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ID PMID Title PublicationDate abstract
21649536 Abatacept: a biologic immune modulator for rheumatoid arthritis. 2011 Aug INTRODUCTION: Abatacept is a biologic drug that belongs to the class of T-cell co-stimulation modulators and is used for the treatment of rheumatoid arthritis (RA). AREAS COVERED: This article covers major randomized clinical trials and meta-analyses concerning abatacept in the treatment of RA, as identified in a Pubmed search. Scientific meeting abstracts describing long-term extension data of the identified trials are also included. Efficacy outcomes and the safety profile are the focus of this evaluation. EXPERT OPINION: Abatacept in combination with methotrexate (MTX) or other synthetic disease-modifying anti-rheumatic drugs (DMARD) has been proven effective for the treatment of RA in different groups of patients: with early RA and no prior exposure to DMARD; with DMARD-resistant RA; and with RA not responding to TNF-α-blocking agents. Significant reductions of disease activity are achieved, with 1-year remission rates reaching up to 41% of DMARD-naïve patients with early RA receiving a combination of abatacept plus MTX. Abatacept treatment has been shown to improve function and quality of life and to suppress radiographic progression. No major safety issues have emerged during clinical trials and long-term extensions. Therefore, abatacept is a drug with a favorable efficacy and safety profile, which may offer substantial benefits to RA patients.
21607710 Induction of clinical remission with adalimumab-methotrexate combination therapy in a pati 2011 Dec The patient described here is a 49-year-old woman who had hepatitis C virus (HCV) infection and rheumatoid arthritis (RA). Her RA had been successfully managed with methotrexate for about 10 years. After a sustained virological response was achieved with interferon therapy, treatment with adalimumab was instituted. This resulted in a rapid and sustained remission that lasted for more than a year, without HCV reactivation. The results in this case suggest that a sequential strategy, with initial HCV clearance followed by the targeting of remission with biologics, may be a favorable option in patients with RA and concomitant HCV infection.
21434343 [Effect of methotrexate in treating patients with rheumatoid arthritis of different Chines 2011 Jan OBJECTIVE: To study whether the effects of methotrexate were different in treating patients with rheumatoid arthritis (RA) of different Chinese medical syndrome patterns. METHODS: Retrospective analysis was conducted in 312 RA patients treated with methotrexate, the Chinese medical syndrome patterns in them were differentiated into the cold-dampness blocking collateral type (SA), the heat-dampness blocking collateral type (SB), the phlegm blood-stasis intermingling type (SC), and the heat-cold complex type (SD). Parameters including numbers of joint with tenderness (Njt) and that with arthroncus (Nja); patient's morning stiffness duration (MSD), scores estimated by visual analog scale (VAS) and health assessment questionnaire (HAQ); as well as laboratory indices involving rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), etc. were recorded before and after treatment and statistically analyzed. RESULTS: After treatment, improvements were shown in all patients in terms of Njt, Nja, MSD, VAS scores and ESR, showing significant difference as compared with those before treatment (P < 0.05); and the improvements among patients with different Chinese medical syndrome types were different in degree, the best curative effect was shown in patients of SB type (chi2 = 45.3, P < 0.05). CONCLUSIONS: Referring to Chinese medical syndrome patterns, the curative effect of methotrexate on patients with Heat-Dampness blocking collateral pattern is better than on those of other pattern.
20349068 Development of interstitial pneumonia in a patient with rheumatoid arthritis induced by is 2012 May Here, we report a 56-year-old patient with rheumatoid arthritis (RA) who had been treated with methotrexate and sulfuasalazine, but the disease activity remained high. Therefore, we planned TNF-blocker treatment for this patient. A tuberculin skin test was positive, we started anti-tuberculosis (TB) chemoprophylaxis with isoniazid (INH). However, liver dysfunction was appeared after 2 weeks from the start of INH. Therefore, we discontinued INH transiently and tried the desensitization of INH. However, interstitial pneumonia was developed 2 weeks after the re-start of INH, we decided to stop the INH prophylaxis. Interstitial pneumonia was improved by corticosteroid treatments. This case report shows that INH-induced IP can be occurred during the course of anti-TB chemoprophylaxis in patients with RA.
21887490 Rheumatoid arthritis in Burkina Faso: clinical and serological profiles. 2011 Dec The objective of this work was to study the clinical and serological profiles of rheumatoid arthritis in Burkina Faso (West Africa). It is a cross-sectional study conducted from March 2006 to February 2009 in the Internal Medicine Department of the University Hospital Yalgado Ouedraogo. All patients seen in the rheumatologic consultation unit during this period, with rheumatoid arthritis fulfilling the ACR criteria, were routinely selected. The determination of anticyclic citrullinated peptide antibodies (ACPA) was carried out with a computerized method (Elia CCP, Phadia AB, Uppsala, Sweden). Values higher than 10 IU/l were considered positive. Forty-eight cases of rheumatoid arthritis (RA) were recruited throughout the study period among 2,194 (2.2 %) patients. Forty-two files were subjected to the study. There were 34 women and 8 men. The average age was 41.70 ± 13 years with extremes of 22 and 71 years. The average duration of the disease was 86.17 ± 82.01 months with extremes of 8 and 360 months. Rheumatoid factors (RF) were positive in 21 out of 30 patients (70.0%). The determination of ACPA carried out in all the patients was positive in 34 (81%) patients; their average value was 217 IU/l with extremes of 38 and 1,170. RF and ACPA were associated to bones erosions (p = 0.0001). Twenty-two patients were placed on methotrexate, eight on hydroxychloroquine, and three on salazopyrine. Nine were given only NSAIDs or prednisolone. No patients had had a biotherapy agent. The frequency of RA was low in our study compared to other African studies published so far. The particularity of RA cases reported in African series, including ours, is the rarity of extra-articular manifestations of the disease. The severity of the disease at presentation in the rheumatology clinic may be due to their late consultation among other causes.
20012868 Functional capacity in rheumatoid arthritis patients: comparison between Spanish and Brazi 2011 Feb The main objective of this study is to compare Spanish and Brazilian self-reported health-related functional capacity in patients with rheumatoid arthritis (RA). 197 patients diagnosed with RA were studied in Spain (n = 127) and Brazil (n = 70). Pain (Visual analog scale) and functional capacity (Health Assessment Questionnaire/HAQ) were assessed. Patients were questioned about regular exercise practice. Comparisons between groups were performed with Chi-square tests and Student t test. Pearson's correlation coefficient and linear regression models were used to analyze the associations. Brazilian patients were younger (p = 0.013), had worse levels of pain (p = 0.001) and a trend to experience worse functional capacity (p = 0.057) than Spanish ones. Spanish RA patients had higher body mass index (BMI) (p = 0.019) and longer disease duration (p = 0.001). Also, a higher percentage of subjects with RA from the Spanish cohort had been elected to take early retirement when compared with Brazilian patients (p = 0.010). Spanish RA patients had received more drugs than Brazilians (oral corticosteroids p = 0.010, Leflunomide p = 0.023, Methotrexate p = 0.072, non-steroidal anti-inflammatory drugs p = 0.064, biologic therapies p = 0.001). The functional capacity (HAQ) was correlated with age (p = 0.001), disease duration (p = 0.001), age at diagnosis (p = 0.001), pain (p = 0.001) and BMI (p = 0.001) in Spanish patients. In Brazilian, these correlations were only found with disease duration (p = 0.004) and pain (p = 0.001). In conclusion, our data suggest a better management of RA in Spanish when compared with Brazilians. Even with less pain and functional capacity, they receive more drug treatment and a higher percentage of them are retired early.
23219774 Different effects of biological drugs in rheumatoid arthritis. 2013 Mar Biological drugs have brought new hope to patients with rheumatoid arthritis (RA) in whom previously existing treatments could not control inflammation, joint destruction, or the progression of disability. The five currently available TNF blockers are approved for treating RA patients, but they have different structures, morphology, pharmacokinetic properties, and activity. Randomised clinical trials (RCTs) have shown that they improve the signs and symptoms of both early and long-standing RA and other inflammatory arthritides, prevent radiographic progression, and improve the patients' health-related quality of life. However, they are more effective in combination with methotrexate (MTX) than alone. Combined treatment is generally well tolerated, and seems to be relatively safe in the short term, as confirmed by RCTs, long-term observational studies and in clinical practice. Patients who fail to respond or develop adverse effects - when treated with one anti-TNF agent can be successfully treated with a second TNF antagonist. However, in the case of primary failure, it is possible that biological agents with a different mechanism of action may be more successful. Tocilizumab alone or in combination with MTX is more effective than MTX monotherapy in reducing disease activity over 24 weeks. Abatacept is well tolerated and retains its efficacy over time, as does rituximab in non-responders to other anti-TNF drugs. Finally, although these drugs improve the quality of life of RA patients, they considerably increase direct medical costs.
22454398 Definition of treatment response in rheumatoid arthritis based on the simplified and the c 2012 Jul BACKGROUND: The simplified disease activity index (SDAI) and the clinical disease activity index (CDAI) are established instruments to measure disease activity in rheumatoid arthritis (RA). To date, no validated response definitions for the SDAI and CDAI are available. OBJECTIVE: The authors aimed to define minor, moderate and major response criteria for the SDAI. METHODS: The authors used data from two clinical trials on infliximab versus methotrexate in early (ASPIRE) or established (ATTRACT) RA, and identified the three SDAI cutpoints based on the best agreement (by κ statistics) with the American College of Rheumatology (ACR)20/50/70 responses. Cutpoints were then tested for different aspects of validity in the trial datasets and in a Norwegian disease modifying antirheumatic drug prescription dataset (NOR-DMARD). RESULTS: Based on agreement with the ACR response, the minor, moderate and major responses were identified as SDAI 50%, 70% and 85% improvement. These cutpoints had good face validity concerning the disease activity states achieved by the different response definitions. Construct validity was shown by a clear association of increasing SDAI response categories with increasing levels of functional improvement, achievement of better functional states and lower annual radiographic progression. Across SDAI 50/70/85, the sensitivities regarding a patient-perceived improvement decreased (73%/39%/22%) and the specificities increased (61%/89%/96%) in a meaningful way. Further, the cutpoints discriminated the different treatment arms in ASPIRE and ATTRACT. The same cutpoints were used for the CDAI, with similar results in the validation analyses. CONCLUSION: These new response criteria expand the usefulness of the SDAI and CDAI for their use as endpoints in clinical trials beyond the definition of disease activity categories.
22915619 Rituximab dissociates the tight link between disease activity and joint damage in rheumato 2013 Jan BACKGROUND/OBJECTIVE: Progression of joint damage is linked to disease activity. This link is dissociated upon treatment with tumour necrosis factor (TNF)- or IL-6-inhibitors plus methotrexate (MTX). It is hitherto unknown if this may also be true for therapies targeting B-cells. We thus evaluated if rituximab (RTX) therapy inhibits joint damage irrespective of its effects on disease activity. METHODS: We used a random 90% sample of data from two arms of the IMAGE trial comprising patients with active early rheumatoid arthritis (RA) receiving MTX (n=188) or MTX+RTX 1000 mg (n=204). Patients were divided into low, moderate and high disease activity at one year of treatment by simplified disease activity index (low disease activity (LDA), moderate disease activity (MDA), high disease activity (HDA)), or by swollen joint count (SJC) or C reactive protein (CRP) tertiles. Progression of damage by the Genant modified total Sharp score (TGSS) was compared between therapies (Kruskal-Wallis, Wilcoxon tests) for each of these subgroups. RESULTS: In patients treated with MTX, 1-year progression of TGSS In LDA, MDA and HDA was 0.40±0.88, 1.04±1.73, and 1.31±3.02, respectively. In contrast, on RTX+MTX, TGSS progression was 0.38±1.07, 0.39±1.28, and -0.05±0.44, respectively (for MDA and HDA the progression of TGSS was significantly lower in the combined group than in the MTX group: p=0.003 and p=0.05, respectively). Additional analyses (tertiles of SJC, CRP, and matching for disease activity) confirmed the primary analysis. CONCLUSIONS: In early RA, progression of joint damage increases with increasing disease activity on MTX. RTX plus MTX retards damage independently of its effects on disease activity, since even in HDA destruction is halted, contrasting MTX monotherapy. This indicates that beyond cytokine blockade (TNF- and IL-6 inhibitors), also cell-directed therapy (anti-CD20 antibody) conveys profound anti-destructive effects and dissociates the link between disease activity and joint damage.
22395595 Adrenergic urticaria and rheumatoid arthritis in a patient with melanoma: an intricate med 2012 Mar A 45-year-old woman with marital and working troubles, a personal history positive for malignant melanoma, and a family history of vitiligo presented with adrenergic urticaria (AU), which at first responded to propranolol, but later became unresponsive to both ?-blockers and antihistamines. Meanwhile, rheumatoid arthritis became apparent. Treatment with corticosteroids and methotrexate led to remission of neither the rheumatologic nor the dermatologic condition. Attempts to taper the immunosuppressive treatment were invariably followed by recurrence of adrenergic urticaria, which still proved unresponsive to propranolol, as did the rheumatoid arthritis. The courses of the diseases strictly paralleled each other. Rheumatoid arthritis could have triggered adrenergic urticaria by simply adding a supplemental stress, but also by systemically activating mast cells, which are known to be involved in the pathogenesis of chronic inflammatory diseases. A brief discussion of either the dermatological manifestations of, or treatments for rheumatoid arthritis is provided, in order to illustrate the kind of clinical difficulties that such atypical patients pose to physicians. Adrenergic urticaria is an uncommon yet probably under-diagnosed form of urticaria, which is considered a form of neurogenic acute reaction mainly triggered by acute stress. The author presents a case of AU, however, that is only partially explained by a stress setting, though it is strongly associated with the course of an autoimmune disease.
21557525 Effect of rituximab on physical function and quality of life in patients with rheumatoid a 2011 May OBJECTIVE: To assess the effect of rituximab plus methotrexate (MTX) compared with MTX alone on patient-reported outcomes (PROs) and health-related quality of life (HRQOL) in patients with active early rheumatoid arthritis (RA) previously untreated with MTX. METHODS: Patients with active early RA were randomized to groups receiving placebo, rituximab 500 mg, or rituximab 1,000 mg. Rituximab was given by intravenous infusion on days 1 and 15. From week 24, patients with a Disease Activity Score in 28 joints-erythrocyte sedimentation rate of ≥2.6 were eligible for retreatment. Physical function was assessed by Health Assessment Questionnaire (HAQ) disability index (DI) and Short Form 36 (SF-36) scores. Patients achieving a minimal clinically important difference (MCID) for PROs were determined. Additional PROs, including fatigue and pain, were assessed. RESULTS: A total of 748 patients were randomized and received the study drug. Patient characteristics were well balanced. At week 52, treatment with rituximab in both dose groups showed significant improvements in the HAQ DI compared to the MTX alone group (-0.905 and -0.916 in the rituximab 500 mg plus MTX and 1,000 mg plus MTX groups, respectively, versus -0.628 in the MTX alone group; P < 0.0001). Higher proportions of patients achieved MCID in the HAQ DI in the rituximab plus MTX groups compared to MTX alone. Treatment with rituximab plus MTX led to a significant reduction in the SF-36 physical component summary for both rituximab dose groups, but did not show statistically significant differences in the SF-36 mental component summary. Compared to the MTX alone group, both doses of rituximab plus MTX were associated with significant reductions in the patient global assessment of disease activity and pain, and a significantly higher improvement in Functional Assessment of Chronic Illness Therapy-Fatigue scores from baseline to 52 weeks. CONCLUSIONS: Rituximab plus MTX was associated with significant improvement in physical function and HRQOL outcomes compared with MTX alone in patients previously untreated with MTX.
21502697 [The importance of pharmacogenetic tests in evaluation of the effectiveness of methotrexat 2011 Mar 30 Much hope is currently associated with individualization of therapy provided to rheumatoid arthritis (RA) patients. The search is underway for biochemical and clinical markers that would be useful in prediction of a good response to methotrexate (MTX) therapy. Along with clinical factors, genetic predisposition may also be helpful. Polymorphism of genes participating in MTX metabolism may affect the drug’s efficacy and the rate of adverse effects. Pharmacogenetic studies may contribute to more effective individualization of therapy for RA patients. The purpose of the study was to determine the significance of gene polymorphisms MTHFR C677T and A1298C for efficacy of MTX therapy in RA patients. Patients possessing determined polymorphisms should be particularly carefully evaluated because of a higher risk of occurrence of adverse effects.
21263416 Adenosine deaminase and C-reactive protein in diagnosing and monitoring of rheumatoid arth 2011 Feb AIM: To determine of catalytic activities of adenosine deaminase (ADA) and values of C-reactive protein (CRP) concentration in serums of patients with rheumatoid arthritis (RA), who were and were not treated with Methotrexate (MTX), and identifying the possibilities of using these biochemical parameters in diagnosing and monitoring of treatment effects in RA. METHODS: The study involved 120 subjects (60 healthy ones, who are in accordance with examined groups concerning age and sex, 30 suffering from RA who were not treated with MTX and 30 suffering from RA who were treated by MTX). Catalytic activities of ADA in serum were determined by spectrophotometric method using adenosine as a substrate. CRP concentrations in serum were determined immunoturbidimetrically. RESULTS: A statistically significant correlation between values of ADA catalytic activities and values of CRP concentrations (r = 0.55, p < 0.01) in serums of subjects with RA without MTX treatment. At subjects with RA treated by MTX, correlation between values of ADA catalytic activities and values of CRP concentrations in serums was not statistically significant (r = 0.33, p > 0.01). CONCLUSION: Study results have shown that ADA catalytic activity in serum can be a useful biochemical marker of inflammatory process in RA.
20514079 Polymorphisms C677T and A1298C in the MTHFR gene in Mexican patients with rheumatoid arthr 2011 Aug Rheumatoid arthritis (RA) is the prototype of the rheumatic diseases worldwide. Methotrexate (MTX) is the drug of first choice in the treatment of this disease due to its immunosuppressant effect. However, side events are present in 30% of the patients. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are involved in the metabolism of MTX. Earlier studies reported an association between these polymorphisms and elevation of hepatic enzymes. We analyzed the frequencies of both polymorphisms and the presence of transaminasemia in 70 Mexican patients with rheumatic arthritis treated with MTX. The 19% (13/70) of patients had an increase in the serum level of transaminases. The A1298C polymorphism was associated with elevation of transaminases (P=0.024). The identification of MTHFR genotypes for C677T and A1298C polymorphisms could lead clinicians to identify patients in risk of elevation of transaminases, and give them an individualized treatment, as is a goal of pharmacogenetics.
22382335 Anticitrullinated protein antibody, but not its titer, is a predictor of radiographic prog 2012 Apr OBJECTIVE: To study the contribution of anticitrullinated protein antibody (ACPA), and especially of its titer, to radiographic progression and disease activity in rheumatoid arthritis (RA). METHODS: Patients with RA (n = 396) who attended a Japanese clinic within 2 years after disease onset were divided into the following groups according to second-generation (ACPA-2) ACPA titer on their first visit: negative (0-4.4 U/ml; n = 115), low-positive (4.5-121 U/ml; n = 141), and high-positive (> 121 U/ml; n = 140). The ACPA-2-positive groups were further subdivided into lowest (4.5-32 U/ml), low (33-121 U/ml), high (122-277 U/ml), and highest (> 278 U/ml) quartiles. All patients were treated with disease-modifying antirheumatic drugs (DMARD) including methotrexate, but not biologics. Subsequent radiographic progression and disease activity for 2 years were prospectively evaluated using the van der Heijde-modified Sharp score (SHS) and 28-joint Disease Activity Score (DAS28). RESULTS: After treatment with DMARD, the disease activity (including number of swollen joints, number of tender joints, duration of morning stiffness, DAS28-erythrocyte sedimentation rate, and DAS28-C-reactive protein) was significantly decreased in all patient groups. Disease activity and radiographic progression as revealed by the change in SHS remained relatively higher in the ACPA-2 low- and high-positive groups as compared with the ACPA-2-negative group. The relationship between the titer of ACPA-2 at baseline and subsequent radiographic progression was not exactly linear, and the extent of disease activity or radiographic progression was similar between ACPA-2 low- and high-positive groups and also between ACPA-2 lowest- and highest-positive quartile groups. The results were demonstrable in cumulative SHS probability plots, and also repeatable in seronegative patients, which indicated that the titer of ACPA-2 is not a predictor of disease activity or radiographic progression in RA, and ACPA-2-negative patients, especially those with < 3 U/ml, showed minimal radiographic progression. CONCLUSION: Presence of ACPA-2, but not its titer, at baseline is a predictor of radiographic progression or disease activity, where radiographic progression is minimal in ACPA-2-negative patients.
22089458 Sex differences in response to anti-tumor necrosis factor therapy in early and established 2012 Jan OBJECTIVE: To investigate sex differences in response to anti-tumor necrosis factor-α (TNF-α) therapy over time in early versus established rheumatoid arthritis (RA). METHODS: Patients with RA who initiated anti-TNF therapy between January 2003 and June 2008 in Denmark were selected from the DANBIO Registry. Sex differences in baseline disease features were examined using chi-square, Mann-Whitney U tests, and t tests. Using a generalized estimating equations (GEE) model for repeated measures, we examined European League Against Rheumatism (EULAR) responses in men and women over 48 months of followup, adjusting for baseline values of age, 28-joint Disease Activity Score (DAS28), disease duration, and anti-TNF, methotrexate, and prednisolone use. RESULTS: At initiation of anti-TNF therapy (baseline), 328 women and 148 men had early RA (≤ 2 yrs), and 1245 women and 408 men had established RA (> 2 yrs). In both early and established RA, men and women had active disease with similar DAS28 scores (mean ± SD 5.2 ± 1.1), physician global scores, swollen joint counts, and radiographic changes. In early RA, men were significantly more likely to achieve a EULAR good/moderate response over 48 months compared to women (GEE; p = 0.003), and a significant interaction between sex and followup time (GEE; p < 0.0005) suggested that men achieved this response sooner than women. CONCLUSION: Better responses to anti-TNF therapy among men compared to women in early but not established RA suggest that disease duration at initiation of therapy may be an important factor to consider when investigating sex differences in treatment responses.
22580535 Effect of ESR1 and ESR2 gene polymorphisms on rheumatoid arthritis treatment with methotre 2012 Rheumatoid arthritis (RA) is a complex autoimmune disease with clinical prevalence in women. Moreover, women have poorer response to treatment than men. Possible reasons for gender differences in response to treatment could be explained on the basis of sex hormones and their receptors. The optimal strategy in treatment of RA is to use effective disease modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX). The aim of the present study was to examine the association between polymorphisms in the ESR1 and ESR2 genes and the response to treatment of RA patients with methotrexate. The study was carried out on 156 women diagnosed with active rheumatoid arthritis, treated with MTX. Good responders were defined as patients who were receiving MTX and had a DAS28 of ≤ 2.4 after 6 months of therapy (patients with remission of disease symptoms). Poor-responders were defined as patients who were receiving MTX and had a DAS28 of > 2.4. There were no statistically significant associations of ESR1 and ESR2 gene polymorphisms with response to treatment. The results of the present study suggest that the polymorphisms rs9340799:A>G and rs2234693:T>C in ESR1 gene and rs4986938:G>A and 1256049:G>A in ESR2 gene are not associated with response to RA treatment with MTX.
22373834 Tocilizumab has no clinically relevant effects on methotrexate pharmacokinetics in patient 2012 Mar OBJECTIVE: To assess the effects of tocilizumab on methotrexate and 7-hydroxymethotrexate pharmacokinetics in patients with rheumatoid arthritis and to explore the pharmacodynamic effect of tocilizumab on C-reactive protein (CRP), a marker of inflammation. METHODS: Methotrexate (10 - 25 mg) was administered orally on Days 1, 8, 15, 22, 29, 36, and 43. On Day 8 patients received 10 mg/kg tocilizumab intravenously. Blood samples for pharmacokinetic analyses were collected on Days 1, 15, and 43 and for pharmacodynamics (CRP) throughout the study. RESULTS: 90% CIs for mean effect ratios (Day 15/Day 1 and Day 43/Day 1) of methotrexate and 7-hydroxymethotrexate (AUClast and Cmax) were close to or within the bioequivalence boundaries (80 - 125%). CRP normalized within 1 week after tocilizumab injection and remained within normal limits for 3 weeks. CONCLUSION: Tocilizumab and methotrexate can be administered concurrently without dosage adjustments.
21738080 Association of Cullin1 haplotype variants with rheumatoid arthritis and response to methot 2011 Sep Aberrations in ubiquitin pathway have been implicated in many diseases and drug response. In a previous study on rheumatoid arthritis (RA) in Japanese population, significant association of Cullin1 gene (CUL1), an ubiquitin E3 ligase, was observed. CUL1 also mediates degradation of IκBα and p27, levels of which has been associated with RA etiology and drug response, respectively. We carried out a replication study of association of CUL1 polymorphisms with RA in a north Indian population. Allelic, genotypic, and haplotypic associations of a promoter and two intronic polymorphisms of CUL1 with RA and with methotrexate response in patients with RA, were tested. A significant association (P=0.00056, adjusted) of a haplotype A-T-T with RA (odds ratio=3.68; 95% confidence interval=1.86-7.27) and in patients with RA poorly responding to methotrexate treatment (P=0.04, adjusted) was observed. Association with CUL1 haplotype indicates a possible role of CUL1 variation(s) in RA and its response to methotrexate.
22089467 Proposed severity and response criteria for Routine Assessment of Patient Index Data (RAPI 2011 Dec BACKGROUND: An index is needed to assess the status of patients with rheumatoid arthritis (RA), as none of the existing measures are applicable to all individual patients. The 28-joint Disease Activity Score (DAS28) is the most specific and widely used index. Routine Assessment of Patient Index Data (RAPID3) is an index containing only the 3 patient self-report core dataset measures, without a laboratory test or formal joint count, and with simple scoring. RAPID3 is correlated significantly with DAS28, but calculated in 5-10 seconds on a Multidimensional Health Assessment Questionnaire (MDHAQ), compared to 114 seconds for DAS28. METHODS: DAS28 (0-10 scale) categories for high, moderate, and low activity, and remission (≤ 2.6, 2.6-3.2, 3.21-5.1, and > 5.1, respectively) and proposed RAPID3 (0-30 scale) categories for severity (0 ≤ 3, 3.1-6, 6.1-12, and > 12) were compared in patients taking abatacept and control-treated patients at the endpoint of the Abatacept in Inadequate Response to Methotrexate (AIM) and the Abatacept Trial in Treatment of Anti-TNF INadequate Responders (ATTAIN) clinical trials, using cross-tabulations and kappa statistics. RESULTS: Overall, 92%-99% of patients classified as having high DAS28 activity had high or moderate RAPID3 severity, while 64%-83% in DAS28 remission had RAPID3 low severity or remission; 50%-82% of patients with good or poor EULAR responses had good or poor RAPID3 responses. Kappa values ranged from 0.25 to 0.48, and weighted kappas from 0.32 to 0.52, indicating fair to moderate agreement for the 2 indices. CONCLUSION: Proposed RAPID3 severity and response categories yield comparable results to DAS28 and EULAR criteria in AIM and ATTAIN. DAS28 is more specific for clinical trials. RAPID3 does not preclude also scoring DAS28, and may be informative in the infrastructure of routine care.