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Activity Index (activity + index)
Kinds of Activity Index Terms modified by Activity Index Selected AbstractsFontolizumab in moderate to severe Crohn's disease: A phase 2, randomized, double-blind, placebo-controlled, multiple-dose studyINFLAMMATORY BOWEL DISEASES, Issue 2 2010Walter Reinisch MD Abstract Background: The safety and efficacy of fontolizumab, a humanized anti-interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms. Methods: A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels. Results: Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%,38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C-reactive protein levels. The overall frequency of adverse events was similar in all groups (58%,75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab. Conclusions: Although a strong clinical response to fontolizumab was not observed, significant decreases in C-reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted. Inflamm Bowel Dis 2009 [source] Ulcerative colitis: Correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytesINFLAMMATORY BOWEL DISEASES, Issue 12 2009Alain M. Schoepfer MD Abstract Background: The accuracy of noninvasive markers for the detection of endoscopically active ulcerative colitis (UC) according the Rachmilewitz Score is so far unknown. The aim was to evaluate the correlation between endoscopic disease activity and fecal calprotectin, Clinical Activity Index, C-reactive protein (CRP), and blood leukocytes. Methods: UC patients undergoing colonoscopy were prospectively enrolled and scored independently according the endoscopic and clinical part of the Rachmilewitz Index. Patients and controls provided fecal and blood samples for measuring calprotectin, CRP, and leukocytes. Results: Values in UC patients (n = 134) compared to controls (n = 48): calprotectin: 396 ± 351 versus 18.1 ± 5 ,g/g, CRP 16 ± 13 versus 3 ± 2 mg/L, blood leukocytes 9.9 ± 3.5 versus 5.4 ± 1.9 g/L (all P < 0.001). Endoscopic disease activity correlated closest with calprotectin (Spearman's rank correlation coefficient r = 0.834), followed by Clinical Activity Index (r = 0.672), CRP (r = 0.503), and leukocytes (r = 0.461). Calprotectin levels were significantly lower in UC patients with inactive disease (endoscopic score 0,3, calprotectin 42 ± 38 ,g/g), compared to patients with mild (score 4,6, calprotectin 210 ± 121 ,g/g, P < 0.001), moderate (score 7,9, calprotectin 392 ± 246 ,g/g, P = 0.002), and severe disease (score 10,12, calprotectin 730 ± 291 ,g/g, P < 0.001). The overall accuracy for the detection of endoscopically active disease (score ,4) was 89% for calprotectin, 73% for Clinical Activity Index, 62% for elevated CRP, and 60% for leukocytosis. Conclusions: Fecal calprotectin correlated closest with endoscopic disease activity, followed by Clinical Activity Index, CRP, and blood leukocytes. Furthermore, fecal calprotectin was the only marker that reliably discriminated inactive from mild, moderate, and highly active disease, which emphasizes its usefulness for activity monitoring. Inflamm Bowel Dis 2009 [source] Fecal calprotectin, lactoferrin, and endoscopic disease activity in monitoring anti-TNF-alpha therapy for Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 10 2008Taina Sipponen MD Abstract Background: Fecal calprotectin and lactoferrin are promising noninvasive biomarkers for intestinal inflammation. In Crohn's disease (CD), during anti-TNF-alpha (TNF-,) treatment, the clinical significance of these markers has, however, been insufficiently explored. Methods: Among CD patients receiving anti-TNF-, therapy we assessed the role of fecal calprotectin and lactoferrin as surrogate markers for mucosal healing. Before and 3 months after the beginning of anti-TNF-, induction, 15 patients underwent ileocolonoscopy with scoring of the Crohn's Disease Index of Severity (CDEIS). Fecal samples for calprotectin and for lactoferrin measurements were collected and the Crohn's Disease Activity Index (CDAI) was calculated at the time of the endoscopies and 2 and 8 weeks after the first treatment. Results: The median CDEIS fell from 13.0 to 4.8 (P = 0.002) and CDAI from 158 to 68 (P = 0.005). Accordingly, the median fecal calprotectin concentration fell from 1173 ,g/g to 130 ,g/g (P = 0.001) and fecal lactoferrin from 105.0 ,g/g to 2.7 ,g/g (P = 0.001). Of the 15 patients, 11 (73%) showed an endoscopic response to treatment and 5 of these achieved endoscopic remission (CDEIS < 3). In those 5 patients the fecal calprotectin concentration declined from 1891 ,g/g (range 813,2434) to 27 ,g/g (13,130) and lactoferrin from 92.4 ,g/g (35.5,235.6) to 1.9 ,g/g (0.0,2.1). Conclusions: Compared to pretreatment values, concentrations of fecal calprotectin and lactoferrin after the anti-TNF-, treatment were significantly lower. During anti-TNF-, therapy these fecal neutrophil-derived proteins may thus be useful surrogate markers for mucosal healing. (Inflamm Bowel Dis 2008) [source] Active Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal floraINFLAMMATORY BOWEL DISEASES, Issue 2 2008Alexander Swidsinski MD Abstract Background: The intestinal microflora is important in the pathogenesis of inflammatory bowel disease (IBD). The impact of its spatial organization on health and disease is unknown. Methods: We investigated sections of paraffin-embedded punched fecal cylinders. Fluctuations in spatial distribution of 11 bacterial groups were monitored in healthy subjects (n = 32), patients with IBD (n = 204), and other gastrointestinal diseases (n = 186) using fluorescence in situ hybridization (FISH). Results: The microbial structure differed in patients with Crohn's disease (CD), ulcerative colitis (UC), and healthy and disease controls. The profiles of CD and UC were distinctly opposite in 6 of 11 FISH probes used. Most prominent were a depletion of Faecalibacterium prausnitzii (Fprau<1 × 109/mL) with a normal leukocyte count in CD and a massive increase of leukocytes in the fecal-mucus transition zone (>30 leukocytes/104,m2) with high Fprau in patients with UC. These 2 features alone enabled the recognition of active CD (Crohn's Disease Activity Index [CDAI] >150) or UC (Clinical Activity Index [CAI] >3) with 79%/80% sensitivity and 98%/100% specificity. The mismatch in the sensitivity was mainly due to overlap between single IBD entities, and the specificity was exclusively due to the similarity of Crohn's and celiac disease. When inflammatory bowel disease (IBD) patients were pooled the sensitivity was 100% for severe disease, 84% for moderate activity, 72% for IBD with ,12 months remission, and 24% for IBD with >12 months remission. Conclusions: The fecal flora is highly structured and spatially organized. Diagnosing IBD and monitoring disease activity can be performed based on analysis of punched fecal cylinders independent from the patient's complaints. (Inflamm Bowel Dis 2007) [source] Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 6 2007M.A. de Bièvre MD Abstract Background: In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies. Methods: We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events. Results: Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred. Conclusion: In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC. (Inflamm Bowel Dis 2007) [source] How adherent to treatment with azathioprine are patients with Crohn's disease in long-term remission?INFLAMMATORY BOWEL DISEASES, Issue 4 2007Gerassimos J. Mantzaris MD Abstract Background: Patients with longstanding quiescent Crohn's disease on azathioprine usually maintain an excellent quality of life but are also concerned about long-term safety. This may affect adherence to treatment. The aim of the present study was to assess the adherence to azathioprine in a cohort of patients with Crohn's disease in long-term remission. Methods: Thirty patients with Crohn's disease in remission on azathioprine for ,48 months were enrolled in the study. All were asked to record the number of azathioprine tablets they consumed daily. Notes were kept every other month for 6 months. Adherence was defined as consumption of ,80% of medication. Results: Most patients (18/28, 74.3%) were not adherent to treatment. The mean (±SD) daily dose of azathioprine in adherent and nonadherent patients was 145 ± 45 mg and 102 ± 20 mg, respectively. However, there were no significant differences between the 2 groups in the mean IBDQ score and mean Crohn's Disease Activity Index (CDAI) score, both throughout the entire study and at each time point of the study. Male gender, single status, and consumption of >5 concomitant medications were associated with nonadherence. Conclusions: Most patients with Crohn's disease in longstanding remission had low self-reported adherence to azathioprine. Both male gender and single status were associated with nonadherence to azathioprine, whereas disease factors were not related to self-reported adherence. Patients considered nonadherent to treatment maintained disease remission and a quality of life similar to patients who were adherent to treatment. (Inflamm Bowel Dis 2006) [source] Azathioprine Maintains first remission in newly diagnosed pediatric Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2006Gerald J. Jaspers Abstract 6-Mercaptopurine (6-MP) maintains remission in pediatric Crohn's disease (CD). Azathioprine, a prodrug of 6-MP, is used for maintenance of remission of CD in Europe. We evaluated to what extent azathioprine is used in newly diagnosed pediatric CD patients and whether maintenance of remission differed between patients using azathioprine or not. Charts of children (diagnosed 1998-2003, follow-up , 18 mo) were reviewed. Active disease was defined as Pediatric Crohn's Disease Activity Index (PCDAI) greater than 10 or systemic corticosteroid use. Remission was defined as PCDAI 10 or less without use of corticosteroids. Eighty-eight children (55M/33F, age 12 ± 3 yr) were included. Seventy-two (82%) patients received azathioprine during the follow-up period (38 ± 17 mo). Patients diagnosed after 2000 received azathioprine significantly earlier during the course of disease compared with those diagnosed earlier (median, at 233 vs. 686 days; P < 0.05). At initial presentation, moderate-severe disease activity and prescription of corticosteroids were more prevalent in patients using azathioprine compared with nonazathioprine patients (75% vs. 52%; P < 0.05; and 89% vs. 58%; P < 0.005, respectively). Duration of corticosteroid use was longer in patients receiving azathioprine (232 vs. 168 days; P < 0.005). Median maintenance of first remission in patients who initially used corticosteroids, however, was longer in patients receiving azathioprine compared with nonazathioprine patients (PCDAI, 544 vs. 254 days, P = 0.08; corticosteroid free, 575 vs. 259 days, P < 0.05, respectively). We conclude that, since 2000, azathioprine is being introduced earlier in the treatment of newly diagnosed pediatric CD patients. The use of azathioprine is associated with prolonged maintenance of the first remission. [source] Muscle performance in patients with Crohn's disease in clinical remissionINFLAMMATORY BOWEL DISEASES, Issue 3 2005Jean-Baptiste Wiroth PhD Abstract Background: Because patients with Crohn's disease (CD) often show increased energy expenditure, nutritional deficiencies, and general fatigue, all which may persist after a flare, we hypothesized that CD could alter muscle mass and function. This study aimed to assess muscle strength and endurance in CD patients in clinical remission and the influencing factors. Methods: Forty-one outpatients (17 men and 24 women; age, 37 ± 10 yr), in remission (CD Activity Index < 150) for >3 months, and 25 age-matched healthy controls (10 men and 15 women; age, 37 ± 13 yr) were evaluated. Evaluation included a sit-up test, hand-grip strength test, hand-grip endurance test, lower limb strength test, and lower limb endurance test (LE), as well as a measure of physical activity. Results: No significant difference was found between CD and control groups regarding weight, height, body mass index, fat mass, and fat-free mass. Strength performance was lower in CD subjects compared with controls, particularly for lower limb indexes: lower limb strength test (,24.6%, P < 0.001), LE (,25.8%, P < 0.001), and sit-up test (,25.1%, P < 0.001). Previous disease severity, disease duration, the cumulative dose of glucocorticosteroids, current inflammation, and global habitual physical activity did not affect muscle performance. A recent use of steroids improved LE. Conclusions: CD patients in clinical remission have decreased muscle function that may affect their quality of life. This pattern is reflected by reduced strength and endurance indexes, particularly for lower limbs. The reasons for these changes need further study. Strength training should be assessed in these patients. [source] Preliminary study of ciprofloxacin in active Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 1 2002Dr. George L. Arnold Abstract Based on limited reports of the successful use of antibiotics in the treatment of Crohn's disease (CD) and on the possibility that intestinal bacteria may be one of the etiologic factors playing a role in the pathogenesis of this condition, we undertook a study to evaluate the use of a broad-spectrum antibiotic in CD. Our team studied the efficacy of adding the antibiotic ciprofloxacin to the treatment of moderately active, but resistant cases of CD. Forty-seven adults with moderately active CD were randomly assigned treatment with ciprofloxacin 500 mg twice daily versus placebo twice daily for 6 months. The primary endpoint was the change in scores on the Crohn's Disease Activity Index (CDAI) from baseline to month 6. Although 47 patients were randomized, at 1 month of follow-up 28 patients received ciprofloxacin and 19 received placebo. The mean entry CDAI scores were not significantly different: 187 for the ciprofloxacin group versus 230 for the placebo group (p = 0.638). Mean CDAI scores at the completion of study were 112 for the ciprofloxacin group (n = 25) and 205 for the placebo group (n = 12), (p < 0.001). Disease remission is defined as a decrease in the CDAI score to less than 150 points. Our preliminary study suggests that ciprofloxacin may be an effective agent when added to the treatment of moderately active, resistant CD. [source] The Ankylosing Spondylitis Quality of Life Questionnaire: validation in a New Zealand cohortINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2010Katherine JENKS Abstract Aim:, To examine the validity of the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) in a New Zealand population with defined axial spondyloarthritis (SpA). Once validated, the ASQoL will be included as an outcome measure in a proposed multicentre New Zealand study. Methods:, Five healthy participants were interviewed to identify any issues related to local dialect or linguistic comprehension of the questionnaire. Cognitive debriefing interviews were conducted with four participants with SpA to assess the relevance and comprehensiveness of the questionnaire. Internal consistency was established by determining the Cronbach's alpha. Finally, convergent validity of the ASQoL was assessed by testing the correlation with the Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and patient global visual analogue scale (VAS) scores in a cohort of 63 SpA patients. Results:, The language used in the ASQoL was considered clear, comprehensible and accessible to speakers of New Zealand English. The questionnaire displayed content validity for patients with SpA. The ASQoL had good internal consistency in the present sample (, = 0.854). A positive correlation was found between the ASQoL and the BASFI (rho = 0.635, P < 0.001), BASDAI (rho = 0.521, P < 0.001) and patient global assessment VAS (rho = 0.546, P < 0.001), providing evidence that the ASQoL has convergent validity among patients with SpA in New Zealand. Test,retest reliability was good over 16 weeks (rho = 0.730, P < 0.001). Conclusions:, The ASQoL has been demonstrated in this study to be feasible, internally consistent and to have content and convergent validity in a New Zealand population of patients with axial spondyloarthritis; it is a measure of quality of life which is both easy to employ and reliable. [source] Clinical trial: the safety and short-term efficacy of recombinant cholera toxin B subunit in the treatment of active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010P. STÅL Aliment Pharmacol Ther,31, 387,395 Summary Background, The cholera toxin B subunit ameliorates experimentally induced colitis in mice. In humans, cholera toxin B subunit has never been tested in the treatment of Crohn's disease (CD). Aim, To evaluate the safety and efficacy of treatment with recombinant cholera toxin B subunit of patients with CD. Methods, An open-label, multicentre, nonrandomized trial including 15 patients with mild/moderate CD. Patients received an oral solution of 5 mg recombinant cholera toxin B subunit three times weekly for 2 weeks. Reduction in CD Activity Index (CDAI) with >100 between baseline and days 15, 29, 42 and 70 defined clinical response. Patients with CDAI score ,150 were defined as being in remission. Results, A significant decrease in CDAI score was observed. Response rates were 40% in the full analysis set and 42% in the per protocol analysis. Two patients receiving adjuvant treatment after day 29 were excluded, after which 40% were in remission at 4 weeks and 30% at 8 weeks post-treatment. Mild side effects (arthralgia, headache and pruritus) were seen in 33% of patients. Conclusions, Treatment with recombinant cholera toxin B subunit was safe. Approximately 40% of patients with active CD responded to treatment. Randomized studies are needed to establish the clinical efficacy of recombinant cholera toxin B subunit. [source] Outcome of active disease in ankylosing spondylitis: A prospective studyMUSCULOSKELETAL CARE, Issue 1 2010Grad Dip Phys, J. Martindale PhD Abstract Background:,People with ankylosing spondylitis (AS) typically experience episodic exacerbations, but the extent to which they subsequently experience a sustained reduction in disease markers below recognized thresholds for active disease is unclear. Objective:,To investigate changes in, and associations between, disease markers over 18 months in people with active AS. Methods:,Within a cohort of 89 participants with AS, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of 4 or higher were used to identify those with active disease. Standard assessment tools were used to monitor participants prospectively at four consecutive six-monthly intervals. Participants received standard treatments but none received anti-tumor necrosis factor-alpha (TNF,) medication during the study. Results:,The median age of the cohort was 50 years (inter-quartile range [IQR] 38.5,55.5), the median age of disease onset was 25 years (IQR 18,33) and the median disease duration was 18 years (IQR 13,27). Forty-seven (53%) participants had a BASDAI score of 4 or higher on the first assessment, of whom 45 (51%) scored 4 or higher on all subsequent assessments. Furthermore, 38 (43%) and 16 (18%) participants scored BASDAI 5 or 6, respectively, or higher, throughout. BASDAI scores correlated strongly with Bath Ankylosing Spondylitis Functional Index (BASFI) scores. Compared with 19 (21%) participants whose BASDAI scores were consistently below 4 throughout, participants with persistently high BASDAI scores showed higher scores for anxiety and depression, and some evidence of functional deterioration during the study period. Conclusions:,In this cohort, disease markers in most people with active AS were sustained above the standard threshold for active disease. This has important implications for planning care pathways and for optimal utilization of anti-TNF, treatment. Copyright © 2009 John Wiley & Sons, Ltd. [source] Safety and efficacy of rituximab in systemic lupus erythematosus: Results from 136 patients from the French autoimmunity and rituximab registryARTHRITIS & RHEUMATISM, Issue 8 2010Benjamin Terrier Objective A number of open-label studies have suggested the potential benefit of rituximab (RTX) in systemic lupus erythematosus (SLE). However, in 2 recent randomized controlled trials (RCTs) of RTX, the primary end points were not met. We undertook this study to evaluate the safety and efficacy of RTX in off-trial patients with SLE seen in regular clinical practice. Methods We analyzed prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with RTX. Results One hundred thirty-six patients received treatment for SLE. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) was 11.3 ± 8.9 at baseline. Severe infections were noted in 12 patients (9%), corresponding to a rate of 6.6/100 patient-years. Most severe infections occurred within the first 3 months after the last RTX infusion. Five patients died, due to severe infection (n = 3) or refractory autoimmune disease (n = 2). Overall response was observed in 80 of 113 patients (71%) by the SELENA,SLEDAI assessment. Efficacy did not differ significantly between patients receiving RTX monotherapy and those receiving concomitant immunosuppressive agents (who had higher baseline disease activity). Articular, cutaneous, renal, and hematologic improvements were noted in 72%, 70%, 74%, and 88% of patients, respectively. Among responders, 41% experienced a relapse of disease, with a response in 91% after retreatment with RTX. Conclusion Data from the AIR registry show a satisfactory tolerance profile and clinical efficacy of RTX in patients with SLE. The contrasting results with those from recent RCTs leave open the question of the therapeutic use of RTX in SLE. Additional controlled studies with new designs are needed to define the place of RTX in the therapeutic arsenal for SLE. [source] Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus,ARTHRITIS & RHEUMATISM, Issue 8 2010Lingyun Sun Objective Umbilical cord (UC),derived mesenchymal stem cells (MSCs) have shown marked therapeutic effects in a number of diseases in animal studies, based on their potential for self-renewal and differentiation. No data are available on the effectiveness of UC MSC transplantation (MSCT) in human autoimmune disease. This study was undertaken to assess the efficacy and safety of allogeneic UC MSCT in patients with severe and treatment-refractory systemic lupus erythematosus (SLE). Methods We conducted a single-arm trial that involved 16 SLE patients whose disease was refractory to standard treatment or who had life-threatening visceral involvement. All of the patients gave consent and underwent UC MSCT. Clinical changes were evaluated before and after transplantation using the SLE Disease Activity Index (SLEDAI), measurement of serum antinuclear antibody (ANA), anti,double-stranded DNA (anti-dsDNA) antibody, serum complement C3 and C4, and albumin levels, and assessment of and renal function. Evaluation of potential mechanisms of MSCT effects focused on the percentage of peripheral blood Treg cells and serum levels of cytokines. Results From April 2007 to July 2009, a total of 16 patients with active SLE were enrolled and underwent UC MSCT. The median followup time after MSCT was 8.25 months (range 3,28 months). Significant improvements in the SLEDAI score, levels of serum ANA, anti-dsDNA antibody, serum albumin, and complement C3, and renal function were observed. Clinical remission was accompanied by an increase in peripheral Treg cells and a re-established balance between Th1- and Th2-related cytokines. Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment-related deaths. Conclusion Our findings indicate that UC MSCT results in amelioration of disease activity, serologic changes, and stabilization of proinflammatory cytokines. These data provide a foundation for conducting a randomized controlled trial of this new therapy for severe and treatment-refractory SLE. [source] Mycophenolic acid area under the curve correlates with disease activity in lupus patients treated with mycophenolate mofetilARTHRITIS & RHEUMATISM, Issue 7 2010Noël Zahr Objective Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil (MMF), which is widely used to treat systemic lupus erythematosus (SLE). In transplantation, MPA area under the plasma concentration,time curve from 0 to 12 hours (MPA AUC0,12) is correlated with clinical outcome. We undertook the present study to assess possible relationships between SLE activity and MPA AUC0,12. Methods Using a Bayesian estimator, MPA AUC0,12 was determined in 71 consecutive SLE patients (61 women and 10 men; mean ± SD age 34 ± 10 years) receiving a stable MMF dose. On the same day, SLE activity was assessed using the SLE Disease Activity Index (SLEDAI; active disease defined as a SLEDAI score ,6) and the British Isles Lupus Assessment Group (BILAG) index (active disease defined as BILAG A or B). Results Two groups were studied: patients with active SLE (mean ± SD SLEDAI score 11.6 ± 4.4; n = 26) and patients with inactive SLE (mean ± SD SLEDAI score 1.9 ± 1.6; n = 45). MPA AUC0,12 correlated weakly with the dose of MMF (r = 0.33, P = 0.005). Mean ± SD MPA AUC0,12 in the group with active SLE was significantly lower than that in the group with inactive SLE (26.8 ± 13.6 ,g.hour/ml versus 46.5 ± 16.3 ,g.hour/ml; P < 0.0001). MPA AUC0,12 was negatively correlated with the SLEDAI (r = ,0.64, P < 0.0001). In multivariate analysis, MPA AUC0,12 was the sole parameter associated with SLE activity (odds ratio 0.89 [95% confidence interval 0.83,0.96], P = 0.002). The MPA AUC0,12 threshold value of 35 ,g.hour/ml was associated with the lowest risk of active SLE. Conclusion Our data show that SLE activity is strongly correlated with MPA AUC0,12. An individualized dosing regimen of MMF, with a target AUC0,12 of 35 ,g.hour/ml, should be considered for SLE patients. [source] Markers of oxidative and nitrosative stress in systemic lupus erythematosus: Correlation with disease activity,ARTHRITIS & RHEUMATISM, Issue 7 2010Gangduo Wang Objective Free radical,mediated reactions have been implicated as contributors in a number of autoimmune diseases, including systemic lupus erythematosus (SLE). However, the potential for oxidative/nitrosative stress to elicit an autoimmune response or to contribute to disease pathogenesis, and thus be useful when determining a prognosis, remains largely unexplored in humans. This study was undertaken to investigate the status and contribution of oxidative/nitrosative stress in patients with SLE. Methods Sera from 72 SLE patients with varying levels of disease activity according to the SLE Disease Activity Index (SLEDAI) and 36 age- and sex-matched healthy controls were evaluated for serum levels of oxidative/nitrosative stress markers, including antibodies to malondialdehyde (anti-MDA) protein adducts and to 4-hydroxynonenal (anti-HNE) protein adducts, MDA/HNE protein adducts, superoxide dismutase (SOD), nitrotyrosine (NT), and inducible nitric oxide synthase (iNOS). Results Serum analysis showed significantly higher levels of both anti,MDA/anti,HNE protein adduct antibodies and MDA/HNE protein adducts in SLE patients compared with healthy controls. Interestingly, not only was there an increased number of subjects positive for anti-MDA or anti-HNE antibodies, but also the levels of both of these antibodies were statistically significantly higher among SLE patients whose SLEDAI scores were ,6 as compared with SLE patients with lower SLEDAI scores (SLEDAI score <6). In addition, a significant correlation was observed between the levels of anti-MDA or anti-HNE antibodies and the SLEDAI score (r = 0.734 and r = 0.647, respectively), suggesting a possible causal relationship between these antibodies and SLE. Furthermore, sera from SLE patients had lower levels of SOD and higher levels of iNOS and NT compared with healthy control sera. Conclusion These findings support an association between oxidative/nitrosative stress and SLE. The stronger response observed in serum samples from patients with higher SLEDAI scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis. [source] Different response to rituximab in tumor necrosis factor blocker,naive patients with active ankylosing spondylitis and in patients in whom tumor necrosis factor blockers have failed: A twenty-four,week clinical trial,ARTHRITIS & RHEUMATISM, Issue 5 2010I.-H. Song Objective Histologic studies have shown B cell clusters in the subchondral bone marrow of the spine of patients with ankylosing spondylitis (AS). An immunotherapy targeting B cells in AS is therefore of interest. We undertook this study to examine the efficacy and safety of rituximab in patients with AS refractory to nonsteroidal antiinflammatory drugs in whom previous treatment with tumor necrosis factor , (TNF,) blockers either had not been tried or had failed. Methods In this phase II clinical trial, 1,000 mg rituximab was administered intravenously at baseline and at week 2 in 20 patients with active AS. Ten of these patients had never received TNF blockers, and treatment with TNF blockers had failed in the other 10 patients. The primary end point was a 20% improvement in disease activity at week 24 according to the criteria of the Assessment of SpondyloArthritis international Society (an ASAS20 response). Results Seventy-five percent of the patients were male, 90% were HLA,B27 positive, their mean age was 39.7 years, and their mean disease duration was 16.8 years. Patients had active disease, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ,4. While there was no clear response at week 24 in the group in whom TNF blockers had failed (30% had achieved an ASAS20 response, 10% had achieved an ASAS40 response, none had achieved partial remission according to the ASAS criteria, and none had achieved 50% improvement on the BASDAI [a BASDAI50 response] beyond an expected placebo response), we observed a good improvement in the TNF blocker,naive group at week 24 (50% had achieved an ASAS20 response, 40% had achieved an ASAS40 response, 30% had achieved partial remission according to the ASAS criteria, and 50% had achieved a BASDAI50 response). Conclusion Although rituximab does not seem to be effective in patients with AS that does not respond to TNF blockers, it had significant efficacy in TNF blocker,naive patients. Therefore, further controlled trials with B cell,directed therapies should be performed in TNF blocker,naive AS patients in the future. [source] Expression of CD44 variant isoforms CD44v3 and CD44v6 is increased on T cells from patients with systemic lupus erythematosus and is correlated with disease activityARTHRITIS & RHEUMATISM, Issue 5 2010José C. Crispín Objective To quantify the expression of CD44 and variant isoforms CD44v3 and CD44v6 on T cells from patients with systemic lupus erythematosus (SLE), and to assess correlations of the level of expression of these molecules with disease manifestations. Methods Information on clinical and demographic characteristics was collected, and blood samples were obtained from 72 patients with SLE and 32 healthy control subjects matched to the patients by sex, race, and age. Expression of CD44 and variants CD44v3 and v6 on T cell subsets was determined by flow cytometry, and Pearson's correlations of their expression levels with clinical variables, SLE Disease Activity Index (SLEDAI) scores, and presence of lupus nephritis were determined. Wilcoxon's rank sum tests and conditional multivariable regression analyses were applied to identify differences in the expression of CD44 between patients with SLE and healthy controls. Results Expression of CD44 was higher on CD4+ and CD8+ T cells from SLE patients compared with controls (P , 0.03). Expression of CD44v3 and CD44v6 was also higher on total T cells and CD4+ and CD8+ T cells from SLE patients compared with controls (P , 0.03). Cell surface levels of CD44v3 on total T cells, CD4+ T cells, and CD8+ T cells as well as cell surface expression of CD44v6 on total T cells and CD4+ T cells were correlated with the SLEDAI score (P < 0.05). The presence of lupus nephritis was associated with the expression of CD44v6 on total T cells, CD4+ T cells, and CD4,CD8, T cells (P < 0.05). Positivity for anti,double-stranded DNA antibodies was associated with the expression levels of CD44v6 on T cells (P < 0.05). Conclusion These results indicate that expression levels of CD44v3 and CD44v6 on T cells may represent useful biomarkers of SLE activity. [source] Erythrocyte C3d and C4d for monitoring disease activity in systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 3 2010Amy H. Kao Objective Disease activity in systemic lupus erythematosus (SLE) is typically monitored by measuring serum C3 and C4. However, these proteins have limited utility as lupus biomarkers, because they are substrates rather than products of complement activation. The aim of this study was to evaluate the utility of measuring the erythrocyte-bound complement activation products, erythrocyte-bound C3d (E-C3d) and E-C4d, compared with that of serum C3 and C4 for monitoring disease activity in patients with SLE. Methods The levels of E-C3d and E-C4d were measured by flow cytometry in 157 patients with SLE, 290 patients with other diseases, and 256 healthy individuals. The patients with SLE were followed up longitudinally. Disease activity was measured at each visit, using the validated Systemic Lupus Activity Measure (SLAM) and the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results At baseline, patients with SLE had higher median levels of E-C3d and E-C4d (P < 0.0001) in addition to higher within-patient and between-patient variability in both E-C3d and E-C4d when compared with the 2 non-SLE groups. In a longitudinal analysis of patients with SLE, E-C3d, E-C4d, serum C3, and anti,double-stranded DNA (anti-dsDNA) antibodies were each significantly associated with the SLAM and SELENA,SLEDAI. In a multivariable analysis, E-C4d remained significantly associated with these SLE activity measures after adjusting for serum C3, C4, and anti-dsDNA antibodies; however, E-C3d was associated with the SLAM but not with the SELENA,SLEDAI. Conclusion Determining the levels of the erythrocyte-bound complement activation products, especially E-C4d, is an informative measure of SLE disease activity as compared with assessing serum C4 levels and should be considered for monitoring disease activity in patients with SLE. [source] Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: Findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial,ARTHRITIS & RHEUMATISM, Issue 1 2010Ellen M. Ginzler Objective To assess the effect of mycophenolate mofetil compared with intravenous pulses of cyclophosphamide on the nonrenal manifestations of lupus nephritis. Methods Patients with active lupus nephritis (renal biopsy class III, IV, or V) were recruited for the study (n = 370) and treated with mycophenolate mofetil (target dosage 3 gm/day) or intravenous cyclophosphamide (0.5,1.0 gm/m2/month), plus tapered prednisone, for 24 weeks. Nonrenal outcomes were determined using measures of whole body disease activity, including the British Isles Lupus Assessment Group (BILAG) disease activity index, the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and immunologic variables. Results Both treatments were effective on whole body disease activity in the systems examined, as indicated by changes in the classic BILAG index. With either treatment, remission was induced, notably in the mucocutaneous, musculoskeletal, cardiovascular/respiratory, and vasculitis systems, and flares were rare, as measured by the SELENA,SLEDAI. Levels of complement C3, C4, and CH50 and titers of anti,double-stranded DNA antibodies were normalized after treatment with either mycophenolate mofetil or intravenous cyclophosphamide. Conclusion In addition to the efficacy of both treatments on the renal system, this analysis showed that remission could also be induced in other systems. There was no clear difference in efficacy between mycophenolate mofetil and intravenous cyclophosphamide in ameliorating either the renal or nonrenal manifestations. Mycophenolate mofetil is, therefore, a suitable alternative to cyclophosphamide for the treatment of renal and nonrenal disease manifestations in patients with biopsy-proven lupus nephritis. [source] Associations between the American College of Rheumatology pediatric response measures and the continuous measures of disease activity used in adult rheumatoid arthritis: A secondary analysis of clinical trial data from children with Polyarticular-Course Juvenile Idiopathic ArthritisARTHRITIS & RHEUMATISM, Issue 12 2009Sarah Ringold Objective To measure associations between the American College of Rheumatology (ACR) pediatric criteria for improvement and the continuous measures of disease activity used for rheumatoid arthritis in adult patients with polyarticular-course juvenile idiopathic arthritis (JIA). Methods In this retrospective analysis of 2 etanercept trials, disease activity was calculated at baseline, 3 months, and 6 months using the Disease Activity Score (DAS), the DAS based on 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). The ACR pediatric response and the European League Against Rheumatism (EULAR) response were also determined for the 3-month and 6-month evaluations. Data were analyzed in 94 patients with JIA independent of the treatment arm. Correlation coefficients between measures were calculated for each visit. The areas under the receiver operating characteristic curve (AUC of ROC) were calculated to assess the discriminative properties of the scores for the ACR pediatric response measures. Results The mean DAS, DAS28, CDAI score, and SDAI score were 3.7, 4.7, 30.8, and 36.4, respectively, at baseline, corresponding to high levels of disease activity (CDAI/SDAI) or moderate levels of disease activity (DAS/DAS28). At 3 months, the mean scores corresponded to low (DAS/DAS28) or moderate (CDAI/SDAI) disease activity. At 6 months, the mean scores corresponded to low disease activity (DAS/DAS28/CDAI) or moderate disease activity (SDAI). Most children met the criteria for a good or moderate EULAR response at 3 months and 6 months. The correlation between continuous outcome measures and each pediatric core set component was moderate to very good. The AUC of ROC values for each measure were high (range 0.76,0.98). Conclusion Good correlation and discriminative abilities were seen between the DAS, DAS28, CDAI, and SDAI for the ACR pediatric criteria for improvement. These disease activity measures may be useful for research and clinical care in polyarticular-course JIA. [source] Distinct subtypes of myelitis in systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 11 2009J. Birnbaum Objective Myelitis causes pain, weakness, and sphincteric deficits, and is 1,000-fold more prevalent in patients with systemic lupus erythematosus (SLE) than in the general population. For the last century, descriptions of SLE myelitis have been primarily limited to case reports. In contrast, larger-scale cohort studies have revealed that myelitis occurring in the idiopathic demyelinating diseases (i.e., multiple sclerosis versus neuromyelitis optica) represents distinct syndromes. This study was undertaken to determine whether SLE myelitis similarly encapsulates distinct syndromes. Methods We analyzed a cohort of 22 patients with SLE and myelitis. Patients were assessed for neurologic variables related to myelitis and for clinical and serologic features of SLE. Magnetic resonance images of the spine, cerebrospinal fluid profiles, and autoantibody profiles were obtained. Results Eleven patients presented with signs of gray matter dysfunction (i.e., flaccidity and hyporeflexia), whereas 11 patients presented with signs of white matter dysfunction (i.e., spasticity and hyperreflexia). Patients with gray matter dysfunction were more likely to have irreversible paraplegia (P < 0.01), despite presenting with a monophasic versus polyphasic course (P = 0.01), higher levels of SLE activity (mean SLE Disease Activity Index 9.8 versus 2.0; P = 0.01), and a cerebrospinal fluid profile indistinguishable from bacterial meningitis. Prior to irreversible paraplegia, these patients presented with prodromes of fever and urinary retention, but were misdiagnosed by physicians of different specialties as having urinary tract infections. Patients with white matter dysfunction were more likely to meet criteria for neuromyelitis optica (P = 0.04) and were also more likely to have antiphospholipid antibodies (lupus anticoagulant) (P = 0.01). Conclusion Our findings indicate that SLE myelitis encapsulates 2 distinct and previously unrecognized syndromes that can be distinguished clinically by gray matter versus white matter findings. Recognition of fever and urinary retention as prodromes of irreversible paraplegia may allow earlier diagnosis and treatment in SLE patients presenting with gray matter findings. [source] Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation studyARTHRITIS & RHEUMATISM, Issue 10 2009Jason W. Bauer Objective Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by unpredictable flares of disease activity and irreversible damage to multiple organ systems. An earlier study showed that SLE patients carrying an interferon (IFN) gene expression signature in blood have elevated serum levels of IFN-regulated chemokines. These chemokines were associated with more-severe and active disease and showed promise as SLE disease activity biomarkers. This study was designed to validate IFN-regulated chemokines as biomarkers of SLE disease activity in 267 SLE patients followed up longitudinally. Methods To validate the potential utility of serum chemokine levels as biomarkers of disease activity, we measured serum levels of CXCL10 (IFN,-inducible 10-kd protein), CCL2 (monocyte chemotactic protein 1), and CCL19 (macrophage inflammatory protein 3,) in an independent cohort of 267 SLE patients followed up longitudinally over 1 year (1,166 total clinic visits). Results Serum chemokine levels correlated with lupus activity at the current visit (P = 2 × 10,10), rising at the time of SLE flare (P = 2 × 10,3) and decreasing as disease remitted (P = 1 × 10,3); they also performed better than the currently available laboratory tests. Chemokine levels measured at a single baseline visit in patients with a Systemic Lupus Erythematosus Disease Activity Index of ,4 were predictive of lupus flare over the ensuing year (P = 1 × 10,4). Conclusion Monitoring serum chemokine levels in SLE may improve the assessment of current disease activity, the prediction of future disease flares, and the overall clinical decision-making. [source] Systemic activation of the immune system induces aberrant BAFF and APRIL expression in B cells in patients with systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 7 2009Van Trung Chu Objective Elevated levels of BAFF and APRIL are characteristic of patients with systemic lupus erythematosus (SLE). The reasons for enhanced cytokine production are not well understood. This study was undertaken to identify the cells responsible for the overproduction of these cytokines. Methods BAFF expression was analyzed on peripheral blood mononuclear cells by multiparameter flow cytometry and in tissue samples by immunofluorescence staining. The levels of BAFF and APRIL mRNA were quantified in sorted B cells. In vitro cultures were used to analyze whether B cell survival and differentiation was supported by autocrine BAFF and/or APRIL. Results Aberrant activation of B cells in patients with SLE was associated with a significant up-regulation of BAFF expression in naive, memory, and plasma cells. Furthermore, strong expression of BAFF and APRIL was found in plasma cells from the lymph node, bone marrow, and kidney. The levels of BAFF and APRIL mRNA in CD19+ B cells correlated both with the titer of anti-double stranded DNA antibodies and with the SLE Disease Activity Index. In vitro experiments demonstrated that B cells released functional BAFF/APRIL upon activation. Conclusion Our data show that B cells contribute to the enhanced levels of circulating BAFF and APRIL. The aberrant up-regulation of these cytokines may initiate a vicious circle in which enhanced levels of BAFF and APRIL act in an autocrine manner to reinforce the systemic activation of the humoral immune system. [source] Rheumatoid arthritis joint progression in sustained remission is determined by disease activity levels preceding the period of radiographic assessmentARTHRITIS & RHEUMATISM, Issue 5 2009D. Aletaha Objective Joint damage is related to disease activity in rheumatoid arthritis (RA), but the degree of its progression and the temporal associations between disease activity and joint damage are unclear. The aim of this study was to evaluate whether there is a latency in the effect of disease activity on radiographic progression in patients with RA. Methods Data were obtained from the PREMIER trial, a 2-year randomized, controlled clinical trial of adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in early RA. Radiographic progression of joint damage was calculated using the modified total Sharp score in a subset of patients whose disease was in remission (Simplified Disease Activity Index ,3.3) in the second year of the trial. The progression of damage in the second year was compared between groups of patients whose disease was already in remission for an additional period of 3, 6, or 9 months during the first year. Analysis of variance was used to test for a linear trend. Results Among 794 patients with early RA, 119 (15%) achieved sustained remission during the second year, with no difference in radiographic progression across the 3 treatment groups. Radiographic progression in the second year was significantly different between patients with 3, 6, or 9 additional months of remission during year 1 (mean change in the modified Sharp score 1.19 in those with 3 additional months of remission versus 0.20 in those with 6 additional months of remission and ,0.32 in those with 9 additional months of remission; P < 0.05). The results were supported by similar findings in a series of sensitivity analyses. Conclusion These data indicate that the level of disease activity as well as the duration of remission affect subsequent progression of radiographic damage in RA. This latency between disease activity and its effects on radiographic progression should be considered when evaluating radiographic outcomes in trials of RA. [source] The sense of smell in systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 5 2009Netta Shoenfeld Objective To assess the olfactory functions in systemic lupus erythematosus (SLE) patients compared with age- and sex-matched healthy controls, and to examine the association between the sense of smell and disease activity and central nervous system (CNS) involvement. Methods Olfactory functions in 50 SLE patients and 50 age- and sex-matched controls were evaluated using the Sniffin' Sticks test, the 3 stages of which are threshold, discrimination, and identification (TDI) of different odors. TDI scores were analyzed according to SLE disease activity and CNS involvement. Results In both the SLE and control groups, smell deficit correlated with male sex and older age. A decrease in the sense of smell was observed in SLE patients (46%) and controls (25%) (P , 0.02), while loss of smell (anosmia) was documented only in SLE patients (10%). Total TDI scores and individual stages of smell correlated with SLE Disease Activity Index (P < 0.001) and CNS manifestations (P < 0.03). Conclusion Our findings suggest that there is a decrease in the sense of smell in SLE patients compared with healthy subjects and that the decrease in the sense of smell among SLE patients correlates with disease activity and CNS involvement. [source] Clinical and imaging efficacy of infliximab in HLA,B27,Positive patients with magnetic resonance imaging,determined early sacroiliitis,ARTHRITIS & RHEUMATISM, Issue 4 2009Nick Barkham Objective To evaluate the efficacy of infliximab in HLA,B27,positive patients with magnetic resonance imaging (MRI),determined early sacroiliitis, using both clinical and MRI assessments. Methods Forty patients with recent-onset inflammatory back pain, as assessed by the Calin criteria, HLA,B27 positivity, clinical disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), pain and morning stiffness, and magnetic resonance imaging (MRI),determined sacroiliac joint bone edema were randomized in a double-blind manner to receive infliximab 5 mg/kg or placebo at 0, 2, 6, and 12 weeks. MRI scans were performed at baseline and 16 weeks and scored by 2 observers (blinded to both the order of the scans and to treatment group), using the Leeds scoring system. Clinical assessments included the BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Ankylosing Spondylitis Quality of Life (ASQoL) instrument, the ASsessment in Ankylosing Spondylitis International Working Group criteria (ASAS) for improvement, and markers of inflammation. Results The mean reduction in the total MRI score from week 0 to week 16 was significantly greater in infliximab-treated patients compared with placebo-treated patients (P = 0.033). On average, significantly more lesions resolved in the infliximab group (P < 0.001), while significantly more new lesions developed in the placebo group (P = 0.004). Significantly greater improvement in the infliximab group versus the placebo group was also observed for changes from week 0 to week 16 in the BASDAI (P = 0.002), BASFI (P = 0.004), and ASQoL (P = 0.007) scores. Responses according to the ASAS criteria for 40% improvement, the ASAS criteria for 20% improvement in 5 of 6 domains, and ASAS partial remission were achieved by 61%, 44%, and 56% of infliximab-treated patients, respectively. Infliximab was well tolerated, and no serious adverse events were observed. Conclusion Infliximab was an effective therapy for early sacroiliitis, providing a reduction in disease activity by week 16. This study is the first to show that infliximab is effective for reducing clinical and imaging evidence of disease activity in patients with MRI-determined early axial spondylarthritis. [source] The early disease stage in axial spondylarthritis: Results from the german spondyloarthritis inception cohort,ARTHRITIS & RHEUMATISM, Issue 3 2009Martin Rudwaleit Objective Ankylosing spondylitis (AS) is diagnosed late, because radiographs of the sacroiliac joints often do not show definite sacroiliitis at the time of disease onset. The aim of this study was to investigate whether patients without definite radiographically defined sacroiliitis, referred to as nonradiographic axial spondylarthritis (SpA), are different from patients with AS with regard to clinical manifestations and disease activity measures. Moreover, we sought to identify determinants of the development of radiographic sacroiliitis. Methods In a cross-sectional analysis of 462 patients, we compared 226 patients with nonradiographic axial SpA (symptom duration ,5 years) and 236 patients with AS (symptom duration ,10 years) who are participants in the German Spondyloarthritis Inception Cohort. Radiographs of the sacroiliac joints and the spine were assessed by 2 readers in a blinded manner. Logistic regression analysis was applied to identify parameters associated with structural damage. Results The 2 groups did not differ in the frequency of HLA,B27 positivity, inflammatory back pain, arthritis, enthesitis, and uveitis and had similar levels of disease activity, using measures such as the Bath Ankylosing Spondylitis Disease Activity Index. In both groups, HLA,B27 positivity determined the age at disease onset. Male sex (adjusted odds ratio [OR] 2.38, 95% confidence interval [95% CI] 1.19,4.73 [P = 0.014]) and an elevated C-reactive protein (CRP) level (adjusted OR 1.85, 95% CI 0.96,3.56 [P = 0.066]) were associated with radiographic sacroiliitis. In patients with AS, male sex and an elevated CRP level were also associated with the presence of syndesmophytes. Conclusion Clinical manifestations and disease activity measures are highly comparable between patients with early nonradiographic axial SpA and those with early AS, suggesting that these 2 entities are part of the same disease. Male sex and an elevated CRP level are associated with structural damage on radiographs, whereas HLA,B27 positivity determines the age at disease onset. [source] CXCR3+CD4+ T cells are enriched in inflamed kidneys and urine and provide a new biomarker for acute nephritis flares in systemic lupus erythematosus patientsARTHRITIS & RHEUMATISM, Issue 1 2009P. Enghard Objective The high frequency of CD4+ T cells in interstitial infiltrates of patients with lupus nephritis suggests a contribution of these cells to local pathogenesis. The aim of this study was to examine the role of CXCR3 and the chemokine CXCL10 in recruiting these cells into the kidney and to determine whether the infiltrating T cells could be monitored in the urine to provide a reliable biomarker for acute lupus nephritis. Methods The frequencies of CD3+ T cells, CXCR3+ cells, and CXCL10+ cells were determined by immunohistochemical and immunofluorescence analyses of kidney sections from 18 patients with lupus nephritis. The frequency of CXCR3+CD4+ T cells was determined by flow cytometry of peripheral blood and urine from 38 patients with systemic lupus erythematosus (SLE), and the values were compared with disease activity as determined by the Systemic Lupus Erythematosus Disease Activity Index. Results In renal biopsy tissues from patients with lupus nephritis, a mean of 63% of the infiltrating cells expressed CXCR3, ,60% of them were T cells, and the CXCR3+ cells colocalized with CXCL10-producing cells. In biopsy tissues from SLE patients with acute nephritis, ,50% of the urinary CD4+ T cells were CXCR3+, as compared with 22% in the peripheral blood, and the frequency of urinary CXCR3+CD4+ T cells correlated with disease activity. Moreover, the number of urinary CD4+ T cells reflected nephritis activity, and elevation above 800 CD4+ T cells per 100 ml of urine sharply delineated active from inactive nephritis. Conclusion CXCR3+ T cells are recruited into the inflamed kidneys, are enriched in the urine, and are a valuable marker of nephritis activity in SLE. They also present a potential target for future therapies. [source] Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: Results of an early phase II clinical trial,ARTHRITIS & RHEUMATISM, Issue 12 2008Sylviane Muller Objective To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131,151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE). Methods An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor , were measured by ELISA and nephelometry. Results IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 × 200 ,g IPP-201101 (group 1), but only in 1 patient in the group receiving 3 × 1,000 ,g IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration. Conclusion IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 ,g significantly improved the clinical and biologic status of lupus patients. [source] | ||||||||||||||||||||||||||||||||||||||||