23R-negative γ/δ T cells in AS patients. Furthermore, γ/δ T cells from AS patients were heavily skewed toward IL-17 production in response to stimulation with IL-23 and/or anti-CD3/CD28. CONCLUSION: Recently, mouse models have shown IL-17-secreting γ/δ T cells to be pathogenic in infection and autoimmunity. Our data provide the first description of a potentially pathogenic role of these cells in a human autoimmune disease. Since IL-23 is a maturation and growth factor for IL-17-producing cells, increased IL-23R expression may regulate the function of this putative pathogenic γ/δ T cell population.
21968544 Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice 2012 Mar OBJECTIVE: Bone destruction is a critical pathology involved in the functional disability caused by rheumatoid arthritis (RA). Osteoclasts, which are specialized bone-resorbing cells regulated by cytokines such as RANKL, are implicated in bone destruction in RA. The aim of this study was to determine whether interleukin-21 (IL-21), a potent immunomodulatory 4-α-helical bundle type 1 cytokine, has osteoclastogenic activity in patients with RA and in mice with collagen-induced arthritis (CIA). METHODS: The expression of IL-21 in synovial tissue was examined using immunohistochemistry. The concentrations of IL-21 in serum and synovial fluid were determined by enzyme-linked immunosorbent assay. The levels of RANKL and osteoclastogenic markers were measured using real-time polymerase chain reaction. CD14+ monocytes from patients with RA or mouse bone marrow cells were cocultured with fibroblast-like synoviocytes (FLS) from patients with RA or CD4+ T cells from mice with CIA in the presence of IL-21 and subsequently stained for tartrate-resistant acid phosphatase activity to determine osteoclast formation. RESULTS: IL-21 was up-regulated in the synovium, synovial fluid, and serum of patients with RA and in the synovium and serum of mice with CIA. IL-21 induced RANKL expression in mixed joint cells and CD4+ T cells from mice with CIA and in CD4+ T cells and FLS from patients with RA. Moreover, IL-21 enhanced in vitro osteoclastogenesis without the presence of RANKL-providing cells and by inducing RANKL expression in CD4+ T cells and FLS. CONCLUSION: Our data suggest that IL-21 promotes osteoclastogenesis in RA. We believe that therapeutic strategies targeting IL-21 might be effective for the treatment of patients with RA, especially in preventing bone destruction.
21904105 Treatment of rheumatoid arthritis with roxithromycin: a randomized trial. 2011 Sep BACKGROUND: High levels of antibodies to oral anaerobic bacteria have been found in the serum and synovial fluid of patients with rheumatoid arthritis (RA). Macrolide antibiotics are active against oral anaerobic bacteria. The aim of this trial was to evaluate the efficacy of roxithromycin in patients with RA who had not responded to disease-modifying antirheumatic drugs. METHODS: This was a 6-month, randomized, double-blind, placebo-controlled trial. We treated 100 patients with active RA with either once-daily oral roxithromycin 300 mg or daily oral placebo for 6 months. The primary efficacy variable was the percentage of patients who had a 20% improvement according to the American College of Rheumatology (ACR) criteria (an ACR20 response) at 6 months. Secondary outcome measures were 50% improvement and 70% improvement according to ACR criteria (an ACR50 response and an ACR70 response, respectively). RESULTS: A significantly greater percentage of patients treated with roxithromycin 300 mg met the ACR 20% improvement criteria (ie, achieved an ACR20 response) at 6 months compared with patients who received placebo (60% vs 34%; P = 0.009). Greater percentages of patients treated with roxithromycin 300 mg also achieved ACR50 responses (38% vs 12%; P = 0.003) and ACR70 responses (18% vs 2%; P = 0.008) compared with patients who received placebo. Roxithromycin was well tolerated, with an overall safety profile similar to that of placebo. CONCLUSION: In patients with active RA, treatment with roxithromycin significantly improved the signs and symptoms of RA.
22688516 Therapeutic effects of lactosyl derivative Gu-4 in a collagen-induced arthritis rat model. 2012 Aug Rheumatoid arthritis (RA) is an inflammatory disorder that is characterized by persistent recurrence of joint inflammation leading to cartilage and bone destruction. The present anti-arthritis therapies failed to achieve satisfactory remission in all patients; therefore, it is still necessary to develop novel approaches to fulfill the demand in clinic. Here, we reported the therapeutic effects of lactosyl derivative Gu-4, a synthetic compound that was previously identified as a selective inhibitor against leukocyte integrin CD11b, in a bovine type II collagen induced arthritis (CIA) rat model. First, prophylactic administration of Gu-4 (1.2728 mg/kg) to rats by intraperitoneal injection every 2 days from the first day of collagen immunization significantly decreased the incidence of CIA, diminished the mean paw volume increase, and reduced the number of swollen paws. Second, administration of Gu-4 (1.2728 mg/kg) to rats at early-onset stage of CIA prevented the progression of the pathological process of RA, accelerated the remission of paw edema, and declined the arthritis score; after 5 weeks treatment, X-ray and histological examinations were carried out, the ankle joint of hind limb of Gu-4 treated CIA rats exhibited slighter bone erosion and much less inflammatory cell infiltration compared to those of saline treated animals; furthermore, Gu-4 remarkably attenuated the production of rheumatoid factor (RF) in the serum of CIA rats as determined by ELISA. Moreover, we performed in vitro lymphocyte proliferation assay and found that Gu-4 significantly inhibited the proliferation of splenic lymphocytes isolated from CIA rats in a dose-dependent manner. Our results suggest that Gu-4 can effectively ameliorate CIA and might be an alternative option for the treatment of RA.