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ID PMID Title PublicationDate abstract
25593232 Anti-carbamylated protein antibodies are present prior to rheumatoid arthritis and are ass 2015 Apr OBJECTIVE: Anti-carbamylated protein (anti-CarP) antibodies could further elucidate early rheumatoid arthritis (RA) pathogenesis and predict clinical disease. We compared the diagnostic accuracy of anti-CarP antibodies for future RA to other RA-related antibodies in military personnel. METHODS: Stored pre-RA diagnosis serum samples from 76 RA cases were tested for anti-CarP fetal calf serum (FCS), anti-CarP fibrinogen (Fib), anticyclic citrullinated peptide antibodies version 2 (anti-CCP2), rheumatoid factor-nephelometry (RF-Neph), and RF isotypes [immunoglobulin M (IgM), IgG, and IgA]. Positivity for all antibodies was determined as ≥ 2 SD of log-transformed means from controls. Relationships between autoantibodies and future RA were assessed in prediagnosis serum for all RA cases compared to controls using sensitivity, specificity, and logistic regression. Differences in diagnostic accuracy between antibody combinations were assessed using comparisons of area under the curves (AUC). RESULTS: Anti-CarP-FCS was 26% sensitive and 95% specific for future RA, whereas anti-CarP-Fib was 16% sensitive and 95% specific for future RA. Anti-CarP-FCS positivity was associated with future RA, while anti-CarP-Fib trended toward association. The antibody combination of anti-CCP2 and/or ≥ 2 RF (RF-Neph and/or RF-isotypes) resulted in an AUC of 0.72 for future RA, where the AUC was 0.71 with the addition of anti-CarP-FCS to this prior combination. CONCLUSION: Adding anti-CarP-FCS to antibody combinations did not improve AUC. However, anti-CarP-FCS was associated with future onset of RA, and was present in prediagnosis serum in ∼10% of RA cases negative for anti-CCP2 but positive for RF.
26846584 Preclinical lung disease in early rheumatoid arthritis. 2016 Feb Early detection and treatment of lung disease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms < 2 years) without respiratory symptoms, who were included in a screening program for lung disease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of <80% of predicted, without a significant reduction in the forced vital capacity. The HRCT detected abnormalities in 11 of the 18 patients. Diffuse bronchiectasis was the main finding. An inverse correlation between the anti-citrullinated peptide antibody (ACPA) levels and DLCO was found. Asymptomatic lung disease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels.
26757747 Anticitrullinated protein antibodies and rheumatoid factor are associated with increased m 2016 Nov OBJECTIVE: Patients with rheumatoid arthritis (RA)-related autoantibodies have an increased mortality rate. Different autoantibodies are frequently co-occurring and it is unclear which autoantibodies associate with increased mortality. In addition, association with different causes of death is thus far unexplored. Both questions were addressed in three early RA populations. METHODS: 2331 patients with early RA included in Better Anti-Rheumatic Farmaco-Therapy cohort (BARFOT) (n=805), Norfolk Arthritis Register (NOAR) (n=678) and Leiden Early Arthritis Clinic cohort (EAC) (n=848) were studied. The presence of anticitrullinated protein antibodies (ACPA), rheumatoid factor (RF) and anticarbamylated protein (anti-CarP) antibodies was studied in relation to all-cause and cause-specific mortality, obtained from national death registers. Cox proportional hazards regression models (adjusted for age, sex, smoking and inclusion year) were constructed per cohort; data were combined in inverse-weighted meta-analyses. RESULTS: During 26 300 person-years of observation, 29% of BARFOT patients, 30% of NOAR and 18% of EAC patients died, corresponding to mortality rates of 24.9, 21.0 and 20.8 per 1000 person-years. The HR for all-cause mortality (95% CI) was 1.48 (1.22 to 1.79) for ACPA, 1.47 (1.22 to 1.78) for RF and 1.33 (1.11 to 1.60) for anti-CarP. When including all three antibodies in one model, RF was associated with all-cause mortality independent of other autoantibodies, HR 1.30 (1.04 to 1.63). When subsequently stratifying for death cause, ACPA positivity associated with increased cardiovascular death, HR 1.52 (1.04 to 2.21), and RF with increased neoplasm-related death, HR 1.64 (1.02 to 2.62), and respiratory disease-related death, HR 1.71 (1.01 to 2.88). CONCLUSIONS: The presence of RF in patients with RA associates with an increased overall mortality rate. Cause-specific mortality rates differed between autoantibodies: ACPA associates with increased cardiovascular death and RF with death related to neoplasm and respiratory disease.
26245356 Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid 2015 Aug 6 Rheumatoid arthritis (RA) is an autoimmune destructive arthritis associated with CD4(+) T cell-mediated immunity. Although expanded CD4(+) T cell clones (ECs) has already been confirmed, the detailed characteristics of ECs have not been elucidated in RA. Using combination of a single-cell analysis and next-generation sequencing (NGS) in TCR repertoire analysis, we here revealed the detailed nature of ECs by examining peripheral blood (PB) from 5 RA patients and synovium from 1 RA patient. When we intensively investigated the single-cell transcriptome of the most expanded clones in memory CD4(+) T cells (memory-mECs) in RA-PB, senescence-related transcripts were up-regulated, indicating circulating ECs were constantly stimulated. Tracking of the transcriptome shift within the same memory-mECs between PB and the synovium revealed the augmentations in senescence-related gene expression and the up-regulation of synovium-homing chemokine receptors in the synovium. Our in-depth characterization of ECs in RA successfully demonstrated the presence of the specific immunological selection pressure, which determines the phenotype of ECs. Moreover, transcriptome tracking added novel aspects to the underlying sequential immune processes. Our approach may provide new insights into the pathophysiology of RA.
25941210 Forefoot Deformity in Rheumatoid Arthritis: A Comparison of Shod and Unshod Populations. 2015 Oct All reported rheumatoid arthritis (RA) forefoot deformities in the literature thus far have arisen from shoe wearing populations. Our aim in this study was to compare hallucal deformities seen in a shod population with an unshod population. A population comparison was undertaken in 2 specialized foot and ankle units, one in India and one in the United Kingdom. In the shod population, there was 1 hallux varus deformity, 10 without hallucal deformity, and 90 hallux valgus deformities. In contrast, in the unshod population, there were 19 hallux varus deformities and 6 hallux valgus deformities. There was great variability in the lesser toe deformity seen. In the shod population, it was most common to see dorsal subluxation or dislocation, with the fifth toe in a varus position. In the unshod population, the most common lesser toe deformity seen was varus deviation or dislocation. Instability of the metatarsophalangeal joint in the rheumatoid foot predisposes it to significant deformity. In the non-shoe wearing population, intrinsic muscle forces and weight bearing forces are the most likely determinants of the deformity, with hallux varus being a more common presenting problem. In the shod population, the external forces of shoe wear dictate the direction of deformity. LEVELS OF EVIDENCE: Prognostic, Level III: Case control study.
27817127 The conversion rate of tuberculosis screening tests during biological therapies in patient 2017 Feb Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory to the initiation of biological therapy in patients with rheumatic diseases. To determine the prevalence of LTBI in patients with rheumatoid arthritis before treatment with biological therapy (anti-TNF, abatacept, and tocilizumab) and the rate of TB conversion during treatment in rheumatoid arthritis (RA) patients, we evaluated the file of 275 patients with RA treated with biological agents. We considered patients with negative baseline TB screening (tuberculin skin test (TST); quantiferon TB gold in tube (QFT-GIT); chest x-ray) and with rescreening for a TB assay every year. Twenty-six patients (10.6%) resulted positive to TB screening at baseline. Two hundred and forty-nine patients (mean age 55.3 ± 11.9; median 55.8 years, range 16-81.9; 210 female) with TB screening negative at baseline were enrolled. One hundred and sixty-eight (67.5%) patients were treated with anti-TNF, 37 (14.9%) patients with abatacept, and 44 (17.7%) patients with tocilizumab. After a period of 12-120 months (median 24), 34 (13.6%) patients displayed conversion of at least one screening assay. Out of the 34 patients with conversion, 6 (16.2%) were treated with abatacept, 7 (15.9%) with tocilizumab, and 21 (12.5%) with anti-TNF. During the follow-up period, no patients developed active TB. Our study shows that a proportion of patients (13.6%) converts at least one TB screening assay during biological therapy. This study underscores the American College of Rheumatology advice for annual screening in some or all biologically treated patients.
26492596 False discovery rate estimation for large-scale homogeneous discrete p-values. 2016 Jun Large-scale homogeneous discrete p-values are encountered frequently in high-throughput genomics studies, and the related multiple testing problems become challenging because most existing methods for the false discovery rate (FDR) assume continuous p-values. In this article, we study the estimation of the null proportion and FDR for discrete p-values with common support. In the finite sample setting, we propose a novel class of conservative FDR estimators. Furthermore, we show that a broad class of FDR estimators is simultaneously conservative over all support points under some weak dependence condition in the asymptotic setting. We further demonstrate the significant improvement of a newly proposed method over existing methods through simulation studies and a case study.
25897997 Long-term repopulation of peripheral B-cell subsets after single and repeated rituximab in 2015 May OBJECTIVES: B-cell depletion using rituximab (RTX) has proven efficacy in patients with RA. Long-term effects on the B-cell system after single and repeated treatments are sparse. Our aim was to study the effect of multiple courses of rituximab to evaluate its impact on repeated B-cell re-population capacity. METHODS: Two cohorts, altogether 20 patients with RA were included in an open label extension study with RTX. Cohort 1 received one cycle RTX and was followed for up to 7 years. In cohort 2 patients were studied under up to 5 cycles of RTX. Immunophenotyping was performed before therapy and during follow-up. RESULTS: After a single therapy with RTX (cohort 1) the frequency of pre-switch (MZ-like) B cells were significantly reduced during the follow-up of 7 years and absolute numbers slowly repopulated to nearly 50% of baseline value without numerical normalisation. The acquisition of mutations in Ig receptors of pre-switch (MZ-like) memory B cells was also significantly reduced 10 years after one course. In contrast, absolute numbers of (classical) post-switch B cells tended to normalise to baseline values after 7 years. Analysing B-cell repopulation capacities after multiple cycles revealed (cohort 2) a comparable repopulation pattern after each cycle with no substantial further impact on memory B cells. CONCLUSIONS: A single therapy with RTX leads to long-term changes in the memory B-cell compartment particularly in pre-switch memory B cells. Multiple cycles of RTX show a comparable repopulation pattern after each cycle with no additional cumulative effect on memory B cells.
25295918 A multi-biomarker disease activity score tracks clinical response consistently in patients 2015 May OBJECTIVES: To assess the ability of a multi-biomarker disease activity (MBDA) score to track clinical response in patients with rheumatoid arthritis (RA) treated with different TNF inhibitors. METHODS: The study included 147 patients who had received adalimumab, etanercept, or infliximab for a year or more, during routine clinical care at the University Hospital of Occupational and Environmental Health, Japan. MBDA scores and clinical measures of disease activity were evaluated at baseline and, after 24 weeks (N = 84) and 52 weeks of treatment. Relationships between the changes (∆) in MBDA score and changes in clinical measures or EULAR response categories were evaluated. RESULTS: The median disease activity was 5.7 by DAS28-ESR and 64 by MBDA score at baseline, and decreased significantly with treatment. ∆MBDA scores over 1 year correlated with ∆DAS28-ESR (r = 0.48) and ∆DAS28-CRP (r = 0.46). Linear relationships between ∆MBDA scores and ∆DAS28-ESR or ∆DAS28-CRP were not significantly different between TNF inhibitors. The MBDA scores declined significantly more in good responders (median change: -29) than moderate (-21), and more in moderate than in non-responders (+ 2), by the EULAR criteria. CONCLUSIONS: MBDA scores tracked disease activity and treatment response in patients with RA treated with three TNF inhibitors. The relationships between ∆MBDA scores and ∆DAS28-ESR or ∆DAS28-CRP were consistent across the three TNF inhibitor groups.
26781785 Ultrasound7 versus ultrasound12 in monitoring the response to infliximab in patients with 2016 Mar This study aimed to assess the responsiveness of ultrasonography (US)-7 in patients with rheumatoid arthritis (RA). Eighty-two RA patients were recruited and followed up for 22 weeks. The clinical, laboratory, and X-ray assessments, along with grayscale US (GSUS) and power Doppler US (PDUS) examinations were performed at baseline, 6, 14, and 22 weeks after infliximab treatment. GSUS for synovitis and PDUS for synovitis and paratendinitis/tenosynovitis were assessed by a semi-quantitative (0 to 3) score, while GSUS for paratendinitis/tenosynovitis and bone erosion was qualitatively assessed as absent or present (0 or 1). US scores in both 7-joint (US7) and 12-joint (US12) systems were evaluated. After 6, 14, and 22 weeks of treatment with infliximab, indices such as US scores, 28-joint disease activity (DAS28) score, and tender and swelling joint count were all significantly improved compared to baseline. US7 scores were significantly correlated with that of US12. Strong correlations were identified between most US7 scores with DAS28, health assessment questionnaire (HAQ), and C-reactive protein (CRP) levels. When DAS28 was used as a reference, the US7 cutoff for disease remission was less than 35 for GS + PD and also less than 29 for GS and 1 for PD, respectively. Additionally, the positive percent agreement, negative percent agreement, and overall percent agreement for GS + PD were 77.78, 76.19, and 76.67 %, respectively, which were all higher than that of GS or PD. US7 may be a feasible tool to assess the therapeutic response in RA patients.
26939710 Differentiation between early rheumatoid and early psoriatic arthritis by the ultrasonogra 2016 May OBJECTIVES: To determine whether ultrasonographic findings of the synovio-entheseal complex of the hand small joints could be used to differentiate between early rheumatoid and early psoriatic arthritis. METHODS: Thirty-four early rheumatoid and 26 early psoriatic arthritis patients with a prevalent involvement of the hands were examined with ultrasound (US). All exams were performed at the first visit by evaluating synovitis, peritendon extensor digitorum tendon oedema, enthesitis of the central slip of extensor tendon, flexor tenosynovitis and soft tissue oedema. In the same patient, the two most clinically involved joints, if possible of the same digit, were evaluated. RESULTS: Sixty-eight clinically involved joints were evaluated in 34 early rheumatoid arthritis patients and 52 joints in 26 early psoriatic arthritis patients.Synovitis was significantly more frequently detected in early rheumatoid arthritis compared to early psoriatic arthritis patients (p=0.0001), in 91.1% joints of the former and in 59.6% joints of the latter. At metacarpohalangeal joint, the presence of peritendon extensor digitorum tendon inflammation was observed in 2.5% of the joints in the early rheumatoid arthritis group and in 54.1% of the joints in the early psoriatic arthritis group (p=0.0001). At PIP joints, central slip enthesitis was exclusively observed in EPsA (p=0.0045). When considering the most clinically involved finger per patient, soft tissue oedema was detected almost exclusively in psoriatic arthritis (p=0.0002). CONCLUSIONS: The US involvement of synovio-entheseal complex and US extrasynovial features may be helpful in the differential diagnosis between early rheumatoid and early psoriatic arthritis.
26727748 [Pulmonary manifestations in rheumatoid arthritis]. 2015 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destructive cartilages, bones and other structures formed joints. RA belongs to connective tissue diseases represented by systemic nature, internal illness, extra-articular features and rapidly progress of atherosceirosis. The extra-articular complications cause the reduction of patient longevity. The frequency of symptoms in patient with RA and respiratory disorders occur in 10-20% of cases. Pulmonary complications are the second most common cause of premature of patient deaths. Respiratory disorders associated with RA are devided into 3 groups: infection, lung disease caused by drugs and pulmonary manifestation connected by RA. These last affect interstitial tissue, bronchioli, pulmonary vessels, pleura, also are presented by pulmonary rheumatoid nodules and pulmonary hypertension.
26912229 Establishment of age- and sex-adjusted reference data for hand bone mass and investigation 2016 Feb 24 BACKGROUND: Rheumatoid arthritis is characterised by progressive joint destruction and loss of periarticular bone mass. Hand bone loss (HBL) has therefore been proposed as an outcome measure for treatment efficacy. A definition of increased HBL adjusted for age- and sex-related bone loss is lacking. In this study, we aimed to: 1) establish reference values for normal hand bone mass (bone mineral density measured by digital x-ray radiogrammetry (DXR-BMD)); and 2) examine whether HBL is normalised in rheumatoid arthritis patients during treatment with tumour necrosis factor alpha inhibitors (TNFI). METHODS: DXR-BMD was measured from hand x-rays in a reference cohort (1485 men/2541 women) without arthritis randomly selected from an urban Danish population. Sex- and age-related HBL/year was estimated. DXR-BMD was measured in rheumatoid arthritis patients (n = 350: at start of TNFI, and ~2 years after TNFI start), of which 135 patients had three x-rays (~2 years prior to TNFI, at start of TNFI, and ~2 years after TNFI start). Individual HBL/year prior to and during TNFI was calculated and compared to reference values. RESULTS: Estimated HBL/year varied strongly with age and sex. Compared to the reference values, 75 % of 135 patients had increased HBL prior to TNFI treatment and 59 % had increased HBL during TNFI treatment (p = 0.17, Chi-squared). In 38 % (38/101) of patients with increased HBL, HBL was normalised during TNFI treatment, whereas 47 % (16/34) of patients with normal HBL prior to TNFI had increased HBL during TNFI treatment. In the 350 patients, increased HBL during TNFI was associated with time-averaged 28-joint disease activity score (odds ratio 1.69 (95 % Confidence Interval 1.34-2.15)/unit increase, p < 0.001), and patients in time-averaged remission had lower HBL than patients without remission (0.0032 vs. 0.0058 g/cm(2)/year; p < 0.001, Mann-Whitney). CONCLUSIONS: We established age- and sex-specific reference values for DXR-BMD in a large cohort without arthritis. HBL was increased in the majority of rheumatoid arthritis patients initiating TNFI in clinical practice, and only normalised in a minority during TNFI.
26018696 FDG PET Imaging in Pneumocystis Pneumonia. 2015 Aug A 69-year-old woman with rheumatoid arthritis and pleuritis presented with dyspnea. On admission, she was afebrile and had an oxygen saturation of 97% on ambient air. Chest radiography and CT revealed only subtle ground-glass opacities. However, FDG PET revealed pathological uptake in both lungs. A diagnosis of Pneumocystis pneumonia was made based on a positive β-D-glucan assay and polymerase chain reaction amplification of Pneumocystis jirovecii from the sputum. Posttreatment FDG PET revealed resolution of the previously noted uptake. This case illustrates that FDG PET can be used to diagnose Pneumocystis pneumonia when the CT findings are equivocal.
27086728 Patient involvement in the development of a handbook for moderate rheumatoid arthritis. 2017 Apr BACKGROUND: Self-management is a key recommendation for people with rheumatoid arthritis (RA). Educational materials may support self-management, and increasingly patients are becoming involved with the development of these materials. The TITRATE trial compares the effectiveness of intensive management to standard care in patients with moderate RA across England. As part of the intensive management intervention, participants are given a handbook. AIM AND OBJECTIVES: The aim of this study was to develop a handbook to support the intensive management. The objectives were to: (i) involve patients in the identification of relevant information for inclusion in the TITRATE handbook; (ii) ensure the content of the handbook is acceptable and accessible. DESIGN: We held an audio-taped workshop with RA patients. The transcript of the workshop was analysed using thematic content analysis. RESULTS: Five main themes were identified as follows: 'rheumatoid arthritis treatment, perceptions of rheumatoid arthritis, the importance of individualized goals, benefits of self-management and the patient handbook'. Feedback from the workshop was incorporated into the handbook, and patients' anonymous testimonies were added. CONCLUSION: This study demonstrates that patient contribution to the development of educational material to support intensive management of RA is both feasible and valuable. A qualitative evaluation of the use and impact of the handbook with patients and practitioners is planned on completion of the TITRATE trial.
26367725 Lack of association between CXCL9 and CXCL10 gene polymorphisms and the outcome of rheumat 2015 Aug OBJECTIVE: Methotrexate (MTX) in low doses is used in the therapy of rheumatoid arthritis (RA). The aim of many studies is to identify factors predicting the outcome of treatment with methotrexate in rheumatoid arthritis. The action of MTX in RA is associated with the inhibition of inflammatory mediators synthesis. CXCL9 and CXCL10 chemokines play the important role in inflammatory response in RA patients. The aim of this study was to examine the association between CXCL9/10 gene polymorphisms and response to therapy of RA patients with MTX. PATIENTS AND METHODS: The study included 422 patients diagnosed with rheumatoid arthritis, treated with MTX in doses 20 mg weekly. Good responders were defined as patients who were receiving MTX and had a DAS28 of ≤ 2.5 at 6 months of therapy. Poor-responders were defined as patients who were receiving MTX and had a DAS28 of > 2.5. RESULTS: There were not statistically significant associations between studied polymorphisms and the outcome of rheumatoid arthritis treatment with methotrexate. CONCLUSIONS: The results of this study suggest lack of associations between the polymorphisms in CXCL9 and CXCL10 genes and the response to MTX in RA patients.
26233497 Does Rheumatoid Cachexia Predispose Patients with Rheumatoid Arthritis to Osteoporosis and 2015 Sep OBJECTIVE: To assess the prevalence and risk factors of rheumatoid cachexia (RC) and evaluate its relationship with osteoporosis and vertebral fractures (VF) in patients with rheumatoid arthritis (RA). METHODS: We enrolled into a cross-sectional study 178 consecutive patients with RA (82.6% women) with a mean age of 54.1 ± 11.5 years (25-82) and who fulfilled the American College of Rheumatology criteria for the classification of RA. Body composition, lateral VF assessment images, and scans of the lumbar spine and proximal femur were obtained using dual-energy x-ray absorptiometry. RC was defined by a fat-free mass index below the 10th percentile and a fat mass index above the 25th percentile compared with a reference population. VF were defined using Genant semiquantitative approach. RESULTS: RC was observed in 96 patients (53.9%) and osteoporosis in 52 patients (29.2%). Comparison between women with and without RC showed that women with RC had a longer disease duration, higher disease activity variables, higher steroid cumulative dose, and higher proportion of patients with erosive arthritis. Women with RC had lower total hip bone mineral density (BMD) and T score than women without RC, while comparison in men found only body mass index to be significantly lower in men with RC. Regression logistic analysis showed an independent and significant association between RC and age and disease activity in women. CONCLUSION: Our study showed that half of the patients with RA may have RC, a condition that was significantly associated with disease activity and low hip BMD, but not with VF.
27988812 CD28, CTLA-4 and CCL5 gene polymorphisms in patients with rheumatoid arthritis. 2017 May Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction caused by infiltrating leukocytes including T cells. An important role in T cell co-stimulation is played by the CD28, as a stimulatory signal transducer and the inhibitory CTLA-4. CCL5 is produced by circulating T cells and plays an active role in the chemotactic activity of T cells in RA. The aim of this study was to examine the associations between polymorphisms within CD28, CTLA-4, and CCL5 genes and RA. We examined 422 patients (340 female, 82 male, mean age 57.5 ± 12.5 years) with rheumatoid arthritis and 338 healthy subjects (261 female, 77 male). Disease activity was determined on the basis of DAS28 score. The patients with DAS28 of ≤2.5 were classified as subjects in remission of disease symptoms; the patients who had DAS28 of >2.5 were classified as subjects with active form of RA. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. A statistically significant difference was observed in the distribution of CTLA4 exon 1 +49A>G rs231775 genotypes between patients with DAS28 ≤ 2.5 and DAS28 > 2.5 where the increased frequency of AA genotype among patients with DAS28 > 2.5 was revealed (OR 1.55; 95% CI 1.01-2.38). The results of our study suggest no significant association between CD28 rs1980422, CCL5 rs2107538, CTLA-4 exon 1 +49A>G rs231775 and rs3087243 gene polymorphisms and RA in the Polish population. Our results indicate a possible association between CTLA-4 exon 1 +49A>G rs231775 gene polymorphism and RA activity.
26976214 Approaching the active conformation of 1,3-diaminopyrimidine based covalent inhibitors of 2016 Apr 15 By applying conformational restrictions, we were able to discover highly potent 1,3-diaminopyrimidine based covalent inhibitors of BTK, such as 8a (IC50=3.76 nM), and providing useful information of its active conformation. We are developing these novel small molecule covalent inhibitors of BTK toward oral agents for Rheumatoid arthritis.
26932312 Prevalence of biologics monotherapy in a cohort of patients with Rheumatoid Arthritis in d 2016 Mar 1 BACKGROUND: Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy, in spite that combination therapy with Disease Modifying Drugs is more efficacious than monotherapy. The aim of our study was to assess the prevalence of biologics monotherapy in a cohort of patients with RA followed at a single center, and to analyze the reasons for monotherapy, including patients with prescriptions that do not take the medication. METHODS: All patients with Rheumatoid Arthritis, with biologic therapy followed at our Rheumatology Unit were included. Prevalence and reasons for biologics monotherapy was calculated in general, for each biologic course and for each biologic. Prescription data was obtained from the Electronic Medical Record, and drugs acquisition was obtained from the Hospital Administrative database. Drug survival was also calculated and compared between monotherapy and combination therapy. RESULTS: Seventy nine patients with 115 courses of biologic treatments were included. In 40 (35 %, 95 % CI: 26-44 %) of all biologics courses, biologics were initiated as monotherapy. In 27 courses (23 %, 95 % CI: 16-32 %) biologic monotherapy was prescribed by the treating rheumatologists, and in the other 13 (11 %, 95 % CI: 6-18 %) it was initiated as such by decision of the patient regardless of the physician indication. Reasons for prescription of biologic monotherapy by the treating rheumatologists were adverse events with previous DMARDs in 55.5 %, and was not specified in the remaining courses. Only 25 % of biologics' courses were monotherapy from the beginning to the end of the biologic therapy. The overall survival on biologics was 45 % (95 % CI: 35-55 %) at 3 years. There were no statistically differences in biologics survival by modality (monotherapy vs combination) (p = 0.543), course (p = 0.4454), or by biologic drug (p = 0.9612). CONCLUSIONS: Almost 1/3 of patients on biologics use them as monotherapy. This is due to physician's preferences in 60 % of the cases, and to patients not compliance with the indication in around 40 % of the cases. Better communications is needed to assure that physicians and patients agree on the prescribed and used medication.