Browse

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

ID PMID Title PublicationDate abstract
26114440 Therapeutic effect of methotrexate encapsulated in cationic liposomes (EndoMTX) in compari 2015 OBJECTIVES: Cationic lipid complexes bind to angiogenic endothelial cells of solid tumours and microvessels of chronic inflammatory tissue. Methotrexate (MTX) is one of the drugs used in the therapy of rheumatoid arthritis (RA); it is applied systemically but can have serious side-effects. The aim of this study was to investigate the impact of MTX encapsulated in cationic liposomes (EndoMTX) in comparison to treatment with free MTX. METHOD: We used an antigen-induced arthritis (AiA) model and investigated the leucocyte- and platelet-endothelial cell interaction in arthritic female C57/Bl6 mice and in healthy controls. The arthritic animals were divided into four different groups receiving either trehalose, free MTX, EndoMTX placebo, or EndoMTX. These parameters and functional capillary density (FCD) were measured and assessed by intravital microscopy (IVM). We controlled clinical parameters such as the knee joint diameter (KJD) throughout the observation period. RESULTS: Animals treated with EndoMTX showed a significant and superior reduction in leucocyte- and platelet-endothelial cell interaction, FCD, and KJD. Free MTX or empty liposomes also showed a reduction in these parameters but not to a significant level. FCD decreased in the EndoMTX group in comparison to using free drugs or empty carrier-like liposomes. CONCLUSIONS: This study demonstrates the advantage of using MTX encapsulated in cationic liposomes in contrast to free and generic MTX, with a higher efficacy in anti-inflammatory and anti-angiogenic abilities. Targeting with cationic liposomes may be a promising treatment option and should be elucidated in further experiments regarding dose reduction and side-effects due to MTX usage.
26733110 Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients 2016 Nov OBJECTIVE: To compare the efficacy and safety between tocilizumab added to methotrexate and tocilizumab switched from methotrexate in patients with active rheumatoid arthritis (RA). METHODS: This is a 2-year randomised, controlled study. RA patients with moderate or high disease activity despite methotrexate were randomly assigned either to tocilizumab added to methotrexate (add-on) or tocilizumab switched from methotrexate (switch). The primary endpoint was the DAS28 remission rate at week 24. Secondary objectives included other clinical efficacy indices, radiological outcomes assessed with the van der Heijde-modified total Sharp scoring system (mTSS), and safety. RESULTS: Of 223 randomised patients, 83% completed 52 weeks. DAS28 remission rates at week 24 were 70% for add-on and 55% for switch (p=0.02), but they became comparable at week 52 (72% vs 70%, p=0.86). Structural remission rates (mTSS≤0.5) at week 52 were not different (66% vs 64%, p=0.92). However, clinically relevant radiographic progression rates (CRRP; mTSS≥3) tended to be higher with the switch than with the add-on (15% vs 7%, p=0.07). Radiographic progression in the CRRP patients was larger with the switch than with the add-on (9.0/year vs 5.0/year, p=0.04). The difference in the mean C-reactive protein of the CRRP patients was significant for the first 24 weeks (1.56 vs 0.49, p=0.001) but not for the following 28 weeks (0.10 vs 0.04, p=0.1). Overall safety was preferable in the switch group. CONCLUSIONS: In RA patients with inadequate response to methotrexate, tocilizumab added to methotrexate more rapidly suppressed inflammation than tocilizumab switched from methotrexate, leading to superior clinical efficacy and prevention of joint destruction. TRIAL REGISTRATION NUMBER: NCT01120366.
27311186 [IL-6 blockade]. 2016 Jun Interleukin-6 (IL-6) plays an important role in the pathogenesis of rheumatoid arthritis (RA). Tocilizumab, anti-human IL-6 receptor monoclonal antibody developed in Japan, prevents IL-6 from binding to IL-6 receptor blocking IL-6 signal. The clinical and radiographic efficacy of tocilizumab has proved in many clinical studies. Tocilizumab monotherapy is superior to methotrexate, which has not proved in TNF inhibitors, although tocilizuab in combination with methotrexate is more effective than tocilizumab monotherapy in inducing remission. Hepatotoxicity and infection are adverse events to be careful about.
27050478 Adherence to current recommendations on the use of methotrexate in rheumatoid arthritis in 2016 May OBJECTIVES: The aim of this study was to assess how the management of rheumatoid arthritis (RA) with methotrexate (MTX) in Italy is adherent to current national recommendations. METHODS: We performed a cross-sectional and retrospective analysis of data collected from the MARI study, a multicentre survey on Italian patients with RA on treatment with MTX for at least 12 months. Retrospective data included patient's clinical history, previous treatment with MTX, screening tests performed before MTX prescription. Cross-sectional data were collected about current treatment with MTX, concomitant medications, and disease activity. Each proposition of the 2013 Italian recommendations on the use of MTX in RA was reformulated in terms of audit criteria, and adherence to provided indications was evaluated for every patient. RESULTS: Among the 1336 included patients, less than 40% had started treatment with MTX within 3-6 months from the diagnosis and nearly 30% of them were prescribed with an initial dose of MTX between 12.5 and 15 mg/week. Screening for HBV and HCV infection as well as chest x-ray was performed in a proportion of patients around 60% and more than 90% of them underwent lab tests before MTX prescription and regularly throughout the treatment. Folic acid supplementation was given at recommended dosages in a high proportion of patients. CONCLUSIONS: Our survey showed a good adherence of Italian rheumatologists to recommendations regarding safety issues with MTX in RA, but a suboptimal approach in terms of time and dosage of the treatment in the early phases of the disease.
25779750 Apremilast in Patients With Active Rheumatoid Arthritis: A Phase II, Multicenter, Randomiz 2015 Jul OBJECTIVE: To study the efficacy/safety of apremilast, an oral phosphodiesterase 4 inhibitor, compared with placebo in patients with active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX). METHODS: Patients were randomized 1:1:1 to receive placebo, apremilast 20 mg twice a day, or apremilast 30 mg twice a day. Patients whose swollen and tender joint counts had not improved by ≥20% were considered nonresponders at week 16 and were required to enter the protocol-defined early escape. At week 24, patients were transitioned in a blinded manner to receive apremilast 20 mg twice a day if they were initially randomized to receive placebo. Patients who were not initially randomized to receive placebo continued to receive their target apremilast dose. Patients were required to take a stable dose of MTX (7.5-25 mg/week) throughout the study. Magnetic resonance imaging (MRI) was performed in a subset of patients. RESULTS: A total of 237 patients who were receiving MTX therapy were randomized and received ≥1 dose of study medication. At week 16, similar proportions of patients receiving placebo (35%), apremilast 20 mg twice a day (28%), and apremilast 30 mg twice a day (34%) met the American College of Rheumatology criteria for 20% improvement in disease activity (the primary efficacy end point). In the MRI substudy, mean change from baseline in total joint damage scores according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system was generally similar with either apremilast dose at week 16. At week 52, no trends were noted for clinical end points by treatment group. Both apremilast doses were generally well tolerated. CONCLUSION: Apremilast efficacy was not demonstrated in patients who had active RA despite stable MTX therapy.
26449724 Serum 14-3-3η level is associated with severity and clinical outcomes of rheumatoid arthr 2015 Oct 9 INTRODUCTION: Treat-to-target strategies to achieve low disease activity or clinical remission are key in the treatment of rheumatoid arthritis (RA). 14-3-3η is a joint-derived biomarker that is expressed at significantly higher levels in patients with RA than in healthy subjects, other autoimmune diseases, or viral and bacterial arthritides. In this study, we sought to investigate the utility of pretreatment levels of 14-3-3η and serial measurement of 14-3-3η to inform therapeutic outcomes. METHODS: Serum 14-3-3η levels were measured in 149 Japanese patients with RA before the initiation of therapy and at 1-year follow-up. Patients were treated with either methotrexate (MTX), adalimumab (ADA), tocilizumab (TCZ), or tofacitinib (TOF). 14-3-3η positivity was defined as ≥0.19 ng/ml and at two times and four times this cutoff. In contingency analysis, we determined the association of 14-3-3η with disease severity. Wilcoxon matched-pairs test was used to evaluate the significance of pre- to post-treatment changes. Mann-Whitney U test was performed for differences between treatment response groups. Fisher's exact test was used to assess associations of 14-3-3η with a good response defined by European League Against Rheumatism criteria as well as remission defined by the Disease activity Score in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index score. RESULTS: 14-3-3η-positive patients had more severe disease before the initiation of treatment. When combined with C-reactive protein (CRP), 14-3-3η positivity added significantly and incrementally to the identification of patients with high disease activity. 14-3-3η levels were significantly decreased at 1 year and were modifiable across all classes of therapeutics. Patients who reverted to negative 14-3-3η levels had better clinical response than patients who remained positive at 1 year or became positive. Pretreatment 14-3-3η levels informed 1-year DAS28-ESR remission in the TCZ-treated group, in contrast to the ADA, MTX, or TOF groups, while no differences in pretreatment 14-3-3η expression based on clinical response. CONCLUSIONS: 14-3-3η is a modifiable marker in identifying patients with RA in a high disease state. Patients who achieve a negative 14-3-3η status following 1-year of treatment do better clinically with pretreatment 14-3-3η informing response to TCZ.
27435295 Prediction of the therapeutic response to methotrexate at 24 weeks by methotrexate-polyglu 2017 May OBJECTIVES: The objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of methotrexate-polyglutamates (MTX-PGs) in erythrocytes in patients with rheumatoid arthritis and correlate them with the efficacy. METHODS: MTX-PG concentrations in erythrocytes were measured in 42 MTX-naïve patients repeatedly for 24 weeks by high-performance liquid chromatography. In 56 patients receiving stable MTX doses for at least 12 weeks, the correlation between MTX doses and MTX-PG concentrations was examined. The efficacy was measured by the change of DAS28CRP (ΔDAS28CRP). RESULTS: There were moderate correlations between MTX dose and MTX-PG 3, 4, and 5. At 24 weeks, MTX-PG2, 3, 4, and 1-5 were higher in patients with ΔDAS28CRP >1.2 than in those with ≤1.2. The cutoff value of MTX-PG1-5 to discriminate ΔDAS28CRP >1.2 from ≤1.2 at 24 weeks was 68.7 nM. Among 20 patients with MTX-PG1-5 > 50.6 nM at 8 weeks, seven already improved at 8 weeks and additional 11 improved at 24 weeks (p < 0.001). On the contrary, among the nine patients with MTX-PG1-5 ≤ 50.6 nM at 8 weeks, none improved at 8 weeks and only one improved at 24 weeks (p = 0.500). CONCLUSIONS: Erythrocyte MTX-PGs might be a potential indicator and predictor of MTX efficacy.
26082314 15-hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid a 2015 Sep 15-Hydroxyprostaglandin dehydrogenase (HPGD) is the key enzyme responsible for the metabolic inactivation of prostaglandin E2 (PGE2) catabolism. PGE2 is one of the predominant catabolic factors involved in rheumatoid arthritis (RA). However, the expression and regulation of HPGD in RA fibroblast‑like synoviocyte (FLS) remain to be elucidated. Disease‑modifying anti‑rheumatic drugs (DMARDs) are the most important anti‑arthritic drugs, which reduce the effect of joint injury. The aim of the present study was to assess the expression of HPGD in RA tissues and cells, and normal synovial tissues and cells. The effect of the most popular DMARDs, hydroxychloroquine, on the expression of HPGD in RA‑FLS was also investigated. Western blotting and immunohistochemical analysis demonstrated that the expression levels of HPGD in human synovium were lower in RA synovium compared with the normal and OA synovium. In RA‑FLS, the expression of HPGD was increased following treatment with several DMARDs, including sulfasalazine, methotrexate, and hydroxychloroquine. Hydroxychloroquine (10 µM) treatment induced the phosphorylation of ERK, SAPK/JNK and p38. Hydroxychloroquine induced a decrease in the release of PGE2, which was restored by mitogen‑activated protein (MAP) kinase pathway inhibitors. Hydroxychloroquine may therefore, affect the pathogenesis of RA through the MAP kinase pathway by regulating the expression of HPGD.
26474192 Clinical efficacy, radiographic progression, and safety through 156 weeks of therapy with 2016 Jul OBJECTIVE: To evaluate the safety and efficacy of golimumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA). METHODS: Japanese patients with active RA despite MTX were randomized to placebo + MTX (Group 1, n = 88), golimumab 50 mg + MTX (Group 2, n = 86), or golimumab 100 mg + MTX (Group 3, n = 87). Patients with <20% improvement in swollen/tender joint counts entered early escape at week 16. At week 24, all remaining placebo patients crossed over to golimumab 50 mg. Efficacy assessments included ACR20, DAS28-ESR, and HAQ-DI. Radiographic progression was assessed with the van der Heijde-modified Sharp (vdH-S) score. RESULTS: ACR20 response rates in Group 1, Group 2, and Group 3 were 67.9, 86.1, and 82.4%, respectively, at week 52 and were maintained through week 104 (87.1, 94.0, and 88.7%) and week 156 (97.1, 94.1, and 89.5%). Proportions of patients with good/moderate DAS28-ESR response or clinically meaningful improvement in HAQ-DI were also maintained through week 156. The majority of patients did not experience radiographic progression through week 156. Among 257 golimumab-treated patients, 251 (97.7%) had ≥1 AE; 54 (21.0%) had ≥1 serious AE through week 156. Infections were the most common type of AE. CONCLUSIONS: Response to golimumab + MTX was maintained over 3 years in Japanese patients with active RA despite MTX. Safety results were consistent with the known safety profile of golimumab.
27886691 Pharmacotherapy Pearls for the Geriatrician: Focus on Oral Disease-Modifying Antirheumatic 2017 Feb Providing safe and effective pharmacotherapy to the geriatric patients with rheumatological disorders is an ongoing struggle for the rheumatologist and geriatrician alike. Cohesive communication and partnership can improve the care of these patients and subvert adverse outcomes. Disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide, and the newest oral agent for treatment of rheumatoid arthritis, tofacitinib, have distinctive monitoring and adverse effect profiles. This article provides the general practitioner or geriatrician with clinically relevant pearls regarding the use of these interventions in older patients.
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.
26608949 High-temporospatial-resolution dynamic contrast-enhanced (DCE) wrist MRI with variable-den 2016 Jan This study is to evaluate highly accelerated three-dimensional (3D) dynamic contrast-enhanced (DCE) wrist MRI for assessment of perfusion in rheumatoid arthritis (RA) patients. A pseudo-random variable-density undersampling strategy, circular Cartesian undersampling (CIRCUS), was combined with k-t SPARSE-SENSE reconstruction to achieve a highly accelerated 3D DCE wrist MRI. Two healthy volunteers and 10 RA patients were studied. Two patients were on methotrexate (MTX) only (Group I) and the other eight were treated with a combination therapy of MTX and anti-tumor necrosis factor (TNF) therapy (Group II). Patients were scanned at baseline and 3 month follow-up. DCE MR images were used to evaluate perfusion in synovitis and bone marrow edema pattern in the RA wrist joints. A series of perfusion parameters was derived and compared with clinical disease activity scores of 28 joints (DAS28). 3D DCE wrist MR images were obtained with a spatial resolution of 0.3 × 0.3 × 1.5 mm(3) and temporal resolution of 5 s (with an acceleration factor of 20). The derived perfusion parameters, most notably transition time (dT) of synovitis, showed significant negative correlations with DAS28-ESR (r = -0.80, p < 0.05) and DAS28-CRP (r = -0.87, p < 0.05) at baseline and also correlated significantly with treatment responses evaluated by clinical score changes between baseline and 3 month follow-up (with DAS28-ESR r = -0.79, p < 0.05, and DAS28-CRP r = -0.82, p < 0.05). Highly accelerated 3D DCE wrist MRI with improved temporospatial resolution has been achieved in RA patients and provides accurate assessment of neovascularization and perfusion in RA joints, showing promise as a potential tool for evaluating treatment responses.
26237830 Effect of sanhuangwuji powder, anti-rheumatic drugs, and ginger-partitioned acupoint stimu 2015 Jun OBJECTIVE: To observe the efficacy and safety of oral sanhuangwuji powder, anti-rheumatic drugs (ARDs), and ginger-partitioned acupoint stimulation at zusanli (ST 36) on the treatment of rheumatoid arthritis (RA) complicated by peptic ulcer. METHODS: This prospective randomized controlled study included 180 eligible inpatients and outpatients randomly assigned to an ARD treatment (n.= 60), ginger-partitioned stimulation (n = 60), or combination treatment (n = 60). Patients assigned to the ARD group were given oral celecoxib, methotrexate, and esomeprazole. Patients assigned to the ginger-partitioned stimulation group were given ginger-partitioned acupoint stimulation at zusanli (ST 36) in addition to the ARDs. Patients in the combination treatment group were given oral sanhuangwuji powder, ginger-partitioned acupoint stimulation at susanli (ST 36), and ARDs. All patients were followed up for 2 months to evaluate clinical effects and safety. The study was registered in the World Health Organization database at the General Hospital of Chengdu Military Area Command Chinese People's Liberation Army (ChiCTR-TCC12002824). RESULTS: The combination treatment group had significantly greater improvements in RA symptoms, laboratory outcomes, and gastrointestinal symptom scores, compared with the other groups (P < 0.05). The peptic ulcer healing rate in the combination treatment group was significantly greater than that in the ARD treatment group (χ2= 16.875, P < 0.05) and the ginger-partitioned stimulation group (χ2= 6.171, P < 0.05). CONCLUSION: Combination treatment with ginger-partitioned acupoint stimulation at zusanli (ST 36), oral sanhuangwuji powder, and ARDs had a better clinical effect for RA with complicated peptic ulcer, compared with ARD treatmentalone or in combination with ginger-partitioned acupoint stimulation.
26305307 Comparison of the Therapeutic Effects of Thymoquinone and Methotrexate on Renal Injury in 2015 Aug OBJECTIVE: To determine the effect of thymoquinone and methotrexate on blood urea and serum creatinine in arthritic rats. STUDY DESIGN: Experimental, comparative study. PLACE AND DURATION OF STUDY: Postgraduate Medical Institute, Lahore, from March to August 2013. METHODOLOGY: Thirty two female Sprague-Dawley rats were randomized into four equal groups (n=8); group A(healthy control), group B (positive control), group C (Thymoquinone treated) and group D (Methotrexate treated). Arthritis developed within two weeks after a single pristane injection. Total leukocyte count, blood urea and serum creatinine were taken at day 0, 15 and 30. While clinical score of inflammation was taken at day 0 and then on every alternate day. RESULTS: Development of arthritis and renal involvement was accompanied by significant raise in total leukocyte count, clinical score of inflammation, blood urea and serum creatinine as compared to healthy control rats (group A) till day 15 (p < 0.001). From day 15 to day 30 both thymoquinone (group C) and methotrexate (group D) significantly lowered the total leukocyte count, clinical score of inflammation and improved blood urea and serum creatinine as compared to arthritic rats (group B) (p < 0.001). Methotrexate was found a bit more effective than thymoquinone. CONCLUSION: Evaluation of results supported the beneficial effects of thymoquinone in renal injury produced by rheumatoid arthritis.
25708452 Alternative Ways to Quantify Sustained Remission: Applying the Continuity Rewarded Score a 2015 Oct OBJECTIVE: Although the Computer Assisted Management in Early Rheumatoid Arthritis Trial-II (CAMERA-II) showed favorable clinical effects in the most intensive methotrexate (MTX)-based strategy with prednisone (MTX ± prednisone) compared to that with placebo (MTX + placebo), this beneficial difference was only seen in 1 of the 3 analyses of remission. Our objective was to investigate whether the Continuity Rewarded (ConRew) score and a simple sum score would better reveal differences regarding remission between the 2 treatment arms of CAMERA-II. Furthermore, we investigated whether the patient vector graph, which plots on patient level, would add visual information on remission compared to a conventional box plot only, which displays data on the group level. METHODS: The ConRew method, which awards continuous periods of remission with a higher score, was applied, in addition to a simple sum score of remission periods of 4 weeks. A patient vector graph was compared with box plots. RESULTS: Both the mean ± SD simple sum score and the ConRew score of remission were significantly higher (favorable) in the MTX + prednisone strategy group versus the MTX + placebo group, respectively: 9 ± 7 versus 12 ± 8; P = 0.003, and 23 ± 16 versus 17 ± 14; P = 0.004. The patient vector graphs show a visual pattern of more and longer periods of remission in the MTX + prednisone strategy and visually add information to the box plots. CONCLUSION: The simple sum of remission periods, the ConRew score, and the patient vector graph add understanding and discrimination to the analysis of the remission outcome in CAMERA-II.
26523025 Incidence and Predictors of Biological Antirheumatic Drug Discontinuation Attempts among P 2015 Dec OBJECTIVE: We conducted a longitudinal observational study of biological disease-modifying antirheumatic drugs (bDMARD) to describe the proportions of patients with rheumatoid arthritis in remission who discontinued these agents, and to assess the potential predictors of the decision to discontinue. METHODS: We used data from the US COnsortium of Rheumatology Researchers Of North America (CORRONA) and the Japanese National Database of Rheumatic Diseases by iR-net in Japan (NinJa) registries, and ran parallel analyses. Patients treated with bDMARD who experienced remission (defined by the Clinical Disease Activity Index ≤ 2.8) were included. The outcome of interest was the occurrence of bDMARD discontinuation while in remission. The predictors of discontinuation were assessed in the Cox regression models. Frailty models were also used to examine the effects of individual physicians in the discontinuation decision. RESULTS: The numbers of eligible patients who were initially in remission were 6263 in the CORRONA and 744 in the NinJa. Among these patients, 10.0% of patients in CORRONA and 11.8% of patients in NinJa discontinued bDMARD while in remission over 5 years, whereas many of the remaining patients lost remission before discontinuing bDMARD. Shorter disease duration was associated with higher rates of discontinuation in both cohorts. In CORRONA, methotrexate use and lower disease activity were also associated with discontinuation. In frailty models, physician random effects were significant in both cohorts. CONCLUSION: Among patients who initially experienced remission while receiving bDMARD, around 10% remained in remission and then discontinued bDMARD in both registries. Several factors were associated with more frequent discontinuation while in remission. Physician preference likely is also an important correlate of bDMARD discontinuation, indicating the need for standardization of practice.
27607411 Early treatment intensification induces favourable radiographic outcomes according to pred 2016 Nov OBJECTIVES: Predicted versus observed radiographic progression in early rheumatoid arthritis (POPeRA) was applied to demonstrate how various treatment modalities affect and potentially minimise radiographic progression over time. METHODS: The POPeRA method utilises the baseline radiographic score and patient-reported symptom duration to predict radiographic outcomes. It was applied at baseline, 2, and 5 years to patients with eRA from the randomised Finnish RA Combination trial (FIN-RACo) (n=144) and New Finnish RA Combination Therapy (NEO-RACo) (n=90) trials. For FIN-RACo, patients were randomised either to a single DMARD (sulfasalazine, with or without prednisolone) or to combination therapy (methotrexate+sulfasalazine+hydroxychloroquine, i.e. triple therapy, with prednisolone). In NEO-RACo, all patients were assigned intensified combination therapy (including 7.5 mg prednisolone/day) plus a randomised 6-month induction of either placebo or anti-TNF treatment (infliximab). RESULTS: In FIN-RACo, combination versus monotherapy resulted in superior outcomes in the change from predicted progression over 2 and 5 years (mean 35.7% reduction vs. -32.9%, a worsening from predicted, p=0.001; 34.2% vs. -17.8%, p=0.003, respectively). In NEO-RACo, combination+anti-TNF induction led to significantly greater reductions from predicted progression than combination+placebo, both at 2 and 5 years of follow-up (98.5% vs. 83.4%, p=0.005; 92.4% vs. 82.5%, p=0.027, respectively). Importantly, anti-TNF add-on led to superior reductions from predicted among RF-positive patients (2 years: 97.4% vs. 80.4%, p=0.009; 5 years: 90.2% vs. 80.1%, p=0.030), but not among RF-negative patients. CONCLUSIONS: These results confirm that conventional combination therapy in eRA has a long-term radiographic benefit versus monotherapy. Through POPeRA, it was made evident that anti-TNF induction therapy for 6 months further increases the long-term radiographic benefit of combination therapy in RF-positive patients.
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.
27883999 Low Prevalence of Nodules in Rheumatoid Arthritis Patients in Kuwait: A Description and a 2017 OBJECTIVES: To describe the prevalence of rheumatoid nodules (RN) in patients with rheumatoid arthritis (RA) and to compare their features with those of patients without RN. SUBJECTS AND METHODS: Adult RA patients (n = 952) in the Kuwait Registry for Rheumatic Diseases from February 2013 to December 2015 were evaluated for RN. Demographic and serological features and disease activity and severity were obtained from the registry. RESULTS: Of the 952 RA patients, 22 (2.3%) had RN and 930 (97.7%) did not. Age, sex, disease duration, smoking, and family history of an autoimmune rheumatic disease were similar. Obesity was more prevalent in the RN group, i.e. 11 (50%) vs. 326 (35.1%), p = 0.016. There was no difference in rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody positivity. Patients with RN had more sicca symptoms, i.e. 8 (36.4%) vs. 152 (16.3%), p = 0.025, a higher mean score on the visual analogue scale pain (3 ± 2.9 vs. 2 ± 2.7, p < 0.001), more tender joints (6.4 ± 8.8 vs. 4.2 ± 7.2, p = 0.001), a higher patient global assessment of disease activity (3.3 ± 2.7 vs. 2.3 ± 2.7, p < 0.001), and more deformities, i.e. 3 (13.6%) vs. 74 (8%), p = 0.034. The mean health assessment questionnaire score in RN patients was 1.1 versus 0.9 in patients without RN (p = 0.08). Patients with RN had a low disease activity (means: disease activity score [DAS-28], 3.02; clinical disease activity index, 7.7; and simple disease activity index, 10.4), similar to the other group. While the rates of methotrexate treatment were comparable, biologic therapy was administered more in patients with RN (i.e. 15 [68.2%] vs. 478 [51.4%], p < 0.001). CONCLUSION: In Kuwait, the prevalence of RN is low among RA patients. Patients with and without RN are similar in terms of demographics and serologic features, except for more obesity. However, patients with RN have more sicca symptoms, joint deformities, and painful and tender joints. Disease activity scores are low with more frequent biologic therapy.
25671614 A HPLC-SRM-MS based method for the detection and quantification of methotrexate in urine a 2015 Mar 21 Rheumatoid arthritis (RA) is a common autoimmune disease that causes significant disability and reduced life expectancy. The folate antagonist methotrexate (MTX) is first-line therapy for RA when used weekly at low doses (5-25 mg). However, the true rate of adherence to MTX is uncertain. This is in part due to the different methods of measurement of adherence employed with no biochemical test currently available to determine adherence to low dose MTX. Common methods of MTX measurement include immunoassays in patients with high dose therapy, but these assays cross-react with MTX metabolites and lack the sensitivity required to measure adherence to low dose MTX. HPLC-SRM-MS (selected reaction monitoring-mass spectrometry) has several theoretical advantages over immunoassays with improved specificity, minimal cross-reaction and higher sensitivity. The aim of this study was to develop an assay to measure MTX and its major metabolite 7-OH-MTX in urine as a tool to monitor adherence to low dose MTX in clinic. As a proof of concept, urine samples from 4 participants with RA were measured after directly observed therapy. The assay showed improved sensitivity compared to that reported by immunoassays, with low carryover and high within-run precision. In participant samples, MTX was measurable in the urine for up to 105 hours after administration and 7-OH-MTX was detectable up to 98 hours after administration, suggesting that this assay is suitable for the measurement of adherence to therapy. The assay requires minimal sample preparation and can be adopted by other laboratories with minimal study set up.