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27564431 Routine Assessment of Patient Index Data 3 and the American College of Rheumatology/Europe 2017 May OBJECTIVE: The American College of Rheumatology/European League Against Rheumatism established definitions of remission for rheumatoid arthritis (RA) based on composite scores, including tender (TJC) and swollen joint counts (SJC), patient global visual analog scale (VAS) score, laboratory tests, and, in the Simplified Disease Activity Index (SDAI), the physician global score. Time constraints on a physician's schedule demand an easy yet accurate tool to measure disease activity. We assessed the predictive ability of the Routine Assessment of Patient Index Data 3 (RAPID3) with and without a single swollen joint versus the SDAI and/or Boolean remission criteria for functional and radiographic outcomes. METHODS: Data were from the Tocilizumab Safety and the Prevention of Structural Joint Damage phase III trial in RA patients. We assessed the ability at year 1 of a RAPID3 score of ≤3 + 1 SJC, RAPID3 score of ≤3 (remission) without SJC, SDAI score of ≤3.3 (remission), and/or Boolean remission (SJC, TJC, patient global VAS, and C-reactive protein level [mg/dl] all ≤1) to predict year 2 Health Assessment Questionnaire (HAQ) disability index (DI) score of ≤0.5 (normal), no worsening of HAQ DI score from year 1, and no worsening of Genant-modified Total Sharp Score from year 1. RESULTS: Among 690 patients, the mean ± SD baseline Disease Activity Score in 28 joints was 6.5 ± 0.96, RAPID3 score was 14.2 ± 5.51, and the SDAI score was 41.7 ± 13.01. Achieving year 1 measures was associated with good functional and radiographic outcomes at year 2. Sensitivity, specificity, positive predictive values, and negative predictive values were 49.1%, 83.2%, 37.4%, and 88.9% (RAPID3 remission); 26.4%, 91.7%, 36.8%, and 87.1% (RAPID3 + 1 SJC); 26.7%, 90.9%, 37.3%, and 85.9% (SDAI remission); and 17.0%, 96.6%, 47.4%, and 86.4% (Boolean remission), respectively. CONCLUSION: The predictive ability of RAPID3 (with or without joint count) was similar to that of SDAI and Boolean criteria.
28778575 High prevalence of gallstone disease in rheumatoid arthritis: A new comorbidity related to 2019 Mar OBJECTIVE: To assess the prevalence of gallstone disease and identify associated risk factors in rheumatoid arthritis (RA) patients compared to the general population. METHODS: Eighty-four women with rheumatoid arthritis were included in the study. Each patient was assessed via a structured interview, physical examination, abdominal ultrasound and blood test including lipid profile. The prevalence of gallstone disease in rheumatoid arthritis was compared with data from a study of the Spanish population matched by age groups. RESULTS: Twenty-eight of the 84 women had gallstone disease (33.3%). RA women with and without gallstone disease were similar in most of the variables assessed, except for older age and menopausal status in the former. A greater prevalence of gallstone disease was seen in rheumatoid arthritis patients compared to the general population of the same age; however, the differences were significant only in women aged 60 or older (45.5% versus 23.1% respectively, P-value .008). The age-adjusted OR of developing gallstone disease in RA women compared with general population women was 2,3 (95% CI: 1.3-4.1). A significantly higher HDL3-c subfraction and higher apoA-I/HDL and HDL3-c/TC ratios were observed in patients with gallstone disease. CONCLUSION: Women with rheumatoid arthritis may have a predisposition to gallstones that can manifest in middle or older age compared with women in the general population. This situation could be related to chronic inflammation and HDL metabolism.
28141515 Automatic Quantification of Radiographic Wrist Joint Space Width of Patients With Rheumato 2017 Nov Objective: Wrist joint space narrowing is a main radiographic outcome of rheumatoid arthritis (RA). Yet, automatic radiographic wrist joint space width (JSW) quantification for RA patients has not been widely investigated. The aim of this paper is to present an automatic method to quantify the JSW of three wrist joints that are least affected by bone overlapping and are frequently involved in RA. These joints are located around the scaphoid bone, viz. the multangular-navicular, capitate-navicular-lunate, and radiocarpal joints. Methods: The joint space around the scaphoid bone is detected by using consecutive searches of separate path segments, where each segment location aids in constraining the subsequent one. For joint margin delineation, first the boundary not affected by X-ray projection is extracted, followed by a backtrace process to obtain the actual joint margin. The accuracy of the quantified JSW is evaluated by comparison with the manually obtained ground truth. Results: Two of the 50 radiographs used for evaluation of the method did not yield a correct path through all three wrist joints. The delineated joint margins of the remaining 48 radiographs were used for JSW quantification. It was found that 90% of the joints had a JSW deviating less than 20% from the mean JSW of manual indications, with the mean JSW error less than 10%. Conclusion: The proposed method is able to automatically quantify the JSW of radiographic wrist joints reliably. SIGNIFICANCE: The proposed method may aid clinical researchers to study the progression of wrist joint damage in RA studies.Objective: Wrist joint space narrowing is a main radiographic outcome of rheumatoid arthritis (RA). Yet, automatic radiographic wrist joint space width (JSW) quantification for RA patients has not been widely investigated. The aim of this paper is to present an automatic method to quantify the JSW of three wrist joints that are least affected by bone overlapping and are frequently involved in RA. These joints are located around the scaphoid bone, viz. the multangular-navicular, capitate-navicular-lunate, and radiocarpal joints. Methods: The joint space around the scaphoid bone is detected by using consecutive searches of separate path segments, where each segment location aids in constraining the subsequent one. For joint margin delineation, first the boundary not affected by X-ray projection is extracted, followed by a backtrace process to obtain the actual joint margin. The accuracy of the quantified JSW is evaluated by comparison with the manually obtained ground truth. Results: Two of the 50 radiographs used for evaluation of the method did not yield a correct path through all three wrist joints. The delineated joint margins of the remaining 48 radiographs were used for JSW quantification. It was found that 90% of the joints had a JSW deviating less than 20% from the mean JSW of manual indications, with the mean JSW error less than 10%. Conclusion: The proposed method is able to automatically quantify the JSW of radiographic wrist joints reliably. SIGNIFICANCE: The proposed method may aid clinical researchers to study the progression of wrist joint damage in RA studies.
27846751 Differential effects of IL-6 blockade tocilizumab and TNF inhibitors on angiogenesis in sy 2017 Sep OBJECTIVE: To compare the influences of tocilizumab (TCZ) and TNF inhibitors (TNFi) on the angiogenesis in synovial tissues of rheumatoid arthritis (RA). METHODS: Synovial tissues were obtained during joint operations from 13 RA patients treated with TCZ for at least 4 months with or without previous use of TNFi, from 13 RA patients with TNFi alone and from 10 RA patients with only conventional synthetic DMARDs (csDMARDs). Synovial tissues were evaluated by hematoxylin and eosin stain as well as by immunohistological staining with anti-CD31 in which the microvessel densities (MVD) were quantitated. Synovial histopathology was scored for various components. RESULTS: The most remarkable change in the synovium with TCZ was reduced angiogenesis as well as degeneration of lining layers irrespective of the previous use of TNFi. Thus, MVD in patients treated with TCZ with or without previous TNFi were significantly decreased compared with those in patients with TNFi alone or with csDMARDs. Moreover, MVD was significantly correlated with lining layer proliferation, but not with synovial stromal proliferation or inflammatory changes. CONCLUSIONS: These results demonstrated that inhibition of angiogenesis is a unique action of TCZ. Moreover, the data also suggest that lining layers proliferation might be closely associated with angiogenesis.
28493076 Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in discrete 2017 Oct OBJECTIVE: Extracellular vesicles (EVs) are subcellular signalosomes. Although characteristic EV production is associated with numerous physiological and pathological conditions, the effect of blood-derived EVs on bone homeostasis is unknown. Herein we evaluated the role of circulating EVs on human osteoclastogenesis. METHODS: Blood samples from healthy volunteers, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients were collected. Size-based EV sub-fractions were isolated by gravity-driven filtration and differential centrifugation. To investigate the properties of EV samples, resistive pulse sensing technique, transmission electron microscopy, flow cytometry and western blot were performed. CD14(+) monocytes were separated from PBMCs, and stimulated with recombinant human M-CSF, RANKL and blood-derived EV sub-fractions. After 7 days, the cells were fixed and stained for tartrate-resistant acid phosphatase and counted. RESULTS: EVs isolated by size-based sub-fractions were characterized as either microvesicles or exosomes (EXO). Healthy (n = 11) and RA-derived (n = 12) EXOs profoundly inhibited osteoclast differentiation (70%, p < 0.01; 65%, p < 0.01, respectively). In contrast, PsA-derived (n = 10) EXOs had a stimulatory effect (75%, p < 0.05). In cross-treatment experiments where EXOs and CD14(+) cells were interchanged between the three groups, only healthy (n = 5) and RA (n = 5)-derived EXOs inhibited (p < 0.01, respectively) the generation of osteoclasts in all groups, whereas PsA (n = 7)-derived EXOs were unable to mediate this effect. CONCLUSIONS: Our data suggest that blood-derived EXOs are novel regulators of the human osteoclastogenesis and may offer discrete effector function in distinct inflammatory arthropathies.
28691459 Periodontal microbioma and rheumatoid arthritis: The role of Porhyromonas gingivalis. 2017 Apr Rheumatoid Arthritis is a disease, which can be described as an autoimmune response after molecular mimicry caused by infective agents. The current study aims at evaluating the correlation between Rhematoid Arthritis (RA) and Periodontal Disease (PD), with special attention to the microbioma detected in the gums. Thirty-four patients with RD were recruited into the current study. Among rheumatic parameters, Rheumatoid Factor (RF), anti-citrullinated protein antibody (CCP), HLA-BDR1 and DAS28 were collected. A dental clinician evaluated the periodontal screening record (PSR). Afterwards, 1 paper cone was inserted for 30 seconds into the gingival sulcus then sent to the laboratory for evaluation. Quantitative PCR of 16S rRNA genes was performed with the hydrolysis probes method to identify and evaluate the amount Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Fusobacterium nucleatum and Campylobacter rectus. There were no statistical differences in the composition of oral microbioma between PSR groups. There were no statistical significant differences between bacterial loads and serum values. On the contrary, a positive correlation was found between the presence of Porphyromonas gingivalis in periodontal pockets on one side and RF and CCP on the other. Therefore, the presence of Porhyromonas gingivalis in periodontal pockets is associated to RA inflammatory indices.
28800780 A novel scoring system based on common laboratory tests predicts the efficacy of TNF-inhib 2017 Aug 11 BACKGROUND: Currently, although several categories of biological disease-modifying antirheumatic drugs (bDMARDs) are available, there are few data informing selection of initial treatment for individual patients with rheumatoid arthritis (RA). Therefore, tumor necrosis factor inhibitor (TNF-i) and tocilizumab (TCZ) are treated as equivalent treatments in the recent disease management recommendations. We focused on two anticytokine therapies, TCZ and TNF-i, and aimed to develop a scoring system that predicts a better treatment for each RA patient before starting an IL-6 or a TNF-i. METHODS: The expression of IL-6 and TNF-α mRNA in peripheral blood from 45 newly diagnosed RA patients was measured by DNA microarrays to evaluate cytokine activation. Next, laboratory indices immediately before commencing treatment and disease activity score improvement ratio after 6 months in 98 patients treated with TCZ or TNF-i were retrospectively analyzed. Some indices correlated with TCZ efficacy were selected and their cutoff values were defined by receiver operating characteristic (ROC) analysis to develop a scoring system to discriminate between individuals more likely to respond to TCZ or TNF-i. The validity of the scoring system was verified in these 98 patients and an additional 228 patients. RESULTS: There was significant inverse correlation between the expression of IL-6 and TNF-α mRNA in newly diagnosed RA patients. The analysis of 98 patients revealed significant correlation between TCZ efficacy and platelet counts, hemoglobin, aspartate aminotransferase, and alanine aminotransferase; in contrast, there was no similar correlation in the TNF-i group. The cutoff values were defined by ROC analysis to develop a scoring system (1 point/item, maximum of 4 points). A good TCZ response was predicted if the score was ≥2; in contrast, TNF-i seemed to be preferable if the score was ≤1. Similar results were obtained in a validation study of an additional 228 patients. If the case scored ≥3, the good responder rates of TCZ/TNF-i were 75.0%/37.9% (p < 0.01) and the non-responder rates were 3.1%/27.6% (p < 0.01), respectively. CONCLUSIONS: The score is easily calculated from common laboratory results. It appears useful for identifying a better treatment at the time of selecting either an IL-6 or a TNF inhibitor.
28743353 Which is the best cutoff of body mass index to identify obesity in female patients with rh 2017 Jul INTRODUCTION: Standard anthropometric measures used to diagnose obesity in the general population may not have the same performance in patients with rheumatoid arthritis. OBJECTIVE: To determine cutoff points for body mass index (BMI) and waist circumference (WC) for detecting obesity in women with rheumatoid arthritis (RA) by comparing these standard anthropometric measures to a dual-energy X-ray absorptiometry (DXA)-based obesity criterion. PATIENTS AND METHOD: Adult female patients with more than six months of diagnosis of RA underwent clinical evaluation, with anthropometric measures and body composition with DXA. RESULTS: Eighty two patients were included, mean age 55±10.7 years. The diagnosis of obesity in the sample was about 31.7% by BMI, 86.6% by WC and 59.8% by DXA. Considering DXA as golden standard, cutoff points were identified for anthropometric measures to better approximate DXA estimates of percent body fat: for BMI value≥25kg/m(2) was the best for definition of obesity in female patients with RA, with sensitivity of 80% and specificity of 60%. For WC, with 80% of sensitivity and 35% of specificity, the best value to detect obesity was 86cm. CONCLUSION: A large percentage of patients were obese. The traditional cutoff points used for obesity were not suitable for our sample. For this female population with established RA, BMI cutoff point of 25kg/m(2) and WC cutoff point of 86cm were the most appropriate to detect obesity.
28884287 Incidence of comprehensive hospitalization due to infection, cardiovascular disease, fract 2017 Nov To comprehensively analyze the overall incidence of hospitalization for comorbidities in patients with rheumatoid arthritis (RA). We prospectively analyzed overall hospitalizations for comorbidities using the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. The incidence of hospitalized comorbidity was calculated. Risk factors for the most frequent hospitalized comorbidities were determined by multivariate logistic regression analysis. Among 5519 RA patients contributing 5336.5 person-years of observation, 435 incidences of hospitalized comorbidity [8.15/100 person-years; 95% confidence interval (CI) 7.40-8.95] were confirmed. The most frequent cause of hospitalized comorbidity was infection (1.52/100 person-years), primarily respiratory system infection (0.77/100 person-years), followed by malignancy (1.03/100 person-years), extra-articular manifestations (0.78/100 person-years), bone fracture (0.77/100 person-years), and acute coronary syndrome (0.22/100 person-years). Death occurred in 0.34/100 person-years (95% CI 0.20-0.53), and in 94.4% of cases the cause of death was the same as that of admission. The risk factors for the most frequent cause of hospitalization, hospitalized infection, were age [odds ratio (OR) 1.03; 95% CI 1.00-1.05], serum albumin level (OR 0.30; 95% CI 0.13-0.69), and corticosteroid use (prednisone > 5 mg/day; OR 3.66; 95% CI 1.81-7.35), but not methotrexate or biological agent use. The present study determined the overall burden of hospitalized comorbidities in patients with RA. These comprehensive data on hospitalized comorbidities may provide a basis for future improvements in the treatment of RA.
28882850 Two new drugs for rheumatoid arthritis. 2017 Sep Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease that causes inflammation and destruction of the joints.(1-3) It can also affect the eyes, the heart and the lungs and is associated with significant disability and increased mortality. RA is estimated to affect just under 1% of the population aged over 16 years, equating to more than 400,000 people in the UK.(4) â–¼Baricitinib (Olumiant) and â–¼tofacitinib (Xeljanz) were launched in the UK in April 2017 and represent a new therapeutic class of medicines known as targeted synthetic disease modifying antirheumatic drugs.(5,6) Here, we review the evidence for the safety and effectiveness of these new oral agents.
28849128 In silico design of colchicine-based bioisosteric inhibitors of tubulin for the treatment 2017 Oct The super-saturation of serum with monosodium urate due to hyperuricemia is the core metabolic disorder of rheumatoid arthritis. When the serum urate concentration is ≥7 mg/dl, this results in the crystallization of monosodium urate in serum at body temperature (37˚C/98.6˚F). Colchicine (COL) is considered to be a first‑line medication for acute arthritis when NSAIDs are contraindicated. COL causes severe side effects, including diarrhea, nausea, cramping, abdominal pain and vomiting, in humans. Experimental studies have additionally demonstrated the presence of mutagenic and reproductive effects in humans. In the present study, molecular docking simulation techniqueswere used to design COL‑derived bioisosteric inhibitors, with the aim of designing an alternative treatment that exhibitedpotent anti‑arthritic activity and was free from the side effects associated with COL.
28836356 Model-Based Discovery and Development of Biopharmaceuticals: A Case Study of Mavrilimumab. 2018 Jan Drug development is a lengthy, costly process with low probability of success. Biopharmaceuticals are highly specific molecules, with efficacy and safety closely tied to target biology and pharmacology. The "learning-predicting-confirming" continuum by translational and clinical modeling and simulation (M&S) was implemented at every decision point for mavrilimumab, a human monoclonal antibody in development for rheumatoid arthritis (RA). This tutorial uses mavrilimumab as an example to demonstrate rational discovery, preclinical development, clinical study design, and dose selection of biotherapeutics by M&S.
29082659 Two-year persistence of golimumab as second-line biologic agent in rheumatoid arthritis as 2018 Feb OBJECTIVES: To evaluate the 2-year retention rate of golimumab compared with etanercept and adalimumab as second-line biologic agent in rheumatoid arthritis (RA) patients who failed a previous tumor necrosis factor inhibitor (TNFi). METHODS: Data on RA patients treated with a second-line subcutaneous TNFi were extracted from a multicentric Italian cohort (the LORHEN registry). The analysis was limited to etanercept, adalimumab and golimumab in the period when all were available in Italy (since October 2010). The 2-year retention rate was calculated by Kaplan-Meier method and the comparative risk for discontinuation among individual TNFi was compared by a stratified log-rank test. RESULTS: One hundred and ninety-five RA patients treated with etanercept (n = 76), adalimumab (n = 68) or golimumab (n = 51) were included in the analysis. The 2-year retention rate (40% with a median time-on-drug of 12.9 months in the whole population) was significantly lower for adalimumab (31.2%, P = 0.018) and numerically lower for etanercept (39.8%, P = 0.068) compared with golimumab (53.4%) because of a higher discontinuation rate due to adverse events (P = 0.042 and P = 0.038 versus golimumab, respectively). Drug survival was greater in concomitant synthetic disease modifying anti-rheumatic drug (sDMARD) users (44.2%) compared with TNFi monotherapy (22.5%, P = 0.036). No difference was found in survival analysis according to first-line TNFi reason for discontinuation and pattern of TNFi switch (antibody-receptor, antibody-antibody or receptor-antibody). CONCLUSIONS: Our real-life data confirmed switching to a second TNFi as a good option for treating first-line TNFi failures in RA, especially in combination with sDMARDs. Second-line golimumab showed an overall better 2-year drug survival compared with adalimumab and etanercept.
29064810 [Nonadherence and ineffective methotrexate treatment of inflammatory arthritis]. 2017 Failure to comply with treatment recommendations in chronic diseases, including inflammatory arthritis, is one of the main reasons why patients do not achieve health benefits. It is widely recognized that effective pharmacotherapy requires a conviction to undertake and continue. In case of methotrexate therapy failure, it is necessary to consider the possibility and cause for non adherence to treatment. In order to achieve chosen therapy goals, cooperation of patient and physician is essential. A review of medical literature brings up a necessity to consider the differences in understanding and definition of both compliance and adherence, and whether the failure in treatment is tied to pharmacology, or inadequate patient knowledge. Patient education should entail thorough understanding of therapy goals, the mainstay role of methotrexate in current strategies and the benefits of consistent treatment. Attention should be paid to the role of methotrexate polyglutamates in monitoring therapy effectiveness, and the choice between subcutaneous and oral administration. A joint consideration of the dosing regimen, convenient methods of administration and dispelling any doubts over adverse events are milestones that will translate into better adherence.
28477538 Ischemic heart disease and rheumatoid arthritis: Do inflammatory cytokines have a role? 2017 Aug BACKGROUND: The increase in Rheumatoid arthritis (RA) associated mortality is predominantly due to accelerated coronary artery and cerebrovascular atherosclerosis with increased risk of ischemic heart disease about 50% in RA patients compared to controls. OBJECTIVE: To study the pathogenesis of ischemic heart disease in RA, role of inflammatory cytokine interplay, disease activity and rheumatoid factor positivity. METHODS: Eighty RA patients and 44 healthy controls were included. All subjects were younger than 45years for females and 55years for males with exclusion of all traditional risk factors for atherosclerosis. Interleukin (IL) 1, 6 and 18 were assessed in all subjects. RA patients fulfilled ACR/EULAR 2010 criteria and were subjected to Dobutaminestress-echocardiography, diseases activity assessed by DAS-28, X-ray hands for Larsen score and function assessment by HAQ. RESULTS: RA patients had significantly higher serum IL 1, 6 and 18 than controls (p=0.00 in all). Thirty four (42.5%) patients had hypertensive reaction on Dobutamine-stress-echocardiography, four of them had ischemic change, and 46 (57.5%) had normal reaction. All patients with hypertensive reaction had positive RF (p=0.00), 10 had DAS-28>5.1, 20 had DAS-28 from 3.2 to5.1 and 4 were in remission (p=0.001). CRP was higher in patients with hypertensive reaction (p=0.003) while serum levels of IL1, 6 and 18 showed no significant difference. In all patients, serum levels of IL1, 6 and 18 showed significant positive correlation with VAS, HAQ and DAS-28 (p<0.001 in all). Only IL18 showed significant positive correlation with X-ray score in all patients. CONCLUSION: Disease activity and RF positivity play an important risk factor for ischemic heart disease in RA. Serum levels of IL1, 6 and 18 did not help much in detecting patients at risk of ischemic heart disease. Better control of RA disease activity with early remission helps in preventing cardiac complications. More studies on larger number of patients are needed for better understanding of mechanism of ischemic heart disease in RA.
28880684 Reduction of methotrexate and glucocorticoids use after the introduction of biological dis 2018 May OBJECTIVES: To evaluate usage patterns for methotrexate (MTX) and/or glucocorticoids in rheumatoid arthritis (RA) patients receiving biological disease-modifying antirheumatic drugs (bDMARDs) in daily practice. METHODS: Data from RA patients who commenced treatment with bDMARDs (infliximab [IFX], etanercept [ETN], tocilizumab [TCZ], or adalimumab [ADA]) from 2008 to 2010 were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The proportions of patients taking concomitant MTX and glucocorticoids and doses of these medications were evaluated before and 2 years after initiation of each bDMARD. RESULTS: A total of 470 RA patients who had initiated a bDMARD (IFX: n = 98, ETN: n = 181, TCZ: n = 90, and ADA: n = 101) were evaluated. The proportion of patients taking MTX decreased over time among ETN and TCZ users, while it increased among ADA users. The MTX dose decreased over time among IFX, ETN, and TCZ users, but not among ADA users. Although the rate of glucocorticoid use and dose decreased after bDMARD initiation in all four bDMARD groups, approximately 50% of patients continued to receive glucocorticoids 2 years after bDMARD initiation. CONCLUSION: MTX and glucocorticoid use and doses in daily practice were commonly reduced after the initiation of bDMARDs, with the dose adjustment varied depending on the bDMARD.
28238009 Results of Total Elbow Arthroplasty with Cementless Implantation of an Alumina Ceramic Elb 2017 Feb We investigated the long-term clinical results of total elbow arthroplasty (TEA) by cementless fixation of alumina ceramic unlinked elbow prostheses (J-alumina ceramic elbows: JACE) for the reconstruction of elbow joints with rheumatoid arthritis (RA). Seventeen elbows in 17 patients (aged 44-72 years, average 54.8) replaced by JACE TEA without bone cement were investigated. The average follow-up period was 10.7 (range, 1.0-19.3) years. Clinical conditions of each elbow before and after surgery were assessed according to the Mayo Elbow Performance Index (MEPI). Radiographic loosening was defined as a progressive radiolucent line of more than 1 mm that was completely circumferential around the intramedullary stem. The average MEPI significantly improved from 46.8 points preoperatively to 66.8 points at final follow-up (p=0.0226). However, aseptic loosening was noted in 10 of 17 elbows (58.8%) and revision surgery was required in 7 (41.2%). Most loosening was observed on the humeral side. With radiographic loosening and revision surgery defined as the end points, the likelihoods of prosthesis survival were 41.2% and 51.8%, respectively, up to 15 years by Kaplan-Meier analysis. The clinical results of JACE implantation without bone cement were disappointing, with high revision and loosening rates of the humeral component.
29199587 Liposome-Based Nanomedicine Therapeutics for Rheumatoid Arthritis. 2017 Rheumatoid arthritis (RA) is a very painful severe autoimmune disease with complex pathology characterized by progressive chronic inflammation, and devastation of the synovium, cartilage, and other joint-associated structures. Significant advances in research in the area of pathophysiology, diagnosis, drug development, and targeted delivery have led to improved RA therapy and better patient compliance. Targeted drug delivery using liposomal nanomedicines significantly alleviate the challenges with conventional anti-RA medications such as off-target effects, short biological half-life, poor bioavailability, high dose-related toxicity, etc. Liposomal nanomedicines in RA drug targeting offer the opportunity for passive targeting [based on size and polyethylene glycol (PEG)-ylation-mediated enhanced permeability and retention] and active targeting (ligation with antibody or peptides, etc.) and encapsulation of lipophilic, hydrophilic drugs, and/or combinational drugs. However, it has been found recently that such injectable nanomedicines raise the concern of an adverse immune phenomenon called complement activationrelated pseudo allergy (CARPA) and failure of therapy on multiple doses due to accelerated body clearance caused many by anti-PEG immunoglobulin M. To ensure safety and efficacy of RA therapy, these need to be considered along with the common formulation quality parameters. Here, we discuss nanotherapeutic targeting in RA therapy using liposomes. Liposomal nanoparticles are investigated for individual anti-RA drug categories. CARPA issues and pathophysiology with such nanomedicines are also discussed in detail.
28967371 Pain and other self-report scores in patients with osteoarthritis indicate generally simil 2017 Sep OBJECTIVES: Osteoarthritis (OA) is regarded as a less severe form of arthritis than rheumatoid arthritis (RA) by health professionals and the general public, based largely on laboratory findings of autoantibodies and acute phase reactants. Relatively few studies have reported data from the patient's perspective to compare directly OA versus RA using the same self-report questionnaire measure. We aimed to summarise reports that compare OA versus RA patient pain scores and other indicators of disease burden according to the same self-report questionnaire. METHODS: A retrospective review identified 5 published reports at 8 rheumatology sites in 4 countries from 1989 to 2017 in which patients with OA versus RA completed the same patient self-report questionnaire for pain and other variables. Most comparisons involved a health assessment questionnaire (HAQ) and derivative multidimensional HAQ (MDHAQ), which include physical function, pain visual analogue scale (VAS) and patient global assessment VAS. Other questionnaires were included in one or two reported studies. RESULTS: Mean or median pain VAS was in a similar range in OA versus RA, though somewhat higher in OA at 7 of 8 sites studied (included in 1989). Physical function and other scores also were in a similar range for RA versus OA. Evidence of higher scores for physical function in RA relative to OA in earlier than more recent studies was seen, although all studies indicated a clinically important disease burden in OA. CONCLUSIONS: OA presents a severe disease burden to patients, which appears similar to RA. The findings suggest revision of current clinical and public policy views concerning OA.
29287749 Phase 1b Study of the Safety, Pharmacokinetics, and Disease-related Outcomes of the Matrix 2018 Jan PURPOSE: Andecaliximab (GS-5745) is a highly selective monoclonal antibody against matrix metalloproteinase-9 (MMP9), a proteolytic enzyme implicated in the pathogenesis of rheumatoid arthritis (RA). This study assessed the safety and pharmacokinetic (PK) parameters of andecaliximab in patients with RA and evaluated the effects of andecaliximab treatment on exploratory disease biomarkers. METHODS: In this double-blind, Phase 1b trial, patients with active RA were randomized (4:1) to receive 400-mg andecaliximab or placebo every 2 weeks for a total of 3 intravenous infusions. The primary and secondary end points were safety and the PK parameters of andecaliximab, respectively. Data were summarized by using descriptive statistics. FINDINGS: A total of 18 patients were randomized; 15 received andecaliximab (participants with confirmed RA diagnosis without current administration of a biologic DMARD a biologic DMARD (disease-modifying antirheumatic drug), aged 18 to 70 years old, weighing >45 to <120 kg). No deaths, serious adverse events, or study discontinuations occurred. All reported adverse events were grade 1 or grade 2 in severity. Mean plasma andecaliximab exposure was 587 d · µg/mL and 878 d · µg/mL at days 1 and 29, respectively, suggesting moderate accumulation. The median terminal t(1/2) was 5.65 days; mean volume of distribution at steady state was 4560 mL. Mean MMP9 coverage (the percentage of total plasma MMP9 bound by therapeutic antibody) was maintained at ~80% after the first administration of andecaliximab. IMPLICATIONS: Andecaliximab administered as 3 infusions over 29 days was generally safe and well tolerated in patients with RA. The majority of total plasma MMP9 was bound by andecaliximab after the first administration. Clinical studies of increased treatment duration in larger patient cohorts are warranted. ClinicalTrials.gov identifier: NCT02176876. Registered on 25 June 2014.