Browse

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

ID PMID Title PublicationDate abstract
30482509 Prognostic Factors for Sustained Remission in a "Real Life" Cohort of Rheumatoid Arthritis 2020 Sep INTRODUCTION: Rheumatoid arthritis (RA) is the most frequent chronic polyarthritis. The current goal of RA treatment is to achieve clinical remission. OBJECTIVE: The goal of this study was to determine the prevalence of remission in a cohort of patients from clinical practice, and to identify potentially modifiable factors associated with remission. METHODS: A retrospective study was performed on a cohort of RA patients seen at the first consultation at the HUGC Rheumatology Service Dr. Negrín (HUGCDN) between first of January 2000 and thirtieth of April 2014. Sustained remission was defined as DAS28 less than 2.6 in the last two available visits in the medical history. RESULTS: A total of 463 patients were consecutively included, most (75%) women, with a mean age at the onset of RA of 50 years and a mean duration of the disease at follow-up of 8 years. 46% of the patients achieved sustained remission. Multiple logistic regression analyses found male sex (P=.031, OR 1.7, 95% CI 1.05-2.82), diagnosis in the first year of symptoms (P=.023, OR 1.7, 95% CI 1.07-2.69) and the initial DAS28 (P=.035) to be independent predictors for sustained remission. CONCLUSIONS: The 46% of the patients with RA followed in the HUGC Dr. Negrín are in persistent remission, being the early diagnosis a modifiable factor predictor of remission. Thus, an objective of the Rheumatology Service should be to improve the diagnostic delay of RA in the health area.
29853822 Disease Characteristics and Change in Arthritis Activity according to Treatment in Hepatit 2018 Jun 4 BACKGROUND: Rheumatoid arthritis (RA) treatment may differ according to hepatitis B state and consequently may bring about different arthritis outcomes. However, whether hepatitis B affects treatment outcome remains unclear. We investigated differences in change in arthritis activity between RA patients according to concomitant hepatitis B virus infection. METHODS: A retrospective medical chart review was performed by two rheumatologic fellows using single center data, from January 2000 to March 2015. Among RA patients older than 18 years, patients with comorbidities that could affect RA treatment aside from hepatitis B were excluded. Using 1:3 propensity score matching, 40 hepatitis B virus surface antigen (HBsAg)-positive patients and 112 HBsAg-negative patients were included in the study. Data were collected longitudinally using standardized electronic forms. The longitudinal relationship between HBsAg-positivity and RA activity was analyzed using generalized estimating equations. RESULTS: RA activity showed time-dependent improvement. Reductions of swollen joint count over time were significantly larger in the HBsAg-negative group. However, changes in disease activity score in 28 joints with three variables (DAS28-3), tender joint count, erythrocyte sedimentation rate and C-reactive protein level did not differ between the groups. There were no differences in alanine aminotransferase level. HBsAg-positive patients were less likely to receive methotrexate (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19; P < 0.001) and more likely to receive sulfasalazine (OR, 3.67; 95% CI, 1.94-6.95; P < 0.001). CONCLUSION: RA medication use varied according to HBsAg-positivity. However, improvement in RA activity was not significantly affected by concomitant hepatitis B infection.
29424904 miR-212-3p reduced proliferation, and promoted apoptosis of fibroblast-like synoviocytes v 2018 Jan OBJECTIVE: Several microRNAs have been reported to contribute the progression of rheumatoid arthritis (RA) due to the ectopic expression of miRNAs in fibroblast-like synoviocytes (FLS). However, the function of miR-212-3p in RA still has not been mentioned before. PATIENTS AND METHODS: We obtained serum, synovial tissues, and FLS samples from RA patients and normal donors. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to analysis the expression level of miR-212-3p. By using miR-212-3p mimics and inhibitors, we detected the effects of miR-212-3p on cell proliferation, cell cycle, and apoptosis in RA-FLS. Dual-luciferase and Western-blot were employed to verify the target of miR-212-3p. In addition, we over-expressed the SOX5 in miR-212-3p mimics treatment FLS to emphasize our results. RESULTS: The level of miR-212-3p in serum, synovial tissues, and FLS from RA patients was lower than these in relative normal group. Up-regulation of miR-212-3p inhibited cell proliferation, promoted cell apoptosis; however, knockdown of miR-212-3p promoted cell growth but reduced cell apoptotic rate. Furthermore, we found SOX5 as a direct target of miR-212-3p in RA-FLS and up-regulation of SOX5 reversed the effects of miR-212-3p over-expression. CONCLUSIONS: miR-212-3p could reduce cell proliferation and promoted cell apoptosis of RA-FLS via repressing SOX5, which may provide a new biological target for RA treatment.
29850963 Exploring the relation between impairment rating by DAS-28 and body function, activity par 2018 Jul Hand problems associated with rheumatoid arthritis lead to subjective impairment, activity limitation, and restrictions on participation. This relation is very complex. Assessment of individuals' activities is important to determine how hand problems affect not only body functions but also daily life activities. The aim of this study was to link and allocate items of disability questionnaires with ICF components based on ICF hand core set. The other objective was to examine the relationship between impairment and ICF components determined on the basis of disability questionnaires in participants with rheumatoid arthritis. Impairment was evaluated by use of Disease Activity Score-28. Disability questionnaires were Disabilities of Arm, Shoulder and Hand Questionnaire, Michigan Hand Outcomes Questionnaire, Duruoz Hand Index, and Arthritis Impact Measurement Scales 2 (n = 100). Items of disability questionnaires were linked with ICF hand core set as a result of three expert opinions. Michigan Hand Outcomes Questionnaire covered the highest number of body function categories and Arthritis Impact Measurement Scales 2 covered the highest number of ICF hand core set. For all questionnaires, while impairment (Disease Activity Score-28) had moderate correlation with subjective impairment (body function scores) and activity/participation; subjective impairment had high and moderate correlation with activity participation. Arthritis Impact Measurement Scale 2 is the most appropriate to perform a more comprehensive biopsychosocial assessment. Clinician's assessments and impairment levels reported by patients with rheumatoid arthritis are interrelated. Impairment levels reported by patients with rheumatoid arthritis are also affected by environmental factors.
30074946 Patient Governance in a Patient-Powered Research Network for Adult Rheumatologic Condition 2018 Oct BACKGROUND: Patient-Powered Research Networks (PPRNs) are a unique type of patient-powered patient registry for patient-centered outcomes research requiring that stakeholder engagement play a key role in governance (eg, research guidance and decision making). The purpose of this report is to describe the governance structure of a newly formed PPRN and the activities undertaken prelaunch and postlaunch to evaluate and improve the engagement of patient stakeholders in governance. METHODS: During the 18-month start-up period of ArthritisPower, a PPRN for adult rheumatologic conditions, 12 members of the patient body of the PPRN governance completed a 12-item preassessment and postassessment based on the Patient-Centered Outcomes Research Institute (PCORI) Engagement Rubric. The assessment was intended to measure Patient Governor (PG) perceptions of their engagement in governance within the first 3 months of their involvement at an in-person orientation. Six months later, the PG Chair initiated a mid-year evaluation with the same group to identify areas for improvement. Semistructured phone interviews were conducted with 11 PGs who were asked to rate and explain their perceptions about their participation in PPRN governance, the progress of the PPRN toward conducting research, the support they receive from staff, and the support they receive from other PGs. Results were compiled and interpreted by the Chair with help from the coprincipal investigator. RESULTS: Preassessment/postassessments indicated that PGs understood their governance role and decision-making authority after in-person orientation and felt that major PPRN decisions were being made with their input. Feedback and scores from the PG-led mid-year evaluation coalesced around 3 themes: a preference for receiving news and updates via email to allow more discussion and decision making during conference calls, a desire for guidance about how best to help advance the PPRN toward the conduct of research, and a need to communicate with each other as a group outside of monthly conference calls. Suggested activities to support patient engagement in PPRN governance include communicating clear expectations, providing well-prepared tools for engagement, and conducting regular assessments. CONCLUSIONS: Members of an online patient community are willing to share their expertise to participate in and shape research governance and bring both their professional and lived health experience to the development and improvement of PPRN governance structure. A patient-initiated and patient-led evaluation of governance communication procedures within the PPRN provided more specific recommendations for improvement than did an investigator-led preevaluation/postevaluation based on the PCORI Engagement Rubric.
31331131 A Study of the Relation Between Clinical Parameters of Rheumatoid Arthritis with Ultrasono 2018 Jun BACKGROUND: Ultrasonography is a safe and effective method which detects synovitis and erosions in joints early, while conventional radiography (CR) detects changes at later stages. These ultrasonographic findings have a relation with clinical parameters which help in predicting outcome. METHODS: 60 patients of diagnosed rheumatoid arthritis (RA) (ACR-EULAR 2010 criteria) were subjected to clinical examination, laboratory investigations, CR and ultrasonography. Data was compiled in Epi Info version 7 software and tests of significance were applied. RESULTS: Mean tender and swollen joint counts were 18.61+6.51 and 9.56+3.94 respectively. USG detected joint changes in 90% patients while CR could do so in 33.3%. 85% patients with a normal CR had an abnormal USG. On USG, tenosynovitis was found in 48.33% patients, synovial thickening with vascularity in 73.33%, synovial effusion in 40%. USG detected erosions in 14(23.33%) patients, while CR did so in 5(8.33%), a statistically significant finding. 80% of patients with less joint counts had positive USG findings and in them, joints other than those clinically involved were also found affected. Out of 16 patients of early RA who had a normal CR, 87.5% had positive findings on USG. 92.86% of patients having erosions on USG had a positive C reactive protein (CRP). 60.4% patients with synovial thickening had a positive CRP. In all the patients who had erosions on USG, anti CCP levels were of high titre, found to be significant. (P=0.022). CONCLUSION: USG can detect inflammatory arthritis and synovitis in RA better than CR in both early and established cases. USG findings may be seen in clinically uninvolved joints. Detection of erosions is also significantly better by USG as compared to CR. USG changes correlated with anti CCP and CRP.
30613013 [Diagnostic value of P2X7 receptor and its role in inflammatory reaction in rheumatoid art 2018 Dec 30 OBJECTIVE: To study the diagnostic value of P2X7 receptor for rheumatoid arthritis (RA) and its role in the inflammatory response. METHODS: With the synovial tissues from 25 patients with bone and joint replacement as the control,the synovial tissues of 25 RA patients were examined for the relative expression of P2X7 receptor mRNA using qRT-PCR.In an immortalized RA synovial cell line (MH7A),the effect of P2X7 receptor knockdown via a small interfering RNA were examined on the productions of the inflammatory cytokines including interleukin-1β(IL-1β),IL-6,and IL-8 using ELISA. RESULTS: The RA patients showed significantly higher levels of P2X7 receptor mRNA expression in the synovial tissue than the control patients.P2X7 receptor had a good diagnostic value for RA.The expression levels of IL-1β,IL-6,and IL-8 were positively correlated with the levels of P2X7 receptor in the synovial tissues of RA patients (P<0.001).In MH7A cells,P2X7 receptor knockdown obviously reduced the secretion of IL-1β and IL-6. CONCLUSIONS: RA patients show elevated P2X7 receptor level in the synovial tissue, which has a good diagnostic value for RA.Blocking P2X7 receptor can inhibit inflammatory factor secretion and suppress inflammatory reactions.
30393209 To evaluate the efficacy and safety of CartiNovex plus tablet in osteoarthritis and rheuma 2018 Sep Interminable arthritis issue, for example, osteoarthritis (OA) and rheumatoid arthritis (RA) have in like manner an upsurge of aggravation, and oxidative anxiety, bringing about dynamic histological modifications and incapacitating indications. As of now utilized allopathic prescription (extending from painkiller executioners to natural operators) is intense, yet regularly connected with genuine, even dangerous symptoms. Utilized for centuries in customary herbalism, restorative plants are a promising option, with bring down rate of unfavorable occasions and productivity every now and again tantamount with that of traditional medications. In any case, their instrument of activity is as a rule smooth and additionally indeterminate. Despite the fact that a large number of them have been demonstrated powerful in ponders done in vitro or on creature models, there is a shortage of human clinical proof. This clinical trial was conducted at Liaquat National Hospital, Karachi, Pakistan. This was a single blind, placebo control phase II clinical trial. Total 200 patients were enrolled in the study, in which 110 received the CartiNovex plus tablet and 90 received the placebo. The age range of patients was 40 years to above 70 years. The sample paired t-test was applied to evaluate the significant level. Different parameters like pain on sitting or lying, morning stiffness, pain on walking, stiffness in sitting, lying or resting later in the day, getting on/off toilet, light domestic duties (such as tidying room, dusting, cooking), WOMAC score % were tested for both group i.e. CartiNovex plus group and placebo group in all parameters CartiNovex plus show significant improvement in all parameters. CartiNovex plus tablet was very effective in the management of OA and RA. The CartiNovex plus tablet was safe and well tolerated in all patients and side effects are non-significant.
30538782 Circulating Semaphorin 4D as a Marker for Predicting Radiographic Progression in Patients 2018 Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (p < 0.001), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (p = 0.001) and IL-6 (p < 0.001) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (p = 0.007) and TNF-α (p = 0.001). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28> 3.2 and with DAS28 ≤ 3.2, RA patients with radiographic progression (ΔSHS change/year ≥ 1) had significantly higher baseline levels of Sema4D than those without progression (p = 0.029). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (p = 0.045). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.
28462710 Endothelial Progenitor Cells as Mediators of the Crosstalk between Vascular Repair and Imm 2018 From the discovery of Endothelial Progenitor Cells (EPC), these bone marrowderived precursors have been placed as crucial mediators of the endothelial repair. Accordingly, altered levels and function of EPC have been found in different scenarios of CV risk. Despite the fact that EPC exhibit important characteristics which support a link of this cell subset with a number of inflammatory and immune networks, little is known on the actual mediators involved and the clinical relevance of these features. Systemic diseases are generally hallmarked by a vascular repair failure and increased cardiovascular disease occurrence, EPC impairment having a pivotal role. Because of their immunemediated etiology, this group of conditions represents an invaluable scenario to unravel the connections between immune dysregulation and EPC dysfunction. In the present review, we summarize the current knowledge regarding the cutting-edge area of the modulation of EPC levels and function by inflammatory cytokines in systemic diseases. We also address the possibility of the available immunomodulatory drugs to counteract this situation. Finally, due to the emerging role of the vitamin D as a common mediator in the immune system and the cardiovascular axis, we cover the topic of the role of vitamin D as a potential player in the inflammatory-mediated EPC dysfunction in systemic diseases.
29321415 Cerebral Toxoplasmosis Diagnosed by Nested-polymerase Chain Reaction in a Patient with Rhe 2018 May 15 A 65-year-old woman with rheumatoid arthritis (RA) visited our hospital because of right facial sensory hypoesthesia. Cerebral toxoplasmosis was suspected on brain magnetic resonance imaging. We discontinued methotrexate for RA and started a sulfamethoxazole/trimethoprim (ST) mixture. Although ST treatment was interrupted because of adverse reactions, her prognosis was favorable. The Toxoplasma 18S rDNA gene was detected by nested-polymerase chain reaction (PCR) from blood and cerebrospinal fluid. Detecting the Toxoplasma 18S rDNA gene by nested-PCR is useful for the diagnosis and safer than a brain biopsy. In addition, the discontinuation of immunosuppressants may be recommended in patients compromised by those immunosuppressants.
29055489 Association between NICE guidance on biologic therapies with rates of hip and knee replace 2018 Apr OBJECTIVE: To estimate the impact of NICE approval of tumor necrosis factor inhibitor (TNFi) therapies on the incidence of total hip replacement (THR) and total knee replacement (TKR) among rheumatoid arthritis (RA) patients in England and Wales. METHODS: Primary care data [Clinical Practice Research Datalink (CPRD)] for the study period (1995-2014) were used to identify incident adult RA patients. The age and sex-standardised 5-year incidence of THR and TKR was calculated separately for RA patients diagnosed in each six-months between 1995-2009. We took a natural experimental approach, using segmented linear regression to estimate changes in level and trend following the publication of NICE TA 36 in March 2002, incorporating a 1-year lag. Regression coefficients were used to calculate average change in rates, adjusted for prior level and trend. RESULTS: We identified 17,505 incident RA patients of whom 465 and 650 underwent THR and TKR surgery, respectively. The modeled average incidence of THR and TKR over the biologic-era was 6.57/1000 person years (PYs) and 8.51/1000 PYs, respectively, with projected (had pre-NICE TA 36 level and trend continued uninterrupted) figures of 5.63/1000 PYs and 12.92 PYs, respectively. NICE guidance was associated with a significant average decrease in TKR incidence of -4.41/1000 PYs (95% C.I. -6.88 to -1.94), equating to a relative 34% reduction. Overall, no effect was seen on THR rates. CONCLUSIONS: Among incident RA patients in England and Wales, NICE guidance on TNFi therapies for RA management was temporally associated with reduced rates of TKR but not THR.
29122245 Methods for segmentation of rheumatoid arthritis bone erosions in high-resolution peripher 2018 Apr OBJECTIVE: The comparison between different techniques to quantify the 3-dimensional size of inflammatory bone erosions in rheumatoid arthritis(RA) patients. METHODS: Anti-cyclic citrullinated peptide antibody(ACPA) positive RA patients received high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the metacarpophalangeal joints (MCP). Erosions were measured by three different segmentation techniques: (1) manual method with calculation by half-ellipsoid formula, (2) semi-automated modified Evaluation Script for Erosions (mESE), and (3) semi-automated Medical Image Analysis Framework (MIAF) software. Bland & Altman plots were used to describe agreement between methods. Furthermore, shape of erosions was classified as regular or irregular and then compared to the sphericity obtained by MIAF. RESULTS: A total of 76 erosions from 65 RA patients (46 females/19 males), median age 57 years, median disease duration 6.1 years and median disease activity score 28 of 2.8 units were analyzed. While mESE and MIAF showed good agreement in the measurement of erosion size, the manual method with calculation by half-ellipsoid formula underestimated erosions size, particularly with larger erosions. Accurate segmentation is particularly important in larger erosions, which are irregularly shaped. In all three segmentation techniques irregular erosions were larger in size than regular erosions (MIAF: 19.7 vs. 3.4mm(3); mESE: 15.5 vs. 2.3mm(3); manual = 7.2 vs. 1.52mm(3); all p < 0.001). In accordance, sphericity of erosions measured by MIAF significantly decreased with their size (p < 0.001). CONCLUSION: MIAF and mESE allow segmentation of inflammatory bone erosions in RA patients with excellent inter reader reliability. They allow calculating erosion volume independent of erosion shape and therefore provide an attractive tool to quantify structural damage in individual joints of RA patients.
29660333 Epitope-based ligation of ICAM-1: Therapeutic target for protection against the developmen 2018 Jun 2 Identification of a particular epitope on the domain 2 of human ICAM-1 led us to focus on its role in the treatment of rheumatoid arthritis (RA). Key observations from our previous xenotransplantation research included the generation of tolerogenic DCs, antigen-specific T-cell tolerance, and reduced production of inflammatory cytokines. The critically important point is the fact that it works initially on DC maturation. Ligation of this epitope with a recognizing antibody, MD-3, was also able to create a tolerogenic environment in RA in a manner sililar to that created by xenotransplantation. In this study, we noted that the disease progression, in terms of arthritis score and histopathology of joints, was significantly less severe in the MD-3-treated group than in the vehicle-treated group. Defective production of IL-6 and reduced proliferation of collagen-specific T cells were most remarkable laboratory findings. This type of ligation has a greater advantage over other types of therapeutics, in a sense that simple injection of this antibody inhibits antigen-specific T cell response. Due to the possibility of viral infection in this process, we regularly monitored cytomegalovirus reactivation status without detection of any viral gene replication. We are hoping that remarkable specializations that this interaction has, would be a promising target for therapeutic antibody in RA.
29409412 Metacarpophalangeal Joint Arthroplasty Using Flexible Hinge Toe Implant with Grommets for 2018 Mar BACKGROUND: MP joint arthroplasty is one of the treatment options for the rheumatoid thumb with boutonniere deformity. The use of flexible hinge toe implant for MP joint reconstruction was introduced; however, the outcome of flexible toe implantation for the reconstruction of the MP joint has not as yet been reported in detail. Therefore, in this study, we retrospectively investigated the clinical outcome and radiological findings. METHODS: We assessed 56 Swanson implant arthroplasties that used flexible hinge toe implants with grommets to address boutonnière deformity of the thumb MP joint. The minimum follow-up period was 6 months. Pain, the range of motion, grip strength, pinch strength, General health Visual analogue scale and DASH (Disabilities of Hand, Shoulder and Hand) were assessed. RESULTS: For most of the patients, the procedure provided painless motion and stability to the thumb. In the radiological assessments, the preoperative flexion angles at the MP joint were 45° improved to 17°. The origin of arc was shifted toward the extended position and the average arc of motion was 21°, with a flexion arc from 23° to 44°. The severity of boutonniere deformity was improved in most cases. The average grip strength changed from 110 to 121 mmHg and the average side pinch power changed from 1.5 to 2.2 kgf. General health VAS improved from 40 to 29 (p = 0.019), and the DAS28-CRP decreased from 3.3 to 2.4 (p < 0.001). Infection occurred in one case, and there were no implant fractures. CONCLUSIONS: Swanson flexible hinge toe implant arthroplasty with grommets applied to the MP joint of the thumb was one of the recommended procedures for the reconstruction of boutonnière deformity of the thumb.
29886430 The predictive role of ultrasound-detected tenosynovitis and joint synovitis for flare in 2018 Sep OBJECTIVE: To define the role of ultrasound (US) for the assessment of patients with rheumatoid arthritis (RA) in clinical remission, including joint and tendon evaluation. METHODS: A multicentre longitudinal study has been promoted by the US Study Group of the Italian Society for Rheumatology. 25 Italian centres participated, enrolling consecutive patients with RA in clinical remission. All patients underwent complete clinical assessment (demographic data, disease characteristics, laboratory exams, clinical assessment of 28 joints and patient/physician-reported outcomes) and Power Doppler (PD) US evaluation of wrist, metacarpalphalangeal joints, proximal interphalangeal joints and synovial tendons of the hands and wrists at enrolment, 6 and 12 months. The association between clinical and US variables with flare, disability and radiographic progression was evaluated by univariable and adjusted logistic regression models. RESULTS: 361 patients were enrolled, the mean age was 56.20 (±13.31) years and 261 were women, with a mean disease duration of 9.75 (±8.07) years. In the 12 months follow-up, 98/326 (30.1%) patients presented a disease flare. The concurrent presence of PD positive tenosynovitis and joint synovitis predicted disease flare, with an OR (95% CI) of 2.75 (1.45 to 5.20) in crude analyses and 2.09 (1.06 to 4.13) in adjusted analyses. US variables did not predict the worsening of function or radiographic progression. US was able to predict flare at 12 months but not at 6 months. CONCLUSIONS: PD positivity in tendons and joints is an independent risk factor of flare in patients with RA in clinical remission. Musculoskeletal ultrasound evaluation is a valuable tool to monitor and help decision making in patients with RA in clinical remission.
30173305 A Practical Approach to the Use of Conventional Synthetic, Biologic and Targeted Synthetic 2018 Sep 1 PURPOSE OF REVIEW: Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) have been used in the treatment of inflammatory arthritis (IA) for many years. More recently, biologic (bDMARDs) and targeted synthetic (tsDMARDs) DMARDs have further improved treatment. Due to increased patient longevity and effective oncology treatment, rheumatologists often encounter patients with IA and previous malignancy. The immunosuppressive effect of DMARDs causes concern regarding impaired tumour surveillance with a potential increased risk of malignancy. We reviewed the literature regarding the risk of malignancy in patients on cs-/b-/tsDMARDS and sought to provide practical advice regarding use of these drugs in patients with previous malignancy. RECENT FINDINGS: Data from randomised controlled trials is limited as patients with pre-existing malignancy are often excluded. Reassuringly, an increasing range of "real world" data from various national b/tsDMARD registries has not provided a convincing signal that these drugs increase tumour recurrence. Nevertheless, awareness of, and adherence to, national screening guidelines for malignancy is important. Given the improvement in quality of life achieved with these novel and well-tolerated therapeutic agents, the benefit/risk profile remains overwhelmingly favourable in most patients.
29532704 Low body mass index and lymphocytopenia associate with Mycobacterium avium complex pulmona 2019 Jan OBJECTIVES: Patients with rheumatoid arthritis (RA) are at an increased risk of Mycobacterium avium complex pulmonary disease (MAC-PD). We aimed to identify factors associated with MAC-PD in RA patients, and investigate their clinical significance for diagnosis of this disease. METHODS: We examined 396 patients with RA for the presence of MAC-PD, using the criteria of the American Thoracic Society and conducted three years of follow-up on these patients. Multivariate logistic analyses were employed for selecting factors associated with MAC-PD. We developed a point system based on these factors which we call MAC-PD score to improve diagnosis of MAC-PD. RESULTS: During this study, 14 out of 396 patients were newly diagnosed with MAC-PD. Multivariate analyses revealed body mass index (BMI) <18.0 kg/m(2) and lymphocyte count <1500/μl were associated with MAC-PD in RA patients. Points were assigned to them and totalled to provide the MAC-PD score. Among 20 patients with high-resolution computer tomography images consistent with MAC-PD, the scores were significantly higher in 14 patients with MAC-PD than those in six patients without MAC-PD. CONCLUSION: Using these data, in the forms of the MAC-PD score, could help to identify patients who should be considered for bronchoscopy more selectively.
29504826 A response adaptive design for ordinal categorical responses. 2018 A two treatment response adaptive design is developed for phase III clinical trials with ordinal categorical treatment outcome using Goodman-Kruskal measure of association. Properties of the proposed design are studied both empirically and theoretically and the acceptability is further illustrated using two real data-sets; one from a clinical trial with trauma patients and the other from a trial with patients having rheumatoid arthritis.
29461286 Recent advances in the treatment of rheumatoid arthritis. 2018 May PURPOSE OF REVIEW: Therapies for rheumatoid arthritis (RA) continue to expand rapidly. The purpose of this review is to discuss novel treatment options, including biosimilars, that are available, as well as to highlight promising agents in development. The purpose is also to discuss new emerging safety signals associated with these drugs and to discuss strategies in tapering therapy. RECENT FINDINGS: There are several novel RA therapies. These include the interleukin-6 (IL-6) receptor blocker sarilumab, which was approved in 2017. In aggregate, the sarilumab studies show that it is effective in RA, including patients with incomplete responses to methotrexate and anti-tumor necrosis factor inhibitor, and showing superior efficacy when used in higher dose (200 mg every 2 weeks) to standard-dose adalilumab. Other drugs that are currently being studied include the IL-6 cytokine blocker sarikumab, the small targeted molecule filgotinib, and many new biosimilars. Baracitinib failed to achieve approval by the Food and Drug Administration primarily over perceived safety concerns. The two biosimilar drugs currently approved are CT-P13 and SB2, which are based on the reference product infliximab. Although this review summarizes trials examining biologic tapering, additional data are needed to guide clinicians in regards to treatment de-escalation in RA. SUMMARY: With the greatly expanded armamentarium of RA treatment options available, it is important for clinicians to understand the data regarding drug efficacy and safety. With remission increasingly attainable, effective drug tapering strategies are needed. Although tapering trials do exist, more studies will be needed to help guide clinical practice.