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ID PMID Title PublicationDate abstract
24445384 Investigation of clinical characteristics as predictive factors for the humoral immune res 2014 Mar The objective of this observational study is to determine characteristics as predictive factors for the humoral immune response to the influenza vaccine in patients with rheumatoid arthritis (RA). Fifty-seven RA patients who visited our department between 2011 and 2012 were recruited for the present study. The anti-influenza antibody titers of a trivalent influenza subunit vaccine (A/California/7/2009 (H1N1)-like strain (A/H1N1 strain), A/Victoria/210/2009 (H3N2)-like strain (A/H3N2 strain), and B/Brisbane/60/2008-like strain (B strain)) were measured at baseline and 4 weeks after the vaccination using the hemagglutination inhibition assay. Associations between the immune response to the influenza vaccine and clinical characteristics such as background, clinical parameters, and "having treatments or not" were examined to determine predictive factors for the immune response to the influenza vaccine. The titers of the three strains were significantly increased in all RA patients after the influenza vaccination. Concerning predictive factors of the immune response, no significant differences were observed in background (age and sex) or clinical parameters (peripheral lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, matrix metalloproteinase-3, and disease activity score-28). No significant differences were observed in the titers of anti-influenza antibodies between the treatment (methotrexate, prednisolone, salazosulfapyridine, or tacrolimus) and no-treatment groups. In contrast, there was a significant difference in A/H3N2 strain between the patients with biologics and without biologics. The only factor that affected anti-influenza antibody titers was "having biologics or not"; therefore, the immune response to the influenza vaccine may not be predicted from the viewpoints of background and clinical parameters.
25182696 The perplexity of prescribing and switching of biologic drugs in rheumatoid arthritis: a U 2014 Sep 2 BACKGROUND: Biologic drugs are expensive treatments used in rheumatoid arthritis (RA). Switching among them is common practice in patients who have had an inadequate response or intolerable adverse events. The National Institute of Health and Clinical Excellence (NICE) UK, which aims to curtail postcode prescribing, has provided guidance on the sequential prescription of these drugs. This study sought to evaluate the extent to which rheumatology centres across the Midlands were complying with NICE guidance on the switching of biologic drugs in RA, as well as analyse the various prescribing patterns of these drugs. METHODS: Data was collected via a web-based tool on RA patients who had undergone at least one switch of a biologic drug during 2011. The standards specified in NICE technology appraisals (TA130, TA186, TA195, TA198, and TA225) were used to assess compliance with NICE guidance. Descriptive statistical analysis was performed. RESULTS: There were 335 biologic drug switches in 317 patients. The most common reason given for switching to a drug was NICE guidelines (242, 72.2%), followed by Physician's choice (122, 33.4%). Lack of effect was the most common reason for discontinuing a drug (224, 67%). For patients on Rituximab, Methotrexate was used in 133 switches (76.9% of the time). Overall NICE compliance for all units was 65% (range 50 to 100%), with anti-TNFα to anti-TNFα switches for inefficacy making up the majority of non-compliant switches. CONCLUSION: This study draws attention to the enigma and disparity of commissioning and prescribing of biologic drugs in RA. Currently the evidence would not support switching of a biologic drug for non-clinical purposes such as economic pressures. Flexibility in prescribing should be encouraged: biologic therapy should be individualised based on the mode of action and likely tolerability of these drugs. Further work should focus on the evidence for using particular sequences of biologic drugs.
23742043 Leflunomide discontinuation in rheumatoid arthritis and influence of associated disease-mo 2013 OBJECTIVES: The aims of this study were to describe the rate of leflunomide discontinuation in rheumatoid arthritis (RA) patients, in standard clinical practice, and to analyse which factors could influence this rate, paying particular attention to the concomitant treatment with other disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We selected RA patients, diagnosed according to the 1987 American College of Rheumatology (ACR) criteria, attending the rheumatology outpatient clinic of the San Carlos Clinical Hospital (Madrid, Spain), who had started treatment with leflunomide between 1 January 2006 and 1 January 2011. Clinical records were examined until withdrawal of the drug, loss of follow-up, or 1 October 2011. Kaplan-Meier curves were set to account for leflunomide withdrawal. Cox bivariate and multivariate regression models were conducted to examine risk factors for leflunomide discontinuation. RESULTS: The incident rate (IR) for leflunomide discontinuation, regardless of the cause, was 27 per 100 patient-years [95% confidence interval (CI) 22-31]. We observed, in both the bivariate and multivariate regression analysis, that those aged > 75 years at the start of the leflunomide treatment and undergoing concurrent treatment with methotrexate (MTX) and/or hydroxychloroquine (HC) had a significantly higher risk of leflunomide discontinuation. CONCLUSIONS: An older age at the start of the treatment with leflunomide, or concomitant treatment with MTX and/or HC, could be associated with a higher risk of leflunomide discontinuation, regardless of the cause. Therefore, when taking MTX or HC, patients receiving leflunomide should be closely monitored early to detect the occurrence of adverse reactions, and hence prevent their aggravation.
23281295 Incidence and time trends of herpes zoster in rheumatoid arthritis: a population-based coh 2013 Jun OBJECTIVE: To determine the incidence, time trends, risk factors, and severity of herpes zoster in a population-based cohort of patients with newly diagnosed rheumatoid arthritis (RA) compared to a group of individuals without RA from the same population. METHODS: All residents of Olmsted County, Minnesota fulfilling for the first time the 1987 American College of Rheumatology criteria for RA between January 1, 1980 and December 31, 2007 and a cohort of similar residents without RA were assembled and followed by retrospective chart review until death, migration, or December 31, 2008. RESULTS: There was no difference in the presence of herpes zoster prior to the RA incidence/index date between the cohorts (P = 0.85). During followup, 84 patients with RA (rate 12.1 cases per 1,000 person-years) and 44 subjects without RA (rate 5.4 cases per 1,000 person-years) developed herpes zoster. Patients with RA were more likely to develop herpes zoster than those without RA (hazard ratio [HR] 2.4 [95% confidence interval (95% CI) 1.7-3.5]). Herpes zoster occurred more frequently in patients diagnosed with RA more recently (HR 1.06 per year [95% CI 1.02-1.10]). Erosive disease, previous joint surgery, and use of hydroxychloroquine and corticosteroids were significantly associated with the development of herpes zoster in RA. There was no apparent association of herpes zoster with the use of methotrexate or biologic agents. Complications of herpes zoster occurred at a similar rate in both cohorts. CONCLUSION: The incidence of herpes zoster is increased in RA and has risen in recent years. There also has been an increasing incidence of herpes zoster in more recent years in the general population. RA disease severity is associated with the development of herpes zoster.
24564933 The separate impact of tight control schemes and disease activity on quality of life in pa 2014 May OBJECTIVES: To examine in patients with early rheumatoid arthritis (RA) whether quality of life (QoL), independently of disease activity, is affected by tight control treatment strategy schemes. METHODS: In the Computer Assisted Management in Early RA (CAMERA) trials, patients with early RA, disease duration <1 year, no prior use of DMARDs) had been randomised to a methotrexate (MTX)-based tight control strategy or usual care (CAMERA study) or to 10 mg/d prednisone or placebo both added from start to a MTX-based tight control strategy (CAMERA-II study). In either study, randomisation to the more intensive strategy resulted in lower disease activity. To assess QoL, the 'Influence of Rheumatic Diseases on General Health and Lifestyle' questionnaire (IRGL) was used. Baseline and 1- and/or 2-year measurements were analysed with regression analyses with the IRGL (sub)scales as outcome variables and treatment strategy and disease activity assessing 28 joints (DAS28) as independent variables, correcting for baseline values of each scale and possible confounders (gender, age, rheumatoid factor status). RESULTS: There was no clear association between either of the treatment strategies and QoL, but a decrease in DAS28 was associated with improvement in the majority of QoL (sub)scales. CONCLUSIONS: No independent effect of the specific tight control strategies schemes on QoL was found, while there was a clear disease activity related effect. Thus frequent outpatient visits or the inclusion of prednisone in a tight control strategy did not negatively influence QoL.
25180998 [Diagnosis and treatment of rheumatoid arthritis]. 2014 Sep Rheumatoid arthritis today is still not curable but satisfactory treatable. Treatment targets include clinical remission (or at least low disease activity), lack of radiological destructions and functional disability as well as acceptable life quality and unimpaired working ability. Diagnosing and adequately treating the disease as early as possible is essential for a favourable long-term outcome. Treatment to target with validation and if necessary modification at least every three months until target is achieved ensures good results. Predominantly treatment starts with a combination of methotrexate and glucocorticoids followed by a conventional DMARD combination and then addition of a biologic DMARD in case of failing target. Presence of adverse risk factors and/or high disease activity a cDMARD/bDMARD combination might be used already after starting treatment failure. Additional treatment options such as physiotherapy should be added. Altogether with current treatment possibilities burden of disease declined dramatically in recent years.
25579963 Sugarcane bagasse lignin, and silica gel and magneto-silica as drug vehicles for developme 2015 Mar The present study clarifies co-therapy action of deliveries from their textural changes point of view. Methotrexate (MTX) was immobilized onto biodegradable lignin, silica gel and iron/silica nanocomposite. Loaded-MTX was i.p. injected into albino rats at doses of 0.25 and 0.5mg/kg/week for 2.5months, after which spleen, liver, testes and knee joint tissues were collected for tests. IFN-γ and IL-17A mRNA gene expressions in spleen in all biological samples were determined by RT-PCR. Physicochemical features of drug carriers were monitored by XRD, BET-PSD, SEM and TEM. Drug inflammatory-site targeting was found to be closely related to the physico-features of deliverers. The interlayered lignin of micro- and meso-pore channels directed MTX toward concealed infected cells in liver and testes tissues, while meso-structured silica flacks satisfied by gathering MTX around knee joints. The magneto-silica nanocomposite targeted MTX toward spleen tissue, which is considered as a lively factory for the production of electron rich compounds.
24231065 Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumat 2014 Apr OBJECTIVE: To review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease-modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice. METHODS: We performed a systematic literature review from 1975 to July 2013 using Medline, Embase, Cochrane, and abstracts from the ACR 2010-2012 and EULAR 2010-2013 annual meetings. Case reports and series that suggest a causative role of nbDMARDs (methotrexate [MTX], leflunomide [LEF], gold, azathioprine [AZA], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) and biologic agents (TNF inhibitors [TNFi], rituximab [RTX], tocilizumab [TCZ], abatacept [ABA], and anakinra) in causing ILD or worsening a pre-existing ILD in RA patients were included. Results from observational and postmarketing studies as well as reviews on this topic were excluded from the qualitative analysis but still considered to discuss the implication of such drugs in generating or worsening ILD in RA patients. Comparisons were made between MTX-induced ILD in RA and the cases reported with other agents, in terms of clinical presentation, radiological features, and therapeutic management and outcomes. RESULTS: The literature search identified 32 articles for MTX, 12 for LEF (resulting in 34 case reports), 3 for gold, 1 for AZA, 4 for SSZ, 27 for TNFi (resulting in 31 case reports), 3 for RTX, 5 for TCZ (resulting in 8 case reports), and 1 for ABA. No case was found for HCQ or anakinra. Common points are noted between LEF- and TNFi-related ILD in RA: ILD is a rare severe adverse event, mostly occurs within the first 20 weeks after initiation of therapy, causes dyspnea mostly in older patients, and can be fatal. Although no definitive causative relationship can be drawn from case reports and observational studies, these data argue for a pulmonary follow-up in RA patients with pre-existing ILD, while receiving biologic therapy or nbDMARDs. CONCLUSION: As previously described for MTX, growing evidence highlights that LEF, TNFi, RTX, and TCZ may induce pneumonitis or worsen RA-related pre-existing ILD. Nonetheless, identifying a causal relationship between RA therapy and ILD-induced toxicity clearly appears difficult, partly because it is a rare condition.
23705580 Primary central nervous system malignant lymphoma in a patient with rheumatoid arthritis r 2013 Dec We report the first case of primary central nervous system lymphoma (PCNSL) developing in a patient with rheumatoid arthritis (RA) undergoing low-dose methotrexate therapy (LD-MTX). The characteristic clinical management and course in our experience of the present case illustrate the important points about PCNSL in methotrexate-associated lymphoproliferative disorders (MTX-LPD). The number of cases of MTX-LPD in RA patients may increase in the future, since current treatment strategies for RA recommend starting MTX use in early stage RA, and recent insights have tended to show an increase with higher doses.
25269199 [Evaluation of methotrexate effect on the acute-phase response in rheumatoid arthritis aft 2014 DAS28 index calculated with regard for ESR, the number of swollen/painful joints and evaluation of the patient's condition by VAS is universally used to estimate activity of rheumatoid arthritis (RA). There is a variant of calculation using C-reactive protein (CRP) instead of ESR. Our experience indicates that ESR decreases more slowly than CRP during treatment and better reflects dynamics of patients' condition. From the practical standpoint it is important to estimate activity of RA because therapeutic modalities are chosen based on the DAS28 value. AIM: To study the influence of pharmaceutical form of methotrexate on the acute-phase response in rheumatoid arthritis. MATERIALS AND METHODS: The study included 32 patients (24 women, 8 men) aged 19-76 (mean 47.5 +/- 28.5) yr with active RA (DAS28 > 3.2) 4-30 months (11.5 +/- 7.4, median 8) in duration. Diagnosis was made using AXR criteria (1987), none of the patients previously received methotrexate injections. Inclusion criteria: initially high ESR (Westegren, mm/hr) and/or CRP (mg/l measured by a highly sensitive method). All patients were given methotrexate subcutaneously for 12 weeks as monotherapy (initial dose 10 mg, maximum one 25 mg/week). The cumulative dose was 211.36 +/- 17.2 mg. RESULTS: Side effects did not require withdrawal of methotrexate. CRP level decreased faster than ERS: a 70% decrease of CRP by week 12 was recorded more frequently than that of ESR. Slow dynamics of the number of swollen joints compared with CRP may be due to the low cumulative dose of methotrexate. Duration of the disease had no effect on dynamics of acute phase characteristics. CONCLUSION: Methotrexate injections resulted in markedly delayed development of clinical signs of improvement compared with laboratory values. CFP levels fell down much faster than ESR, Remission or low activity of RA (estimated from DAS28) occurred only in 38% of the cases after 3 month monotherapy by methotrexate injections. It is concluded that efficacy of this drug should be estimated no sooner than 4 months after the onset of the treatment.
24988987 Synoviocyte apoptosis may differentiate responder and non-responder patients to methotrexa 2014 Oct We aimed to evaluate whether methotrexate (MTX) in vitro induces apoptosis in synoviocytes obtained from rheumatoid arthritis patients and whether the apoptosis inducing effect of MTX to synoviocytes is correlated with the clinical responsiveness to MTX in patients with rheumatoid arthritis (RA). We evaluated 18 patients with RA taking MTX 15-20 mg/week as the subject group (nine responders and nine non-responders) and ten patients with osteoarthritis (OA) and nine patients with ankylosing spondylitis (AS) as the control group. Synoviocytes, cultured from the synovial fluid of the knee joint of each subject, were used for experiments between passages 4 and 6, and were treated with MTX. The induction of apoptosis was determined by the quantification of DNA hypoploidy by flow cytometry, nuclear morphology, caspases activation, DNA electrophoresis, and mitochondrial membrane potential measurements. The viability of synoviocytes treated with MTX was different between the MTX responders and nonresponders. MTX induced apoptosis in cultured synoviocytes by mitochondria- and caspase-dependent manners in the MTX responders but did not in the MTX non-responder, OA, and AS patients. The apoptotic responsiveness of the synoviocytes to MTX predicts the sensitivity to MTX treatment and provides a method determine the early application of an anti-tumor necrosis factor-α agent in RA treatment.
23669798 Assessing process of care in rheumatoid arthritis at McGill University hospitals. 2013 Jun OBJECTIVE: In rheumatoid arthritis (RA), quality indicators (QIs) are tools used to measure process of care. This study aimed to assess performance of selected QIs from the 2004 Arthritis Foundation's QI Set at 2 major sites of a university network of teaching hospitals. METHODS: The charts and electronic hospital records of 76 RA patients were audited to determine adherence to QIs. Logistic multivariate regression analyses were performed to investigate potential determinants of nonadherence and propose measures to facilitate better QI compliance, as a potential strategy towards RA care improvement. RESULTS: We identified consistent observance of QIs mandating prescription of disease-modifying antirheumatic drug therapy for all patients, drug adjustment with disease activity, prednisone tapering, and bisphosphonate therapy if indicated for patients on glucocorticoids. However, there was either lack of documentation or true inconsistent adherence to QIs dealing with radiograph performance, functional capacity assessment, and screening for hepatitis and tuberculosis before commencement of methotrexate and biologic agents, respectively. For the specific QIs analyzed, we did not find any definite independent associations with the studied variables. CONCLUSIONS: Our findings indicate that while there is frequent evidence for adherence to certain RA quality care standards at our centers, there is less compliance to others. Strategies to optimize the performance or documentation of those found most lacking, namely, functional capacity and screening for specific drug contraindications, could improve patient care. Radiographic disease monitoring, while lacking, may represent a move toward other more sensitive methods of RA progression detection, such as joint ultrasound. The inclusion of patient- and physician-derived information could help elucidate the reasons underlying nonadherence.
25274241 Successful treatment with tocilizumab in a case of intralymphatic histiocytosis associated 2014 A 75-year-old woman with rheumatoid arthritis (RA) presented with long-term painful erythema on the right upper arm and left elbow. The patient was diagnosed with intralymphatic histiocytosis (ILH) based on the biopsy findings. Because the patient was unresponsive to single-agent treatment with methotrexate, infliximab and etanercept, we switched to tocilizumab (TCZ) treatment, which induced remission of the ILH. Our case suggests that TCZ may be a treatment option for ILH in patients with RA.
24584757 Therapeutic effect of dimethyl dimethoxy biphenyl dicarboxylate on collagen-induced arthri 2015 Nov OBJECTIVE: To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis (CIA). METHODS: Wistar rat model of CIA was set up using bovine collagen type II. Fifty rats were divided into five groups randomly: normal, CIA model, DDB treatment, methotrexate (MTX) treatment, and combined DDB+MTX treatment. Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints. Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining. Plasma levels of vascular endothelial growth factor (VEGF), platelet derived growth factor, interleukin-8 (IL-8), IL-4, tumor necrosis factor α (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were detected by Griess reagent. RESULTS: Compared with the CIA model group, a remarkable reduction in various angiogenic (VEGF and IL-8) and inflammatory mediators (TNF-α, IL-4 and COX-2) after treatment with DDB either alone or combined with MTX P<0.05 or P<0.01). Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal. CONCLUSION: Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis (RA) compared with a choice drug (MTX) and it may be offered as a second-line drug in the treatment of RA.
23097311 Immunogenicity, safety, and efficacy of abatacept administered subcutaneously with or with 2013 May OBJECTIVE: To evaluate the impact of concomitant methotrexate (MTX) on subcutaneous (SC) abatacept immunogenicity, and to assess safety and efficacy. METHODS: This phase III, open-label study had a 4-month short-term (ST) period and an ongoing long-term extension (LTE) period. Rheumatoid arthritis patients were stratified to receive SC abatacept (125 mg/week) with (combination) or without MTX (monotherapy), with no intravenous loading dose; patients receiving monotherapy could add MTX in the LTE period. Immunogenicity (percentage of anti-abatacept antibody-positive patients) was assessed. ST and LTE period data are reported, including efficacy through LTE month 14 and safety through LTE month 20. RESULTS: Ninety-six of 100 enrolled patients completed the ST period; 3.9% (combination) and 4.1% of patients (monotherapy) developed transient immunogenicity, and no patients were antibody positive at month 4. Serious adverse events (SAEs) were reported in 3.9% (combination) and 6.1% of patients (monotherapy); 5.9% (combination) and 8.2% of patients (monotherapy) experienced SC injection reactions, and all were mild in intensity. Mean 28-joint Disease Activity Score (DAS28) changes were -1.67 (95% confidence interval [95% CI] -2.06, -1.28; combination) and -1.94 (95% CI -2.46, -1.42; monotherapy) at month 4. Ninety patients entered and were treated in the LTE period; 83.3% (75 of 90) remained ongoing at month 24. One LTE-treated patient (1.1%) developed immunogenicity, 14.4% of patients experienced SAEs, and no SC injection reactions were reported. For patients entering the LTE period, mean DAS28 changes from baseline were -1.84 (95% CI -2.23, -1.34; combination) and -2.86 (95% CI -3.46, -2.27; monotherapy) at month 18. CONCLUSION: SC abatacept did not elicit immunogenicity associated with loss of safety or efficacy, either with or without MTX.
24706412 Moving the injectable methotrexate service closer to home: a practice development initiati 2014 Sep OBJECTIVE: The aim of this practice development project was to make it quicker and easier for patients to switch to subcutaneous (s/c) methotrexate and thereby introduce a nurse-led methotrexate clinic into a district general hospital, which would make the best use of the advanced knowledge and skills of the rheumatology specialist nurses; empower patients and improve their experience; and introduce cost savings for the Trust. METHODS: Over a period of four months, meetings were held with pharmacists, clinicians, administrative and support staff to formulate a plan to introduce the changes and agree the benefits to patients. A detailed plan for the practice development project addressed the procedures to follow, the safety issues for patients and the revision of current documentation. RESULTS: A review of service in the year before and after the change revealed that the number of rheumatoid arthritis patients who had switched to s/c methotrexate had increased by 80%. This was a significant difference (p = 0.049), which strongly suggested that the change in service was the reason for the increased number of patients who were able to switch their route of administration of methotrexate. CONCLUSION: This project demonstrated that not only do nurse specialists have the skills to make clinical decisions and judgements, prescribe medications and escalate therapies with no detriment to the patients, but also that this practice can lead to a more efficient and effective service, at a reduced cost to the Trust.
23987246 Methotrexate analogues display enhanced inhibition of TNF-α production in whole blood fro 2014 OBJECTIVES: Although methotrexate (MTX) is the anchor drug in the treatment of rheumatoid arthritis (RA), patients experience clinical resistance to MTX upon prolonged treatment. We explored whether new-generation antifolates elicit superior anti-inflammatory properties when compared to MTX, based on their capacity to inhibit tumour necrosis factor (TNF)-α production. METHOD: T cells in whole blood from 18 RA patients (including MTX-naïve, MTX- responsive, and MTX non-responsive patients) and seven healthy volunteers were stimulated with αCD3/αCD28 antibodies and incubated ex vivo for 72 h with MTX and eight novel antifolate drugs with potentially favourable biochemical and pharmacological properties. Drug concentrations exerting 50% inhibition (IC-50) of TNF-α production (by enzyme-linked immunosorbent assay, ELISA) were determined as an estimate for their anti-inflammatory capacity. In addition, induction of T-cell apoptosis was evaluated by flow cytometry. RESULTS: The new-generation antifolates PT523, PT644, raltitrexed, and GW1843 proved to be potent inhibitors of TNF-α production in activated T cells from all three groups of RA patients and from healthy volunteers. Based on IC-50 values, these antifolates were up to 10.3 times more potent than MTX. The anti-inflammatory effects were observed at drug concentrations that provoked suppression of T-cell activation and induction of apoptosis in 20-40% of activated T cells. CONCLUSION: In an ex-vivo setting, novel antifolates elicited marked inhibition of TNF-α production in activated T cells from RA patients. Further clinical evaluation is warranted to investigate whether a low dosage of these antifolates can elicit immunosuppressive effects equivalent to MTX, and whether they are superior to MTX in patients who fail to respond to MTX.
23819240 [Efficacy and safety evaluation of fire needling for rats with rheumatoid arthritis]. 2013 Apr OBJECTIVE: To explore the therapeutic effect and safety of fire needling on rat with rheumatoid arthritis. METHODS: Forty female Wistar rats were randomly divided into a normal group, a model group, a methotrexate (MTX) group and a fire needling group, 10 rats in each group. The 0.1 mL of normal saline was subcutaneously injected in rat's right back paw in the normal group, while the other groups received subcutaneous injection of 0.1 mL of complete Freund's adjuvant to establish the model. The pricking method was applied in the fire needling group at "Jiaji" (EX-B 2), "Zusanli" (ST 36) and Ashi points with a depth of 5 mm, once every three days, and totally eight times were required. In the MTX group, with intragastric administration of 2.0 mg/kg per rat, the treatment was given once every seven days, and totally four times were required. The weight, swelling rate of foot, joint pain score and polyarthritis index of rats in each group as well as the pathological change of liver tissue under light microscope were observed. RESULTS: The weight, swelling rate of foot, joint pain score and polyarthritis index in the model group were significantly higher than those in the normal group (P < 0.05, P < 0.01), after the treatment, the above-mentioned indexes in the two treatment groups were obviouly dereased as componed with those in the model group (all P < 0.01), and there were statistical differences between the fire needling group and MTX group (P < 0.05, P < 0.01). Compared with the normal group, inflammatory cells were appeared with a cluster distribution in the liver cells of rats in the model group. The inflammatory cells were reduced in the MTX group and fire needling group, and liver cells had degenerative edema and cell nucleus were largen and deformed in the MTX group. CONCLUSION: The fire needling has significant efficacy for rats with adjuvant arthritis (AA) without any damage to the liver, which coud have a better control of disease progression of rheumatoid arthritis .
24448345 Humoral immune response to vaccines in patients with rheumatoid arthritis treated with toc 2015 May OBJECTIVE: To evaluate the effect of tocilizumab (TCZ), an interleukin 6 receptor inhibitor, on humoral immune responses to immunisations in patients with rheumatoid arthritis (RA). METHODS: Patients with RA with inadequate response/intolerance to one or more anti-tumour necrosis factor-α agents were randomly assigned (2:1) to TCZ 8 mg/kg intravenously every 4 weeks plus methotrexate (MTX) or MTX alone up until week 8. Serum was collected before vaccination at week 3, antibody titres were evaluated at week 8, and then all patients received TCZ+MTX through week 20. End points included proportion of patients responding to ≥6/12 pneumococcal polysaccharide vaccine (PPV23) serotypes (primary) and proportions responding to tetanus toxoid vaccine (TTV; secondary) at week 8. RESULTS: 91 patients were randomised. At week 8, 60.0% of TCZ+MTX and 70.8% of MTX patients responded to ≥6/12 PPV23 serotypes, with insufficient evidence for any difference in treatments (10.8% (95% CI -33.7 to 12.0)), and 42.0% and 39.1%, respectively, responded to TTV. Two of three TCZ+MTX patients with non-protective baseline TTV antibody titres achieved protective levels by week 8. The safety profile of TCZ was consistent with previous reports. CONCLUSIONS: Short-term TCZ treatment does not significantly attenuate humoral responses to PPV23 or TTV. To maximise vaccine response, patients should be up to date with immunisations before starting TCZ treatment. CLINICALTRIALSGOV IDENTIFIER: NCT01163747.
24447348 Folic acid pathway single nucleotide polymorphisms associated with methotrexate significan 2014 May OBJECTIVES: Methotrexate (MTX) is the cornerstone medication in the treatment of rheumatoid arthritis (RA). We examined whether single nucleotide polymorphisms (SNPs) in enzymes of the folic acid pathway (folylpoly-gamma-glutamate synthetase [FPGS], gamma-glutamyl hydrolase [GGH], and methylenetetrahydrofolate reductase [MTHFR]) associate with significant adverse events (SigAE). METHODS: Patients (n=319) enrolled in the Veterans Affairs RA (VARA) registry taking MTX were genotyped for HLA-DRB1-SE and the following SNPs: FPGS (rs7033913, rs10760503, rs10106), GGH (12548933, rs7010484, rs4617146, rs719235, rs11988534), MTHFR (rs1801131, rs1801133). AE were abstracted from the medical record using a structured instrument. SigAE were defined as an AE leading to MTX discontinuation. Covariates included: age, gender, race, RA antibody status, tobacco, RA disease duration between diagnosis and MTX course, Charlson-Deyo comorbidity index, glucocorticoids, use of prior RA medications, and mean 4-variable disease activity score. Cox regression was performed to determine factors associated with time-to-SigAE. A p-value ≤ 0.005 established significance in the final model. RESULTS: The presence of ≥ 1 copy of the minor allele in MTHFR rs1801131 was associated with an increased hazard ratio (HR) of SigAE (HR 3.05, 95% CI 1.48-6.29, p-value 0.003 and HR 3.88, 95% CI 1.62-9.28, p-value 0.002 for heterozygotes and homozygotes for the minor allele, respectively). An interaction term, between FPGS rs7033913 heterozygotes and GGH rs11988534 homozygotes for the minor allele, had a p-value <0.0001. CONCLUSIONS: RA subjects taking MTX may have decreased time-to-SigAE with ≥ 1 copy of the minor allele in MTHFR rs1801131. Further investigation is warranted, as these SNPs may indicate susceptibility to MTX toxicity.