Background Methotrexate is the most commonly used disease-modifying antirheumatic drug recommended in the treatment of juvenile idiopathic arthritis. It can be administered orally or subcutaneously, the latter method is associated with fewer side effects and higher drug bioavailability. Nevertheless, the pain associated with injection is a considerable drawback of this treatment option in the pediatric population. Currently, there are two single-use subcutaneous injection devices available: the prefilled syringe and the prefilled pen. This prospective, two-sequence crossover study aimed to compare ease of use, frequency of therapy side effects, injection-site pain and parent/patient preference of those methotrexate parenteral delivery systems. Methods Twenty-three patients with juvenile idiopathic arthritis, already treated with subcutaneous methotrexate in the form of prefilled syringe in the period October 2018 – April 2019 completed a questionnaire evaluating their experience with this device. Subsequently, children received a one-month supply of pen autoinjector and completed the same questionnaire, regarding their experience with the new methotrexate delivery system. If the patient was not performing the injections himself the questionnaires were completed by the caregiver administrating MTX. The results obtained in both questionnaires were compared using the Wilcoxon matched-pairs signed-rank test. Results 82,6% patients and their caregivers voted for the prefilled pen as their preferred method of subcutaneous methotrexate administration. Moreover, the injection with the prefilled pen was reported as less painful in comparison to the prefilled syringe ( p < 0.01). Side effects of methotrexate were less pronounced after the prefilled pen treatment, this difference was most prominent regarding gastrointestinal adverse events associated with the injection ( p < 0.01). Conclusion Administration of methotrexate using the pen device is a promising way of subcutaneous methotrexate delivery in children with juvenile idiopathic arthritis, as the injection is less painful and associated with fewer side effects.

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Aim: Methotrexate (MTX) administered at the dose 10-15 mg/m 2 is recommended as the first-line therapy in most juvenile idiopathic arthritis (JIA) subtypes. The diseasemodifying effect of methotrexate is associated with release of adenosine and mediated via binding to adenosine receptor A2A (ADORA2A) and 3 (ADORA3). The aim of our study was to determine the association between single nucleotide polymorphisms in ADORA2A (rs2236624, rs2298383) and ADORA3 (rs3393) receptor genes on the disease activity and presence of MTX therapy side effects in patients with JIA. Methods: One hundred children with JIA of all subtypes treated with MTX were recruited to the study. Demographic and clinical parameters were collected at the baseline of MTX therapy and on a control visit 4-6 months after starting MTX. Single nucleotide polymorphism genotyping was performed using genomic DNA isolated from peripheral blood samples. Results: The polymorphic variant of ADORA2A rs2236624 was associated with ~3.5 times higher odds of gastrointestinal side effects occurrence (odds ratio: 3.59, 95% CI: 1.15-11.22, P = 0.0282). Children with the ADORA3 rs3393 polymorphic variants (CT/CC) after 6 months of MTX treatment had significantly lower number of joints with active arthritis (median: 0.00 vs 1.00, P = 0.0400) and value of C-reactive protein (0.60 vs 2.40, P = 0.0242) in comparison to TT variant. Conclusion: Although future studies are needed to verify our findings, polymorphisms in ADORA2A and ADORA3 genes may become the determinants of MTX treatment efficacy and gastrointestinal toxicity in children with JIA.

Introduction: Among the diseases associated with psoriasis linked to smoking are primarily cardiovascular diseases (including atherosclerosis) and metabolic syndrome. In addition, cigarette smoking also affects the effectiveness of systemic treatment of psoriasis. Aim: Assessment of the effect of cigarette smoking on biomarkers of atherosclerosis in patients with psoriasis treated with methotrexate and adalimumab. Material and methods: The serum levels of vascular cell adhesion molecule 1 (VCAM-1), E-selectin, oxidized low density lipoprotein (oxLDL) and anti-oxLDL antibodies, IL-10, IL-35, TGFß1, were assessed in 34 patients with psoriasis (15 smokers and 19 non-smokers), and 8 healthy, non-smoking volunteers. Results and discussion: Smoking patients had significantly higher body mass index, lower high density lipoprotein (HDL), higher risk of 10-year fatal cardiovascular disease, higher IL-10 levels and lower IL-35 levels at baseline compared to healthy, non-smoking volunteers. We observed decreases in IL-10, VCAM-1, E-selectin, and oxLDL levels during 12 weeks of methotrexate treatment and, a decrease in IL-35 during adalimumab treatment, based on enzyme-linked immunosorbent assays. Conclusions: Our results indicate the need for a holistic approach to psoriasis treatment that includes lifestyle modifications like smoking cessation to slow the development of atherosclerosis and increase the possibility of improving skin lesions.

BACKGROUND: Methotrexate is the most commonly used disease-modifying antirheumatic drug recommended in the treatment of juvenile idiopathic arthritis. It can be administered orally or subcutaneously, the latter method is associated with fewer side effects and higher drug bioavailability. Nevertheless, the pain associated with injection is a considerable drawback of this treatment option in the pediatric population. Currently, there are two single-use subcutaneous injection devices available: the prefilled syringe and the prefilled pen. This prospective, two-sequence crossover study aimed to compare ease of use, frequency of therapy side effects, injection-site pain and parent/patient preference of those methotrexate parenteral delivery systems.METHODS: 23 patients with juvenile idiopathic arthritis, already treated with subcutaneous methotrexate in the form of prefilled syringe in the period October 2018 – April 2019 completed a questionnaire evaluating their experience with this device. Subsequently, children received a one-month supply of pen autoinjector and completed the same questionnaire, regarding their experience with the new methotrexate delivery system. If the patient was not performing the injections himself the questionnaires were completed by the caregiver administrating MTX. The results obtained in both questionnaires were compared using the Wilcoxon matched-pairs signed-rank test.RESULTS: 82,6% patients and their caregivers voted for the prefilled pen as their preferred method of subcutaneous methotrexate administration. Moreover, the injection with the prefilled pen was reported as less painful in comparison to the prefilled syringe (p<0.01). Side effects of methotrexate were less pronounced after the prefilled pen treatment, this difference was most prominent regarding gastrointestinal adverse events associated with the injection (p<0.01).CONCLUSION: Administration of methotrexate using the pen device is a promising way of subcutaneous methotrexate delivery in children with juvenile idiopathic arthritis, as the injection is less painful and associated with fewer side effects.