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ID PMID Title PublicationDate abstract
24394142 [A case of iatrogenic immunodeficiency-associated lymphoproliferative disease in a patient 2013 Nov We report our experience with a case of iatrogenic immunodeficiency-associated lymphoproliferative disease in a patient who had been treated with methotrexate (MTX) for rheumatoid arthritis for 9 consecutive years, which showed natural remission after discontinuation of the MTX therapy. The patient was a 64-year-old woman who was admitted emergently to our hospital with hematemesis and melena. She presented with multiple gastric ulcers and bilateral tonsillitis with a central ulcer. Biopsy of these lesions raised the suspicion of diffuse large B-cell lymphoma. Positron emission tomography (PET)- computed tomography( CT) showed increased fluorodeoxyglucose( FDG) accumulation in the pharynx, cervical lymph nodes, liver, spleen, stomach, distal part of the ileum, and para-aortic lymph nodes, with a maximum standard uptake value of 26.85. Blood test showed elevated lactate dehydrogenase( LDH)( 321 U/L) and interleukin( IL)-2R( 3,531 U/mL) levels. After discontinuation of MTX, the sore throat subsided, and the tonsillitis, lymph node enlargement, and ulcers were resolved. The levels of LDH and IL-2R returned to within the normal range. The patient could be categorized into a regressive disease group with relatively favorable prognosis among patients with MTX-induced lymphoproliferative disease. However, she should continue to be followed up regularly because there remains a possibility that lymphoproliferative disease may relapse after the discontinuation of MTX.
24261756 Estimates of the prevalence of and current treatment practices for rheumatoid arthritis in 2014 Jan OBJECTIVES: The prevalence of rheumatoid arthritis (RA) and its current treatment practices in Japan are poorly documented. Therefore, we examined these factors in a Japanese health insurance database. METHODS: We analyzed reimbursement data provided by health insurance societies for 1 million individuals, including healthy individuals, registered from January 2005 to June 2011. Changes in treatments were determined in 320 thousand individuals originally registered in 2005. The treatment patterns were compared with those of the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort managed by Tokyo Women's Medical University. RESULTS: The estimated prevalence of RA was 1.24 million (1.0 % of the Japanese population), excluding suspected cases, and 706 thousand (0.6 %) in a sensitivity analysis. Seventy-nine percent of patients were treated for RA. Methotrexate was used by 27 % of patients. In 2005, 5 % of patients were prescribed methotrexate at >8 mg/week, which increased to 13 % in 2011. These rates were lower than those in the IORRA cohort. CONCLUSIONS: Our results indicate that the prevalence of RA in Japan is somewhere between 0.6 and 1.0 %. Considering that methotrexate is infrequently used, the implementation of aggressive treatment regimens such as the 'Treat to Target' strategy is important to achieve tight control of RA in Japan.
25550338 Changes in the anticitrullinated peptide antibody response in relation to therapeutic outc 2016 Feb OBJECTIVE: To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA). METHODS: Baseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and α-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24 months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression. RESULTS: During the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression. CONCLUSIONS: The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA. TRIAL REGISTRATION NUMBER: WHO database at the Karolinska institute: CT20080004; and clinicaltrials.gov: NCT00764725.
25326335 Meta-analysis of associations between functional HLA-G polymorphisms and susceptibility to 2015 Jun The aim of this study was to determine whether the functional HLA-G 14 bp insertion (I)/deletion (D) and +3142 G/C polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the HLA-G 14 bp I/D, and +3142 G/C polymorphisms and SLE or RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of 14 comparison studies from 11 articles met our inclusion criteria, comprising eight on SLE (1,284 patients and 1,885 controls) and four on RA (820 patients and 772 controls), and three studies investigated response to methotrexate (MTX) in RA according to the HLA-G 14 bp I/D polymorphisms (249 responders and 205 nonresponders). Meta-analysis revealed an association between the II + ID genotype of the HLA-G 14 bp I/D polymorphism in overall group (OR = 1.205, 95% CI = 1.036-1.403, P = 0.016). Ethnicity-specific meta-analysis showed no association between the II + ID genotype and SLE in the South American, European, and Asian population. Meta-analysis revealed a significant association between SLE and the HLA-G +3142 G allele in all study subjects (OR = 1.367, 95% CI = 1.158-1.613, P = 2.2 × 10(-5)) and in the South American group (OR = 1.531, 95% CI = 1.242-1.888, P = 6.7 × 10(-5)). However, no association between HLA-G 14 bp I/D, and +3142 G/C polymorphisms and RA was found (OR for HLA-G I allele = 1.013, 95 % CI = 0.879-1.167, P = 0.859; OR for +3142 G allele = 0.980, 95% CI = 0.742-1.294, P = 0.888). Furthermore, HLA-G 14 bp I/D polymorphism was not found to be associated with response to MTX in RA. This meta-analysis demonstrates that the HLA-G 14 bp I/D polymorphism is associated with susceptibility to SLE, and HLA-G +3142 G/C polymorphisms are associated with susceptibility to SLE in South Americans.
24290736 Is it possible to withdraw biologics from therapy in rheumatoid arthritis? 2013 Dec BACKGROUND: Biologic agents targeting tumor necrosis factor (TNF) have revolutionized the treatment of rheumatoid arthritis (RA). Clinical remission is perceived as a realistic primary goal, and its maintenance leads to structural and functional remission. OBJECTIVE: This study reviews whether discontinuation of biologic agents is possible after sustained remission and discusses its significance from the risk/benefit point of view (including safety and health economic considerations). METHODS: Using a strategic PubMed search, 45 original research articles regarding discontinuation of biologic agents were identified; 7 were selected that had an obvious focus on discontinuation of biologic agents. These articles included the TNF20, BeSt (Behandel Strategieen), and RRR (Remission Induction by Remicade in RA) studies. However, because of the limitations of the original search, we also review here some articles that did not focus mainly on discontinuation of biologic agents but that presented data regarding biologic-free control. These studies included OPTIMA (Optimal Protocol for Treatment Initiation With MTX and Adalimumab), PRESERVE, and CERTAIN, as well as some recent findings in the HONOR (Humira Discontinuation Without Functional and Radiographic Damage Progression Following Sustained Remission) study from our department. RESULTS: In BeSt and OPTIMA, clinical remission was sustained without functional progression by discontinuing TNF inhibitors, after reducing disease activity by using TNF inhibitors and methotrexate (MTX), in patients with early RA and who were MTX naive. In some studies (including RRR and HONOR), the discontinuation of TNF inhibitors after sustained remission was possible in some patients with long-standing RA who had an inadequate response to MTX. When disease activity flared up after treatment discontinuation, re-treatment with infliximab or adalimumab was highly effective and safe in the majority of patients. It is also clear that tight control with TNF inhibitors and MTX seems to be a prerequisite for having a better chance of biologic-free remission. CONCLUSIONS: Intensive treatment with TNF inhibitors may change the disease process of RA and potentially offers the possibility of a "treatment holiday" from biologic agents.
23754245 Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid 2013 Nov OBJECTIVE: To determine the effect of methotrexate (MTX) on plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and to investigate their associations with clinical and radiographic responses in patients with early rheumatoid arthritis (RA). METHODS: Sixty-two untreated RA patients with the disease duration of ≤36 months in whom MTX was initiated were consecutively identified in our prospective RA cohort and included in this study. Concomitant use of prednisolone and synthetic disease-modifying anti-rheumatic drugs with MTX was allowed, but patients who used biological agents were excluded. Plasma IL-6 and TNF-α levels were measured at the time of diagnosis (baseline) and 1 year later. The relationships of the clinical and radiographic data with plasma levels of IL-6 and TNF-α were analyzed. RESULTS: The median age of the patients was 57 years, 49 patients were female, and the median disease duration was 3 months. Forty-six (74.2 %) patients were anti-cyclic citrullinated protein antibody-positive. Serum C-reactive protein (CRP), plasma IL-6, and DAS28 decreased significantly (p <0.001) after MTX treatment, but plasma TNF-α did not. Radiographic progression was significantly correlated with disease activity score and plasma IL-6 levels but not with CRP or TNF-α after MTX treatment. Patients with plasma IL-6 level above 4.03 pg/ml showed clinically relevant radiographic progression with a sensitivity of 91.7 % and a specificity of 88.0 %. CONCLUSION: In this early RA cohort, we demonstrated a significant (p <0.001) reduction of plasma IL-6, but not TNF-α, during MTX treatment. The post-treatment IL-6 level was a strong indicator of radiographic progression.
23588939 Clinical response within 12 weeks as a predictor of future low disease activity in patient 2013 May OBJECTIVE: Rapidly predicting future outcomes based on short-term clinical response would be helpful to optimize rheumatoid arthritis (RA) management in early disease. Our aim was to derive and validate a clinical prediction rule to predict low disease activity (LDA) at 1 year among patients participating in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial escalating RA therapy by adding either etanercept or sulfasalazine + hydroxychloroquine [triple therapy (TT)] after 6 months of methotrexate (MTX) therapy. METHODS: Eligible subjects included in the derivation cohort (used for model building, n = 186) were participants with moderate or higher disease activity [Disease Activity Score 28-erythrocyte sedimentation rate (DAS-ESR) > 3.2] despite 24 weeks of MTX monotherapy who added either etanercept or sulfasalazine + hydroxychloroquine. Clinical characteristics measured within the next 12 weeks were used to predict LDA 1 year later using multivariable logistic regression. Validation was performed in the cohort of TEAR patients randomized to initially receive either MTX + etanercept or TT. RESULTS: The derivation cohort yielded 3 prediction models of varying complexity that included age, DAS28 at various timepoints, body mass index, and ESR (area under the receiver-operator characteristic curve up to 0.83). Accuracy of the prediction models ranged between 80% and 95% in both derivation and validation cohorts, depending on the complexity of the model and the cutpoints chosen for response and nonresponse. About 80% of patients could be predicted to be responders or nonresponders at Week 12. CONCLUSION: Clinical data collected early after starting or escalating disease-modifying antirheumatic drug/biologic treatment could accurately predict LDA at 1 year in patients with early RA. For patients predicted to be nonresponders, treatment could be changed at 12 weeks to optimize outcomes.
25074866 Association of MDR1 C3435T and RFC1 G80A polymorphisms with methotrexate toxicity and resp 2014 Sep OBJECTIVES: Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 G80A) and multi-drug resistance-1 (MDR1 C3435T) might affect MTX response and/or toxicity. The aim of this study was to find out if there is an association between those polymorphisms and MTX toxicity and/or response in Jordanian RA patients. METHOD: A genotyping approach was used to determine the studied polymorphisms in 159 RA patients. RESULTS: There was an association between RFC1 G80A and MDR1 C3435T polymorphisms with MTX toxicity. Patients with RFC1 80GG genotype were at higher risk for gastrointestinal toxicity (p = 0.036). Patients carrying at least one MDR1 3435T variant allele were at higher risk for MTX overall toxicity (p = 0.04), especially hepatotoxicity (p = 0.028). Furthermore, the distribution of RFC1 G80A polymorphism between males and females was significantly different. The variant genotype 80AA was found to be more in males than in females (60% vs. 31%) (p = 0.011). CONCLUSIONS: Our results suggest that genetic polymorphisms in methotrexate transporters affect the toxicity but not the response of MTX treatment. Further studies should be performed to have more conclusive results.
24125429 Cardiovascular risk in rheumatoid arthritis: how to lower the risk? 2013 Nov Patients with rheumatoid arthritis (RA) carry an excess risk for cardiovascular disease, which is comparable to the risk in patients with type 2 diabetes mellitus. The mechanisms involved are partly related to traditional cardiovascular risk factors, disease-associated inflammation and undertreatment of traditional cardiovascular disease (CVD) risk factors. Since atherosclerosis is an inflammatory disease, the auto-immune mediated inflammation observed in RA patients contributes to increased endothelial dysfunction, oxidative stress and activation and vascular migration of leukocytes. This concept is underscored by the CVD risk reduction that is seen by anti-inflammatory disease modifying anti-rheumatic drugs such as methotrexate and TNFα inhibitors. The evidence for underdiagnosis and undertreatment of traditional CVD risk factors in RA strengthens the potential benefit of structured CVD risk management in these patients. Current cardiovascular guidelines recommend screening and treatment of CVD risk factors in RA patients, without well defined treatment targets. At present, there is a lack of scientific evidence to establish treatment targets for CVD risk factors in RA. Therefore, expanding research regarding screening and treatment of traditional CVD risk factors in RA patients is needed.
23772583 Copper levels in patients with rheumatoid arthritis. 2013 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, autoimmune-based disease of the connective tissue with still unknown etiology. Numerous studies have indicated the association between Copper (Cu) and ceruloplasmin (Cp) concentrations and pathogenesis of RA. OBJECTIVE: To compare the concentrations of Cu and Cp in different biological samples and their correlation with the inflammatory process, between a group of patients with RA and a control group of healthy individuals. MATERIALS AND METHODS: The study enrolled 74 Caucasian patients (20 men and 54 women), aged 29-50 (mean age 39.8±6.1 years) diagnosed with RA. The control group consisted of 30 healthy Caucasian individuals. Copper levels were assessed by atomic absorption spectroscopy. RESULTS: Among RA patients the mean Cu level was significantly higher in serum and hair compartments and significantly lower in erythrocytes, compared with the control group (p<0.01). The Cp concentration was also higher in serum of RA patients (p<0.001). A statistically significant, positive correlation between the Cp serum concentration and the ESR values (r(s)=0.38; p<0.007) was found. No significant influence of pharmaceutical treatment (methotrexate, non-steroidal anti-inflammatory drugs, glucocorticoids, calcium, vitamin D3 and sulphasalazine) on serum Cu was found. CONCLUSIONS: It seems that the 'copper status' in patients with RA, based on the measurement of Cu and Cp levels in blood serum is correlated with presence of the inflammatory process. The hair could serve as a useful, additional diagnostic material. Some other factors, different from the applied treatment, can probably influence the Cu levels in patients with RA.
23881438 The relationship between disease activity and depressive symptoms severity and optimism--r 2013 Dec To assess depressive symptoms severity and dispositional optimism in patients with recent onset arthritis both before and after 4 months treatment. Two hundred twenty-two patients with recent onset RA and undifferentiated arthritis in the IMPROVED study filled out the Beck Depression Inventory (BDI-II) to assess depressive symptoms severity and the Life Orientation Test Revised (LOT-R) to measure optimism before and after 4 months of treatment. All patients were treated with methotrexate 25 mg/week and prednisone 60 mg/day (tapered to 7.5 mg/day in 7 weeks). Linear regression analysis was used to assess the association between the disease activity score (DAS) and its components (tender joint count, general well-being measured with a visual analogue scale (VAS), swollen joint count, and erythrocyte sedimentation rate) with the BDI-II an LOT-R scores. In general, depressive symptoms were mild. The DAS was an independent predictor of depressive symptoms scores both at baseline and after 4 months follow-up, in particular tender joint count and VAS global health. Disease activity was not associated with the level of optimism. Nevertheless, patients who achieved clinical remission improved significantly more in both depression score and optimism score than patients who did not. Patients with early arthritis report improvement in depressive symptoms and optimism with improvement in disease activity and achieving clinical remission. Depression scores are associated with pain and unwell being but not with swollen joint counts and inflammatory parameters.
24794492 Association of the MTHFR C677T and A1298C polymorphisms with methotrexate toxicity in rheu 2014 Dec The aim of this study was to explore whether the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) play a role in methotrexate (MTX) toxicity in rheumatoid arthritis (RA). MEDLINE and EMBASE database searches and subsequent manual searches were utilized to identify articles in which C677T and A1298C MTHFR polymorphisms were evaluated in RA patients taking MTX. A meta-analysis was conducted to identify associations between MTHFR polymorphisms and MTX toxicity. Twelve studies comprising a total of 2,288 RA patients were included in our meta-analysis. Meta-analysis revealed an association between the overall toxicity of MTX and the MTHFR 677TT genotype (odds ratio [OR] = 1.615, 95 % confidence interval [CI] = 1.185-2.200, p = 0.002). Stratification by ethnicity indicated an association between the MTHFR 677TT genotype and the overall toxicity of MTX in East Asians (OR = 1.583, 95 % CI = 1.075-2.331, p = 0.020). The toxicity of MTX also was found to be associated with the TT genotype in patients taking folate (OR = 1.893, 95 % CI = 1.283-2.793, p = 0.001). Stratification by toxicity type indicated an association between the MTHFR 677TT genotype and any adverse effects (OR = 1.716, 95 % CI = 1.127-2.612, p = 0.012). Meta-analysis stratified by toxicity type indicated an association between the MTHFR 1298CC genotype and any adverse effects (OR = 0.501, 95 % CI = 0.284-0.886, p = 0.017). The results of our meta-analysis suggest that the MTHFR C677T and A1298C polymorphisms are associated with MTX toxicity in RA patients.
25169728 Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuat 2015 Jan OBJECTIVE: To assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission. METHODS: ACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR <2.6 at two consecutive visits 12 weeks apart) discontinued TCZ and were assessed every 4 weeks for 1 year. If sustained remission was maintained, added csDMARDs, then MTX/PBO, were discontinued. RESULTS: Of the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%). CONCLUSIONS: Treat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement. TRIAL REGISTRATION NUMBER: NCT00810199.
24773941 The positive influence of methotrexate on the mortality of patients with rheumatoid arthri 2014 May OBJECTIVES: Methotrexate (MTX) is the anchor drug in the treatment of patients with rheumatoid arthritis (RA). MTX shows effects on disease activity and mortality. However, it is unclear whether the effect of MTX on mortality depends on its effect on disease activity. METHODS: In a post-hoc analysis we analysed the data of our cohort established in Ratingen, Germany, and included all patients starting treatment with MTX (n=271) between 1980 and 1987. One year after baseline (BL), response to MTX treatment was assessed using a modified ACR 20 response. Follow-up data of 250 patients were available after 10 and 18 years. RESULTS: After 1 year, there were 66% responders and 20% non-responders; only 14% had discontinued MTX treatment due to side effects or lack of efficacy. Most patients continued MTX treatment irrespective of efficacy. Ten years after BL, 61% of the patients were still treated with MTX. After 18 years, the responder-group showed a standardised mortality ratio of 1.6 compared to 3.2 for the group of non-responders. However, when adjusting for age, gender, response to MTX treatment one year after BL, number of swollen joints and comorbidities after 10 years an independent association of continued MTX treatment with lower mortality was found for the period 10 to 18 years after BL (hazard ratio (HR): 0.63, 95% confidence interval: 0.43-0.92, p=0.015). CONCLUSIONS: In this cohort, the mortality lowering effect of continued MTX use was partly independent of its effect on disease activity. This finding may affect treatment decisions concerning RA patients with insufficient response to MTX.
24372368 Methotrexate-induced pneumonitis: heterogeneity of bronchoalveolar lavage and differences 2014 Feb PURPOSE: Our knowledge on bronchoalveolar lavage (BAL) of methotrexate-induced pneumonitis (MTX-P) is fragmentary and based on data that are sometimes apparently conflicting. Aim of this review was to provide a comprehensive overview on the BAL features of MTX-P arising from cases published to date, and to determine the cytological patterns and any differences between cancer and rheumatoid arthritis patients, the two patient subsets among which this complication more often occurs. METHODS: English-language articles published up to November 2013 were systematically searched through PUBMED, EMBASE, and other databases. Adult patients with a proven diagnosis of MTX-P and careful mention of each BAL parameter were examined. RESULTS: Seventeen articles for a total of 47 patients were included. Four BAL patterns with a variably combined lymphocytosis and two with prominent neutrophilia were identified. A more intense lymphocytosis (P=0.004) and a more depressed CD4/CD8 ratio (P=0.01) were found in cancer patients compared with rheumatoid arthritis patients. CONCLUSIONS: In MTX-P, cytological analysis of BAL may disclose up to six different patterns. In MTX-P affecting cancer patients, BAL tends to show the typical features of hypersensitivity pneumonitis, while, in rheumatoid arthritis patients, it is more heterogeneous, with a less intense lymphocytosis, a more pronounced neutrophilia, and a higher CD4/CD8 ratio. These differences could be related to a disparity in baseline pulmonary conditions between the two background diseases, i.e., to the presence of previously healthy lungs in cancer patients, and lungs already involved by the immune-mediated inflammatory processes, often not manifestly, in rheumatoid arthritis patients.
24517212 Health-related quality of life and functional ability in patients with early arthritis dur 2013 Oct 31 INTRODUCTION: The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment. METHODS: In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models. RESULTS: During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL. CONCLUSIONS: In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms. TRIAL REGISTRATIONS: ISRCTN11916566 and EudraCT2006-006186-16.
25748133 Five-year administration of tocilizumab to a patient with rheumatoid arthritis complicated 2014 We herein described the long-term administration of tocilizumab (TCZ) to a patient with rheumatoid arthritis (RA) complicated by three vessel coronary artery disease and severe heart failure (HF). A 41-year-old male was admitted to our hospital with exacerbated RA and congestive HF. Cardiac ultrasonography revealed diffuse hypokinesis with a left ventricular ejection fraction (LVEF) of 16.8% and New York Heart Association (NYHA) class III/IV HF. Swelling and tenderness were noted in most of his joints. Methotrexate (MTX) was initiated during his hospitalization and TCZ was introduced 6 months later. Our patient has been treated with MTX and TCZ for five years without any adverse events, and RA and HF have remained stable. Although it may be anecdotal, we suggest that TCZ may be used as a treatment option in patients with RA complicated by severe HF.
23918169 Development of an algorithm for identifying rheumatoid arthritis in the Korean National He 2013 Dec This study aimed to develop an identification algorithm for validating the International Classification of Diseases-Tenth diagnostic codes for rheumatoid arthritis (RA) in the Korean National Health Insurance (NHI) claims database. An individual copayment beneficiaries program for rare and intractable diseases, including seropositive RA (M05), began in South Korea in July 2009. Patients registered in this system pay only 10 % of their total medical costs, but registration requires an official report from a doctor documenting that the patient fulfills the 1987 ACR criteria. We regarded patients registered in this system as gold standard RA and examined the validity of several algorithms to define RA diagnosis using diagnostic codes and prescription data. We constructed nine algorithms using two highly specific prescriptions (positive predictive value >90 % and specificity >90 %) and one prescription with high sensitivity (>80 %) and accuracy (>75 %). A total of 59,823 RA patients were included in this validation study. Among them, 50,082 (83.7 %) were registered in the individual copayment beneficiaries program and considered true RA. We tested nine algorithms that incorporated two specific regimens [biologics and leflunomide alone, methotrexate plus leflunomide, or more than 3 disease-modifying anti-rheumatic drugs (DMARDs)] and one sensitive drug (any non-steroidal anti-inflammatory drug (NSAID), any DMARD, or any NSAID plus any DMARD). The algorithm that included biologics, more than 3 DMARDs, and any DMARD yielded the highest accuracy (91.4 %). Patients with RA diagnostic codes with prescription of biologics or any DMARD can be considered as accurate cases of RA in Korean NHI claims database.
24261761 Rheumatoid arthritis of the hand: a five-year longitudinal analysis of clinical and radiog 2014 Jan OBJECTIVES: Treatments for rheumatoid arthritis (RA) have improved since methotrexate and biological agents were approved; however, few longitudinal analyses have tracked joint destruction, deformity progression, or functional impairments that directly affect the activities of daily living. Due to the consequences of functional impairments, we conducted this study to glean more information regarding deformity progression over time. METHODS: This study enrolled 134 hands in 67 RA patients with hand deformities in 2004. After 5 years, 100 hands in 52 patients were eligible for the final assessment. Analyses consisted of morphological and radiographical evaluations of deformities, functional evaluations by questionnaires and the modified Kapandji index, and activity evaluations. RESULTS: In this period, the type I deformity (Nalebuff and Millender, Orthop Clin North Am 6(3):753-63, 1975) was the most common thumb deformity. Swan-neck and boutonnière finger deformities also progressed. At the 5-year follow-up, questionnaire score worsened, when disease activity was high. CONCLUSIONS: Our study showed that there was a marked progression in hand deformities in RA patients over a 5-year period. In order to assist RA patients in performing the activities of daily living, medical and rehabilitative interventions should target the restoration of functional loss through joint destruction as well as the prevention of disease progression.
25389048 Intensive intervention can lead to a treatment holiday from biological DMARDs in patients 2014 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate (MTX), a synthetic disease-modifying anti-rheumatic drug (sDMARD) and biological DMARDs (bDMARDs) has revolutionized treatment of RA and clinical remission or low disease activity (LDA) are now realistic targets, achieved by a large proportion of RA patients. We are now in a position to evaluate if it is possible to maintain remission or LDA while at the same time reducing the burden of treatment on the patient and healthcare system. Data are emerging from large, well-conducted studies designed to answer this question, shedding light on which patient populations and treatment algorithms can survive treatment discontinuation or tapering with low risk of disease flare. For early RA, approximately half of early RA patients could discontinue TNF-targeted bDMARDs without clinical flare and functional impairment after obtaining clinical remission by bDMARDs with MTX. In contrast, for established RA, fewer patients sustained remission or LDA after the discontinuation of bDMARDs and "deep remission" at the discontinuation was a key factor to maintain the treatment holiday of bDMARDs. Thus, this article provides a brief outline on withdrawing or tapering bDMARDs once patients have achieved remission or LDA in RA.