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ID PMID Title PublicationDate abstract
21360522 Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients 2011 Jun OBJECTIVE: To conduct a meta-analysis of the rates of serious infection and malignancy in patients with early rheumatoid arthritis (RA) who have started anti-tumor necrosis factor (anti-TNF) therapy and had not received treatment with disease-modifying antirheumatic drugs (DMARDs) or methotrexate (MTX). METHODS: A systematic literature search was conducted through the summer of 2009. All studies included were randomized, double-blind, placebo-controlled trials involving patients with early RA who were started on anti-TNF therapy without prior DMARD/MTX use. Six trials met the inclusion criteria for the meta-analysis, comprising a total of 2,183 patients receiving biologic therapy and 1,236 patients receiving MTX. The data extracted were from published trials. RESULTS: A pooled odds ratio (OR) (determined using Mantel-Haenszel methods, with a continuity correction designed for sparse data) was calculated for serious infections (requiring hospitalization) and malignancies, comparing anti-TNF therapy to MTX control. The pooled OR for serious infections was 1.28 (95% confidence interval [95% CI] 0.82-2.00) and that for malignancies was 1.08 (95% CI 0.50-2.32). There was no significant difference in either the rate of serious infections or the rate of malignancies between the anti-TNF therapy group and the control group. CONCLUSION: Whereas other meta-analyses have shown an increased risk of serious infection and malignancy in patients receiving anti-TNF therapy, the results of the present meta-analysis show that there is not an increased risk when the patients have early disease and have not previously been treated with DMARDs and/or MTX.
23540824 Primary care attitudes to methotrexate monitoring. 2012 BACKGROUND: Rheumatoid arthritis affects 1% of the UK population. First-line treatment is with the immunosuppressant, methotrexate (MTX). This is generally regarded as a safe and effective medication when taken at the right dose, with appropriate monitoring. Very occasionally it causes serious harm or death. In 2006, the National Patient Safety Agency issued a safety alert following increasing reports of prescribing errors and toxicity. Over the last decade, Northwick Park Hospital has seen two MTX-related deaths and other morbidity. Repeat prescriptions and monitoring are generally undertaken in primary care, although concerns have been raised about variation in local practice. Poor communication and inadequate monitoring are safety concerns. Duplication of monitoring has cost implications. Local (hospital Shared Care Guidelines (SCG) ) and national guidelines, from the British Society of Rheumatology (BSR), on MTX monitoring are freely available and accessible. METHOD: We surveyed our local GP community to better understand their practice and establish where patient care could be improved. RESULTS: We contacted 86 practices, of which 31 replied (a response rate of 36%). On average, there was one patient on MTX per 743 in the practice (0.13%), ranging from 0-0.5%. All GPs admitted they repeated MTX prescriptions, but only 77.4% monitored these. Of those who did monitor, 58.6% were aware of local guidelines and only 48.4% were aware of national guidelines. A total of 26.7% of GPs were monitoring and prescribing MTX but not aware of any guidelines. Among this number, 37.5% did not feel they needed further education. CONCLUSION: Serious safety concerns have been raised, including the poor response rate. Any doctor prescribing MTX should also be monitoring according to guidelines. Low numbers of patients on MTX per practice are surprising, possibly reflecting inadequate records or under-diagnosis. With these data, we have encouraged commissioners to fund a computer monitoring system accessible to primary and secondary care for improved patient safety, and to ultimately save costs by reducing duplication of work.
22328739 A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in pa 2012 Jul BACKGROUND: Interleukin 6 (IL-6) plays a key role in the inflammatory cascade in rheumatoid arthritis. BMS945429 is a humanised, monoclonal antibody that potently binds IL-6. OBJECTIVE: To conduct aphase II study to determine the efficacy and safety of BMS945429 in patients with active rheumatoid arthritis and an inadequate response to methotrexate. METHODS: Patients were randomised 1:1:1:1 to BMS945429 (80, 160 or 320 mg; administered intravenously) or placebo plus methotrexate during this 16-week, double-blind trial. The primary efficacy end point was the proportion of patients with a 20% improvement in American College of Rheumatology responses (ACR20) at week 12. Additional end points included ACR50 and ACR70 responses and 28-joint Disease Activity Scores (DAS28). RESULTS: Of 127 randomised and treated patients, 116 completed the trial. ACR20 responders at week 12 were 81% (80 mg; p<0.0001 vs placebo), 71% (160 mg; p=0.0005 vs placebo), 82% (320 mg; p<0.0001 vs placebo) and 27% (placebo), respectively. By week 16, 14% (80 mg), 28% (160 mg) and 44% (320 mg) of BMS945429 patients were in DAS28 remission (DAS28 score <2.6). Statistically significant and clinically meaningful improvements in health-related quality of life (HRQoL) were reported in all active treatment groups. Administration of BMS945429 was associated with increases in liver enzymes and in serum cholesterol. There were no serious infections, infusion reactions or apparent immunogenicity. CONCLUSIONS: In this phase II study, BMS945429 was associated with rapid and significant improvements in disease activity and HRQoL in patients with active rheumatoid arthritis and an inadequate response to methotrexate.
22739990 Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate 2013 Jun OBJECTIVE: To investigate the long-term effects of induction therapy with adalimumab (ADA) plus methotrexate (MTX) in comparison with placebo (PBO) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis (RA). METHODS: Patients with active early RA (disease duration of ≤12 months) were randomly assigned to receive 40 mg ADA subcutaneously every other week (eow) plus MTX 15 mg/week subcutaneously or PBO plus MTX subcutaneously at 15 mg/week over 24 weeks. Thereafter, all patients received MTX monotherapy up to week 48. The primary outcome was the Disease Activity Score 28 (DAS28) at week 48. Secondary outcomes included proportions of patients in remission (DAS28<2.6), ACR responses, Health Assessment Questionnaire (HAQ) score and radiographic progression. RESULTS: 87 patients were assigned to ADA/MTX and 85 patients to PBO/MTX. At baseline, DAS28 was 6.2±0.8 in the ADA/MTX and 6.3±0.9 in the PBO/MTX groups. At week 24, treatment with ADA/MTX compared with PBO/MTX resulted in a greater reduction in DAS28 (3.0±1.2 vs 3.6±1.4; p=0.009) and other secondary outcomes such as DAS28 remission rate (47.9% vs 29.5%; p=0.021) and HAQ (0.49±0.6 vs 0.72±0.6; p=0.0014). At week 48, the difference in clinical outcomes between groups was not statistically significant (DAS28: 3.2±1.4 vs 3.4±1.6; p=0.41). Radiographic progression at week 48 was significantly greater in patients administered PBO/MTX (Sharp/van der Heijde score: ADA/MTX 2.6 vs PBO/MTX 6.4; p=0.03, Ratingen score: 1.7 vs 4.2; p=0.01). CONCLUSIONS: A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).
21466780 [Level of evidence for therapeutic drug monitoring of low dose methotrexate in inflammator 2011 Jan Methotrexate is prescribed to low-dose, ranging from 7.5 mg to 15 mg and until 25 mg if necessary, pulse once a week, in inflammatory pathologies, in particular in rheumatoid arthritis and psoriasis. The therapeutic answer and the frequency of adverse reactions are very variable from a patient to the other one, consequences of a large interindividual variability of the pharmacokinetic parameters of methotrexate, in particular bioavailability, suggesting a genetic support. Numerous polymorphisms being involved (carriers of influx and efflux, enzymes of the metabolism and of the mechanism of action of methotrexate), their determination with the aim of an individualized prescription does not seem realistic at the moment. On the other hand, an exposure-effect relationship, not so much by considering the plasma concentrations of methotrexate, but those of its polyglutamate derivatives in red blood cells, was described. Their determination should be able to contribute to a faster adaptation of dosages, or to a well-argued change of molecule in case of non clinical response. Although other studies are necessary to specify which markers would be the most relevant, which would be the best moment for their determination and to refine the therapeutic range, this approach seems promising. But currently, the level of proof of the therapeutic drug monitoring of low dose methotrexate in inflammatory disease was classified "remaining to evaluate".
22046778 [Bone mineral density in patients with rheumatoid arthritis]. 2011 Jul Patients with rheumatoid arthritis (RA), an immune-mediated inflammatory rheumatic disease with peripheral and systemic involvement, are at increased risk of bone loss and fractures. There are many reasons for the high prevalence of osteoporosis (OP) in RA, including both traditional and specific risk factors such as pain and loss of joint function, medication (corticosteroids, methotrexate), and increased proinflammatory cytokines. AIM: To evaluate bone mineral density status in RA patients, focusing on potential relation with classical risk factors for OP. MATERIAL AND METHODS: One-year prospective observational study on 83 consecutive postmenopausal women, 43 diagnosed with RA (group I), and 40 healthy controls (group II) with no previous condition and medication known to affect bone metabolism and turnover. Bone mineral density (BMD) and T-score evaluated by dual X-ray absorbtiometry (DXA) at three standard skeletal sites (L1-L4 lumbar spine, hip and forearm) (Hologique QDR 100 device), and classical risk factors for osteoporosis were assessed in all patients according to a predefined protocol. Data were analyzed in SPSS-13 using ANOVA, t-Student, chi-square and ROC (Receiver Operator Characteristic). RESULTS: Decreased BMD was reported in the majority of RA cases, mainly in the spine and femoral neck (86%), but also in total hip (72%); moreover, osteoporosis was commonly demonstrated in lumbar spine and osteopenia at hip level. Statistically significant differences between diagnostic categories (normal, osteopenia, osteoporosis, WHO 1994) (p<0.05), while no significant differences between mean BMD levels in women with and without RA at different skeletal sites were found (t-student, p>0.05). However, considerable BMD variation (51.7% to 102.3%) was suggested in RA as compared to non-RA patients (14.3% to 27%) (ANOVA). Significant differences in mean T-score at total hip and forearm (mainly 33% radius) were noted in patients with and without RA (p<0.05). No relation between osteodensitometric parameters and classical risk factors for OP has been identified in RA, except menopause. Indirect weak statistically significant correlations were found between mean T-score and menopause duration at all skeletal levels (Pearson's rank correlation, p<0.05), except for the femoral neck (r=+0.03, p<0.05). CONCLUSIONS: Decreased BMD is commonly seen in RA patients. Several characteristics based on DXA assessment have been identified, including preference for distinct skeletal sites (spine, hip, distal forearm), and the particular intervention of menopause.
22895833 Twenty-four-week clinical results of adalimumab therapy in Japanese patients with rheumato 2013 May OBJECTIVE: We evaluated patient drug adherence to and efficacy and safety of adalimumab (ADA) based on data collected from approximately 200 patients to retrospectively examine the best use of ADA in Japanese patients with longstanding rheumatoid arthritis (RA) managed in daily practice. METHODS: For explorative comparisons, patients were stratified by prior use or no use of biologics (Bio-naïve vs. Bio-switch) and concomitant use (+) or no use (-) of methotrexate (MTX) into four subgroups. The primary efficacy endpoint was extent of improvement in the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) from baseline to 24 weeks assessed as European League Against Rheumatism (EULAR) good response. Secondary endpoints included ADA treatment continuation as represented by Kaplan-Meier survival curves and percentages of patients achieving remission as defined by DAS28-ESR <2.6. RESULTS: Overall, mean DAS28-ESR significantly decreased from 5.6 ± 1.2 at baseline to 4.1 ± 1.7 at week 24 (p < 0.0001), and >30 % of patients achieved EULAR good response. Subgroup analyses indicated that patients in the Bio-naïve and MTX (+) subgroup showed the highest EULAR good response rate of 37.3 % at week 24. The three most commonly reported adverse events (AEs) were skin allergies such as injection-site reactions, infections, and respiratory disorders such as interstitial lung lesions and organizing pneumonia. CONCLUSION: In conclusion, ADA therapy resulted in significant clinical response in established Japanese patients with RA treated in daily practice. It also demonstrated generally good safety and tolerability. It was suggested that the best use of ADA may be in biologically naïve patients with concomitant administration of MTX.
21862107 Comparative effectiveness of rituximab in combination with either methotrexate or leflunom 2011 Dec OBJECTIVE: To compare the effectiveness and safety of a combination of rituximab (RTX) with either methotrexate (MTX) or leflunomide (LEF) in the treatment of patients with active rheumatoid arthritis (RA) and inadequate response to anti-tumor necrosis factor agents or traditional disease-modifying antirheumatic drugs (DMARD) in a real-world setting. METHODS: Data from 77 consecutive unselected patients with active RA and treated with at least 1 cycle of RTX (1 g × 2 weeks) plus MTX or LEF were retrospectively collected. A comparative study between the 2 combinations of treatment (RTX+MTX and RTX+LEF) was performed at 6 months of follow-up considering 3 outcomes: the improvement of RA disease activity, the evolution of functional disability, and the tolerability and side effect profile. RESULTS: Of the 77 patients, 45 received RTX+MTX and 32 RTX+LEF. At baseline there were no significant differences between the groups in terms of the main clinical and laboratory data, or in the number of previous DMARD and anti-tumor necrosis factor agents used. At 6 months of follow-up, we did not find significant differences between the 2 combinations in the evolution of RA disease activity (DAS28 response, according to the European League Against Rheumatism (EULAR) improvement criteria) and functional disability progression (health assessment questionnaire) over time. Minor adverse events occurred in 9% of RTX+MTX patients and in 9% of RTX+LEF patients. None of the patients had serious adverse events and none discontinued the treatment during the study period. CONCLUSIONS: Our preliminary data support the view that LEF is a useful alternative if MTX is contraindicated, since its effectiveness and safety seem similar.
22389919 Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate 2012 Feb OBJECTIVE: To evaluate the safety and efficacy of ocrelizumab plus methotrexate (MTX) or leflunomide (LEF) in patients with active rheumatoid arthritis (RA) and an inadequate response to tumor necrosis factor α inhibitors. METHODS: This was a multicenter randomized, double-blind, placebo-controlled, parallel-group study that continued over 48 weeks. Patients receiving stable doses of MTX or LEF were randomized to receive 2 infusions of placebo (n = 277), ocrelizumab 200 mg (n = 278), or ocrelizumab 500 mg (n = 285) on days 1 and 15 as well as at weeks 24 and 26. Coprimary end points were the proportion of patients with response according to the American College of Rheumatology 20% improvement criteria (ACR20) at weeks 24 and 48. Secondary end points included the change from baseline in the modified Sharp/van der Heijde score (SHS) and the ACR50/70 responses. RESULTS: ACR20 responses were 22.0% in the placebo group, 42.2% in the ocrelizumab 200 mg group, and 47.9% in the ocrelizumab 500 mg group at 24 weeks and 19.5%, 48.7%, and 50.7%, respectively, at 48 weeks (P < 0.0001 versus placebo for each comparison at each time point). At 48 weeks, patients receiving both doses of ocrelizumab showed significantly improved ACR50 and ACR70 responses of ~3-fold versus placebo. Only those in the ocrelizumab 500 mg group showed statistically significant (P = 0.0017) inhibition of joint damage progression (mean change in the SHS) relative to placebo (61% inhibition) at 48 weeks. Overall adverse events and infections during the 48 weeks of study were comparable in all treatment groups. Serious infections were observed more frequently in patients taking ocrelizumab (5.1% and 4.3%) than in those taking placebo (2.5%). CONCLUSION: Patients in both of the ocrelizumab groups met the clinical primary efficacy end points. Inhibition of change in the SHS was statistically significant at 48 weeks for those in the ocrelizumab 500 mg group. The rate of serious infections in this trial was higher for both ocrelizumab doses as compared with placebo.
21277482 [Tuberculosis and pneumocystis: an unusual co-infection]. 2011 Jan INTRODUCTION: Modern immunosuppressive therapy may be responsible for toxic, immunologic and infectious pulmonary diseases. CASE REPORT: We report the case of a 58-year old woman treated for rheumatoid arthritis who received leflunomide, corticosteroids, methotrexate and adalimumab. She developed disseminated tuberculosis, which presented with neurological symptoms (brainstem) and also pneumocystis pneumonia. CONCLUSION: Modern immunosuppressive therapy used to treat inflammatory disorders in connective tissue diseases and in transplantation may induce new respiratory diseases, new patterns of known respiratory diseases or co-infections that are very seldom seen outside the context of HIV. Pulmonologists, rheumatologists, internists and intensivists should be aware of this new spectrum of diseases whose presentation may be atypical.
22028728 Polymerized-type I collagen induces upregulation of Foxp3-expressing CD4 regulatory T cell 2012 Previous studies showed that polymerized-type I collagen (polymerized collagen) exhibits potent immunoregulatory properties. This work evaluated the effect of intramuscular administration of polymerized collagen in early and established collagen-induced arthritis (CIA) in mice and analyzed changes in Th subsets following therapy. Incidence of CIA was of 100% in mice challenged with type II collagen. Clinimorphometric analysis showed a downregulation of inflammation after administration of all treatments (P < 0.05). Histological analysis showed that the CIA-mice group had extensive bone erosion, pannus and severe focal inflammatory infiltrates. In contrast, there was a remarkable reduction in the severity of arthritis in mice under polymerized collagen, methotrexate or methotrexate/polymerized collagen treatment. Polymerized Collagen but not methotrexate induced tissue joint regeneration. Polymerized Collagen and methotrexate/polymerized collagen but not methotrexate alone induces downregulation of CD4(+)/IL17A(+) T cells and upregulation of Tregs and CD4(+)/IFN-γ(+) T cells. Thus, Polymerized Collagen could be an effective therapeutic agent in early and established rheumatoid arthritis by exerting downregulation of autoimmune inflammation.
22002809 Model-based determination of abatacept exposure in support of the recommended dose for Jap 2011 Dec The objective of this study was to provide support for a body weight-tiered dosing regimen by characterizing abatacept pharmacokinetics (PK) and the relationship between exposure and the ACR20 (American College of Rheumatology criteria for 20% improvement) response in Japanese patients with rheumatoid arthritis (RA). A population PK model was developed using NONMEM with 2,535 samples from 344 Japanese RA patients in two clinical trials. The exposure-response relationship was characterized using a Generalized Estimating Equation (GEE) logistic regression model, with time-varying actual trough concentrations and ACR20 responder rates over 6 months in a randomized, placebo-controlled phase 2 trial for stable methotrexate. Abatacept exposure was well characterized using a linear, two-compartment model, in which body weight and the empirically calculated glomerular filtration rate were significant covariates for clearance. The ACR20 response model was developed by examining the quasi-likelihood information criterion, and the cumulative logit in the final model was specified by the log-transformed trough concentration. The predicted ACR20 responder rate was consistent with the actual values in the clinical trial and this model revealed trough concentrations higher than the recommended body weight-tiered dose are unlikely to result in substantial increases in clinical efficacy. Considering that ACR20 is a longitudinal binary variable and the response to RA treatment is delayed, the GEE model was useful for predicting the probability of an ACR20 response. In conclusion, the same dosing regimen as non-Japanese patients is recommended because a body weight-tiered dosing regimen achieves similar exposures across the wide range of body weight.
22833377 Concomitant iguratimod therapy in patients with active rheumatoid arthritis despite stable 2013 May OBJECTIVES: To investigate the efficacy and safety of iguratimod (T-614) in Japanese patients with active rheumatoid arthritis who had inadequate response to stable background methotrexate (MTX) alone. METHODS: In this multicenter, double-blind, controlled trial, a total of 253 patients were randomized at 2:1 ratio to either the iguratimod group or the placebo group. Iguratimod was orally administered at dosages of 25 mg/day for the first 4 weeks (25 mg once daily) and 50 mg/day for the subsequent 20 weeks (25 mg twice daily). MTX at dosage of 6 or 8 mg/week was administered to patients in both groups. RESULTS: The rate of 20 % improvement in American College of Rheumatology criteria (ACR20) at week 24 was 69.5 % in the iguratimod group compared with 30.7 % in the placebo group (P < 0.001). Significant improvements in the ACR50, ACR70, Health Assessment Questionnaire Disability Index, Disease Activity Score 28 <3.2, and rheumatoid factor were also observed. The most commonly reported adverse events (AEs) were blood iron decrease, nasopharyngitis, and lymphocyte decrease. These AEs were mild or moderate in severity. No deaths occurred. CONCLUSION: The study results suggest that iguratimod in combination with MTX was efficacious and had a manageable safety profile.
22147649 A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and 2012 Jun OBJECTIVE: CXCL10 (also known as interferon-γ-inducible 10-kd protein [IP-10]) is a chemokine that potentially plays a role in the immunopathogenesis of rheumatoid arthritis (RA). We undertook this phase II study to evaluate the efficacy and safety of MDX-1100, a fully human, anti-CXCL10 (anti-IP-10) monoclonal antibody, in RA patients whose disease responded inadequately to methotrexate (MTX). METHODS: Patients with active RA receiving stable doses of MTX (10-25 mg weekly) were randomized to receive intravenous doses of 10 mg/kg MDX-1100 (n = 35) or placebo (n = 35) every other week. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) on day 85, and patients were followed up for safety to day 141. RESULTS: The ACR20 response rate was significantly higher among MDX-1100-treated patients than among placebo-treated patients (54% versus 17%; P = 0.0024). Statistically significant differences in the ACR20 response rate between treatments were observed starting on day 43 (P < 0.05). The ACR50 and ACR70 response rates on day 85 did not differ between the groups. Overall, 51.4% of MDX-1100-treated patients and 30.3% of placebo-treated patients experienced at least 1 adverse event (AE). No study drug-related serious AEs were reported. CONCLUSION: MDX-1100 was well tolerated and demonstrated clinical efficacy in RA patients whose disease responded inadequately to MTX. This is the first study to demonstrate clinical efficacy of a chemokine inhibitor in RA and supports the notion of a potential role of IP-10 in the immunopathogenesis of RA.
22661646 Intravenous golimumab is effective in patients with active rheumatoid arthritis despite me 2013 Mar OBJECTIVES: Evaluate the efficacy of intravenous golimumab 2 mg/kg+methotrexate (MTX) in patients with active rheumatoid arthritis (RA) receiving MTX. METHODS: Patients (n=592) with active disease (≥6/66 swollen, ≥6/68 tender joints, C-reactive protein ≥1.0 mg/dl, rheumatoid factor positive and/or anticyclic citrullinated protein antibody positive at screening) despite MTX (15-25 mg/week) participated in this double-blind, placebo-controlled, phase 3 study. Patients were randomised (2:1) to receive intravenous golimumab 2 mg/kg, or placebo infusions at weeks 0 and 4 and every (q) 8 weeks; patients continued MTX. Placebo patients with <10% improvement in combined swollen/tender joint counts at week 16 could early escape to intravenous golimumab 2 mg/kg. The primary endpoint was week 14 American College of Rheumatology 20% (ACR20) response. Analyses employed non-responder imputation and last-observation-carried-forward. RESULTS: At week 14, significantly (p<0.001) larger proportions of golimumab+MTX than placebo+MTX patients achieved ACR20 response (59% vs 25%, respectively), a disease activity score of good/moderate (EULAR) response (81% vs 40%), and greater median improvement in health assessment questionnaire scores (0.500 vs 0.125). Improvements versus placebo+MTX were observed by week 2. Similar proportions of patients receiving golimumab+MTX and placebo+MTX, respectively, reported adverse events through week 16 (47% and 44%) and week 24 (53% and 49%). Serious adverse events were reported by more golimumab+MTX (4.1%) than placebo+MTX (2%) patients at week 24. CONCLUSION: The addition of intravenous golimumab rapidly and significantly improved signs and symptoms in patients with active RA despite ongoing MTX, in some patients by week 2.
21933041 Clinicopathological analyses in patients with other iatrogenic immunodeficiency-associated 2012 Apr Despite numerous attempts to uncover the mechanism of other iatrogenic immunodeficiency-associated lymphoproliferative diseases (OIIA-LPDs), this mechanism remains poorly understood, especially in rheumatoid arthritis (RA) patients. We analyzed the data on 23 patients with LPDs and RA. Patients were categorized into three groups according to whether they had methotrexate (MTX); MTX-regressive LPDs, MTX-persistent LPDs or other drugs-mediated LPDs. The LPDs seen in OIIA-LPDs-RA might have a unique behavior to think about several rare phenotypes. The overall survival of all patients was 74% at 5 years, and those of the three groups were 100%, 64% and 60%, respectively. Among the 6 patients who died, 4 had LPDs that were detected late, and thus adequate treatment was not given. In addition, several patients with diffuse large B cell lymphoma with a complex karyotype achieved complete remission (CR). Only one among the 17 patients who achieved CR relapsed. OIIA-LPDs-RA appeared to have a better prognosis than other more common types of lymphomas. Regarding RA treatment, various anti-RA drugs were given to the patients after developing LPDs, including MTX, but no recurrent patients were documented.
20937671 Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate 2011 Jan OBJECTIVES: Rituximab is an effective treatment in patients with established rheumatoid arthritis (RA). The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate (MTX) in patients initiating treatment with MTX. METHODS: In this double-blind randomised controlled phase III study, 755 MTX-naïve patients with active RA were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX. The primary end point at week 52 was the change in joint damage measured using a Genant-modified Sharp score. RESULTS: 249, 249 and 250 patients were randomly assigned to MTX alone, rituximab 2×500 mg + MTX or rituximab 2×1000 mg + MTX, respectively. At week 52, treatment with rituximab 2×1000 mg + MTX compared with MTX alone was associated with a reduction in progression of joint damage (mean change in total modified Sharp score 0.359 vs 1.079; p=0.0004) and an improvement in clinical outcomes (ACR50 65% vs 42%; p<0.0001); rituximab 2×500 mg + MTX improved clinical outcomes (ACR50 59% vs 42%; p<0.0001) compared with MTX alone but did not significantly reduce the progression of joint damage. Safety outcomes were similar between treatment groups. CONCLUSIONS: Treatment with rituximab 2×1000 mg in combination with MTX is an effective therapy for the treatment of patients with MTX-naïve RA. ClinicalTrials.gov identifier NCT00299104.
21473812 Bridging the gap between aggregate data and individual patient management: a Bayesian appr 2011 Apr OBJECTIVES: The aim of this study was to explore whether Bayesian reasoning can be applied to therapeutic questions in a way that is similar to its application in diagnostics. METHODS: A clinically relevant, therapeutic question was formulated in accordance with Bayesian reasoning for the clinical management of patients with newly diagnosed rheumatoid arthritis (RA). Prior probability estimates of response to drug treatment (methotrexate, MTX) were obtained from the literature. As a marker of treatment response, changes in the Health Assessment Questionnaire (HAQ) scores were assessed after three months of treatment. Likelihood ratios for this marker were calculated on the basis of data from a clinical registry, using changes in the Disease Activity Score (DAS) as gold standard. Using Bayes' theorem, prior probability and likelihood ratios were combined to estimate posterior probabilities of treatment response in individual patients. RESULTS: On the basis of the literature, the prior probability of response of RA patients to MTX was estimated 45 percent. At 3 months follow-up, this probability increased to 80 percent or decreased to 23 percent, depending on the changes that were observed in Health Assessment Questionnaire scores. CONCLUSIONS: Bayesian reasoning can be applied to therapeutic issues in a way that is conceptually fully compatible with its use in diagnostics. As such, it can be used to bridge the gap between aggregate data and individual patient management.
21773713 Single-center, retrospective analysis of efficacy and safety of tacrolimus as a second-lin 2012 Feb To retrospectively evaluate the efficacy and safety of combination therapy with tacrolimus (TAC) and other disease-modifying antirheumatic drugs (DMARDs). One hundred fifteen rheumatoid arthritis (RA) patients treated with tacrolimus were enrolled in this retrospective analysis. We collected clinical information, including patient background, treatment efficacy (evaluated using the DAS score), and adverse events observed. Multiple logistic regression analysis was conducted to analyze factors contributing to clinical response and adverse effects. The disease activity score of 28 joints (DAS28) improved significantly at 24 weeks, and continuation rate at 1 year was 57.9%. There was no difference in continuation rate between different DMARD combinations, and not only methotrexate (MTX) but also bucillamine (BUC) and salazosulfapyridine (SSZ) were effective combination partners with TAC. No serious adverse events were observed, and no different inefficacy or safety was observed between non-elderly (<65 years old) and elderly (≥65 years old) RA patients. By conducting multiple logistic regression analysis, combination therapy with MTX and TAC, the number of baseline DMARDs (specifically, ≥3), and old age were identified as risk factors for adverse events. Our findings indicate that TAC is a valuable DMARD for second-line combination therapy in RA.
22660798 Relations of serum COMP to cardiovascular risk factors and endothelial function in patient 2012 Jul OBJECTIVE: To examine whether serum level of cartilage oligomeric matrix protein (S-COMP) is related to methotrexate (MTX) or to MTX and tumor necrosis factor-α (TNF-α) combination treatment for rheumatoid arthritis (RA); and to investigate whether S-COMP is related to cardiovascular risk factors including endothelial dysfunction and level of anticitrullinated protein antibodies (ACPA) in patients with RA. METHODS: Clinical and laboratory measures, including S-COMP and reactive hyperemic index (RHI), were examined in 55 consecutive patients with RA starting with either MTX (n = 34) or MTX and anti-TNF-α treatment (n = 21) at baseline, and after 6 weeks and 6 months. RESULTS: S-COMP was similar in the 2 treatment regimens during followup. We found a positive relationship between S-COMP at baseline and the use of disease-modifying antirheumatic drugs the last year preceding the study (p = 0.001), and a negative relation to current use of systemic glucocorticosteroids (p = 0.044). The nonsignificant change in S-COMP between baseline and the 6-month followup was positively and independently related to change in ACPA level (p = 0.009). There was no significant association between RHI and level of S-COMP at baseline. CONCLUSION: The cartilage turnover marker S-COMP did not change significantly after 6 months' treatment with MTX with or without a TNF-α inhibitor in patients with RA. The positive association between S-COMP and ACPA suggests that these factors might interact, and could both be contributors to an unknown link between inflammation and cartilage destruction in patients with RA. S-COMP was not related to endothelial function in patients with RA, or to other cardiovascular risk factors studied. Clinical Trials registration number NCT00902005.