Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease with unknown cause. It mainly affects joints and, without proper treatment, negatively impacts their movement, causes painful deformities, and reduces the patients' quality of life. Current treatment options consist of various types of disease-modifying antirheumatic drugs (DMARDs), however 20-30% of patients are partially resistant to them. Therefore, development of new drugs is necessary. Possible option are compounds exhibiting their action via endocannabinoid system, which plays an important role in pain and inflammation modulation. One such compound - cannabidiol (CBD) has already been shown to attenuate synovitis in animal model of RA in in vivo studies. However, it has low bioavailability due to its low water solubility and lipophilicity. This issue can be addressed by preparation of a lipid containing formulation targeting lymphatic system, another route of absorption in the body. Materials and Methods: CBD-containing emulsion was prepared by high-shear homogenization and its droplet size distribution was analysed by optical microscopy. The relative oral bioavailability compared to oil solution as well as total availability of CBD were assessed in a cross-over study in rats and absorption of CBD via lymphatic system was observed. The effect of CBD on the animal model of RA was determined. Results: Compared to oil solution, the emulsion exhibited higher absolute oral bioavailability. Significant lymphatic transport of CBD was observed in all formulations and the concentrations in lymph were calculated. The therapeutic effect of CBD on RA was confirmed as an improvement in clinical symptoms as well as morphological signs of disease activity were observed during the study. Conclusion: In this work, we prepared a simple stable emulsion formulation, determined the pharmacokinetic parameters of CBD and calculated its absolute bioavailability in rats. Moreover, we successfully tested the pharmaceutical application of such a formulation and demonstrated the positive effect of CBD in an animal model of RA.
- MeSH
- aplikace orální MeSH
- bolest farmakoterapie MeSH
- emulze MeSH
- kanabidiol * farmakologie chemie MeSH
- klinické křížové studie MeSH
- krysa rodu rattus MeSH
- kvalita života MeSH
- revmatoidní artritida * farmakoterapie MeSH
- voda MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.
- MeSH
- antirevmatika * terapeutické užití MeSH
- azetidiny * MeSH
- inhibitory Janus kinas * terapeutické užití MeSH
- inhibitory TNF terapeutické užití MeSH
- lidé MeSH
- puriny * MeSH
- pyrazoly * MeSH
- revmatoidní artritida * farmakoterapie MeSH
- sulfonamidy * MeSH
- TNF-alfa MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND: Individuals with anti-citrullinated protein antibodies (ACPAs) and subclinical inflammatory changes in joints are at high risk of developing rheumatoid arthritis. Treatment strategies to intercept this pre-stage clinical disease remain to be developed. We aimed to assess whether 6-month treatment with abatacept improves inflammation in preclinical rheumatoid arthritis. METHODS: The abatacept reversing subclinical inflammation as measured by MRI in ACPA positive arthralgia (ARIAA) study is a randomised, international, multicentre, double-blind, placebo-controlled trial done in 14 hospitals and community centres across Europe (11 in Germany, two in Spain, and one in the Czech Republic). Adults (aged ≥18 years) with ACPA positivity, joint pain (but no swelling), and signs of osteitis, synovitis, or tenosynovitis in hand MRI were randomly assigned (1:1) to weekly subcutaneous abatacept 125 mg or placebo for 6 months followed by a double-blind, drug-free, observation phase for 12 months. The primary outcome was the proportion of participants with any reduction in inflammatory MRI lesions at 6 months. The primary efficacy analysis was done in the modified intention-to-treat population, which included participants who were randomly assigned and received study medication. Safety analyses were conducted in participants who received the study medication and had at least one post-baseline observation. The study was registered with the EUDRA-CT (2014-000555-93). FINDINGS: Between Nov 6, 2014, and June 15, 2021, 139 participants were screened. Of 100 participants, 50 were randomly assigned to abatacept 125 mg and 50 to placebo. Two participants (one from each group) were excluded due to administration failure or refusing treatment; thus, 98 were included in the modified intention-to-treat population. 70 (71%) of 98 participants were female and 28 (29%) of 98 were male. At 6 months, 28 (57%) of 49 participants in the abatacept group and 15 (31%) of 49 participants in the placebo group showed improvement in MRI subclinical inflammation (absolute difference 26·5%, 95% CI 5·9-45·6; p=0·014). Four (8%) of 49 participants in the abatacept group and 17 (35%) of 49 participants in the placebo group developed rheumatoid arthritis (hazard ratio [HR] 0·14 [0·04-0·47]; p=0·0016). Improvement of MRI inflammation (25 [51%] of 49 participants in the abatacept group, 12 [24%] of 49 in the placebo group; p=0·012) and progression to rheumatoid arthritis (17 [35%] of 49, 28 [57%] of 49; HR 0·14 [0·04-0·47]; p=0·018) remained significantly different between the two groups after 18 months, 12 months after the end of the intervention. There were 12 serious adverse events in 11 participants (four [8%] of 48 in the abatacept group and 7 [14%] of 49 in the placebo group). No deaths occurred during the study. INTERPRETATION: 6-month treatment with abatacept decreases MRI inflammation, clinical symptoms, and risk of rheumatoid arthritis development in participants at high risk. The effects of the intervention persist through a 1-year drug-free observation phase. FUNDING: Innovative Medicine Initiative.
- MeSH
- abatacept škodlivé účinky MeSH
- antirevmatika * škodlivé účinky MeSH
- artralgie chemicky indukované MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- revmatoidní artritida * diagnostické zobrazování farmakoterapie MeSH
- výsledek terapie MeSH
- zánět farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
There is increasing knowledge in the recognition of individuals at risk for progression to rheumatoid arthritis (RA) before the clinical manifestation of the disease. This prodromal phase preceding the manifestation of RA may represent a "window of opportunity" for preventive interventions that may transform the clinical approach to this disease. However, limited evidence exists in support of effective interventions to delay the onset or even halt the manifestation of RA. Given the multifactorial nature of RA development and disease progression, the latest guidelines for established RA stress the use of integrative interventions and multidisciplinary care strategies, combining pharmacologic treatment with non-pharmacological approaches. Accordingly, individuals at risk of RA could be offered an integrative, multifactorial intervention approach. Current data point toward pharmacological intervention reverting the subclinical inflammation and delay in the disease onset. In addition, targeting life style modifiable factors (smoking cessation, dental health, physical activity, and diet) may presumably improve RA prognosis in individuals at risk, mainly by changes in epigenetics, autoantibodies, cytokines profiles, and microbiome. Nonetheless, the benefits of multidisciplinary interventions to halt the manifestation of RA in at-risk individuals remain unknown. As there is a growing knowledge of possible pharmacological intervention in the preclinical phase, this narrative review aims to provide a comprehensive overview of non-pharmacological treatments in individuals at risk of RA. Considering the mechanisms preceding the clinical manifestation of RA we explored all aspects that would be worth modifying and that would represent an integrative non-pharmacological care for individuals at risk of RA.
- MeSH
- autoprotilátky MeSH
- lidé MeSH
- prognóza MeSH
- revmatoidní artritida * terapie farmakoterapie MeSH
- zánět MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Moderní strategie léčby pacientů s revmatoidní artritidou (RA) jsou zaměřeny na časnou a důslednou kontrolu synovitidy a prevenci vzniku nevratného poškození kloubů. Včasná diagnóza a rychlé zahájení léčby chorobu modifikujícími antirevmatiky jsou základním principem moderní léčby RA. Aktivita onemocnění by měla být pravidelně monitorována, hodnocena pomocí kompozitních indexů a léčba eskalována podle zásad léčby k cíli (T2T). Cílem léčby je dosažení remise nebo alespoň nízké aktivity onemocnění. Základem farmakoterapie RA jsou syntetické a biologické chorobu modifikující antirevmatické léky (DMARD), které ovlivňují dlouhodobý průběh onemocnění a zpomalují strukturální progresi.
Modern treatment strategies for patients with rheumatoid arthritis (RA) focus on early and consistent control of synovitis and prevention of irreversible joint damage. Early diagnosis and prompt initiation of treatment with disease-modifying antirheumatic drugs (DMARDs) are fundamental principles of modern RA treatment. Disease activity should be regularly monitored, assessed using composite indices and treatment escalated according to the principles of treatment to target (T2T). The goal of treatment is to achieve remission or at least low disease activity. The mainstay of RA pharmacotherapy is synthetic and biologic disease-modifying antirheumatic drugs, which affect the long-term course of the disease and slow structural progression.
- MeSH
- antirevmatika farmakologie terapeutické užití MeSH
- časná diagnóza MeSH
- glukokortikoidy farmakologie terapeutické užití MeSH
- lidé MeSH
- revmatoidní artritida * diagnóza farmakoterapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Klíčová slova
- tofacitinib,
- MeSH
- inhibitory Janus kinas farmakokinetika terapeutické užití MeSH
- inhibitory proteinkinas farmakokinetika terapeutické užití MeSH
- klinické zkoušky jako téma MeSH
- kouření tabáku MeSH
- lidé MeSH
- piperidiny terapeutické užití MeSH
- pyrimidiny terapeutické užití MeSH
- pyrroly terapeutické užití MeSH
- revmatoidní artritida * farmakoterapie MeSH
- tělesná hmotnost MeSH
- věkové faktory MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- filgotinib,
- MeSH
- inhibitory Janus kinas * aplikace a dávkování farmakokinetika farmakologie škodlivé účinky MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- methotrexát terapeutické užití MeSH
- revmatoidní artritida * farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- upadacitinib,
- MeSH
- ankylózující spondylitida * farmakoterapie MeSH
- biologická terapie * MeSH
- inhibitory Janus kinas aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- metaanalýza jako téma MeSH
- psoriatická artritida * farmakoterapie MeSH
- revmatoidní artritida * farmakoterapie MeSH
- Check Tag
- lidé MeSH
OBJECTIVES: This article aimed to count and compare treatment's direct (only biological drugs) and indirect (loss of productivity) costs in patients with rheumatoid arthritis from 2019 to 2021. METHODS: The friction cost approach was used to establish indirect costs. Elasticity factor values and friction period for the Slovak Republic from 2019 to 2021 were determined. Direct drug costs were calculated based on average prices from 2019 to 2021 and the number of dispensed medication packages. RESULTS: The average productivity loss reached €2984.54 in 2019, €3338.46 in 2020, and €3154.01 in 2021. Total indirect costs include productivity loss and sick pay, and from 2019 to 2021 came the values of €8.4 million, €10.1 million, and €8.1 million, respectively. CONCLUSIONS: Indirect costs were almost 2.5 to 3 times lower than the biological and targeted treatment costs.
