Bernadette Rojkovich - Academia.edu (original) (raw)
Papers by Bernadette Rojkovich
Annals of the Rheumatic Diseases, 2015
Background: There are limited data to guide the selection of the first non-anti-TNF biologic DMAR... more Background: There are limited data to guide the selection of the first non-anti-TNF biologic DMARD (bDMARDs) after anti-TNF failure in rheumatoid arthritis (RA) patients. Objectives: To evaluate the drug survival of non-anti-TNF IV bDMARDs in RA patients with inadequate response to ≥1 TNF inhibitors (TNF-IR) in daily clinical practice. Methods: All TNF-IR patients treated with different non-anti-TNF bDMARDS in our center between 01/01/2007 to 31/12/2014 were included in the study. Analyses were stratified by the first biologic agent used after TNF failure (Tocilizumab-TCZ, Rituximab-RTX, Abatacept-ABA) and then by RF status and conventional synthetic DMARD (csDMARD) administration. Kaplan-Meier survival analysis and log-rank test of equality pairwise over strata were performed. Results: 94 TNF-IR consecutive RA patients treated with TCZ (n=24), RTX (n=49) or ABA (n=21) were included and followed for 24.2±18.8 months. 84/94 (89.4%) were women with a mean age of 64.5±15 years, rheumatoid factor (RF) positive were 49/94 (52%) patients. The baseline characteristics did not differ between the 3 groups, except from RF positivity which was more common in the RTX group compared to the TCZ group (p=0.01). The drug survival rates for TCZ, RTX and ABA were 79%, 83% and 76% at 12 months and 60%, 68%, 44% at 24 months, respectively (p=NS). Similarly, the mean time for drug discontinuation was 29.7, 41.7 and 27.1 months respectively and did not differ between groups (p=NS). Among RF+ patients, RTX (p=0.007) and TCZ (p=0.05) demonstrated better survival compared to ABA while there was no difference in drug survival among RF negative patients. There was a tendency for better drug survival among RA patients treated with RTX in combination with csDMARDs compared to combination ABA therapy (p=0.06) but this did not reach statistical significance. Conclusions: In this observational retrospective study, overall there was no significant difference in drug survival, between non-anti-TNF bDMARDs after anti-TNF failure, with the exception of RF+ patients where RTX and TCZ demonstrated better survival compared to ABA.
Abstracts Accepted for Publication, 2017
Results: of the 64 patients included in the study, 59 (92.2%) were women and 5 (7.8%) men, mean a... more Results: of the 64 patients included in the study, 59 (92.2%) were women and 5 (7.8%) men, mean age 57.55±9.42 years. After 6 months, 7 patients were declared nonresponders, 38 achieved a moderate response and 19 good response. Following baseline COMP titres and the EULAR response at 6 months, general tests identified significant differences between groups. Lower baseline titres had predictive value for achieving a good response (746.04±130.095 ng/ml) comparing with moderate responders (1032.8±188.671ng/ml) and nonresponders (1042.2±181.717 ng/ml, p=0.0000). After 12 months 11 patients achieved moderate response, 44 a good response and just 1 patient was declared nonresponder. At this visit, even if we didn't find significant differences between baseline COMP titres and the EULAR response (p=0.1430), we observed lower baseline titres for good responders (917.8±219.943 ng/ml) versus moderate responders (1042.7±193.117 ng/ml). Grouping patients in 2 categories (responders/nonresponders) there were no differences between groups at 6 months (937.27±218.106 ng/ml versus 1042.2±181.717 ng/ml, p=0.227) or 12 months (942.82±219.025 ng/ml versus 896.5±0.000 ng/ml, p=0.9753). Following the status pretreatment of COMP and EULAR response at 6 months, we identified differences between groups (p=0,0001), all 7 patients declared nonresponders were COMP positive and only 13/19 (68.4%) of good responders were tested positive. At 12 months there were no differences between pretreatment status of COMP and response to treatment (p=0.2805). Regarding the evolution of serum levels, we noticed a decrease statistically significant from baseline (948.75±215.683 ng/ml) to 12 months (740.88±227.04 ng/ml, p=0.0000). Conclusions: COMP could be one of the biomarkers for identifying pretreatment the patients who will respond to biologic therapy in Rheumatoid Arthritis.
Frontiers in Immunology
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder affecting the joints. Man... more Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder affecting the joints. Many patients carry anti-citrullinated protein autoantibodies (ACPA). Overactivation of the complement system seems to be part of the pathogenesis of RA, and autoantibodies against the pathway initiators C1q and MBL, and the regulator of the complement alternative pathway, factor H (FH), were previously reported. Our aim was to analyze the presence and role of autoantibodies against complement proteins in a Hungarian RA cohort. To this end, serum samples of 97 ACPA-positive RA patients and 117 healthy controls were analyzed for autoantibodies against FH, factor B (FB), C3b, C3-convertase (C3bBbP), C1q, MBL and factor I. In this cohort, we did not detect any patient with FH autoantibodies but detected C1q autoantibodies in four patients, MBL autoantibodies in two patients and FB autoantibodies in five patients. Since the latter autoantibodies were previously reported in patients with kidney ...
Orvosi Hetilap
Bevezetés: A COVID–19-pandémiát okozó SARS-CoV-2 koronavírusnak folyamatosan újabb variánsai jele... more Bevezetés: A COVID–19-pandémiát okozó SARS-CoV-2 koronavírusnak folyamatosan újabb variánsai jelennek meg, 2021. november óta a legtöbb fertőzést az omikron koronavírus-variáns okozta. Célkitűzés: A prospektív megfigyeléses kohorszvizsgálat célja a COVID–19-fertőzésre nagyobb rizikóval bíró, egészségügyben dolgozók körében két Pfizer–BioNTech-vakcina és az ezt követően önkéntesen felvett emlékeztető vakcina utáni COVID–19-fertőzések előfordulásának, a vakcina hatásosságának, biztonságosságának és immunogenitásának vizsgálata volt. Módszer: A Betegápoló Irgalmasrend Budai Irgalmasrendi Kórháza egészségügyi és egészségügyben dolgozó munkatársainak két Pfizer–BioNTech (BNT162b2)-oltását 2021. január 7. és március 8. között kezdték meg. A harmadik, emlékeztető védőoltás típusának választása és időpontjának meghatározása önkéntes volt. 2021. január 7. és 2022. június 29. között követtük nyomon a dolgozókat. Felmértük a COVID–19-fertőzés előfordulását, az oltási reakció súlyosságát, a fer...
Orvosi hetilap, Jan 3, 1989
The authors studied the distribution of acetylator phenotypes among 136 AS patients (100 male, 36... more The authors studied the distribution of acetylator phenotypes among 136 AS patients (100 male, 36 female). 67 per cent of all patients were slow acetylators, 72 per cent of the males. Both rates are higher than that of the healthy Hungarian population. The authors draw attention to the clinical importance of investigating the acetylator type before sulphasalazine treatment because it may help in prescribing the effective dose and avoiding side effects.
Annals of the Rheumatic Diseases, 1998
Objective-An attempt was made to see if rheumatoid arthritis (RA) patients can use visual analogu... more Objective-An attempt was made to see if rheumatoid arthritis (RA) patients can use visual analogue scales (VAS) to distinguish and grade the severity of pain at night, during rest, and on joint movement and to determine if discriminate measurement of these three pain components enhances the value of VAS estimation. Methods-Two hundred and fifty two consecutive RA patients were evaluated by a single observer using 10 cm VAS for pain at night, at rest during the day, and on movement. Values were correlated against age, disease duration, joint tenderness, swollen joint count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Larsen x ray scores. Results-Night pain was recorded by 71 (28%) and this component of pain was lower than VAS scores for daytime rest and movement. However, those with nocturnal pain had significantly more joint tenderness (p<0.0001), swollen joints (p<0.0001), and higher ESR and CRP. Age, disease duration, and radiographic scores were similar in those with and without night pain. Correlations of joint tenderness were apparent for all three pain scores but only nocturnal pain correlated with swollen joints (p<0.001) and CRP (p<0.005). Age, disease duration, and radiographic severity correlated with daytime rest or movement scores but not nocturnal pain. Conclusion-Patients were able to distinguish and estimate the severity of pain at rest, on movement, and at night. The occurrence of night pain characterised those with more active disease and night pain VAS measurement correlated best with measures of joint inflammation whereas daytime pain scores, both at rest and on movement, seemed influenced by the degree of permanent joint damage. Thus, discrete measurement of rest, movement, and nocturnal pain may provide useful information about RA disease status.
Annals of the Rheumatic Diseases, 2011
Objectives: Osteopontin (OPN) is an extracellular matrix protein with diverse immunomodulatory fu... more Objectives: Osteopontin (OPN) is an extracellular matrix protein with diverse immunomodulatory functions. We assessed safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks OPN. Methods: In this double-blind, multicentre, combined first-in-man, single-dose escalation (Phase I, Part A) and proof-of-concept, multiple-dose (Phase IIA, Part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. Expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (Part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in number of CD68 + synovial sublining macrophages, both assessed on Day 43 (Part B). Results: ASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 + sublining macrophages between ASK8007-and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers. Conclusions: OPN blockade is well tolerated and not related to safety concerns. These results consistently show that OPN blockade is unlikely to induce robust clinical improvement in RA patients.
International Journal of Molecular Sciences
Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arth... more Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arthritis. N-glycosylation pattern of ACPA-IgG and healthy IgG Fc differs. The aim of this study is to determine the relative sialylation and galactosylation level of ACPAs and control IgG to assess their capability of inducing TNFα production, and furthermore, to analyze the correlations between the composition of Fc glycans and inflammatory markers in RA. We isolated IgG from sera of healthy volunteers and RA patients, and purified ACPAs on a citrulline-peptide column. Immunocomplexes (IC) were formed by adding an F(ab)2 fragment of anti-human IgG. U937 cells were used to monitor the binding of IC to FcγR and to trigger TNFα release determined by ELISA. To analyze glycan profiles, control IgG and ACPA-IgG were digested with trypsin and the glycosylation patterns of glycopeptides were analyzed by determining site-specific N-glycosylation using nano-UHPLC-MS/MS. We found that both sialylatio...
Annals of the Rheumatic Diseases, 2015
Background Regulatory B cells (Breg) are newly defined B cell subsets that downregulate the immun... more Background Regulatory B cells (Breg) are newly defined B cell subsets that downregulate the immune response. The pleiotrophic cytokine, IL-10 seemed to be responsible for this function. B cells play a crucial role in the development and maintenance of Rheumatoid arthritis (RA). Therefore this study was undertaken to identify the optimal stimuli (BCR, CpG, CD40L) that induce Breg cells, furthermore, our aim was to compare the number of Breg in RA patients and healthy controls. We also aimed to examine, which inflammatory cytokines are produced by B cells in response to the same stimuli. Materials and methods Blood samples were collected from healthy donors and RA patients. Intracellular IL-6, IL-10 and TNF were measured in purified B cells and in PBMC. Cytokines were detected in B cells prior or after stimulation by intracellular fluorescent staining using specific antibodies. IL-10, IL-6, TNF, IL-1b and INFg were measured in the supernatants of purified B cell with FlowCytomix multiplex bead array. Results At our experimental conditions, dual stimulation by CpG and CD40L for 48 h was found to be optimal for IL-10 induction in B cells. We identified CD19+ CD27+ memory B cells as the main source of IL-10. The dual stimuli induced significantly lower number of IL-10 producing B cells from RA patients as compared to healthy controls, while we didn’t find a difference in the inflammatory cytokine (IL-6 and TNF) production. However, in unstimulated samples the frequency of IL-6 producing B cells was lower in healthy controls, than in RA patients. Furthermore, we observed that in the supernatant of purified B cells, beside IL-10, other inflammatory cytokines (IL-6, TNF, IL-1b and INFg) were also present. Therefore we double stained B cells with anti-IL-10 and anti-TNF antibodies and found that these cytokines were produced by different subsets. Conclusion We detected a significant difference between the number of IL-10 producing CD27+Breg cells of RA patients and healthy controls. The lower frequency of activation-induced IL-10 producing Bregs and on the other hand, the increased ratio of spontaneously IL-6 secreting B cells in RA patients may contribute to the exacerbation of the disease. Support: OTKA NK 104846
Clinical and experimental rheumatology
To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. T... more To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). Th...
Poster presentations, 2018
mice treated with monoclonal anti-TNF: 5/15 (33%) with TN3 (p=0.03/ controls), 4/12 (33%) with AD... more mice treated with monoclonal anti-TNF: 5/15 (33%) with TN3 (p=0.03/ controls), 4/12 (33%) with ADA (p=0.054/ controls), 0/15 with ETA and 1/22 (5%) in controls. Conclusions Higher mortality and increased risk of lymphoma were observed in BAFF Tg mice treated with monoclonal anti-TNF compared to etanercept. This result may be linked either to the different mechanism of action between the soluble receptor and the monoclonals or to a difference of trough level observed in the different groups even if higher levels of ADA was mandatory given the difference of effect on mouse TNF. This study demonstrates the negative impact of a prolonged anti-TNF treatment on the risk of lymphoma in the context of BAFF increase.
The Journal of rheumatology, 2001
The objective of the present study was to assess the excretion of urinary thiol compounds in pati... more The objective of the present study was to assess the excretion of urinary thiol compounds in patients with active and inactive rheumatoid arthritis (RA). Urinary thiol compounds were measured by the method of Kokonov (M. T. Kokonov, Lab. Delo 5:273–276, 1965) in 51 outpatients with active and inactive RA. Those with active disease had significantly higher levels of urinary thioamine excretion. The reaction of Kokonov (6) measures the levels of thiol compounds excreted in the urine. Kokonov (6) published a description of this simple method for the detection of the thiol compounds in patients with neoplasms. This method was found to be suitable for the screening of patients with a high risk of malignancy (4, 7, 13), but patients with viral infection also displayed a positive test result (12). Patients suffering from bacterial infections, active autoimmune diseases, and acute pancreatitis or myocardial infarction also had positive test re-sults. We assumed that the reaction is suitable...
18 Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs... more 18 Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) 19 are responsible for disease onset and progression, however, our knowledge is limited on ligand 20 binding affinities of autoantibodies with different citrulline-peptide specificity. 21 Methods: Citrulline-peptide specific ACPA IgGs were affinity purified and tested by ELISA. 22 Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon 23 resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide 24 and a complement activating peptide were used to induce selective depletion of ACPA producing 25 B cells. 26 Results: KD values of affinity purified ACPA IgGs varies between 10-6-10-8 M and inversely correlate 27 with disease activity. Based on their cross-reaction with citrulline-peptides we designed a novel 28 multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two-two copies, separated with a 29 short, neutr...
Orvosi hetilap, 2002
Rheumatoid arthritis is a chronic, progressive, inflammatory joint disease, affecting primarily t... more Rheumatoid arthritis is a chronic, progressive, inflammatory joint disease, affecting primarily the small joints of the hands and feet symmetrically and characterized by joint destruction, progressive disability, and premature death. Rheumatoid arthritis shows a wide spectrum of clinical phenotypes from mild disease to severe arthritis. Aggressive disease implies a rapidly progressive course affecting most joints, with little or no response to drug therapy, and sometimes complicated by life-threatening extraarticular involvement. The eventual multiple joint destruction requires major surgery, and severe disability results in loss of occupation and dependence on others. Many prospective cohort studies have attempted to predict outcomes and develop prognostic markers, especially in early disease. Probably most useful are those factors that independent of disease activity, such as the presence of rheumatoid factor, the so-called shared epitope of HLA-DR. In addition, clinical indicator...
Patient Preference and Adherence
Background: Patients' needs and perspectives are important determinants of treatment success in r... more Background: Patients' needs and perspectives are important determinants of treatment success in rheumatoid arthritis (RA). Assessing patients' perspectives can help identify unmet needs and enhance the understanding of treatment benefits. Objective: The SENSE study assessed the impact of inadequate response to diseasemodifying antirheumatic drugs (DMARDs) on treatment satisfaction, disease outcomes, and patient perspectives related to RA disease management. Methods: SENSE was a noninterventional, cross-sectional study conducted in 18 countries across Europe, Asia, and South America. Adult patients with poorly controlled RA of moderate/high disease activity were eligible. Patient satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM v1.4). Treatment adherence, healthcare resource utilization (HRU), quality of life (QoL), work ability, digital health literacy (DHL), patient preference information, and treatment strategy were also assessed. Results: A total of 1624 patients were included in the study: most were female (84.2%) and middle-aged, and mean disease duration was 10.5 years. Mean TSQM global satisfaction subscore was 60.9, with only 13.5% of patients reporting good treatment satisfaction (TSQM global ≥80). The strongest predictor of good treatment satisfaction was treatment with advanced therapies. Most patients (87.4%) reported good treatment adherence. In general, patients had impaired QoL and work ability, high HRU, and 67.4% had poor DHL. Leading treatment expectations were "general improvement of arthritis" and "less joint pain". Most patients preferred oral RA medications (60.7%) and rapid (≤1 week) onset of action (71.1%). "Increased risk for malignancies" and "increased risk for cardiovascular disease" were the least acceptable side effects. Despite suboptimal control, advanced therapies were only used in a minority of patients, and DMARD switches were planned for only half of the patients. Conclusion: Suboptimal disease control negatively impacts treatment satisfaction, work ability, QoL, and HRU. Data collected on patient perspectives may inform shared decisionmaking and optimize treat-to-target strategies for improving patient outcomes in RA.
Annals of the Rheumatic Diseases
Background and objectives Anti-citrullinated peptide/protein antibodies (ACPA) have diagnostic si... more Background and objectives Anti-citrullinated peptide/protein antibodies (ACPA) have diagnostic significance and a pathological role in rheumatoid arthritis (RA). Multiple specificities of ACPA have been described, targeting various proteins such as filaggrin, fibrin, vimentin, collagen, enolase and some citrullinated peptides of Epstein-Barr virus nuclear antigen (EBNA) as well. Specificities as well as affinities of ACPA may influence its ability to trigger inflammatory cytokine production, modifying local and systemic inflammation in patients. Therefore we compared binding affinities of serum samples from 60 RA patients to citrullinated 19mer filaggrin peptide. Materials and methods The peptide specific IgG was affinity purified from sera of RA patients on insolubilized citrullinated peptides derived from filaggrin, fibrin, collagen, and vimentin. Peptide specific IgG concentrations in sera were calculated by ELISA, using a calibration curve prepared from the affinity purified IgG. Binding affinities of IgG and serum samples were tested on citrullinated peptide covalently coupled to the surface of ProteOn XPR36 GLH sensor chip. The 1:1 binding model was employed to calculate the apparent affinity constant, KD. Results 26 of the 60 serum samples have shown measurable binding affinity to citrullinated filaggrin peptide with KD values between 10–5–10–7M. In general, individual sera showing multiple specificities to citrullinated peptides in ELISA possess a higher KD to filaggrin peptide. An inverse correlation was observed between disease severity (DAS28 index) and binding affinities. Surprisingly, high degree of cross-reactivity was detected between affinity purified IgGs specific for citrullinated filaggrin, fibrin, vimentin and collagen. Conclusions Biosensor analysis has shown that ACPA are very heterogeneous regarding both specificities and affinities, furthermore, the affinity purified IgGs from individual ACPA are highly cross-reactive. Support: National Research, Development and Innovation Office (OTKA104846) and ELTE KMOP-4.2.1/B-10–2011–0002
Annals of the Rheumatic Diseases
Background and objectives The most important feature of B-cells is the production antibodies upon... more Background and objectives The most important feature of B-cells is the production antibodies upon activation; additionally, B-cells produce both pro-inflammatory and anti-inflammatory cytokines in response to certain stimuli. IL-10 producing B10 cells represent a major subset of regulatory B-cells (Bregs). Bregs suppress autoimmune and inflammatory responses by multiple mechanisms. B-cells play crucial role in the development and maintenance of the chronic inflammatory autoimmune disease, Rheumatoid arthritis (RA); however, controversial data are available on B10 population in RA. Our aim was to identify the optimal conditions inducing B10 cells in samples from healthy controls and RA patients; furthermore, to shed light on signalling pathways resulting in the expansion of the B10 subset. Materials and methods Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood of healthy donors and RA patients. B cells were purified by magnetic separation, using negative selection. We assessed IL-10 and TNF expressing B-cells after intracellular staining by flow cytometry, and measured the secreted cytokines with multiplex bead array. Phosphorylation of key signalling molecules was monitored by phospho-flow method. Results The results show that dual stimulation by CpG and CD40L for 48h was optimal for IL-10 induction, which was synergistically boosted by IL-21. We identified CD19+ CD27+ memory B-cells as the major source of B10 cells. IL-21 increased the ratio of BLIMP1 and IL-10 double positive plasmablasts. In RA patients we detected significantly less CD27+ B10 cells as compared to the controls, while addition of IL-21 to the dual stimuli significantly elevated the number of B10 cells both in the CD19+CD27+ and in the CD19+ CD27- population. Different combinations of stimuli induced preferentially the secretion of pro-inflammatory cytokines (TNF, IFNγ, IL-17) and the suppressor cytokine, IL-10. We assumed that activation of ERK, p38 and CREB are indispensable to induce IL-10, while STAT3 appears to be a co-activator for IL-10 transcription in human Bregs. Conclusions CD19+CD27+ memory B-cells are the major source of human B10 cells, which may expand and differentiate to IL-10 producing plasmablasts in the presence of IL-21. CREB and the co-activator STAT3 are the key transcription factors responsible for the expansion of the B10 population. Support: National Research, Development and Innovation Office (OTKA104846), and ELTE TÁMOP 4.2.1./B-09/1/KMR-2010–0003
Acta pharmaceutica Hungarica, 2010
Continuous NSAID (nonsteroidal anti-inflammatory drug) therapy is associated with gastrointestina... more Continuous NSAID (nonsteroidal anti-inflammatory drug) therapy is associated with gastrointestinal (GI) and cardiovascular (CV) side effects. In this paper, the oral NSAID use of 143 patients with rheumatoid arthritis was assessed focusing on safety and farmacoeconomic aspects in a cross sectional non interventional study. The most widely used NSAIDs were meloxicam (n = 55, 38.5%) and diclofenac (n = 30, 21%). We found that coxibs were overused (n = 13, 9.1%) compared with the average total coxib consumption in Hungary. According to our results, drugs associated with GI friend side effect profile (meloxicam, celecoxib, etoricoxib) were much preferred in patients with previous GI events, than in patients with low GI risk. The previous occurrence of GI events were significantly higher (p = 0.019) in patients currently treated with safer NSAIDs, probably because of the so-called 'indication bias'. No statistically significant difference in patient's quality of life could be...
Annals of the Rheumatic Diseases, 2015
Background: There are limited data to guide the selection of the first non-anti-TNF biologic DMAR... more Background: There are limited data to guide the selection of the first non-anti-TNF biologic DMARD (bDMARDs) after anti-TNF failure in rheumatoid arthritis (RA) patients. Objectives: To evaluate the drug survival of non-anti-TNF IV bDMARDs in RA patients with inadequate response to ≥1 TNF inhibitors (TNF-IR) in daily clinical practice. Methods: All TNF-IR patients treated with different non-anti-TNF bDMARDS in our center between 01/01/2007 to 31/12/2014 were included in the study. Analyses were stratified by the first biologic agent used after TNF failure (Tocilizumab-TCZ, Rituximab-RTX, Abatacept-ABA) and then by RF status and conventional synthetic DMARD (csDMARD) administration. Kaplan-Meier survival analysis and log-rank test of equality pairwise over strata were performed. Results: 94 TNF-IR consecutive RA patients treated with TCZ (n=24), RTX (n=49) or ABA (n=21) were included and followed for 24.2±18.8 months. 84/94 (89.4%) were women with a mean age of 64.5±15 years, rheumatoid factor (RF) positive were 49/94 (52%) patients. The baseline characteristics did not differ between the 3 groups, except from RF positivity which was more common in the RTX group compared to the TCZ group (p=0.01). The drug survival rates for TCZ, RTX and ABA were 79%, 83% and 76% at 12 months and 60%, 68%, 44% at 24 months, respectively (p=NS). Similarly, the mean time for drug discontinuation was 29.7, 41.7 and 27.1 months respectively and did not differ between groups (p=NS). Among RF+ patients, RTX (p=0.007) and TCZ (p=0.05) demonstrated better survival compared to ABA while there was no difference in drug survival among RF negative patients. There was a tendency for better drug survival among RA patients treated with RTX in combination with csDMARDs compared to combination ABA therapy (p=0.06) but this did not reach statistical significance. Conclusions: In this observational retrospective study, overall there was no significant difference in drug survival, between non-anti-TNF bDMARDs after anti-TNF failure, with the exception of RF+ patients where RTX and TCZ demonstrated better survival compared to ABA.
Abstracts Accepted for Publication, 2017
Results: of the 64 patients included in the study, 59 (92.2%) were women and 5 (7.8%) men, mean a... more Results: of the 64 patients included in the study, 59 (92.2%) were women and 5 (7.8%) men, mean age 57.55±9.42 years. After 6 months, 7 patients were declared nonresponders, 38 achieved a moderate response and 19 good response. Following baseline COMP titres and the EULAR response at 6 months, general tests identified significant differences between groups. Lower baseline titres had predictive value for achieving a good response (746.04±130.095 ng/ml) comparing with moderate responders (1032.8±188.671ng/ml) and nonresponders (1042.2±181.717 ng/ml, p=0.0000). After 12 months 11 patients achieved moderate response, 44 a good response and just 1 patient was declared nonresponder. At this visit, even if we didn't find significant differences between baseline COMP titres and the EULAR response (p=0.1430), we observed lower baseline titres for good responders (917.8±219.943 ng/ml) versus moderate responders (1042.7±193.117 ng/ml). Grouping patients in 2 categories (responders/nonresponders) there were no differences between groups at 6 months (937.27±218.106 ng/ml versus 1042.2±181.717 ng/ml, p=0.227) or 12 months (942.82±219.025 ng/ml versus 896.5±0.000 ng/ml, p=0.9753). Following the status pretreatment of COMP and EULAR response at 6 months, we identified differences between groups (p=0,0001), all 7 patients declared nonresponders were COMP positive and only 13/19 (68.4%) of good responders were tested positive. At 12 months there were no differences between pretreatment status of COMP and response to treatment (p=0.2805). Regarding the evolution of serum levels, we noticed a decrease statistically significant from baseline (948.75±215.683 ng/ml) to 12 months (740.88±227.04 ng/ml, p=0.0000). Conclusions: COMP could be one of the biomarkers for identifying pretreatment the patients who will respond to biologic therapy in Rheumatoid Arthritis.
Frontiers in Immunology
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder affecting the joints. Man... more Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder affecting the joints. Many patients carry anti-citrullinated protein autoantibodies (ACPA). Overactivation of the complement system seems to be part of the pathogenesis of RA, and autoantibodies against the pathway initiators C1q and MBL, and the regulator of the complement alternative pathway, factor H (FH), were previously reported. Our aim was to analyze the presence and role of autoantibodies against complement proteins in a Hungarian RA cohort. To this end, serum samples of 97 ACPA-positive RA patients and 117 healthy controls were analyzed for autoantibodies against FH, factor B (FB), C3b, C3-convertase (C3bBbP), C1q, MBL and factor I. In this cohort, we did not detect any patient with FH autoantibodies but detected C1q autoantibodies in four patients, MBL autoantibodies in two patients and FB autoantibodies in five patients. Since the latter autoantibodies were previously reported in patients with kidney ...
Orvosi Hetilap
Bevezetés: A COVID–19-pandémiát okozó SARS-CoV-2 koronavírusnak folyamatosan újabb variánsai jele... more Bevezetés: A COVID–19-pandémiát okozó SARS-CoV-2 koronavírusnak folyamatosan újabb variánsai jelennek meg, 2021. november óta a legtöbb fertőzést az omikron koronavírus-variáns okozta. Célkitűzés: A prospektív megfigyeléses kohorszvizsgálat célja a COVID–19-fertőzésre nagyobb rizikóval bíró, egészségügyben dolgozók körében két Pfizer–BioNTech-vakcina és az ezt követően önkéntesen felvett emlékeztető vakcina utáni COVID–19-fertőzések előfordulásának, a vakcina hatásosságának, biztonságosságának és immunogenitásának vizsgálata volt. Módszer: A Betegápoló Irgalmasrend Budai Irgalmasrendi Kórháza egészségügyi és egészségügyben dolgozó munkatársainak két Pfizer–BioNTech (BNT162b2)-oltását 2021. január 7. és március 8. között kezdték meg. A harmadik, emlékeztető védőoltás típusának választása és időpontjának meghatározása önkéntes volt. 2021. január 7. és 2022. június 29. között követtük nyomon a dolgozókat. Felmértük a COVID–19-fertőzés előfordulását, az oltási reakció súlyosságát, a fer...
Orvosi hetilap, Jan 3, 1989
The authors studied the distribution of acetylator phenotypes among 136 AS patients (100 male, 36... more The authors studied the distribution of acetylator phenotypes among 136 AS patients (100 male, 36 female). 67 per cent of all patients were slow acetylators, 72 per cent of the males. Both rates are higher than that of the healthy Hungarian population. The authors draw attention to the clinical importance of investigating the acetylator type before sulphasalazine treatment because it may help in prescribing the effective dose and avoiding side effects.
Annals of the Rheumatic Diseases, 1998
Objective-An attempt was made to see if rheumatoid arthritis (RA) patients can use visual analogu... more Objective-An attempt was made to see if rheumatoid arthritis (RA) patients can use visual analogue scales (VAS) to distinguish and grade the severity of pain at night, during rest, and on joint movement and to determine if discriminate measurement of these three pain components enhances the value of VAS estimation. Methods-Two hundred and fifty two consecutive RA patients were evaluated by a single observer using 10 cm VAS for pain at night, at rest during the day, and on movement. Values were correlated against age, disease duration, joint tenderness, swollen joint count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Larsen x ray scores. Results-Night pain was recorded by 71 (28%) and this component of pain was lower than VAS scores for daytime rest and movement. However, those with nocturnal pain had significantly more joint tenderness (p<0.0001), swollen joints (p<0.0001), and higher ESR and CRP. Age, disease duration, and radiographic scores were similar in those with and without night pain. Correlations of joint tenderness were apparent for all three pain scores but only nocturnal pain correlated with swollen joints (p<0.001) and CRP (p<0.005). Age, disease duration, and radiographic severity correlated with daytime rest or movement scores but not nocturnal pain. Conclusion-Patients were able to distinguish and estimate the severity of pain at rest, on movement, and at night. The occurrence of night pain characterised those with more active disease and night pain VAS measurement correlated best with measures of joint inflammation whereas daytime pain scores, both at rest and on movement, seemed influenced by the degree of permanent joint damage. Thus, discrete measurement of rest, movement, and nocturnal pain may provide useful information about RA disease status.
Annals of the Rheumatic Diseases, 2011
Objectives: Osteopontin (OPN) is an extracellular matrix protein with diverse immunomodulatory fu... more Objectives: Osteopontin (OPN) is an extracellular matrix protein with diverse immunomodulatory functions. We assessed safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks OPN. Methods: In this double-blind, multicentre, combined first-in-man, single-dose escalation (Phase I, Part A) and proof-of-concept, multiple-dose (Phase IIA, Part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. Expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (Part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in number of CD68 + synovial sublining macrophages, both assessed on Day 43 (Part B). Results: ASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 + sublining macrophages between ASK8007-and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers. Conclusions: OPN blockade is well tolerated and not related to safety concerns. These results consistently show that OPN blockade is unlikely to induce robust clinical improvement in RA patients.
International Journal of Molecular Sciences
Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arth... more Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arthritis. N-glycosylation pattern of ACPA-IgG and healthy IgG Fc differs. The aim of this study is to determine the relative sialylation and galactosylation level of ACPAs and control IgG to assess their capability of inducing TNFα production, and furthermore, to analyze the correlations between the composition of Fc glycans and inflammatory markers in RA. We isolated IgG from sera of healthy volunteers and RA patients, and purified ACPAs on a citrulline-peptide column. Immunocomplexes (IC) were formed by adding an F(ab)2 fragment of anti-human IgG. U937 cells were used to monitor the binding of IC to FcγR and to trigger TNFα release determined by ELISA. To analyze glycan profiles, control IgG and ACPA-IgG were digested with trypsin and the glycosylation patterns of glycopeptides were analyzed by determining site-specific N-glycosylation using nano-UHPLC-MS/MS. We found that both sialylatio...
Annals of the Rheumatic Diseases, 2015
Background Regulatory B cells (Breg) are newly defined B cell subsets that downregulate the immun... more Background Regulatory B cells (Breg) are newly defined B cell subsets that downregulate the immune response. The pleiotrophic cytokine, IL-10 seemed to be responsible for this function. B cells play a crucial role in the development and maintenance of Rheumatoid arthritis (RA). Therefore this study was undertaken to identify the optimal stimuli (BCR, CpG, CD40L) that induce Breg cells, furthermore, our aim was to compare the number of Breg in RA patients and healthy controls. We also aimed to examine, which inflammatory cytokines are produced by B cells in response to the same stimuli. Materials and methods Blood samples were collected from healthy donors and RA patients. Intracellular IL-6, IL-10 and TNF were measured in purified B cells and in PBMC. Cytokines were detected in B cells prior or after stimulation by intracellular fluorescent staining using specific antibodies. IL-10, IL-6, TNF, IL-1b and INFg were measured in the supernatants of purified B cell with FlowCytomix multiplex bead array. Results At our experimental conditions, dual stimulation by CpG and CD40L for 48 h was found to be optimal for IL-10 induction in B cells. We identified CD19+ CD27+ memory B cells as the main source of IL-10. The dual stimuli induced significantly lower number of IL-10 producing B cells from RA patients as compared to healthy controls, while we didn’t find a difference in the inflammatory cytokine (IL-6 and TNF) production. However, in unstimulated samples the frequency of IL-6 producing B cells was lower in healthy controls, than in RA patients. Furthermore, we observed that in the supernatant of purified B cells, beside IL-10, other inflammatory cytokines (IL-6, TNF, IL-1b and INFg) were also present. Therefore we double stained B cells with anti-IL-10 and anti-TNF antibodies and found that these cytokines were produced by different subsets. Conclusion We detected a significant difference between the number of IL-10 producing CD27+Breg cells of RA patients and healthy controls. The lower frequency of activation-induced IL-10 producing Bregs and on the other hand, the increased ratio of spontaneously IL-6 secreting B cells in RA patients may contribute to the exacerbation of the disease. Support: OTKA NK 104846
Clinical and experimental rheumatology
To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. T... more To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). Th...
Poster presentations, 2018
mice treated with monoclonal anti-TNF: 5/15 (33%) with TN3 (p=0.03/ controls), 4/12 (33%) with AD... more mice treated with monoclonal anti-TNF: 5/15 (33%) with TN3 (p=0.03/ controls), 4/12 (33%) with ADA (p=0.054/ controls), 0/15 with ETA and 1/22 (5%) in controls. Conclusions Higher mortality and increased risk of lymphoma were observed in BAFF Tg mice treated with monoclonal anti-TNF compared to etanercept. This result may be linked either to the different mechanism of action between the soluble receptor and the monoclonals or to a difference of trough level observed in the different groups even if higher levels of ADA was mandatory given the difference of effect on mouse TNF. This study demonstrates the negative impact of a prolonged anti-TNF treatment on the risk of lymphoma in the context of BAFF increase.
The Journal of rheumatology, 2001
The objective of the present study was to assess the excretion of urinary thiol compounds in pati... more The objective of the present study was to assess the excretion of urinary thiol compounds in patients with active and inactive rheumatoid arthritis (RA). Urinary thiol compounds were measured by the method of Kokonov (M. T. Kokonov, Lab. Delo 5:273–276, 1965) in 51 outpatients with active and inactive RA. Those with active disease had significantly higher levels of urinary thioamine excretion. The reaction of Kokonov (6) measures the levels of thiol compounds excreted in the urine. Kokonov (6) published a description of this simple method for the detection of the thiol compounds in patients with neoplasms. This method was found to be suitable for the screening of patients with a high risk of malignancy (4, 7, 13), but patients with viral infection also displayed a positive test result (12). Patients suffering from bacterial infections, active autoimmune diseases, and acute pancreatitis or myocardial infarction also had positive test re-sults. We assumed that the reaction is suitable...
18 Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs... more 18 Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) 19 are responsible for disease onset and progression, however, our knowledge is limited on ligand 20 binding affinities of autoantibodies with different citrulline-peptide specificity. 21 Methods: Citrulline-peptide specific ACPA IgGs were affinity purified and tested by ELISA. 22 Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon 23 resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide 24 and a complement activating peptide were used to induce selective depletion of ACPA producing 25 B cells. 26 Results: KD values of affinity purified ACPA IgGs varies between 10-6-10-8 M and inversely correlate 27 with disease activity. Based on their cross-reaction with citrulline-peptides we designed a novel 28 multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two-two copies, separated with a 29 short, neutr...
Orvosi hetilap, 2002
Rheumatoid arthritis is a chronic, progressive, inflammatory joint disease, affecting primarily t... more Rheumatoid arthritis is a chronic, progressive, inflammatory joint disease, affecting primarily the small joints of the hands and feet symmetrically and characterized by joint destruction, progressive disability, and premature death. Rheumatoid arthritis shows a wide spectrum of clinical phenotypes from mild disease to severe arthritis. Aggressive disease implies a rapidly progressive course affecting most joints, with little or no response to drug therapy, and sometimes complicated by life-threatening extraarticular involvement. The eventual multiple joint destruction requires major surgery, and severe disability results in loss of occupation and dependence on others. Many prospective cohort studies have attempted to predict outcomes and develop prognostic markers, especially in early disease. Probably most useful are those factors that independent of disease activity, such as the presence of rheumatoid factor, the so-called shared epitope of HLA-DR. In addition, clinical indicator...
Patient Preference and Adherence
Background: Patients' needs and perspectives are important determinants of treatment success in r... more Background: Patients' needs and perspectives are important determinants of treatment success in rheumatoid arthritis (RA). Assessing patients' perspectives can help identify unmet needs and enhance the understanding of treatment benefits. Objective: The SENSE study assessed the impact of inadequate response to diseasemodifying antirheumatic drugs (DMARDs) on treatment satisfaction, disease outcomes, and patient perspectives related to RA disease management. Methods: SENSE was a noninterventional, cross-sectional study conducted in 18 countries across Europe, Asia, and South America. Adult patients with poorly controlled RA of moderate/high disease activity were eligible. Patient satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM v1.4). Treatment adherence, healthcare resource utilization (HRU), quality of life (QoL), work ability, digital health literacy (DHL), patient preference information, and treatment strategy were also assessed. Results: A total of 1624 patients were included in the study: most were female (84.2%) and middle-aged, and mean disease duration was 10.5 years. Mean TSQM global satisfaction subscore was 60.9, with only 13.5% of patients reporting good treatment satisfaction (TSQM global ≥80). The strongest predictor of good treatment satisfaction was treatment with advanced therapies. Most patients (87.4%) reported good treatment adherence. In general, patients had impaired QoL and work ability, high HRU, and 67.4% had poor DHL. Leading treatment expectations were "general improvement of arthritis" and "less joint pain". Most patients preferred oral RA medications (60.7%) and rapid (≤1 week) onset of action (71.1%). "Increased risk for malignancies" and "increased risk for cardiovascular disease" were the least acceptable side effects. Despite suboptimal control, advanced therapies were only used in a minority of patients, and DMARD switches were planned for only half of the patients. Conclusion: Suboptimal disease control negatively impacts treatment satisfaction, work ability, QoL, and HRU. Data collected on patient perspectives may inform shared decisionmaking and optimize treat-to-target strategies for improving patient outcomes in RA.
Annals of the Rheumatic Diseases
Background and objectives Anti-citrullinated peptide/protein antibodies (ACPA) have diagnostic si... more Background and objectives Anti-citrullinated peptide/protein antibodies (ACPA) have diagnostic significance and a pathological role in rheumatoid arthritis (RA). Multiple specificities of ACPA have been described, targeting various proteins such as filaggrin, fibrin, vimentin, collagen, enolase and some citrullinated peptides of Epstein-Barr virus nuclear antigen (EBNA) as well. Specificities as well as affinities of ACPA may influence its ability to trigger inflammatory cytokine production, modifying local and systemic inflammation in patients. Therefore we compared binding affinities of serum samples from 60 RA patients to citrullinated 19mer filaggrin peptide. Materials and methods The peptide specific IgG was affinity purified from sera of RA patients on insolubilized citrullinated peptides derived from filaggrin, fibrin, collagen, and vimentin. Peptide specific IgG concentrations in sera were calculated by ELISA, using a calibration curve prepared from the affinity purified IgG. Binding affinities of IgG and serum samples were tested on citrullinated peptide covalently coupled to the surface of ProteOn XPR36 GLH sensor chip. The 1:1 binding model was employed to calculate the apparent affinity constant, KD. Results 26 of the 60 serum samples have shown measurable binding affinity to citrullinated filaggrin peptide with KD values between 10–5–10–7M. In general, individual sera showing multiple specificities to citrullinated peptides in ELISA possess a higher KD to filaggrin peptide. An inverse correlation was observed between disease severity (DAS28 index) and binding affinities. Surprisingly, high degree of cross-reactivity was detected between affinity purified IgGs specific for citrullinated filaggrin, fibrin, vimentin and collagen. Conclusions Biosensor analysis has shown that ACPA are very heterogeneous regarding both specificities and affinities, furthermore, the affinity purified IgGs from individual ACPA are highly cross-reactive. Support: National Research, Development and Innovation Office (OTKA104846) and ELTE KMOP-4.2.1/B-10–2011–0002
Annals of the Rheumatic Diseases
Background and objectives The most important feature of B-cells is the production antibodies upon... more Background and objectives The most important feature of B-cells is the production antibodies upon activation; additionally, B-cells produce both pro-inflammatory and anti-inflammatory cytokines in response to certain stimuli. IL-10 producing B10 cells represent a major subset of regulatory B-cells (Bregs). Bregs suppress autoimmune and inflammatory responses by multiple mechanisms. B-cells play crucial role in the development and maintenance of the chronic inflammatory autoimmune disease, Rheumatoid arthritis (RA); however, controversial data are available on B10 population in RA. Our aim was to identify the optimal conditions inducing B10 cells in samples from healthy controls and RA patients; furthermore, to shed light on signalling pathways resulting in the expansion of the B10 subset. Materials and methods Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood of healthy donors and RA patients. B cells were purified by magnetic separation, using negative selection. We assessed IL-10 and TNF expressing B-cells after intracellular staining by flow cytometry, and measured the secreted cytokines with multiplex bead array. Phosphorylation of key signalling molecules was monitored by phospho-flow method. Results The results show that dual stimulation by CpG and CD40L for 48h was optimal for IL-10 induction, which was synergistically boosted by IL-21. We identified CD19+ CD27+ memory B-cells as the major source of B10 cells. IL-21 increased the ratio of BLIMP1 and IL-10 double positive plasmablasts. In RA patients we detected significantly less CD27+ B10 cells as compared to the controls, while addition of IL-21 to the dual stimuli significantly elevated the number of B10 cells both in the CD19+CD27+ and in the CD19+ CD27- population. Different combinations of stimuli induced preferentially the secretion of pro-inflammatory cytokines (TNF, IFNγ, IL-17) and the suppressor cytokine, IL-10. We assumed that activation of ERK, p38 and CREB are indispensable to induce IL-10, while STAT3 appears to be a co-activator for IL-10 transcription in human Bregs. Conclusions CD19+CD27+ memory B-cells are the major source of human B10 cells, which may expand and differentiate to IL-10 producing plasmablasts in the presence of IL-21. CREB and the co-activator STAT3 are the key transcription factors responsible for the expansion of the B10 population. Support: National Research, Development and Innovation Office (OTKA104846), and ELTE TÁMOP 4.2.1./B-09/1/KMR-2010–0003
Acta pharmaceutica Hungarica, 2010
Continuous NSAID (nonsteroidal anti-inflammatory drug) therapy is associated with gastrointestina... more Continuous NSAID (nonsteroidal anti-inflammatory drug) therapy is associated with gastrointestinal (GI) and cardiovascular (CV) side effects. In this paper, the oral NSAID use of 143 patients with rheumatoid arthritis was assessed focusing on safety and farmacoeconomic aspects in a cross sectional non interventional study. The most widely used NSAIDs were meloxicam (n = 55, 38.5%) and diclofenac (n = 30, 21%). We found that coxibs were overused (n = 13, 9.1%) compared with the average total coxib consumption in Hungary. According to our results, drugs associated with GI friend side effect profile (meloxicam, celecoxib, etoricoxib) were much preferred in patients with previous GI events, than in patients with low GI risk. The previous occurrence of GI events were significantly higher (p = 0.019) in patients currently treated with safer NSAIDs, probably because of the so-called 'indication bias'. No statistically significant difference in patient's quality of life could be...