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ID PMID Title PublicationDate abstract
23176063 Impact of a multi-biomarker disease activity test on rheumatoid arthritis treatment decisi 2013 Jan OBJECTIVE: To assess how use of a multi-biomarker disease activity (MBDA) blood test for rheumatoid arthritis (RA) affects treatment decisions made by health care providers (HCPs) in clinical practice. RESEARCH DESIGN AND METHODS: At routine office visits, 101 patients with RA were assessed by their HCPs (N = 6), and they provided blood samples for MBDA testing. HCPs completed surveys before and after viewing the MBDA test result, recording dosage and frequency for all planned RA medications and physician global assessment of disease activity. Frequency and types of change in treatment plan that resulted from viewing the MBDA test result were determined. MAIN OUTCOME MEASURE: Percentage of cases in which the HCP changed the planned treatment after viewing the MBDA test result. RESULTS: Prior to HCP review of the MBDA test, disease modifying anti-rheumatic drug (DMARD) use by the 101 patients included methotrexate in 62% of patients; hydroxychloroquine 29%; TNF inhibitor 42%; non-TNF inhibitor biologic agent 19%; and other drugs at lower frequencies. Review of MBDA test results changed HCP treatment decisions in 38 cases (38%), of which 18 involved starting, discontinuing or switching a biologic or non-biologic DMARD. Other changes involved drug dosage, frequency or route of administration. The total frequency of use of the major classes of drug therapy changed by <5%. Treatment plans changed 63% of the time when the MBDA test result was perceived as being not consistent or somewhat consistent with the HCP assessment of disease activity. STUDY LIMITATIONS: Limited sample size; lack of control group; no longitudinal follow-up. CONCLUSIONS: The addition of the MBDA test to clinical assessment led to meaningful changes in the treatment plans of 38% of RA patients being cared for by HCPs in office practice. Even though treatment was potentially improved, the overall quantity of drug use was minimally affected.
21859684 National EQ-5D tariffs and quality-adjusted life-year estimation: comparison of UK, US and 2011 Dec OBJECTIVE: To study how the choice of national EQ-5D tariff may affect utility and incremental quality-adjusted life-year (QALY) estimates. METHODS: South Swedish rheumatoid arthritis patients in an observational study, starting and continuing anti-tumour necrosis factor (TNF) monotherapy (n=54) or anti-TNF plus methotrexate (n=215) for 1 year during May 2002 to April 2009, were included. EQ-5D questionnaires were completed at baseline, 3, 6 and 12 months. Utilities and accumulated QALY were compared using the UK, US and Danish EQ-5D tariffs. Utilities for all 243 possible EQ-5D health states were also compared. RESULTS: US utilities were generally higher than UK, with Danish falling in between. A substantial 1-year mean utility improvement was seen in both study groups using all tariffs (UK 0.28 vs 0.29; US 0.18 vs 0.19; Danish 0.20 vs 0.22). Adjusting for baseline differences between groups, the incremental QALY gain of combined treatment was 0.09 using the UK tariff, while 0.06 according to both US and Danish tariffs. Inter-tariff disagreement in utility and accumulated QALY varied irregularly across the range of utilities. CONCLUSIONS: Applying different national EQ-5D tariffs to the same data may result in substantially different incremental QALY estimates, crucial knowledge when interpreting cost-utility analyses. Studies using different tariffs cannot be directly compared.
21499875 Pulmonary function test: its correlation with pulmonary high-resolution computed tomograph 2012 Jul Our objective was to try to evaluate lung affection and to correlate an easier and cheaper method with the high-resolution computed tomography (HRCT) findings in patients with RA. Thirty-six RA patients were selected for HRCT lung scan (twelve patients with altered pulmonary function test (PFT) and 24 with normal PFT). The American Thoracic Society criteria were followed for the pulmonary test. Clinical and laboratory variables were recorded. A statistical analysis was done by Kaplan-Meyer survival curve and ROC curve. When HRCT was evaluated in all patients, only sixteen had an HRCT normal and twenty patients showed some radiologic alteration under HRCT such as: pleural thickness, bronchiectasis, interstitial pattern, micro-nodules pattern, ground-glass opacity, and a reticular pattern. A logistic regression showed that methotrexate use, evolution of the disease (beta 0.018), and FEV1 (beta 0.89) were statistically associated with HRCT alterations. A projection of patients, free from event (HRCT lung scan altered), was obtained through a Kaplan-Meyer analysis, using FEV1 as a predictor over time. The curve shows that in the next 240 months (20 years) nearly 40% of the patients with rheumatoid arthritis will have FEV1 values less than 80% of the normal values predicted for the same age and sex. The FEV1 values have demonstrated a good correlation between PFT and HRCT lung scan. Therefore, they provide an accessible tool for tracking early pulmonary alterations. Methotrexate use and time evolution of the disease have been associated with altered FEV1.
22562973 Clinical, functional and radiographic consequences of achieving stable low disease activit 2013 Jan OBJECTIVE: To assess the efficacy and safety of adalimumab plus methotrexate (ADA+MTX) compared with methotrexate monotherapy in achieving stable low disease activity (LDA; disease activity score (DAS28(CRP)) <3.2 at weeks 22 and 26) and clinical, radiographic and functional outcomes in methotrexate-naive patients with early rheumatoid arthritis (RA). METHODS: 1032 patients with active RA were randomly assigned 1:1 to ADA+MTX or placebo plus methotrexate (PBO+MTX) for 26 weeks. Treatment modifications were to be made in a subsequent study period based on the achievement of DAS28(CRP) <3.2 at weeks 22 and 26. Post-hoc analyses compared patients achieving stable remission using DAS28 and 2010 ACR/EULAR criteria with those achieving LDA but not remission. RESULTS: Among patients completing 6 months, 44% (207/466) ADA+MTX versus 24% (112/460) PBO+MTX patients achieved stable LDA at weeks 22 and 26 (p<0.001). Combination therapy was statistically superior to methotrexate in obtaining higher ACR20/50/70 responses, more clinical remissions, greater mean reductions in DAS28(CRP), no radiographic progression, and normal functional status at week 26 (p<0.001 for all). The only factor predicting stable LDA was disease activity at week 12. Patients achieving ACR/EULAR remission, particularly in the PBO+MTX group, had some advantage in radiographic outcomes compared with patients who only achieved LDA (but not remission). The overall frequency of adverse events was comparable between groups. There were more serious infections and deaths in the ADA+MTX group, with a possible age effect. CONCLUSIONS: Treatment with ADA+MTX was significantly superior to methotrexate alone with respect to clinical, radiographic and functional outcomes in patients with early active RA. Before initiating treatment with adalimumab, individual patient evaluation of the benefit/risk ratio should be carefully considered.
22826971 [Possible association of gynecological cancer and rheumatoid arthritis]. 2012 Jun BACKGROUND: The association between rheumatoid arthritis and cancer is controversial. Previous studies have shown a correlation between rheumatoid arthritis and the development of lymphoma. OBJECTIVE: Describe a case of rheumatoid arthritis and associated breast cancer plus the identification of the clinical features of a set of cases in which arthritis and cancer go along. MATERIAL AND METHOD: This is a retrospective clinical series study. A database of Hospital General ISSSTECALI of Mexicali, Mexico, containing information on patients suffering from both rheumatoid arthritis and cancer until 2012 was checked. The medical files confirmed the diagnoses. The data available included age, date of arthritis diagnosis, date of cancer diagnosis, related conditions, results of serological tests, type of cancer, treatments used and follow-up information. RESULTS: Fifteen cases of women suffering from both rheumatoid arthritis and cancer were identified on the database of the Hospital General ISSSTECALI in Mexicali. The case described here is the number four on that list. The average age was 54 years and the average time between arthritis and cancer diagnoses was four years. Ten patients were administered methotrexate. Nine patients (60%) suffered from breast cancer and six more from cervical cancer. Three patients suffered from cervical dysplasia. CONCLUSIONS: These cases emphasize the need of strict follow-up on patients suffering from inflammatory rheumatoid condition. If cancer follows chronic inflammation, immunosuppression, or it is pure coincidence, is still a matter of debate.
22986992 Patients' access to biologics in rheumatoid arthritis: a comparison between Portugal and o 2013 Dec BACKGROUND: Despite the widespread availability of biologics across Europe, rheumatoid arthritis (RA) patients' access to these drugs differs significantly among countries. OBJECTIVES: To compare the proportion of RA patients treated with biologics across Europe and investigate the factors that most influence it, with focus on the Portuguese case, reportedly with low access rates to biologics. METHODS: The biologics' market was characterized for 15 selected European countries. Variables potentially influencing patients' access to biologics (PAB) in RA were also collected, including demographic, disease, economic, funding and biologics' market-related data. A multivariable regression model identified the factors that best explain PAB. Based on these determinants, a cluster analysis was performed to group the countries with most similar behaviour regarding PAB allowing the evaluation of Portugal's relative position among these countries. RESULTS: The regression model (R(2) = 0.953) indicated that PAB in selected countries is explained mostly by its gross domestic product (GDP) per capita, the usage of methotrexate (MTX) and the biologics' distribution channel. Current MTX usage in Portugal shows similarity with practice from UK, France, Germany or Spain 5 years before, explaining why PAB in Portugal stood at 7% in 2010, 12 percentage points below the average of selected countries. CONCLUSIONS: Variations in RA PAB were found across selected countries with Portugal showing the lowest proportion. GDP per capita, biologics distribution channel and consumption of MTX appear to be the best explanatory factors for these fluctuations in European countries.
23027887 Multiple courses of rituximab produce sustained clinical and radiographic efficacy and saf 2012 Dec OBJECTIVE: This 5-year observational posthoc analysis of the REFLEX study and its open-label extension assessed clinical efficacy, radiographic response, and safety of rituximab (RTX) in patients with rheumatoid arthritis (RA) who had an inadequate response to tumor necrosis factor (TNF) inhibitors. METHODS: Patients in REFLEX were originally randomized to placebo (PBO) + methotrexate (MTX; PBO-randomized) or RTX + MTX (RTX-randomized). PBO-randomized patients were rescued with RTX as appropriate. Patients responding to initial RTX treatment could receive further RTX courses. For clinical efficacy and safety analyses, PBO-randomized patients were re-baselined prior to first RTX treatment and the data were pooled with RTX-randomized patient data. Efficacy outcomes 24 weeks after each course were calculated relative to first RTX pretreatment baseline. Radiographic outcomes were assessed relative to randomization baseline for both PBO-randomized and RTX-randomized groups. RESULTS: A total of 480 patients received ≥ 1 RTX course. At 24 weeks, American College of Rheumatology 20/50/70 responses were 62.0%, 30.8%, and 13.0%, respectively at course 1 (n = 400) and 70.3%, 41.8%, and 22.0% at course 5 (n = 91). European League Against Rheumatism good/moderate responses were 77.2% and 84.4% at courses 1 (n = 390) and 5 (n = 90). Rates of adverse events (AE), serious AE, and infections generally remained stable. Rate of progressive joint damage (PJD; change in mean Total Sharp Score) decreased over time in both PBO-randomized (n = 79) and RTX-randomized (n = 105) groups. Mean change from baseline in PJD over 5 years was greater in PBO-randomized versus RTX-randomized patients (5.51 vs 3.21). CONCLUSION: RTX re-treatment over 5 years is associated with maintained or improved efficacy, continued inhibition of PJD, and a safety profile consistent with that previously reported. A delay in initiating RTX treatment may result in increased PJD.
21965646 Safety and effectiveness of rituximab in patients with rheumatoid arthritis following an i 2011 Dec OBJECTIVE: To evaluate the safety and effectiveness of rituximab (RTX) in combination with methotrexate in patients with active rheumatoid arthritis (RA) after failure of a single tumor necrosis factor-α (TNF-α) inhibitor. Changes in patient-reported outcomes after primary treatment or retreatment with RTX and factors determining retreatment in clinical practice were also evaluated. METHODS: In this phase 3b open-label, multicenter trial, patients received 2 slow infusions of RTX 1000 mg 14 days apart after premedication (primary treatment). Patients with a clinically relevant response could receive retreatment between 24 and 48 weeks. The primary endpoint was evaluation of safety. Secondary outcomes were safety of retreatment, effectiveness of primary treatment and retreatment, and changes in patient-reported outcomes after primary treatment or retreatment. RESULTS: Of 120 patients enrolled at 36 centers and receiving primary RTX treatment, 77 received retreatment, 112 completed the 24-week primary treatment period, and 25 completed the 48-week primary treatment and retreatment period following a single course of RTX. The most common adverse events were mild to moderate nausea, vomiting, nasopharyngitis, and headache. No infections or infusion reactions were considered life-threatening. At 24 weeks, 58%, 27%, and 7% of patients achieved American College of Rheumatology 20, 50, and 70 improvements, respectively, and similar improvements were seen after retreatment. CONCLUSION: RTX was well tolerated, with a low incidence of infusion reactions and infections. Efficacy results, including enhanced response in rheumatoid factor-positive patients, were comparable to those reported in the literature. Based on its efficacy and safety profile and retreatment schedule, RTX is an attractive treatment option for patients that have not responded to a single TNF-α inhibitor.
23072741 Treat-to-target: not as simple as it appears. 2012 Jul Treat-to-target as a strategy for rheumatoid arthritis (RA) is now widely advocated based on strong evidence. Nonetheless, implementation of treat-to-target raises caveats, as is the case with all clinical care strategies. The target of remission or even low disease activity does not apply to all individual patients, some of whom are affected by concomitant fibromyalgia, other comorbidities, joint damage, and/or who simply prefer to maintain current status and avoid risks of more aggressive therapies. No single universal 'target' measure or index exists for all individual RA patients. An emphasis in most studies on radiographic progression, rather than physical function or mortality, as the most important outcome to document the value of treat-to-target may be inappropriate. Many reports imply that the only limitation to treating all RA patients with biological agents involves costs, ignoring effective results in most patients with methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs) and adverse events associated with biological agents. Indeed, the best outcomes in reported RA clinical trials result from tight control with DMARDs, rather than from biological agents, as does better overall status of RA patients at this time compared to previous decades. Pharmacoeconomic reports may ignore that RA patients are older, less educated, and have more comorbidities than the general population, as well as critical differences in patient status according to the gross domestic product of different countries. While treating to a target of remission or low disease activity, including with biological agents, is appropriate for many patients, awareness of these concerns could improve implementation of treat-to-target for optimal care of all RA patients.
21953645 Prescribing practices in a US cohort of rheumatoid arthritis patients before and after pub 2012 Mar OBJECTIVE: To examine prescribing practices in the use of biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs) to treat patients with rheumatoid arthritis (RA), before and after publication of the American College of Rheumatology (ACR) treatment recommendations. METHODS: Biologics-naive RA patients under the care of a rheumatologist in the US were identified from the Consortium of Rheumatology Researchers of North America registry. Patients were included if their visits occurred prior to and/or at least 6 months after publication of the ACR treatment recommendations (time periods of February 2002-June 2008 versus December 2008-December 2009). The population was divided into 2 mutually exclusive cohorts: 1) methotrexate (MTX) monotherapy users, and 2) multiple nonbiologic DMARD users. Initiation or dose escalation of biologic and nonbiologic DMARDs in response to active disease was assessed cross-sectionally and longitudinally in comparison to the ACR recommendations. The impact of the publication of the ACR recommendations on treatment practices was assessed using logistic regression, stratified by disease activity and adjusted for clustering of physicians and geographic region. RESULTS: After 1 visit, 24-37% of patients receiving MTX monotherapy who had moderate disease activity and a poor prognosis or high disease activity received care consistent with the ACR recommendations; after 2 visits, 34-56% of the MTX monotherapy group received care consistent with the recommendations. In the patients receiving multiple nonbiologic DMARDs, 31-47% of those with moderate or high disease activity received care consistent with the recommendations after 1 visit, and 43-51% received such care after 2 visits. Publication of the recommendations did not significantly change treatment patterns for those with active disease. CONCLUSION: Substantial numbers of RA patients with active disease did not receive care consistent with the current ACR treatment recommendations. Innovative approaches to improve care are necessary.
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.
21780650 [Methotrexate-induced changes in the concentration of antibodies to mutaded citrullinated 2011 AIM: To study effects of methotrexate on the titer of antibodies to mutated citrullinated vimentin (anti-MCV) and ascertain possibility of using this marker for control of treatment results and choice of individual effective dose of the drug. MATERIAL AND METHODS: A 12-month trial included 76 patients with verified rheumatoid arthritis (RA). Methotrexate per os was given in a dose 7.5-10 mg/week to 44 (57.9%) patients, 25 patients received no basic therapy. Anti-MCV (IU/ml) were detected with commercial chemicals made in Germany (ORGENTEC). RESULTS: RA patients given methotrexate doses 7.5 and 10 mg/week and untreated with basic anti-inflammatory drugs showed no significant differences by basic clinical and device parameters, level of anti-MCV at primary examination and 12 months later. CONCLUSION: Anti-MCV titer cannot be used for control of efficacy of methotrexate treatment in doses 75 and 10 mg/week, choice of individual effective doses.
21607552 Current smoking status is associated to a non-ACR 50 response in early rheumatoid arthriti 2011 Dec The purpose of this study is to determine factors associated with a non-ACR 50 response at 6 months of follow-up, in a cohort of patients with early rheumatoid arthritis (RA). Early RA patients (symptom duration <1 year), treated with the same combination treatment (methotrexate and sulfasalazine), were included. Demographic characteristics of the patients including current smoker status (defined as a patient that smokes at least one cigarette per day), years of formal education, a 28-joint count for swelling and tenderness were registered. A basal HAQ questionnaire, visual scales for global assessment, and pain were answered by all patients, and a CDAI basal score was calculated. The ACR 50 response was determined at 6 months follow-up. Multivariable logistic regression analysis was used to calculate adjusted ORs. Two hundred twenty-five patients were evaluated, but only 144 had a complete follow-up, 43% of the latter did not reach an ACR 50 response. The only factor associated with this outcome was current smoking (OR 3.58, P < 0.008, 95% CI 1.23-11.22). Low level of formal education (≤6 years) had a tendency towards a statistical difference (P < 0.08). After controlling with low level of formal education, sex, age in years, and CDAI baseline value with multivariable logistic regression analysis, current smoking status had an adjusted OR of 3.91 (P < 0.009, 95% CI 1.41-10.81). Smoking is associated with a non-ACR 50 response in early rheumatoid arthritis in patients treated with a combination therapy with methotrexate and sulfasalazine.
21965639 Effects of changing from oral to subcutaneous methotrexate on red blood cell methotrexate 2011 Dec OBJECTIVE: To determine the effects of changing from oral to subcutaneous (SC) methotrexate (MTX) in patients with rheumatoid arthritis (RA) on red blood cell MTX polyglutamate (RBC MTXGlu(n)) concentrations, disease activity, and adverse effects. METHODS: Thirty patients were changed from oral to SC MTX. Trough RBC MTXGlu(n) concentrations were measured for 24 weeks and concentrations fitted to a first-order accumulation model. Disease activity was assessed by 28-joint Disease Activity Score (DAS28). RESULTS: MTXGlu(3), MTXGlu(4), and MTXGlu(5) concentrations, but not MTXGlu(1) and MTXGlu(2), increased significantly over 24 weeks, reaching 90% of new steady-state concentrations by about 40 weeks. A decrease in DAS28 was associated with increased RBC MTXGlu(5) (p = 0.035) and RBC MTXGlu(3-5) (p = 0.032). No change in adverse effect frequency occurred. CONCLUSION: Changing to SC MTX results in increased long-chain MTXGlu(n). However, it takes at least 6 months for RBC steady-state concentrations to be achieved. Increased long-chain MTXGlu(n) concentrations were significantly associated with reduced disease activity.
22971639 A single nucleotide polymorphism of reduced folate carrier 1 predicts methotrexate efficac 2013   Methotrexate (MTX) exhibits large inter-individual and inter-ethnic differences in the dose required for its anti-rheumatic effect. To maintain low disease activity, patients may require increased MTX doses or co-administration of biologic disease-modifying anti-rheumatic drugs (bDMARDs). The availability of a marker predicting the effect of MTX will make it possible to increase the MTX dose and prescribe bDMARDs to patients at an early stage. To establish individualized medication for rheumatoid arthritis (RA), we investigated genetic polymorphisms of the folate pathway in Japanese RA patients. Eighty-nine patients were treated with MTX alone (MTX group). MTX and bDMARDs were co-administered to 81 patients because of insufficient MTX efficacy (MTX + bDMARDs group); an equally stable therapeutic effect was achieved in both groups. Polymorphism analyses using bDMARD co-treatment as the objective variable revealed a significant association between age and the G80A polymorphism of the reduced folate carrier 1 gene (RFC1) as an explanatory variable. Compared to patients with the A allele, patients with the G allele may have less intracellular MTX uptake and, therefore, poor efficacy; a greater number of them were found to be bDMARD concomitant cases. The results of this study suggest that the RFC1 G80A polymorphism may be a useful marker for predicting MTX efficacy in Japanese patients with RA.
21953215 Joint damage in rheumatoid arthritis progresses in remission according to the Disease Acti 2011 Dec OBJECTIVE: Remission has been defined as the ultimate target for patients with rheumatoid arthritis. The Disease Activity Score in 28 joints (DAS28) has been criticized for the amount of disease activity that remains in patients despite their achieving DAS28 remission. This study was undertaken to investigate the significance of residual inflammation in remission in relation to radiographic progression. METHODS: We pooled 1-year clinical data, kindly provided by the respective sponsors, on 864 patients in methotrexate monotherapy arms of recent pivotal trials. We identified patients who had attained persistent DAS28 remission from month 6 through month 12 (a DAS28(6-12) of <2.6). Among these patients we then assessed radiographic progression in total Sharp/van der Heijde scores (SHS) from baseline to 12 months between those with residual joint swelling (defined as a swollen joint count from month 6 through month 12 [SJC(6-12) ] of ≥2) and those without residual joint swelling (defined as an SJC(6-12) of <2). RESULTS: One hundred fourteen patients (13.2%) achieved a DAS28(6-12) of <2.6, of whom those without residual joint swelling (n = 92, 80.7%) had less radiographic progression over 1 year than those with residual joint swelling (n = 22, 19.3%) (mean ± SD SHS progression 0.2 ± 2.6 versus 2.2 ± 4.2; P = 0.11). Likewise, the proportion of patients with a total SHS progression of >0.5/year was significantly lower among those without joint swelling than among those with joint swelling (27.2% versus 50.0%; P = 0.039). DAS28 remitters without joint swelling showed progression comparable to that in the total group of remitters by the Simplified Disease Activity Index (remission defined as ≤3.3) and Clinical Disease Activity Index (remission defined as ≤2.8), namely, 0.2 versus -0.07 versus 0.16, respectively (P = 0.66). CONCLUSION: Radiographic progression with nonbiologic treatment is minimal only when patients in DAS28 remission have no persistent residual joint swelling. Under these conditions, progression is comparable to that in patients with disease in remission according to other disease activity indices.
21930734 In early rheumatoid arthritis, patients with a good initial response to methotrexate have 2012 Feb OBJECTIVE: To investigate the 2-year clinical and radiological outcomes of patients with early rheumatoid arthritis (RA; symptom duration <1 year) who had initially responded well to methotrexate monotherapy. METHODS: In the SWEFOT trial, all 487 patients started methotrexate (target dose 20 mg/week). After 3-4 months, 147 had low disease activity, 28-joint based disease activity score (DAS28) ≤3.2. These patients were not randomly selected but were followed in regular care for 2 years. Clinical outcomes and radiographic progression according to the van der Heijde modified Sharp (SvdH) score were analysed. RESULTS: The majority of the 147 patients continued on methotrexate monotherapy. After 1 and 2 years, DAS28 remission was achieved in 59.6% and 71.8% and mean observed DAS28 values were 2.53 and 2.25, respectively. Despite the favourable clinical course, a proportion of the patients progressed radiographically with a mean (SD) increase in the SvdH score after 2 years of 3.90 (6.84). There was no significant difference in progression between patients in DAS28 remission versus not in remission (p=0.73). At baseline, approximately half the patients had no radiographic damage, while after 2 years the proportion was approximately 20%. CONCLUSION: Most early RA patients who achieve low disease activity after 3-4 months of methotrexate monotherapy continue to have low disease activity during 2 years follow-up, and additional treatment is needed infrequently. Some radiological progression occurs in most patients, and may be marked or severe in some, even despite sustained DAS28 remission. Close monitoring for radiological progression is thus warranted.
22916341 Tofacitinib for the treatment of moderate to severe rheumatoid arthritis. 2012 Aug The autoimmune disease rheumatoid arthritis (RA) causes severe disability through chronic and destructive inflammation of the synovial joints. Currently available therapeutic options, including disease-modifying antirheumatic drugs (DMARDs) and biologic agents, often fail to adequately prevent disease progression. Tofacitinib (CP-690550) is an inhibitor of the Janus kinase family; tyrosine kinase receptors expressed in lymphoid cells that are involved in the signaling of cytokines important for the production and function of various immune cells implicated in RA pathogenesis. Tofacitinib has been evaluated in phase II, phase III and long-term extension studies, as both monotherapy and in combination with methotrexate and other DMARDs, and demonstrates statistically significant and clinically meaningful improvements in the signs and symptoms of RA, patient health, physical functioning and quality of life, while having a manageable safety profile. It is currently under evaluation for approval for the treatment of adults with RA by several regulatory agencies around the world.
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.
22984272 Infliximab is associated with improvement in arterial stiffness in patients with early rhe 2012 Dec OBJECTIVE: To determine the efficacy of methotrexate (MTX) with infliximab (IFX) compared with MTX alone in the prevention of atherosclerosis and arterial stiffness in patients with early rheumatoid arthritis (RA). METHODS: A randomized, open-label study in which early RA patients with active disease were treated with MTX alone (n = 20) and MTX plus IFX (n = 20) for 6 months. Patients were assessed every 3 months. Patients from the MTX-alone group who failed to achieve 28-joint Disease Activity Score remission (DAS28 ≤ 2.6) at 6 months were permitted to escape to open-label IFX. Intima-media thickness (IMT), pulse wave velocity (PWV), and augmentation index (AIx) were measured at baseline, 6 months, and 12 months. RESULTS: At 6 months, there was a significantly greater reduction in PWV in the MTX-alone group (0.18 ± 1.59 m/s) compared with the MTX plus IFX group (-0.78 ± 1.13 m/s; p = 0.044), accompanied by significantly greater reduction in patient's global assessment, number of swollen joints, C-reactive protein, and DAS28 in the MTX plus IFX group compared to the MTX-alone group. The changes in IMT and AIx were similar between the 2 groups. At 12 months, there was a trend favoring early combination treatment with regard to the reduction in PWV (p = 0.06). CONCLUSION: MTX plus IFX causes a more significant reduction in PWV than MTX alone in patients with early RA after 6-month treatment, and further improvement may be achieved in patients who continued on longterm tumor necrosis factor-α blockers, suggesting that early, effective suppression of inflammation may prevent progression of atherosclerosis by improving vascular function.