The current study investigate the disease activity and effectiveness of treatment in patients with RA on biological disease modifying antirheumatic drugs (bDMARDs) in combination with a conventional ...synthetic DMARD (csDMARD) and determine whether or not the benefits of different therapies were sustained over a follow up period of 1 year. 124 patients were selected with a mean age 55.26 ± 13, 18SD years, meeting the 1987 ACR and /or ACR/ EULAR (2010) classification criteria for Rheumatoid arthritis (RA). Patients were arranged according to treatment regimens: Tocilizumab (TCL) - 30 patients, Certolizumab (CZP) - 16, Golimumab (GOL) - 22, Etanercept (ETN) 20, Adalimumab (ADA) 20, Rituximab (RTX) - 16. Disease activities was the primary concern. Independent joint assessor evaluated 28 joints on baseline, 6th and 12th month's thereafter. C-reactive protein (CRP) was used to measure the inflammatory process. DAS28-CRP, clinical disease activity index (CDAI) and simplified disease activity index (SDAI) were calculated. On baseline all of the patients' groups had severe disease activity (mean DAS28-CRP > 5.2, mean CDAI > 22, mean SDAI > 26. It was noted that, during the 6th month follow-up period all of the treatment groups significantly decreased DAS28-CRP, CDAI, SDAI and reach moderate disease activity. After 6th and 12th months of treatment all of the groups on bDMARDs had significantly lower disease activity. The GOL group reach remission only according to DAS28-CRP: 2.49 ± 0.76, and low disease activity as measured by CDAI: 6.78 ± 4.51 and SDAI 7.80 ± 5.67. The other 5 groups after 12 months reach the level of low disease activity according to the three activity parameters: DAS28-CRP (TCL 3.07 ± 0.73, CZP 3.06 ± 0.65, ETN 2.85 ± 0.55, ADA 3.15 ± 0.82, RTX 2.90 ± 0.70), CDAI (TCL 9.80 ± 4.91, CZP - 9.33 ± 4.22, ETN 7.97 ± 3.80, ADA 10.00 ± 5.25, RTX 7.48 ± 2.99) and SDAI (TCL 10.45 ± 5.14, CZP 9.94 ± 4.43, ETN 9.03 ± 4.25, ADA 10.50 ± 5.61, RTX 8.08 ± 3.24). The therapy with different bDMARDs added to a csDMARD led to very similar results - a minimal disease activity and a state of remission in the GOL treatment group only as per DAS28-CRP.
Takayasu arteritis (TA) is a chronic large-vessel vasculitis characterized by immune-mediated panarteritis, which predominantly affects the aorta and its main branches and is most prevalent in young ...women. TA is unusually associated with the presence of antiphospholipid antibodies. We present a case report of a 48-year-old Caucasian woman with acute aortic dissection as an initial feature of TA, where detailed clinical, imaging and laboratory studies were performed. Computed tomography angiography (CTA) of the chest and abdomen revealed aortic dissection DeBakey I. Bentall and De Bono surgery was performed. Additional immunological tests revealed positive antineutrophil cytoplasmic antibodies (ANCAs) with the simultaneous presence of pANCA and cANCA antibodies on indirect immunofluorescence, along with anti-MPO+PR3+antibodies positivity in the absence of a clinically relevant disease. Surprisingly, antiphospholipid antibodies (aPLs) were detected. Then, we performed a thorough review of the current literature. The coexistence of aPL antibodies and dual specificity for MPO and PR3 in a patient diagnosed with Takayasu arteritis is unusual and poses a diagnostic challenge. The presented case report outlines a rare case of aortic dissection as a presenting symptom of TA, along with atypical ANCA positivity and positive APL antibodies.
This narrative review provides a brief horizon scanning on the available literature on cost-effectiveness of therapeutic drug monitoring (TDM) in rheumatology for biological medicines. The PubMed ...database was used to search for articles containing the key words 'cost-effectiveness' AND 'therapeutic drug monitoring' AND 'rheumatology' or 'rheumatoid' with no limits on year of publication. CHEERS pharmacoeconomic criteria were applied to review the robustness of the studies. Out of 42 initial hits, only 4 full-text articles and 2 abstracts matched the specified search criteria fully. They conclude that proactive TDM was more cost-effective for patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab. For rheumatoid arthritis (RA) patients, the adalimumab dose tapering based on TDM led to an increased quality of life and quality-adjusted life year (QALY) gain and entailed lower costs. Patient-initiated service on the basis of TDM resulted in reductions in primary and secondary healthcare services, and hence, lower costs than the usual care. The use of a JAK1/JAK2 inhibitor instead of a biologic disease modifying drug (DMARD) in a treat-to-target approach is cost-effective in conventional synthetic DMARD refractory RA patients; monitoring of patients with chronic inflammatory diseases and low disease activity or in remission undergoing biological therapy can be achieved with less resources. The findings in our mini-review suggest that TDM might result in cost-saving. Given the benefit other patients may gain from the resources saved, we encourage further clinical and cost-effectiveness studies.
Biological medicines are considered as a cornerstone in the therapy of rheumatoid arthritis (RA). They change the course of the disease and improve the quality of life of patients. To this date there ...has been no study comparing the quality of life of and cost of RA therapy in Bulgaria. This fact is what provoked our interest toward this research. The aim of this study is to analyse the cost and quality of life of patients with RA threated with biological medicines in Bulgaria. This is an observational, real life study of 124 patients treated with biological medicines during 2012-2016 at the University hospital "St. Ivan Riskli" in Sofia, specialized in rheumatology disease therapy. Patients were recruited after their consecutive transfer from non-biological to biological medicines. The yearly pharmacotherapy cost was calculated with tocilizumab (
= 30), cetrolizmab (
= 16), golimumab (
= 22), etanercept (
= 20), adalimumab (
= 20), rituximab (
= 16). Three measurements of the quality of life (QoL) were performed with EQ5D-at the beginning of the therapy, after 6 months and after 1 year of therapy. Both section of EQ5D were used-VAS and EQ5D questionnaire. Cost-effectiveness was calculated for unit of improvement in EQ5D score for a one year period and decision model was built with TreeAgePro software. The observed cost of therapy varied between 12 thousand Euros for tocilizumab to 6 thousand Euros for rituximab. All biological medicines let to substantial increase in the quality of life of the patients. Patients on tocilizumab increased their QoL from 0.43 to 0.63 after 1 year; on cetrolizumab from 0.32 to 0.56; on golimumab from 0.41 to 0.67; on etanercept from 0.45 to 0.62; on adalimumab from 0.43 to 0.57; on rhituximab from 0.46 to 0.66. The cost-effectiveness estimates of different biological therapies also varied between 66 to 30 thousand Euros for unit of improvement in the EQ5D during one the course of the year. Therapy with biological medicines improves statistically significant the quality of life of patients, measured through VAS and EQ5D scales. Despite the improvement in the quality of life all biological medicines appears not to be note cost-effective due to their high incremental cost-effectiveness ration (ICER). Rituximab's incremental ratio has (ICER) falls closer to the three times gross domestic product per capita threshold and should be considered as preferred alternatives for RA therapy. In general we can conclude that the treatment of rheumatoid arthritis with biologicals improves quality of life significantly. Only rituximab was cost-effective.
This study analysed the changes in the reimbursed cost, prices and utilization of biological medicines for a 5-year time horizon, encompassing three major arthropathic diagnoses, rheumatoid arthritis ...(RA), psoriatic arthropathies (PsA) and ankylosing spondylitis (AS), from the point of view of the third-party payer in Bulgaria. National; population based; macroeconomic; top-down budget analysis was performed based on official data about the number of inhabitants, reimbursed diagnoses and medicines, reimbursed cost, treated patients, and prices of medicines. The utilization of medicines was calculated in DDD per 1000/inh/day. There was an increase of 41% in the number of patients treated with biological medicines. The reimbursement cost of biologicals increased by 21%; however, the per-patient reimbursement costs per diagnosis fell by 40% due to price decreases. Out of 21 reimbursed diagnoses, we saw a significant difference in prevalence (612 SD in 2016 to 1216 SD in 2020; p < 0.05). RA accounted for 2736 patients in 2016, increasing by 131% to 4662 patients in 2020; AS with 1933 patients in 2016 reached 3196 patients by 2020, and PsA with 1128 patients ranked third with a 75% increase. The cost of therapy of RA was the highest, accounting for appr. 15 mill Euro in 2016. The utilization decreased only for 2 INNs (infliximab and rituximab). All INNs experienced a nearly two-fold increase in their utilization: from 0.5244 to 0.9252 DDD/1000inh/day. The cost analysis shows an important place of biologicals for arthropathic diseases therapy; introduction of biosimilars leads to prices and cost decreases.
This study aims to analyze and compare the disease activity control and quality of life of patients with rheumatoid arthritis (RA) who were treated with biological products in real-life settings. We ...tried to determine whether there is a symmetry in the performance of the biological molecules between each other and with the first Janus kinase (JAK) inhibitor. This is an observational, longitudinal, real-life study performed in the biggest rheumatology clinic during the period 2012–2020 comparing quality of life, cost of therapy, and disease control via different clinical measures. In all three disease activities measurement instruments, we observed an improvement for all biologic and target synthetic medicines. The disease activity score (DAS28) score decreased from 5.06 to 3.01, on average, for all INNs, suggesting that the majority of patients move away from moderate to low disease activity. The clinical disease activity index (CDAI) score decreased from 25.9 to 9.4, also indicating that patients with moderate disease activity reached a low level of activity. Similar results are reflected in the score, which fell from 27.7 to 10.3, again confirming the improvement to a low level of disease activity for patients treated with all INNs. Logically, with the successful control of disease activity, the quality of life (QoL) of the observed patients improved from 0.77 to 0.83 after a one-year follow up, as measured with the EuroQuol 5D-3L (EQ5D). Based on these results, we can consider that the observed biological INNs perform symmetrically in terms of the control of disease activity and improvement in the QoL of the observed patients. Biological therapy improves the disease control and quality of life of suitable patients with RA in real-life settings. All available biological therapies could be used interchangeably.
Background: This study examines the relationship between the presence of crystals in the synovial fluid of patients with psoriatic arthritis (PsA) and disease activity. Methods: The synovial fluid of ...156 PsA patients was analyzed and compared to 50 patients with gonarthrosis (GoA). The Leica DM4500P polarization microscope was used for crystal detection. Results: The presence of crystals was observed in 23.71% of PsA patients and none of the GoA patients, p < 0.001. Monosodium urate crystals (67.58%) and calcium pyrophosphate crystals (21.62%) were prevalent. The presence of crystals in the synovial fluid of PsA patients was associated with high disease activity according to the Composite Psoriatic Disease Activity Index (OR = 18.75, 95%; CI: 7.13 to 49.25) and the Disease Activity for Psoriatic Arthritis (OR = 15.96, 95%; CI: 5.76 to 44.23), with severe disability according to the Health Assessment Questionnaire Disability Index (OR = 13.60, 95%; CI: 5.09 to 36.31), and with severe pain on the Visual Analog Scale (OR = 157.25, 95%; CI: 39.50 to 625.94). Conclusion: Our results suggest that synovial fluid examination should be included in the treatment pathway for PsA patients with active disease, to aid in determining whether urate-lowering therapy is required.
Managed entry agreements are applied in almost all European countries in order to improve patients’ access to therapy. The current study aims to evaluate the changes in the affordability of ...biological medicines for patients in Bulgaria during 2019–2022. The study is a top-down macroeconomic analysis of the key economic indicators and reimbursed costs of biologic therapies. Affordability was determined as the number of working hours needed to pay for monthly therapy. The average NHIF budget for pharmaceuticals increased significantly along with inflation in the healthcare sector. Bulgarian patients had to devote a large part of their income to buying medicines if a co-payment existed. The percentage of the monthly income of pensioners needed for therapy co-payment varied between 10% and 280%. The hours of work required to purchase a package of biologicals varied between 7 and 137 working hours. The global economic crisis has affected Bulgaria and led to worsening economic parameters. There are still no well-established practices to control public spending, as the measures taken to reduce the final cost of medicines mainly affect the pharmaceutical companies. This type of cost-containment policy provides an opportunity for innovative treatment with biologicals for patients with inflammatory diseases. Most of the therapies cost more than the patients’ monthly income.
ObjectiveTo perform a systematic literature review (SLR) on different outcomes of remote care compared with face-to-face (F2F) care, its implementation into clinical practice and to identify drivers ...and barriers in order to inform a task force formulating the EULAR Points to Consider for remote care in rheumatic and musculoskeletal diseases (RMDs).MethodsA search strategy was developed and run in Medline (PubMed), Embase and Cochrane Library. Two reviewers independently performed standardised data extraction, synthesis and risk of bias (RoB) assessment.ResultsA total of 2240 references were identified. Forty-seven of them fulfilled the inclusion criteria. Remote monitoring (n=35) was most frequently studied, with telephone/video calls being the most common mode of delivery (n=30). Of the 34 studies investigating outcomes of remote care, the majority addressed efficacy and user perception; 34% and 21% of them, respectively, reported a superiority of remote care as compared with F2F care. Time and cost savings were reported as major benefits, technical aspects as major drawback in the 13 studies that investigated drivers and barriers of remote care. No study addressed remote care implementation. The main limitation of the studies identified was the heterogeneity of outcomes and methods, as well as a substantial RoB (50% of studies with high RoB).ConclusionsRemote care leads to similar or better results compared with F2F treatment concerning efficacy, safety, adherence and user perception outcomes, with the limitation of heterogeneity and considerable RoB of the available studies.
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, with prevalence of 16-150 cases per 100,000 children. The etiopathogenesis of JIA is a challenge incorporating a ...complex network with only 18% attributed to genetic factors. The remaining part should therefore be explained by non-hereditary factors. Given that around 70% of the immune cells are located in the gut, the potential role of the gut microbiota in the etiopathogenesis of JIA has been recently investigated. The aim of this review is to discuss the complexity of the link between gut microbiota and JIA, the different methods for identifying bacteria, the shape-up of the microbiota from birth to adulthood. The objectives are to discuss various pathways involved in this process: changes in the microbiota contents in healthy individuals and JIA patients, increased gut permeability, influence on T-cell differentiation and proliferation. Factors that have been associated with dysbiosis: diet, pathogens and drug use, are discussed. JIA is not a benign disease, it is a chronic disease and an important cause of short- and long-term disability-significant joint contractures, leg-length inequalities and uveitis, which can lead to impaired vision. It is known that at least one-third of children will have ongoing active disease into their adult years, and many will have some limitation in their daily life activities. A deeper understanding of the pathways by which disturbances in the microbiome may evolve to disease may open doors to the development of new treatment or prevention strategies in the future.
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