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ID PMID Title PublicationDate abstract
20507292 The impact of Rituximab therapy on the chromosomes of patients with Rheumatoid arthritis. 2010 May The open prospective combined cytogenetic and clinical study investigated the impact of biological therapy Rituximab on number and structure of chromosomes in Rheumatoid arthritis patients. The purpose of this study was to investigate safety of Rituximab on chromosomes as well as cytotoxic therapy Methotrexate. A total of 8 seropositive Rheumatoid arthritis patients were analyzed for primary end point of eventual cytotoxic effect of Rituximab. Assessment was done before and 1 month later, actually 2 weeks after the administration of full course of Rituximab in infusion. Patients suffering from active Rheumatoid arthritis were randomly assigned according to established protocol to receive infusion of Rituximab in a full dose of 2.0 grams divided in a two doses of 1.0 gram on days 1 and 15. The lymphocytes from peripheral blood were cultured according to Moorhead method. The results obtained from this investigation showed that normal male and female karyogram was found after the full therapy of Rituximab. The results from this study, that was done on a rather small number of subjects, indicate that Rituximab does not express either clastogenic or aneugenic effects. But, co-finding of this study was that Methotrexate had a side effect on chromosomal aberration in one female RA patient, and after discontinuation of this treatment the normal karyogram was observed.
20379839 Precore mutant hepatitis B virus-associated fulminant hepatitis during infliximab therapy 2013 Mar A 73-year-old female, who suffered from rheumatoid arthritis for 10 years, developed precore mutant hepatitis B virus-associated fulminant hepatitis after 1 year of infliximab therapy and subsequent methotrexate withdrawal. We emphasize the importance of preemptive antiviral therapy before starting infliximab administration and withdrawing immunosuppressive drugs.
21113712 Anti-cyclic citrullinated peptide antibody predicts functional disability in patients with 2012 Feb To clarify the clinical significance of anti-cyclic citrullinated peptide antibody (anti-CCP) in the long-term outcome of RA, we established a large observational cohort of RA patients (IORRA) in our institute beginning in 2000. Essentially all RA patients who consulted our institute were registered, and clinical parameters, including disease activity and drug use, were assessed biannually based on patient reports, physician examinations, and laboratory data. In the third phase (October 2001) of the IORRA survey, anti-CCP levels were measured in 1,226 RA patients. In a cross-sectional analysis, clinical variables were compared in anti-CCP-positive versus -negative patients and in RF-positive versus -negative patients. In a longitudinal analysis, subsequent progression of disability was analyzed in anti-CCP-positive versus -negative and in RF-positive versus -negative patients. A verified Japanese version of the Health Assessment Questionnaire (J-HAQ) was used to measure functional disability. In the cross-sectional analysis, anti-CCP-positive patients (84.2%) had a significantly longer disease duration and higher disease activity score and more frequently used corticosteroids and methotrexate compared to anti-CCP-negative patients statistically. Similar phenomena were noted between RF-positive and -negative patients. In contrast, the longitudinal analysis revealed that J-HAQ slopes-a measure of progression of functional disability-were strongly associated with anti-CCP positivity but not with RF positivity. In a linear regression model, J-HAQ scores significantly worsened in anti-CCP-positive patients compared to anti-CCP-negative patients at the third year (annual progression 0.0317, P = 0.001) and the fifth year (annual progression 0.0199, P = 0.0012); however, J-HAQ progression was not influenced by RF status. Anti-CCP is a better predictive and discriminative marker for progression of disability in the long-term outcome of RA patients compared to RF.
19144159 Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristic 2009 INTRODUCTION: Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). METHODS: The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. RESULTS: Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies. CONCLUSIONS: In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself.
18663553 The changes in serum chemokines following leflunomide therapy in patients with rheumatoid 2009 Jan We undertook this study to evaluate the effects of leflunomide, an oral pyrimidine synthesis inhibitor, on the serum chemokine levels in patients with active rheumatoid arthritis (RA) who were refractory to treatment with methotrexate (MTX) or did not tolerated MTX treatment. RA patients were supposed to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally for the 12 months). Serum concentrations of RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) were assessed by enzyme-linked immunosorbent assay before and after 3, 6, 9, and 12 months of treatment with leflunomide. Three months therapy with leflunomide caused reduction in serum RANTES and MCP-1 (in both cases, p < 0.001) levels. Decrease in the concentration of these chemokines persisted until the end of the study period but was less significant. In the case of IL-8, its serum levels significantly diminished after 6 months of therapy with leflunomide (p < 0.01) and remained stable to the end of the study. Changes in serum chemokine levels were accompanied by significant decrease of disease activity score (DAS; p < 0.001). Prior to the first dose of leflunomide, serum concentrations of studied chemokines correlated with marker of RA activity such as the erythrocyte sedimentation rate and IL-8 level with DAS. Furthermore, we demonstrated significant correlations between serum levels of RANTES, MCP-1, and IL-8. During study period, such associations were far less or not significant. Leflunomide, beside a clinical improvement, reduce serum chemokines concentrations in RA patients. Leflunomide seems to be an effective treatment for RA, alternative to current therapies.
20039405 Direct comparison of treatment responses, remission rates, and drug adherence in patients 2010 Jan OBJECTIVE: To compare tumor necrosis factor alpha inhibitors directly regarding the rates of treatment response, remission, and the drug survival rate in patients with rheumatoid arthritis (RA), and to identify clinical prognostic factors for response. METHODS: The nationwide DANBIO registry collects data on rheumatology patients receiving routine care. For the present study, we included patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment was initiated (29% received adalimumab, 22% received etanercept, and 49% received infliximab). Baseline predictors of treatment response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number of previous disease-modifying drugs, center, and functional status (Health Assessment Questionnaire score). RESULTS: Seventy percent improvement according to the American College of Rheumatology criteria (an ACR70 response) was achieved in 19% of patients after 6 months. Older age, concomitant prednisolone treatment, and low functional status at baseline were negative predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response were 2.05 (95% CI 1.52-2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28-2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82-1.60) for adalimumab versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63-2.40), 1.35 for infliximab versus adalimumab (95% CI 1.15-1.58), and 1.47 for adalimumab versus etanercept (95% CI 1.20-1.80). CONCLUSION: Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission. Infliximab had the lowest rates of treatment response, disease remission, and drug adherence, adalimumab had the highest rates of treatment response and disease remission, and etanercept had the longest drug survival rates. These findings were consistent after correction for confounders and sensitivity analyses and across outcome measures and followup times.
19449016 [How effective is rituximab in rheumatoid arthritis?: lessons learned from clinical practi 2010 Jun OBJECTIVES: Does experience with rituximab treatment of rheumatoid arthritis (RA) in daily clinical practice confirm the results of controlled randomized studies? METHODS: This is a retrospective data-analysis of the first 50 patients from one center with rituximab treatment for RA. The patients received at least one cycle of 2 rituximab infusions (1000 mg, respectively) within 2 weeks. Clinical assessment was performed 3-5 months after the first infusion. RESULTS: The patients were older (mean age, 59 years) as compared to previously published controlled studies. The DAS28 was lower (5.5). The mean prednisolone dose was high (13.4 mg/d). The rheumatoid factor was positive in 88% of patients. Only six patients would have fulfilled inclusion criteria for controlled studies such as prednisolone dose
19246078 The effect of infliximab and timing of vaccination on the humoral response to influenza va 2010 Jun OBJECTIVES: To assess the effect of the timing of vaccination in relation to administration of infliximab on the efficacy and safety of influenza vaccine in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: The study population comprised 38 patients treated with infliximab at a mean dosage of 3 mg/kg (20 RA patients; 18 AS patients; 23 RA controls (treated with disease modifying antirheumatic drugs other than anti-tumor necrosis factor-alpha; and 17 healthy controls). Split-virion inactivated vaccine containing 15 mug hemagglutinin/dose of each of A/New Caledionan/20/1999 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 (M) was used. Patients treated with infliximab were divided into 2 groups: 22 were vaccinated on the day of administration of infliximab, while 16 received the vaccine 3 weeks after infliximab. Baseline and 4- to 6-week clinical assessment of disease activity included erythrocyte sedimentation rate and C-reactive protein for all patients, the 28-joint disease-activity score for RA patients, and Bath Ankylosing Spondylitis Disease Activity Index for AS patients. Hemagglutination inhibition (HI) antibodies were tested by a standard World Health Organization procedure. Response was defined as >or=4-fold rise in HI antibodies 4 to 6 weeks after vaccination, or seroconversion in patients with a nonprotective baseline level of antibodies (<1/40). Geometric mean titers (GMT) were calculated to assess the immunity of the whole group. RESULTS: At baseline, RA patients and controls had similar occurrence of protective levels of HI antibodies and GMT, while AS patients had lower levels reflecting lower rates of previous vaccination. Four weeks after vaccination, a significant and similar increase in GMT for each antigen was observed in all groups (P < 0.004) except in the RA-infliximab group, vaccinated 3 weeks after administration of infliximab, in whom the increase in GMT was not significant for H1N1 (P = 0.12) and H3 (P = 0.06). AS patients demonstrated an increase in GMT, independently of the time of vaccination. The percentage of responders was similar in all groups. The response was not affected by variables such as age, gender, methotrexate, or prednisone use. Parameters of disease activity remained unchanged. No adverse effects other than injection site pain were recorded. CONCLUSIONS: Influenza virus vaccine generated a good humoral response in RA and AS patients treated with infliximab.
20423835 [Therapeutic effect of infliximab on moderate and severe active rheumatoid arthritis]. 2010 Apr OBJECTIVE: To evaluate the clinical efficacy of infliximab in the treatment of moderate and severe active rheumatoid arthritis (RA). METHODS: This randomized double-blind II/III clinical trial involved 30 patients with moderate and severe active RA, who were randomly allocated into 3 groups (groups A, B, and C) at the ratio of 3:1:1. At weeks 0, 2, 6, and 14, the patients in groups A and C received infliximab or placebo, and those in group B had placebo at week 14 with a stable background dose of methotrexate. The indicators for efficacy evaluation included the proportions of ACR20/50/70 of the responders and DAS28. The sharp scores of the hand joints were recorded before and after the treatment. RESULTS: Twenty-nine patients completed the clinical trial (18 in group A, 5 in group B, and 6 in group C). At week 14, the proportions of ACR20/50/70 in the 3 groups reached 83.33%, 60%, and 33.33%, respectively (P<0.05), as compared to 100%, 100%, and 33.33% at week 18 (P<0.05). The other indicators for clinical efficacy evaluation also suggested similar clinical improvement of the patients (P=0.000). The proportions of the patients with DAS28<3.2 and DAS28<2.6 were significantly different. Compared to the baseline, the Sharp scores in group A showed no significant changes at week 18 (P>0.930), while those in group C exhibited significant radiographic progression (P<0.044). CONCLUSION: Infliximab produces good short-term therapeutic effect against moderate and severe active RA and may help arrest the radiographic progression of the diseases, which can be more obvious in patients with moderate severity.
18388160 MRI bone oedema is the strongest predictor of subsequent radiographic progression in early 2009 Mar OBJECTIVE: To identify predictors of radiographic progression in a 2-year randomised, double-blind, clinical study (CIMESTRA) of patients with early rheumatoid arthritis (RA). METHODS: Patients with early RA (n = 130) were treated with methotrexate, intra-articular betamethasone and ciclosporin/placebo-ciclosporin. Baseline magnetic resonance imaging (MRI) of the wrist (wrist-only group, n = 130) or MRI of wrist and metacarpophalangeal (MCP) joints (wrist+MCP group, n = 89) (OMERACT RAMRIS), x-ray examination of hands, wrists and forefeet (Sharp/van der Heijde Score (TSS)), Disease Activity Score (DAS28), anti-cyclic citrullinated peptide antibodies (anti-CCP), HLA-DRB1-shared epitope (SE) and smoking status were assessed. Multiple regression analysis was performed with delta-TSS (0-2 years) as dependent variable and baseline DAS28, TSS, MRI bone oedema score, MRI synovitis score, MRI erosion score, anti-CCP, smoking, SE, age and gender as explanatory variables. RESULTS: Baseline values: median DAS28 5.6 (range 2.4-8.0); anti-CCP positive 61%; radiographic erosions 56%. At 2 years: DAS28 2.0 (0.5-5.7), in DAS remission: 56%, radiographic progression 26% (wrist+MCP group, similar for wrist-only group). MRI bone oedema score was the only independent predictor of delta-TSS (wrist+MCP group: coefficient = 0.75 (95% CI 0.55 to 0.94), p<0.001; wrist-only group: coefficient = 0.59 (95% CI 0.40 to 0.77), p<0.001). Bone oedema score explained 41% of the variation in the progression of TSS (wrist+MCP group), 25% in wrist-only group (Pearson's r = 0.64 and r = 0.50, respectively). Results were confirmed by sensitivity analyses. CONCLUSION: In a randomised controlled trial aiming at remission in patients with early RA, baseline RAMRIS MRI bone oedema score of MCP and wrist joints (and of wrist only) was the strongest independent predictor of radiographic progression in hands, wrists and forefeet after 2 years. MRI synovitis score, MRI erosion score, DAS28, anti-CCP, SE, smoking, age and gender were not independent risk factors. TRIAL REGISTRATION NUMBER: NCT00209859.
19945329 A report of 21 cases of rheumatoid arthritis following Chikungunya fever. A mean follow-up 2009 Dec OBJECTIVE: In 2005, after an epidemic infection of Chikungunya fever in islands in the Indian Ocean, infected patients exhibited severe musculoskeletal disorders. We report 21 cases of rheumatoid arthritis (RA) after Chikungunya infection that were diagnosed at a rheumatological centre in Reunion Island. METHODS: Patients were examined by the same rheumatologist from February 2006 to July 2007. Inclusion criteria were (1) Chikungunya infection confirmed by IgM and IgG antibodies, (2) RA according to ACR criteria, (3) no other definite diagnosis of arthritis and (4) persistent arthritis symptoms from the onset of viral infection to RA diagnosis. RESULTS: Twenty-one patients (13 females; mean age, 57+/-12 years) fulfilled the inclusion criteria. Eighteen patients (85.7%) had symmetric polyarthritis and three had oligoarthritis. The mean symptom duration was 10 months (range 4-18). The mean ESR was 40.7+/-28.1 mm/hr and C-reactive protein level 37+/-41 mg/l; 12 patients were positive for rheumatoid factor (57.1%), and six had anti-CCP antibodies (28.6%) and 14 HLA DRB1*04 or 01 alleles (66.6%). Radiographs of hands and feet of 12 patients showed erosions and/or joint space narrowing (JSN). During a mean follow-up of 27.6+/-6.4 months, all patients were treated with DMARDs including methotrexate (n=19) and TNF blockers (n=6). Structural damage progressed, with 17 cases of erosion and/or JSN at follow-up. CONCLUSION: We diagnosed RA in 21 patients with Chikungunya fever. The first symptoms occurred at the time of viral infection. Outcome was severe in most of the cases despite low rate of anti-CCP antibodies. These cases suggest a role of viral infection in RA initiation.
20980282 No overall progression and occasional repair of erosions despite persistent inflammation i 2011 Feb AIM: To monitor joint inflammation and destruction in rheumatoid arthritis (RA) patients receiving adalimumab/methotrexate combination therapy using MRI and ultrasonography. To assess the predictive value of MRI and ultrasonography for erosive progression on CT and compare MRI/ultrasonography/radiography for erosion detection/monitoring. METHODS: Fifty-two erosive biological-naive RA patients were followed with repeated MRI/ultrasonography/radiography (0/6/12 months) and clinical/biochemical assessments during adalimumab/methotrexate combination therapy. RESULTS: No overall erosion progression or repair was observed at 6 or 12 months (Wilcoxon; p > 0.05), but erosion progressors and regressors were observed using the smallest detectable change cut-off. Scores of MRI synovitis, grey-scale synovitis (GSS) and power Doppler ultrasonography decreased after 6 and 12 months (p < 0.05), as did DAS28, HAQ and tender and swollen joint counts (p < 0.001). Patients with progression on CT had higher baseline MRI bone oedema scores. The RR for CT progression in bones with versus without baseline MRI bone oedema was 3.8 (95% CI 1.5 to 9.3) and time-integrated MRI bone oedema, power Doppler and GSS scores were higher in bones/joints with CT progression (Mann-Whitney; p < 0.05). With CT as the reference method, sensitivities/specificities for erosion in metacarpophalangeal joints were 68%/92%, 44%/95% and 26%/98% for MRI, ultrasonography and radiography, respectively. Median intraobserver correlation coefficient was 0.95 (range 0.44-0.99). CONCLUSION: During adalimumab/methotrexate combination therapy, no overall erosive progression or repair occurred, whereas repair of individual erosions was documented on MRI, and MRI and ultrasonography synovitis decreased. Inflammation on MRI and ultrasonography, especially MRI bone oedema, was predictive for erosive progression on CT, at bone/joint level and MRI bone oedema also at patient level.
21092476 [An open-label, multicentric clinical trial to evaluate the efficacy and impact on bone me 2010 Sep 21 OBJECTIVE: To evaluate the efficacy, radiographic changes and safety of the combination of recombinant human tumor necrosis factor-α receptor II IgG Fc fusion protein (rhTNFR:Fc) and methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: 30 RA patients were treated with rhTNFR:Fc (25 mg subcutaneously twice weekly) and oral MTX (up to 15 mg weekly) in an open-label manner. Clinical response was assessed by American College of Rheumatology (ACR) criteria and Disease Activity Score in 28 joints (DAS28). Radiographs of hands and wrist were assessed by the modified Sharp score. RESULTS: At Week 24, ACR20, ACR50 and ACR70 responses were achieved by 90%, 76.67% and 46.67% respectively. At Week 24, the mean DAS28 was 3.65 ± 1.26 versus 6.41 ± 0.61 at baseline (P < 0.001). And 20% patients achieved remission and 16.67% patients had a low disease activity. At week 24, EULAR good and moderate responses were attained by 36.67% and 60% respectively. Similarly, Health Assessment Questionnaire (HAQ) improved significantly, declining from 1.12 at baseline to 0.36 at week 24 (P < 0.001). No radiographic progression (based on change of total Sharp score) was found in 27 cases. Adverse events were mild. CONCLUSION: rhTNFR:Fc in combination with MTX shows an excellent efficacy of reduced disease activity, improved function and slowed radiographic progression through 24 weeks. A combination therapy for 24 weeks can lead to disease remission and an inhibition of radiographic progression. Further study is warranted.
20610442 Clinical synovitis in a particular joint is associated with progression of erosions and jo 2010 Dec OBJECTIVES: To assess the relationship between joint tenderness, swelling and joint damage progression in individual joints and to evaluate the influence of treatment on these relationships. METHODS: First-year data of the Behandel Strategieën (BeSt) study were used, in which patients recently diagnosed as having rheumatoid arthritis (RA) were randomly assigned into four different treatment strategies. Baseline and 1-year x-rays of the hands and feet were assessed using the Sharp-van der Heijde score (SHS). With generalised estimating equations, 3-monthly assessments of tender and swollen joints of year 1 were related to erosion progression, joint space narrowing (JSN) progression and total SHS progression at the individual joint level (definition > 0.5 SHS units) in year 1, corrected for potential confounders and within-patient correlation for multiple joints per patient. RESULTS: During year 1, 59% of all 13 959 joints analysed were ever tender and 45% ever swollen, 2.1% showed erosion progression, 1.9% JSN progression and 3.6% SHS progression. Swelling and tenderness were both independently associated with erosion and JSN progression with comparable OR, although with higher OR in the hands than in the feet. Local swelling and tenderness were not associated with local damage progression in patients initially treated with infliximab. CONCLUSION: Clinical signs of synovitis are associated with erosion and JSN progression in individual joints after 1 year in RA. A disconnect between synovitis and joint damage progression was observed at joint level in patients who were treated with methotrexate and infliximab as initial treatment, confirming the disconnect between synovitis and the development of joint damage in tumour necrosis factor blockers seen at patient level.
20436075 Golimumab for rheumatoid arthritis: a systematic review. 2010 Jun OBJECTIVE: To perform a Cochrane systematic review of benefit (American College of Rheumatology 50% improvement criteria; ACR50) and safety (adverse events and withdrawals) of golimumab in patients with rheumatoid arthritis (RA). METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), OVID Medline, CINAHL, Embase, Science Citation Index (Web of Science), and Current Controlled Trials databases for randomized or controlled clinical trials of golimumab compared to placebo or disease-modifying antirheumatic drug in adults with RA. Two authors independently selected appropriate studies and abstracted study characteristics and safety and efficacy data and performed risk-of-bias assessment. We calculated mean differences for continuous measures, and relative risks for categorical measures. RESULTS: Four randomized controlled trials with 1231 golimumab-treated and 483 placebo-treated patients were included. Of these, 436 were treated with golimumab at 50 mg every 4 weeks [a dosage approved by the US Food and Drug Administration (FDA)]. At an average of 4-6 months, compared to patients treated with placebo and methotrexate (MTX), patients treated with the FDA-approved dosage of golimumab and MTX were 2.6 times more likely to reach ACR50 (p = 0.005, 95% CI 1.3, 4.9; absolute percentage, 38% vs 15%) and 0.5 times as likely to have overall withdrawals (p = 0.005, 95% CI 0.3, 0.8; absolute percentage, 5% vs 10%). Golimumab-treated patients were significantly more likely than those taking placebo to achieve remission (22% vs 4%; p < 0.00001), and to have improvement in functional ability on the Health Assessment questionnaire [0.2 points lower (p < 0.00001, 95% CI 0.25, 0.15); absolute risk difference, -20% (95% CI -25% to -15%); relative percentage difference, -11% (95% CI -14% to -8.3%)]. The studies were too small and short to be powered sufficiently for safety outcomes, but no substantive statistically significant differences were noted between golimumab and placebo regarding adverse events, serious adverse events, infections, serious infections, lung infections, tuberculosis, cancer, withdrawals due to adverse events, and withdrawals due to inefficacy and deaths. CONCLUSION: At the approved dosage, in patients with active RA taking background MTX, golimumab is significantly more beneficial than placebo. The short-term safety profile is reasonable. Longterm surveillance studies are needed for safety assessment.
20374310 Histological analysis of synovium by treatment of etanercept for rheumatoid arthritis. 2009 Apr AIMS: In order to investigate the histological change in effect attenuation cases of etanercept compared with methotrexate (MTX), we performed immunohistochemical examination by seven different molecules. METHODS: We histologically assessed synovial tissue from five MTX-treated rheumatoid arthritis (RA) patients as control and six etanercept and MTX-treated RA patients after synovectomy by arthroscopy. The synovium of both groups were assessed by hematoxylin and eosin (HE) and we also analysed the expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), B-cell precursors and mature B-cell transmembrane protein, CD20, macrophage marker, CD68, bromodeoxyuridine (BrdU) and vascular endothelial growth factor (VEGF) by immunohistochemistry. RESULTS: HE staining showed vascular and cell proliferations of the synovium of the RA patients who received etanercept compared with the control MTX group. TNF-alpha and IL-6 were expressed in both groups.MMP-3 and CD68 expressed less significantly in the etanercept group compared with the control (P < 0.05). CD20 strongly expressed in the etanercept group significantly (P < 0.05). BrdU expressed in the synovium in the etanercept group significantly (P < 0.05). VEGF was not found overall in both group. CONCLUSION: Based on the histological change of synovium, treatment by etanercept may be involved in vascular and cell proliferations with inhibition of the expression of CD68 and MMP-3 in synovium of RA patients. These findings indicate immunohistochemical change of synovium with etanercept is one of the mechanism of efficacy of etanercept.
21046421 Management of rheumatoid arthritis: consensus recommendations from the Hong Kong Society o 2011 Mar Given the recent availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), the Hong Kong Society of Rheumatology has developed consensus recommendations on the management of RA, which aim at providing guidance to local physicians on appropriate, literature-based management of this condition, specifically on the indications and monitoring of the biologic disease-modifying anti-rheumatic drugs (DMARDs). The recommendations were developed using the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis as a guide, along with local expert opinion. As significant joint damage occurs early in the course of RA, initiating therapy early is key to minimizing further damage and disability. Patients with serious disease or poor prognosis should receive early, aggressive therapy. Because of its good efficacy and safety profile, methotrexate is considered the standard first-line DMARD for most treatment-naïve RA patients. Patients with a suboptimal response to methotrexate monotherapy should receive step-up (combination) therapy with either the synthetic or biologic DMARDs. In recent years, combinations of methotrexate with tocilizumab, abatacept, or rituximab have emerged as effective therapies in patients who are unresponsive to traditional DMARDs or the anti-tumor necrosis factor (TNF)-α agents. As biologic agents can increase the risk of infections such as tuberculosis and reactivation of viral hepatitis, screening for the presence of latent tuberculosis and chronic viral hepatitis carrier state is recommended before initiating therapy.
20080919 Clinical improvement in rheumatoid arthritis is associated with healthier microvascular fu 2010 Mar OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) mortality. Microvascular endothelial dysfunction occurs early in the development of CV disease and is worsened by inflammation. The effect of drug treatment for RA on microvascular function has been poorly studied. We assessed the effect of antirheumatic treatment on microvascular endothelial function in patients with RA, particularly to examine responders versus nonresponders to therapy. METHODS: Fifty-one patients with active RA and no previous history of CV disease were assessed at baseline and after 2 and 4 months' therapy with either anti-tumor necrosis factor-alpha drugs (etanercept, n = 27, adalimumab, n = 3) or methotrexate, n = 21. RA disease activity, inflammatory measures, and skin microvascular responses, measured using laser Doppler imaging after iontophoretic delivery of acetylcholine (ACh) and sodium nitroprusside (SNP), were assessed at each study visit. RESULTS: Disease Activity Score (DAS28) decreased significantly from baseline to visit 2 and 3 (6.04 +/- 1.2, 4.34 +/- 1.3, 4 +/- 1.3, respectively; p < 0.0001). Endothelium-dependent (ACh) and independent (SNP) responses for the whole cohort did not improve significantly after drug treatment (p = 0.250, p = 0.062, respectively). When patients who responded to antirheumatic therapy (n = 31) were analyzed, there were significant improvements in both ACh (p = 0.028) and SNP responses (p = 0.019). CONCLUSION: Microvascular endothelial function improves in patients who respond to antirheumatic therapy. These results support the importance of effective therapy for RA patients in terms of CV effects, which might extrapolate to reduced CV events in the future. Clinical trial registration no. ISRCTN57761809.
20067328 Associations between the C677T and A1298C polymorphisms of MTHFR and the efficacy and toxi 2010 BACKGROUND AND OBJECTIVE: The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene have been reported to be associated with the toxicity and efficacy of methotrexate in rheumatoid arthritis (RA), although the results of previous studies have been inconsistent. The aim of this study was to explore whether the C677T and A1298C polymorphisms of MTHFR play a role in the toxicity and efficacy of methotrexate in RA. METHODS: The authors identified and evaluated studies conducted on the association between the C677T and A1298C polymorphisms of MTHFR and on the toxicity and efficacy of methotrexate in RA. A meta-analysis was then conducted to compare the toxicity and efficacy of methotrexate with respect to the 677CC and 677CT/TT genotypes and the 1298AA and 1298AC/CC genotypes. RESULTS: Eight studies, which included a total of 1514 patients with RA, were included in this meta-analysis. Meta-analysis did not show any association between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in RA in all patients or in Asian patients. The odds ratios (ORs) for adverse effects with 677CC versus 677CT/TT in all patients and in Asian patients were 0.633 (95% CI 0.325, 1.234; p = 0.180) and 0.621 (95% CI 0.233, 1.655; p = 0.341), respectively. The ORs for adverse effects with 1298AA versus 1298AC/CC in all patients and in Asian patients were 0.942 (95% CI 0.479, 1.851; p = 0.861) and 0.978 (95% CI 0.569, 1.681; p = 0.936), respectively. Heterogeneities were evident among the included studies. In addition, no association was found between the C677T and A1298C polymorphisms and the efficacy of methotrexate in RA in all patients. CONCLUSIONS: Our meta-analysis including 1514 patients with RA found no association between the C677T and A1298C polymorphisms of MTHFR and the toxicity and efficacy of methotrexate in RA. Because of the paucity of pharmacogenetic data, further studies are needed to determine the role of MTHFR polymorphisms in the toxicity and efficacy of methotrexate.
21365950 [Nodular changes in lungs in a patient with rheumatoid arthritis. Diagnostic and therapeut 2010 Rheumatoid arthritis is a systemic inflammatory disease characterized by destructive synovitis and systemic extra-articular involvement exemplified by rheumatoid nodules occurring in the skin, lungs, and other parenchymatous organs. Antirheumatic drugs like methotrexate and leflunomide are known to predispose to the development of pulmonary rheumatoid nodules. We report the case of a 60-year-old male with rheumatoid arthritis previously treated with methotrexate and cyclosporin, in whom multiple pulmonary nodules were disclosed. The patient was extensively diagnosed to exclude any malignancy. Pulmonary rheumatoid nodules were recognized, methotrexate was withdrawn, and cyclophosphamide pulses were started. The size of the nodules decreased and the patient was started on cyclosporin.