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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
26725744 Monitoring of Epstein-Barr virus (EBV)/cytomegalovirus (CMV)/varicella-zoster virus (VZV) 2016 Jul INTRODUCTION: IL-6 is involved in viral immunosurveillance. We studied the effect of tocilizumab (TCZ) on the evolution in viral load (VL) for the Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella-zoster virus (VZV) in patients with rheumatoid arthritis (RA). METHODS: EBV, CMV and VZV loads were prospectively determined in whole blood of 22 RA patients at TCZ initiation and during treatment follow-up. A difference of 0.5 log10 or of threefold copies/mL between two VL was considered significant. RESULTS: There were 20 (91%) women, (mean age of 57.8±11.2 years, mean disease duration 11.3±9.7 years) with 16 (73%) seropositive and 16 (73%) erosive patients. TCZ was administered alone for 8 patients (36.7%) or in combination with methotrexate for 11 patients (50%). At baseline, the EBV VL was positive in 8 patients with a mean VL value of 1777.2±3518.3 (3.5±0.4 log10) copies/mL. Only one patient had a positive CMV VL with 2337 copies/mL (3.4 log10). The VZV VL was negative in all patients. After 9.2±4.8 months, EBV VL became negative in 6 of 8 patients (P=0.01) and did not significantly vary in the remaining 2 patients. CMV VL became also negative. No VL (EBV, CMV, VZV) became positive. A positive EBV VL did not correlate with disease activity or with inflammatory biomarkers (ESR and CRP). CONCLUSION: TCZ does not seem to increase the VL of EBV, CMV or VZV. Studies involving larger patient populations are necessary.
25936374 No increased cardiovascular mortality among early rheumatoid arthritis patients: a nationw 2015 May OBJECTIVES: To assess cardiovascular (CV) mortality in early rheumatoid arthritis (RA), and the impact of RA medications on CV mortality. METHODS: We identified all incident RA patients over 18 years of age diagnosed between 2000 and 2007 in Finland. Causes of death were analysed until the end of the year 2008. We used competing-risks regression models to assess the impact of different variables such as RA medications on CV mortality. CV mortality was compared with that of the age- and sex-specific general population. RESULTS: We identified 14,878 incident RA patients (68% women, 63% rheumatoid factor (RF) positive, mean age 55.8/57.5 years in men/women), of whom more than 80% received RA medications for longer than 90% of their individual patient-years. By the end of 2008, 1,157 patients died, 501 (43%) of whom of CV causes. The standardised mortality ratio (SMR) for CV deaths in the entire RA cohort was 0.57 (95% CI 0.52 to 0.62). Along with traditional CV risk factors, the presence of RF and the use of glucocorticoids was associated with a higher risk of CV death, whereas the use of methotrexate was associated with a lower risk. CONCLUSIONS: These nationwide results suggest that patients with recent-onset RA who receive consistent RA medication have no increased risk for CV mortality compared to the general population, at least in the early years of the disease. The use of methotrexate is associated with lower CV mortality, whereas the use of glucocorticoids is associated with a higher than average CV mortality.
26021985 Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of 2015 May 29 BACKGROUND: To measure circulating anti-citrullinated peptide antibodies (ACPA) and cytokines pre- and 6 months post-therapy as a strategy to predict and optimize responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA, which is an unmet need in developing countries. PATIENTS AND METHODS: A cohort of 140 predominantly (88.5 %) black female South African patients with early RA was treated with synthetic DMARDs, mostly methotrexate (MTX) alone, or in combination with low-dose oral corticosteroids (CS). Circulating ACPA and a panel of circulating cytokines/chemokines/growth factors were measured at baseline and after 6 months of therapy in relation to disease activity and Shared Epitope (SE). RESULTS: Following 6 months of therapy, the median simplified disease activity index (SDAI) declined from a baseline of 41.4 to 16.0 (p = 0.0001) for the entire cohort, which was paralleled by significant falls in median serum ACPA levels (516.6 vs. 255.7 units/ml, p = <0.0001) and several of the circulating cytokines (IL-4, IL-7, IL-8, G-CSF, VEGF; p < 0.0010 - p < 0.0001) which were most evident in the subgroup of patients treated with a combination of MTX and CS. Although biomarker concentrations decreased most notably in the low-disease activity group post-therapy, no significant correlations between these biomarkers and disease activity were observed, Baseline ACPA levels, but not SDAI or cytokines, were significantly higher in the subgroup of risk allele-positive patients (561.1 vs. 331.9 units/ml, p < 0.05), while no associations with ACPA and a smoking history were evident. CONCLUSIONS: The use of DMARDs in RA is associated with significant decreases in ACPA and cytokines which did not correlate with changes in SDAI, precluding the utility of serial measurement of these biomarkers to monitor early responses to therapy, but may have prognostic value.
27636122 Association of 63/91 length polymorphism in the DHFR gene major promoter with toxicity of 2016 Oct AIM: Our aim was to explore the influence of 9-bp insertion/deletion and variable number of 9 bp elements (63/91) length polymorphism in noncoding interfering RNA and major promoter of DHFR gene on methotrexate (MTX) efficacy and toxicity in patients with rheumatoid arthritis (RA). PATIENTS & METHODS: Response to the MTX therapy and adverse effects were estimated in 243 RA patients genotyped for the selected polymorphism. RESULTS: The presence of allele 1 of analyzed polymorphism had significant protective effect against MTX toxicity (odds ratio: 0.37 [95% CI: 0.19-0.70]; p = 0.002). Results remained significant in multiple logistic regression analysis with the inclusion of disease and treatment features in the model (p = 0.03). CONCLUSION: Polymorphism 63/91 in DHFR gene promoter can modulate the onset of MTX-related adverse effects in RA patients.
25676124 [Pathogenic cells of rheumatic inflammation as the target of modern therapies]. 2015 Feb In the 1970s and 1980s the course of rheumatoid arthritis (RA) could be defined as fateful despite the introduction of methotrexate as well as other immunosuppressive treatments. In most patients at this time RA was combined with an early disability due a progressive destruction of joints. In addition, comorbidity was known to be one of the major causes for a decreased life expectancy. These less than optimal options for treating RA patients led to intensive research in the pathogenesis with the aim to develop new treatment principles. Based on the increasing knowledge of pathogenically important mechanisms, so-called biologicals were developed targeting T and B cells and proinflammatory cytokines, such as tumor necrosis factor alpha. Over the past 10 years the repertoire of biologicals for treating RA has steadily and significantly increased, which was necessary especially for those patients classified as non-responders to available biological compounds. In the present overview cellular structures, T and B cells as well as cells of the monocyte/macrophage system are discussed as targets for immune interventions.
25351212 Therapeutic effects of micheliolide on a murine model of rheumatoid arthritis. 2015 Jan Rheumatoid arthritis (RA) is a systemic autoimmune disease and collagen-induced arthritis (CIA) is an animal model for RA. Micheliolide (MCL) is a novel compound with strong anti-inflammatory effects. The present study was conducted to evaluate the therapeutic effects of MCL on RA. Mice were randomly divided into four groups and the CIA model mice were treated with methotrexate (MTX), MCL and dimethyl sulfoxide. A score associated with the severity of arthritis was assigned on alternate days from the 22nd day for 60 days. Histopathological changes and the serum levels of cytokines were measured on day 85. The results demonstrated that the MCL treatment group had arthritis scores lower than the CIA group and higher than the MTX group; compared with the CIA group, MCL and MTX significantly reduced the swelling of the paws and suppressed the degeneration of articular cartilage. Expression levels of macrophage colony-stimulating factor (M-CSF), tissue inhibitors of metalloproteinases-1 (TIMP-1) and complement component 5a (C5/C5a) were lower in the mice with arthritis compared with normal mice, however, following treatment with MCL and MTX, all the mice exhibited significant recovery to differing degrees. Unlike the MTX group, the MCL group failed to recover the level of soluble intercellular adhesion molecule-1. In addition, the cytokine of B-lymphocyte chemoattractant (BLC) solely presented in the MCL group. These results suggest that MCL may be considered for use as a novel therapeutic treatment against RA and that changes in the expression of cytokines C5/C5a, TIMP-1, M-CSF and BLC may underlie the mechanism by which MCL effects changes in this disease.
28049958 [Treatment strategy of elderly rheumatoid arthritis]. 2016 Since the general population is ageing, the number and the mean age of elderly patients of rheumatoid arthritis (RA) have increased. Elderly RA is classified into two clinical subsets, younger onset elderly RA (YORA) and elderly-onset RA (EORA). In the past literature, onset after 60 years of age is mainly adopted as the classical definition of EORA. Elderly-YORA patients, in addition to disease-modifying antirheumatic drugs, sometimes need analgestics, joint surgery and rehabilitation taking into account their bone destruction and their activities of daily living. Early phase EORA patients should be treated using the treat-to-target strategy, although low disease activity is the realistic goal due to their co-morbidities, patient factors and drug-related risks. Methotrexate (MTX) is the anchor drug in the treatment of EORA. It should be started at low dose (2-4 mg/day) and if tolerated, the dosage is carefully increased. In the case of renal dysfunction or dementia, and MTX is intolerable, biologics monotherapy could be a choice of treatment. Tapering of glucocorticoid, as far as possible, is needed because it is one of the risk factors of infection. Treatment of super-aged RA patients is a future agenda.
25986276 Mycobacterium abscessus Pulmonary Infection under Treatment with Tocilizumab. 2015 Although biological agents are of considerable benefit to patients with rheumatoid arthritis (RA), the potential for opportunistic infections is a critical issue. It is therefore important to achieve a balance between treatment efficacy and controlling opportunistic infection. We herein report the successfully managed case of a 53-year-old patient with RA who developed pulmonary Mycobacterium abscessus infection during treatment with tocilizumab and methotrexate.
27479367 Rheumatoid arthritis: previously untreated early disease. 2016 Aug 1 INTRODUCTION: Rheumatoid arthritis is a chronic autoimmune disease, which most often presents as a symmetrical polyarthritis of the hands and feet. Pharmacological treatments include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs) and other disease-modifying anti-rheumatoid drugs (DMARDs), which may be synthetic (either conventional [csDMARDs] or targeted [tsDMARDs]) or biological (bDMARDs). METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of methotrexate in combination with other csDMARDs versus methotrexate monotherapy in people with rheumatoid arthritis who have not previously received any DMARD treatment (first-line treatment)? What are the effects of bDMARDs as monotherapy versus methotrexate or other csDMARDs in people with rheumatoid arthritis who have not previously received any DMARD treatment (first-line treatment)? What are the effects of bDMARDs in combination with methotrexate versus methotrexate monotherapy or other csDMARDs in people with rheumatoid arthritis who have not previously received any DMARD treatment (first-line treatment)? What are the effects of glucocorticoids in combination with methotrexate or with other csDMARDs versus methotrexate or other csDMARDs in people with rheumatoid arthritis who have not previously received any DMARD treatment (first-line treatment)? We searched: Medline, Embase, The Cochrane Library and other important databases up to December 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 2058 studies. Of the full articles evaluated, 10 systematic reviews, 22 RCTs, and one follow-up report were added at this update. We performed a GRADE evaluation for 18 PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for 22 comparisons based on information about the effectiveness and safety of bDMARDs (monotherapy or combined with csDMARDs), csDMARDs (monotherapy or combined with other csDMARDs), glucocorticoids combined with methotrexate or other csDMARDs, and methotrexate (monotherapy or combined with other csDMARDs), identifying interventions which were likely or unlikely to be beneficial.
26962704 Rediscovering the therapeutic use of glucocorticoids in rheumatoid arthritis. 2016 May PURPOSE OF REVIEW: This review will focus on new information obtained on how to apply glucocorticoids in the treatment of rheumatoid arthritis, aiming at an optimal risk-benefit ratio. Moreover, advances in the development of new preparations such as liposomal glucocorticoids will be discussed. RECENT FINDINGS: In early rheumatoid arthritis, treatment regimens with a disease-modifying drug and initially medium-dose glucocorticoids (>7.5 but ≤30 mg prednisone equivalent) are noninferior compared with regimens with disease-modifying drugs and initially high-dose glucocorticoids (>30 mg prednisone equivalent) and have repeatedly been proven to be more effective than methotrexate monotherapy. Use of glucocorticoids following such a scheme during a period of 6 months to 2 years was not associated with increased mortality, nor with substantial bone loss if bone protective measures had been taken. New drug delivery systems, and in particular long-circulating liposomes, aiming at enhancing the biodistribution and the target site accumulation of glucocorticoids and thereby improving the balance between their efficacy and toxicity, are promising; more results on the effects in rheumatoid arthritis patients are expected to be reported during the years to come. SUMMARY: Combination therapy including methotrexate and glucocorticoids should be the initial treatment in patients with early rheumatoid arthritis. Treatment regimens including medium-dose glucocorticoids are noninferior compared with regimens with initially high-dose glucocorticoids. Studies on new glucocorticoid preparations and new drug delivery systems improving the balance between efficacy and toxicity of glucocorticoid therapy are ongoing.
27373691 The Suppressive Effects of the Petroleum Ether Fraction from Atractylodes lancea (Thunb.) 2016 Oct In Chinese traditional medicine, the rhizome of Atractylodes lancea (Thunb.) DC. (A. lancea) is used extensively for the treatment of several diseases such as rheumatic diseases, but its actions on rheumatoid arthritis have not been clarified. The purpose of this article was to investigate the pharmacological effect of an A. lancea rhizome extract on collagen-induced arthritis (CIA) in rats. The CIA model was induced by the injection of bovine type II collagen. The rats were orally administered the petroleum ether (PE) fraction of the A. lancea rhizome (0.82 and 1.64 mg/kg), methotrexate (0.3 mg/kg body weight), or a vehicle from day 7 to day 15 after the model was established. The histological examination and radiological observation showed that the PE fraction significantly reduced the inflammatory responses and collagen loss in the joints of the rats with CIA. The PE fraction inhibited the production of tumor necrosis factor-α, interleukin (IL)-1β, IL-17, and IL-6 in the sera. Moreover, the treatment with the PE fraction in vivo was able to reduce the level of Beclin 1 protein in the synovial tissue of the rats. These results highlight the antiarthritic potential of the PE fraction of the A. lancea rhizome and provide further evidence of the involvement of Beclin 1 inhibition in the effects of the PE fraction of the A. lancea rhizome. Copyright © 2016 John Wiley & Sons, Ltd.
26774261 DAS steered therapy in clinical practice; cross-sectional results from the METEOR database 2016 Jan 16 BACKGROUND: Little is known on how well targeted treatment, for instance targeting towards low DAS, is implemented in clinical practice. Our aim was to evaluate treatment adjustments in response to DAS in RA patients in clinical practice. METHODS: We used data from one referral centre, multiple rheumatologists, from the METEOR database. Generalized Estimating Equations (GEE) were used to assess whether in case of non-low disease activity (DAS > 2.4) treatment intensifications in DMARD therapy occurred ((change or increase in dose or number of DMARDs, including synthetic (s)DMARDs, biologic (b)DMARDs and corticosteroids compared to the visit before)). Determinants of not intensifying the treatment when DAS > 2.4 were investigated using GEE. RESULTS: Five thousand one hundred fifty-seven registered visits of 1202 patients were available for the analyses. A DAS > 2.4 was weakly (OR: 1.19; 95% CI 1.07-1.33) associated with a treatment intensification. In 69% (n = 3577) of the visits patients were in low disease activity. In 66% (n = 1028) of the visits with DAS > 2.4 treatment was not intensified. These patients had a higher tender joint count and received more often methotrexate plus a bDMARD, or csDMARD monotherapy, as compared to patients that received treatment intensification. CONCLUSION: In the majority of visits in the METEOR database patients were already in a state of low disease activity, reflecting appropriate treatment intensity. When DAS was greater than 2.4, treatment was often not intensified due to high tender joint count or specific treatment combinations. This data suggest that while aiming for low DAS, physicians per patient weigh whether all DAS elements indicate disease activity or will respond to DMARD adjustment or not, and make treatment decisions accordingly.
24252054 Confirmation of effectiveness of tocilizumab by ultrasonography and magnetic resonance ima 2015 Efficacy of tocilizumab in active early-stage RA patients despite methotrexate was evaluated for 12 months. One out of 5 patients was quitted by infusion reaction whereas tocilizumab continued for 12 months in the remaining 4 patients. Power Doppler articular synovitis was reduced in every patient and disappeared in 2 patients. Marked MRI osteitis, found in 1 patient, had disappeared at 12 months. Present results confirm the efficacy of tocilizumab by ultrasonography and MRI.
26903239 Effects of synthetic and biological disease modifying antirheumatic drugs on lipid and lip 2016 Jun BACKGROUND: Dyslipidemia in rheumatoid arthritis (RA) patients is frequently observed, and treatment with anti-rheumatic drugs has an impact on lipid profiles. Pathophysiologically, inflammation leads to decreased blood lipids and lipoproteins; RA treatment reduces inflammation and therefore may increase lipids and lipoproteins. Whether the lipid changes with RA treatment confer an increased risk of cardiovascular disease or just reflect their potentially atheroprotective anti-inflammatory effect is currently unclear due to limited and conflicting data. OBJECTIVE: The aim of this review is to summarize the current knowledge on the effects of synthetic and biological disease modifying antirheumatic drugs for the treatment of RA on lipid and lipoprotein parameters. RESULTS: Recent studies on methotrexate emphasize its anti-atherogenic effect. Golimumab combined with methotrexate revealed a trend towards an anti-atherogenic potential. The known pro-atherogenic lipid-spectrum alterations caused by tofacitinib can be effectively treated with atorvastatin. Tocilizumab signals a favorable impact on the extent of lipid modifications when combined with methotrexate. Abatacept indicated a trend towards an anti-atherogenic lipid profile demonstrated by favorable effects on HDL-C and on the TC/HDL-C ratio. Rituximab has beneficial effects on HDL-C and ApoA1, as well as on the ApoB/ApoA1 ratio. CLINICAL IMPLICATIONS: Anti-rheumatic drugs have various effects on lipid parameters, which in part appear pro-atherogenic. However, because many of these lipid changes may well reflect their potentially atheroprotective anti-inflammatory action the cardiovascular impact of these changes remains unclear. Whatsoever, cardiovascular safety trials for antirheumatic drugs would be valuable.
27450487 Medical ozone increases methotrexate clinical response and improves cellular redox balance 2016 Oct 15 Medical ozone reduced inflammation, IL-1β, TNF-α mRNA levels and oxidative stress in PG/PS-induced arthritis in rats. The aim of this study was to investigate the medical ozone effects in patients with rheumatoid arthritis treated with methotrexate and methotrexate+ozone, and to compare between them. A randomized clinical study with 60 patients was performed, who were divided into two groups: one (n=30) treated with methotrexate (MTX), folic acid and Ibuprophen (MTX group) and the second group (n=30) received the same as the MTX group+medical ozone by rectal insufflation of the gas (MTX+ozone group). The clinical response of the patients was evaluated by comparing Disease Activity Score 28 (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), Anti-Cyclic Citrullinated (Anti-CCP) levels, reactants of acute phase and biochemical markers of oxidative stress before and after 20 days of treatment. MTX+ozone reduced the activity of the disease while MTX merely showed a tendency to decrease the variables. Reactants of acute phase displayed a similar picture. MTX+ozone reduced Anti-CCP levels as well as increased antioxidant system, and decreased oxidative damage whereas MTX did not change. Glutathione correlated with all clinical variables just after MTX+ozone. MTX+ozone increased the MTX clinical response in patients with rheumatoid arthritis. No side effects were observed. These results suggest that ozone can increase the efficacy of MTX probably because both share common therapeutic targets. Medical ozone treatment is capable of being a complementary therapy in the treatment of rheumatoid arthritis.
25534420 Risk of venous thromboembolism in patients with rheumatoid arthritis: initiating disease-m 2015 May OBJECTIVES: Recent research suggests that rheumatoid arthritis increases the risk of venous thromboembolism. This study compared the risk of venous thromboembolism in patients with newly diagnosed rheumatoid arthritis initiating a biologic disease-modifying antirheumatic drug (DMARD) with those initiating methotrexate or a nonbiologic DMARD. METHODS: We conducted a population-based cohort study using US insurance claims data (2001-2012). Three mutually exclusive, hierarchical DMARD groups were used: (1) a biologic DMARD with and without nonbiologic DMARDs; (2) methotrexate without a biologic DMARD; or (3) nonbiologic DMARDs without a biologic DMARD or methotrexate. We calculated the incidence rates of venous thromboembolism. Cox proportional hazard models stratified by propensity score (PS) deciles after asymmetric PS trimming were used for 3 pairwise comparisons, controlling for potential confounders at baseline. RESULTS: We identified 29,481 patients with rheumatoid arthritis with 39,647 treatment episodes. From the pairwise comparison after asymmetric PS trimming, the incidence rate of hospitalization for venous thromboembolism per 1000 person-years was 5.5 in biologic DMARD initiators versus 4.4 in nonbiologic DMARD initiators and 4.8 in biologic DMARD initiators versus 3.5 in methotrexate initiators. The PS decile-stratified hazard ratio of venous thromboembolism associated with biologic DMARDs was 1.83 (95% confidence interval [CI], 0.91-3.66) versus nonbiologic DMARDs and 1.39 (95% CI, 0.73-2.63) versus methotrexate. The hazard ratio of venous thromboembolism in biologic DMARD initiators was the highest in the first 180 days versus nonbiologic DMARD initiators (2.48; 95% CI, 1.14-5.39) or methotrexate initiators (1.80; 95% CI, 0.90-3.62). CONCLUSIONS: The absolute risk for venous thromboembolism was low in patients with newly diagnosed rheumatoid arthritis. Initiation of a biologic DMARD seems to be associated with an increased short-term risk of hospitalization for venous thromboembolism compared with initiation of a nonbiologic DMARD or methotrexate.
25721154 MIF and TNFα serum levels in rheumatoid arthritis patients treated with disease-modifying 2015 Apr Macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNFα) play a pivotal role in rheumatoid arthritis (RA). MIF is considered a relevant cytokine because it appears before TNFα in the inflammatory cascade thus stimulating TNFα production and MIF's relationship with traditional synthetic disease modifying antirheumatic drugs (sDMARDs) is unknown. In this cross-sectional study, we investigated the association of MIF and TNFα serum levels with methotrexate (MTX) and in combination with chloroquine (CLQ) and sulfasalazine (SSZ) in RA patients classified according to the ACR/EULAR 2010 criteria. Patients were divided into three groups: MTX-monotherapy group (n = 40), MTX combination therapy groups: MTX + CLQ (n = 41), and MTX + CLQ + SSZ (n = 42). MIF and TNFα serum levels were determined by ELISA. We found high levels of ESR, CRP, RF, and anti-CCP in all therapy groups. Furthermore, we subclassified 97 patients with established RA (≥2 years of disease duration) and found that TNFα serum levels were lower in the combination therapy group (MTX + CLQ + SSZ) in comparison with the monotherapy MTX group (16.7 pg/mL versus 13.6 pg/mL, p = 0.02). However, we did not find differences between sDMARD therapies in MIF serum levels. We did find a significant reduction in MIF serum levels in patients treated with oral steroids compared with patients without oral steroids (1.7 ng/mL versus 4.3 ng/mL, p < 0.001). In conclusion, this study supports the role of sDMARDs in modifying TNFα serum levels and oral steroids MIF serum levels. Nevertheless, we found that MIF serum levels are not modified by sDMARD treatment.
26085073 [Treatment reduction in well-controlled rheumatoid arthritis. State of knowledge]. 2015 Jun Nowadays, the excellent treatment options available for rheumatoid arthritis (RA) result in ambitious therapeutic goals, such as remission, which can actually be achieved for many RA patients. In a state of sustained remission many patients request reduction in drug treatment and this as well as economic reasons makes treatment reduction or even drug-free remission a reasonable target. Increasingly successful reduction of disease-modifying antirheumatic drug (DMARD) treatment has been shown in studies for approximately 30-60 % of patients in sustained remission, at least for some period of time. Because flare retreatment is successful in nearly all cases, the risk of treatment de-escalation can be minimized, so long as patients are continuously monitored after reduction or termination of drug treatment. No study has yet shown an elevated risk for unfavorable long-term outcome in cases of controlled treatment reduction. Current treatment recommendations are that glucocorticoids should first be withdrawn followed by reduction and termination of biologics and in cases of sustained remission finally, conventional DMARDs, such as methotrexate should be reduced and possibly terminated to achieve the defined target of drug-free remission. Factors facilitating success of tapering antirheumatic drugs are low disease activity at initiation, negative serological tests and short disease duration after starting DMARD treatment. A joint decision between rheumatologists and patients as well as continuous remission for at least 6 months are prerequisites for drug reduction.
27481904 Active Rheumatoid Arthritis in Central Africa: A Comparative Study Between Sudan and Swede 2016 Oct OBJECTIVE: To compare clinical characteristics and treatment between simultaneously investigated Sudanese and Swedish outpatients with rheumatoid arthritis (RA). METHODS: Outpatients with RA from Sudan (n = 281) and Sweden (n = 542) diagnosed according to the 1987 American College of Rheumatology criteria were recruited between December 2008 and September 2010 and compared concerning clinical presentation, treatment, and laboratory findings, including immunoglobulin M with rheumatoid factor (IgM-RF). RESULTS: Sudanese patients had lower inclusion age (median 49 vs 68 yrs), disease duration (48 vs 107 mos), and disease onset age (43 vs 56 yrs) as compared with Swedish patients (p < 0.0001 for all). When stratified concerning the age of inclusion, Swedish patients between 41-50 years had, however, a significantly lower age of onset, with a similar trend for all age groups above 30 years. The female preponderance was higher among Sudanese patients (89.3% vs 72.5%, p < 0.0001), and smoking was nonexistent among Sudanese female patients (p < 0.0001). Erythrocyte sedimentation rate levels and number of tender joints were significantly higher among Sudanese patients. The proportion of IgM-RF positivity was lower among Sudanese patients with RA (52.4% vs 75.5%, p < 0.0001). Higher proportions of Sudanese patients with RA were treated with methotrexate (MTX) and disease-modifying antirheumatic drug combinations, but none of them used biologics. Sudanese patients used lower doses of MTX and sulfasalazine (p < 0.0001) and higher doses of prednisolone (p < 0.0001) than Swedish patients. CONCLUSION: Sudanese patients with RA have significantly higher disease activity and are often IgM-RF-seronegative. Together with reports from Uganda and Cameroon, our data indicate a cluster of highly active and often seronegative RA in central Africa.
27323187 Overexpression of P-glycoprotein on fibroblast-like synoviocytes in refractory rheumatoid 2016 Jun 17 This study aims to investigate the role of P-glycoprotein (P-gp) expression level in drug resistance to disease-modifying anti-rheumatic drugs in refractory rheumatoid arthritis (RRA). We evaluated and compared the expression levels of P-gp in fibroblast-like synoviocyte (FLS) cells in patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and investigated the potential mechanism of P-gp-induced multidrug resistance in RRA. Ten patients were enrolled and divided into two groups: six in the RA group and four in the OA group. The expression level of P-gp in FLS cells was detected by western blotting following cell culture. A linear correlation algorithm was used to assess the association between the level of P-gp and disease activity  (using DAS28 scoring), as well as the duration of methotrexate (MTX) treatment in the RRA patients. The level of P-gp in the RRA patients was markedly higher than that in the OA patients (P < 0.05, t = -4.179). There was a positive linear correlation between the P-gp level in FLS cells and the duration of MTX treatment in the RRA group (Г = 0.733, P < 0.05), whereas there was no significant correlation between the P-gp level and DAS28 scoring (Г = 0.206, P > 0.05). P-gp might be upregulated during the progression of RRA, which possibly correlates with the development of resistance to MTX.