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ID PMID Title PublicationDate abstract
35566466 Personalized Therapeutic Strategies in the Management of Osteoporosis in Patients with Aut 2022 Apr 22 Bone mineral density (BMD) reduction and fragility fractures still represent a major source of morbidity in rheumatoid arthritis (RA) patients, despite adequate control of the disease. An increasing number of clinical and experimental evidence supports the role of autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in causing localized and generalised bone loss in ways that are both dependent on and independent of inflammation and disease activity. The human receptor activator of nuclear factor kappa B and its ligand-the so-called RANK-RANKL pathway-is known to play a key role in promoting osteoclasts' activation and bone depletion, and RANKL levels were shown to be higher in ACPA-positive early untreated RA patients. Thus, ACPA-positivity can be considered a specific risk factor for systemic and periarticular bone loss. Through the inhibition of the RANK-RANKL system, denosumab is the only antiresorptive drug currently available that exhibits both a systemic anti-osteoporotic activity and a disease-modifying effect when combined with conventional synthetic or biologic disease-modifying anti-rheumatic drugs (DMARDs). Thus, the combination of DMARD and anti-RANKL therapy could be beneficial in the prevention of fragility fractures and structural damage in the subset of RA patients at risk of radiographic progression, as in the presence of ACPAs.
35398152 A new pattern of citrullinated peptides improves the sensitivity for diagnosing rheumatoid 2022 Apr 6 OBJECTIVES: Anti-citrullinated protein antibody (ACPA) is found almost exclusively in patients with rheumatoid arthritis (RA). Commercial cyclic citrullinated peptide (CCP) assays that target ACPAs yield specificities as high as 95% for RA diagnoses, but their sensitivities only reach 50-70%. To improve the sensitivity of the CCP assay, a new pattern of citrullinated peptide was identified and named the MCSM (multiple citrulline-similar motif). DESIGN & METHODS: The MCSM comprised a citrulline core surrounded by citrulline-similar amino acids. A series of peptides with or without the MCSM was synthesized to evaluate the function of the citrulline core and citrulline-similar amino acids. These peptides were used in the enzyme-linked immunosorbent assay to compare samples from 94 RA patients, 117 non-RA patients and 116 healthy subjects. Additionally, the MCSM assay was compared with a commercial CCP assay. RESULTS: When the cutoff value was set at 0.274, the sensitivity and specificity of the MCSM assay were 79.6% and 96.6%, respectively. When one citrulline was substituted in the citrulline core, the sensitivity of the assay decreased from 79.6% to 61%. If all three citrulline-similar amino acids were substituted in the backbone, the sensitivity of the MCSM assay decreased from 79.6% to 58.5%. The coincidence rate of the MCSM assay to the commercial CCP assay was 97.6%. CONCLUSIONS: The citrulline core and citrulline-similar amino acids are crucial components of the MCSM pattern. This new MCSM assay could be used to diagnose RA.
35110931 Quality of Life, Social Support, Coping Strategies, and Psychiatric Morbidity in Patients 2022 Jan Background and Objectives  Patients with rheumatoid arthritis (RA) have greater psychological morbidity, despite that research in this area is scarce from developing countries. This study was aimed to assess the association of quality of life, social support, coping strategies, and psychological morbidity in patients with RA. Materials and Methods  In this cross-sectional study, 40 patients with RA, who were not receiving steroids or disease modifying antirheumatic drugs, were recruited through purposive sampling. Social support questionnaire, coping strategy check list, and World Health Organization quality of life-BREF (WHOQOL-BREF) were administered to assess social support, coping, and quality of life, respectively. Results  More than half of the patients had psychiatric disorders (60%), with depression being the commonest disorder (52.5%). Internalization coping and disease severity indicators like tender joints counts, swollen joints counts, pain, and disease activity were found as significant predictors for psychiatric disorders, while externalization coping, quality of life (all domains), and physical functions were found to protect against psychiatric morbidity. Conclusions  Coping, quality of life, disease severity, and physical functions predicted the psychiatric disorders in RA. Multipronged interventions to enhance quality of life with promoting adaptive coping and timely treatment may further improve their mental health and overall disease course.
35628915 The Influence of Rheumatoid Arthritis on Higher Reoperation Rates over Time Following Lumb 2022 May 16 This study aimed to compare the rates of reoperation over time following first lumbar fusion in rheumatoid arthritis (RA) patients and non-RA patients. This study was conducted using Korean Health Insurance Review and Assessment (HIRA) data. We identified the RA group as 2239 patients who underwent their first lumbar fusion with RA and the control group as 11,195 patients without RA. This reflects a ratio of 1:5, and the participants were matched by sex, age, and index surgery date. The index dates were between 2012 and 2013. When comparing the rate of patients undergoing reoperation, the adjusted HR was 1.31 (95% CI: 1.10-1.6) in the RA group (p = 0.002). In terms of the three time intervals, the values in the time frames of <3 months and 3 months-1 year were not statistically significant. However, at 1 year post-surgery, there was a higher risk of reoperation in the RA group, as demonstrated by the Kaplan-Meier cumulative event analysis. This higher risk of reoperation continued to increase throughout 5 years of follow-up, after which it was stable until the last follow-up at 7 years. This population-based cohort study showed that the RA patients had a 1.31 times higher risk of reoperation following lumbar fusion than did the controls. This difference was more pronounced at 1 year post-surgery.
35631047 Therapeutic Penetrating Keratoplasty in a Case of Corneal Perforation Caused by Colletotri 2022 Apr 29 Background: Corneal infection of Colletotrichum gloeosporioides is uncommon and usually limited to the anterior stroma. However, we observed a case of corneal stromal perforation caused by this fungus under a compromised condition. Case: A 73-year-old woman consulted us with a severe corneal ulceration. She was a tangerine orange farmer who suffered from rheumatoid arthritis for more than ten years. Before consultation with us, she received pterygium excision in her right eye. She then developed a corneal ulceration and received topical glucocorticoid therapy upon diagnosis of rheumatoid arthritis-related stromal ulcer in the eye. At the first consultation with us, a corneal ulceration was observed in the inferotemporal area of her right cornea. Biological examination detected a filamentous fungus, Colletotrichum gloeosporioides. Topical and systemic antifungal treatments were not significantly effective. Fourteen days after consultation, the lesion grew worse, leading to stromal perforation, which was treated by therapeutic penetrating keratoplasty using a preserved corneal button. Conclusions: Topical glucocorticoid could accelerate the growth of Colletotrichum gloeosporioides before diagnosis, even though the primary cause of corneal ulceration development might be rheumatoid arthritis.
35127719 Diverse Roles of F-BoxProtein3 in Regulation of Various Cellular Functions. 2021 Accumulated evidence shows that the F-box protein 3 (FBXO3) has multiple biological functions, including regulation of immune pathologies, neuropathic diseases and antiviral response. In this review article, we focus on the role of FBXO3 in inflammatory disorders and human malignancies. We also describe the substrates of FBXO3, which contribute to inflammatory disorders and cancers. We highlight that the high expression of FBXO3 is frequently observed in rheumatoid arthritis, leukemia, pituitary adenoma, and oral squamous cell carcinoma. Moreover, we discuss the regulation of FBXO3 by both carcinogens and cancer preventive agents. Our review provides a comprehensive understanding of the role of FBXO3 in various biological systems and elucidates how FBXO3 regulates substrate ubiquitination and degradation during various physiological and pathological processes. Therefore, FBXO3 can be a novel target in the treatment of human diseases including carcinomas.
35462993 Prevalence of Metabolic Syndrome in Patients With Rheumatoid Arthritis: An Updated Systema 2022 INTRODUCTION: Rheumatoid arthritis (RA) due to systemic inflammation and insulin resistance increases the risk of cardiovascular disease and reduces life expectancy. In order to develop cardiac death prevention strategies, it is necessary to estimate the prevalence of metabolic syndrome (MetS) in these patients. METHODS: This systematic review and meta-analysis was performed to estimate the prevalence of MetS among patients with RA. International databases (i.e., Scopus, PubMed, Web of Science, and Google Scholar) were searched during the period of October 1 and October 10, 20121. Heterogeneity among the included studies was assessed through the Cochrane Q test statistics and I(2) test. Finally, a random-effects meta-analysis model was computed to estimate the pooled prevalence of MetS. RESULTS: Sixty-one articles with 96 groups and a sample size of 13,644 people were analyzed. The pooled prevalence of MetS was 32% (95% CI: 29.6-34.4). The highest prevalence of MetS is related to studies conducted in Asia (32.7%, 95% CI: 29-36.3) and Europe (32.7%, 95% CI: 27.5.37.9) and the lowest Prevalence was also related to studies conducted in Africa (28%, 95% CI: 28.8-32.2). The prevalence of MetS in men was 33% (95% CI: 26-39) and 34% (95% CI: 29-40) in women. Findings by diagnostic criteria showed that the highest and lowest prevalence of MetS was related to ATP III (37.5%, 95% CI: 30.9-44.2) and EGIR (14.4%, 95% CI: 10.5-18.5), respectively. CONCLUSIONS: MetS is highly prevalent in patients with RA and identification of high-risk patients is necessary to prevent cardiovascular mortality.
35442122 Improvement in clinical disease activity index when treatment selection is informed by the 2022 Apr 20 BACKGROUND: A blood-based molecular signature response classifier (MSRC) predicts non-response to tumor necrosis factor-É‘ inhibitors (TNFi) in rheumatoid arthritis (RA). RESEARCH DESIGN AND METHODS: This is an interim analysis of data collected in the Study to Accelerate Information of Molecular Signatures (AIMS) in RA from patients who received the MSRC test between September 2020 and November 2021. Absolute changes in clinical disease activity index (CDAI) scores from baseline were evaluated at 12 weeks (n=470) and 24 weeks (n=274). RESULTS: Predicted TNFi non-responders who received a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) with an alternative mechanism of action (altMOA) experienced up to 1.8-fold greater improvements in CDAI scores than those treated with a TNFi (12 weeks: 12.2 vs 8.0; p-value = 0.083; 24 weeks: 14.2 vs 7.8 p-value = 0.009). In patients with a molecular signature of non-response to TNFi in high disease activity at baseline, this corresponded to 43.2% relative improvement in achieving a lower CDAI disease activity level when likely TNFi non-responders were treated with a non-TNFi therapy (38.9% vs 55.7%). Commensurate improvements in efficiency of spend are expected when TNFi are avoided in favor of altMOA. CONCLUSIONS: RA treatment selection informed by MSRC test results improves clinical outcomes in real-world care and offers improvements in efficiency of healthcare spending.
35268496 Distal Interphalangeal Joint Involvement May Be Associated with Disease Activity and Affec 2022 Mar 4 We investigated the relationship between distal interphalangeal (DIP) joint involvement and disease activity in 10,038 patients with adult-onset rheumatoid arthritis (RA). The affected joint distribution was investigated using the joint indices (JI) x, y, and z, corresponding to the upper and lower joints, and the predominance of large-joint involvement, respectively. DIP joint involvement (defined by the presence of tenderness and/or swelling in DIP joints) was present in 206 (2.1%) of 10,038 patients with RA. Patients with RA exhibiting DIP joint involvement were significantly younger, and more frequently women. DIP joint involvement was positively associated with Disease Activity Score-28 using C-reactive protein, and clinical variables related to high RA disease activity, including JIs x and y, and was negatively associated with JI z. JI x was significantly higher than JI y in RA patients with DIP joint involvement. An odds ratio analysis revealed that small-to-medium sized and upper-extremity joints ranked first, second, and fourth among the eight variables significantly associated with DIP joint involvement. The correlation coefficients revealed that small-sized and upper-extremity joints ranked first and second among the five significant variables. DIP joint involvement, albeit rare, is significantly associated with high RA disease activity with predominance of small-sized and upper-extremity joints.
35264888 Quality of Life and Depression in Rheumatoid Arthritis Patients Treated with Biologics - A 2022 INTRODUCTION: Patients with rheumatoid arthritis (RA) often experience depression, which has a very negative impact on the assessment of the quality of life (QoL). However, there are not many studies that assess the relationship between depression and QoL in RA patients. The aim of the study was to assess the level of QoL and determine the mutual relationship between anxiety and depression levels and QoL in patients treated for RA. MATERIAL AND METHODS: The study included 101 patients (aged:52.4±16.97), who met the established criteria for a diagnosis of RA and treatment with a biological agent. Only standardized tools were used to examine the patients: WHO-QoL, HADS and the VAS scale. RESULTS: The mean RA duration in the group studied was 13.54±9.51 years and the disease activity score was 4.8±0.8. The mean QoL perception score was 3.48± 0.8. Nearly 40% of the respondents could not clearly determine their QoL, perceiving it as neither poor nor good, and 10% believed their QoL is poor or very poor. The correlation analysis revealed that anxiety is significantly and negatively associated with QoL in the psychological domain (r = -0.472, p < 0.001) and social domain (r = -0.298, p = 0.023) and depression is significantly and negatively associated with QoL in the psychological domain (r = -0.322, p = 0.01) and physical health domain (r = -0.209, p = 0.04). In the multiple linear regression model, depression was an independent negative predictor affecting the following domains: perception of QoL and perception of health, and physical health. CONCLUSION: RA patients treated with biologics present a low level of health perception and an average level of QoL perception. Depression and anxiety negatively correlate with QoL domains: the higher the anxiety and depression levels, the poorer the QoL in the psychological and social relationships domains. Depression is an independent determinant of decreased QoL.
35072287 Exposure-response relationships for the efficacy and safety of filgotinib and its metaboli 2022 Jan 23 AIMS: Filgotinib is a potent, oral, JAK1-preferential inhibitor for the treatment of rheumatoid arthritis (RA). This report describes exposure-response (ER) analyses of filgotinib for dose confirmation based on three phase 3 and two phase 2 studies in moderate to severe RA patients. METHODS: The pharmacokinetic exposures used in ER analyses were derived from population pharmacokinetic analysis. The exposure-efficacy relationships were assessed for efficacy endpoints (ACR20/50/70 and DAS28) over effective area under curve (AUC(eff) ), the combined exposures of filgotinib and GS-829845 (major, active metabolite), with nonlinear logistic regression models developed. Also, a t-test was performed to compare the exposure between subjects who achieved response and those who did not. For the ER analyses of safety, exposures were examined between subjects who experienced and who did not experience the evaluated safety events, which was conducted separately for filgotinib and GS-829845. RESULTS: The nonlinear logistic regression showed increasing response with increasing exposure, with exposures at 200 mg dose primarily residing on the curve plateau. Also, AUC(eff) was significantly higher in the subjects who achieved responses compared to those who did not (10 900 vs 9900 h*ng/mL for ACR20, P value < .0001). For exposure-safety analyses, filgotinib and GS-829845 exposures were similar irrespective of the presence/absence of the evaluated safety endpoints, indicating no exposure-safety relationship for common treatment-emergent adverse events (TEAEs)/laboratory abnormalities and serious TEAEs/infections. CONCLUSIONS: ER analyses confirmed that filgotinib produced more robust therapeutic effects across the exposure range observed at 200 mg once daily compared to lower doses, and collectively with the lack of exposure-safety relationship, the 200 mg once daily dose was supported for commercialization.
35593234 Potential therapeutic application of biophenols - plants secondary metabolites in rheumato 2022 May 20 Rheumatoid arthritis (RA) is a chronic autoimmune disease showed that persistent inflammation in the joints, induces the cartilage destruction, bone erosion, and leukocyte infiltration in the synovium. RA mostly affects the joints of hands, feet, wrists, ankles, and knees. Each year, approximately 20-40 new cases are reported per lac population and the disease affects women more than men. The etiology of RA is still unknown, but many pathways have been identified as potential targets in its pathophysiology, including the PI3K/AKT signaling pathway, NF-κB signaling, Adenosine signaling, Wnt, SYK/BTK, and mTOR signaling pathways. Biophenol, plant secondary metabolite, is considered one of the most abundantly phytoconstituents to have potential anti-inflammatory effects associated with multiple pathways. These indicate that biophenols can be used for its protective effect on the development and symptoms of RA. The current review explores and discusses the role of different biophenols in the treatment of RA disease.
35133578 Anti-TNF Induced Sarcoidosis-Like Disease in Rheumatoid Arthritis Patients: Review Cases f 2022 Apr INTRODUCTION: Drug-induced sarcoidosis-like disease is a rare side effect of anti-tumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA) patients. The most commonly involved organs in such condition are the lungs, skin, and lymph nodes. The aim of this study is to report the number of cases and the clinical manifestations of sarcoidosis induced by anti-TNF in our RA UCLouvain Brussels cohort. METHODS: All case records of RA patients ever treated with a TNF inhibitor and presenting anti-TNF induced sarcoidosis in our rheumatology centers from 2000 to 2021 were retrospectively reviewed. RESULTS: Our RA UCLouvain Brussels cohort includes 2492 patients. Among them, 697 patients have been or are exposed to a TNF inhibitor. Only four patients with sarcoidosis induced by anti-TNF were identified and reviewed. Patient 1 was classified as incomplete Heerfordt syndrome. Patient 2 was a case of sarcoid-like granulomatosis manifesting as life-threatening hypercalcemia, acute kidney injury and atypical parenchymal pneumopathy. Patients 3 and 4 developed pulmonary sarcoidosis with hilar adenopathies. The TNF inhibitor was etanercept for the first three patients and infliximab for the last one. The time occurrence of sarcoidosis was highly variable after anti-TNF exposure. All patients recovered after glucocorticoid treatment and the discontinuation of the anti-TNF agent. CONCLUSIONS: This case highlights this rare paradoxical side effect and the variability of the clinical presentation. Further studies should analyze the immunopathology of such conditions.
34983213 [Systemic Inflammatory Response in a Young Woman]. 2022 Jan Systemic Inflammatory Response in a Young Woman Abstract. A 21-year-old patient with fever attacks, arthralgias, salmon-colored skin rash, neutrophilic leukocytosis, elevated CRP, ferritin, ASAT and ALAT was diagnosed with the rare systemic autoinflammatory disease, called adult Still disease, after having excluded other possible causes. An initial treatment with non steroidal anti-inflammatory drugs (NSAID) and prednisolone was not sufficiently effective, consecutively the therapy was escalated with the IL-6 antagonist tocilizumab. This immunosuppressive therapy resulted in fairly well controlled symptoms.
35328191 24 h Holter ECG Monitoring of Patients with Rheumatoid Arthritis-A Potential Role for a Pr 2022 Mar 5 BACKGROUND: Patients with rheumatoid arthritis (RA) have increased systemic inflammatory burden associated with elevated cardiovascular mortality. Prolonged ventricular repolarisation evaluated by QT interval duration is a risk factor for cardiovascular and total mortality. In RA, mortality risk is correlated with dynamics and cumulative incidence of QTc prolongation rather than QTc value. The aim is to evaluate if QT parameters evaluated with 24 h Holter ECG are a better option to complete the cardiovascular profile of RA patients than parameters from short ECG recordings. MATERIALS AND METHODS: A total of 58 patients (22 males, 36 females) with RA were submitted to short ECG recordings at admission and to 24 h Holter ECG. QT interval parameters and ventricular ectopy generated from both types of recordings were analyzed. RESULTS: QTc interval values obtained from Holter ECG were significantly higher than the values from short term ECG and were correlated with severity of inflammatory process. The number of QRS complexes with QTc > 450 ms recorded during 24 h Holter was strongly correlated with the number of ventricular events and severity of the inflammatory process. CONCLUSIONS: In patients with RA, the Holter ECG recordings could realize a more precise evaluation of the extent and dynamics of QTc interval duration and of ventricular ectopic events with potential risk of sudden death.
35207457 Serum Adropin Levels in Patients with Rheumatoid Arthritis. 2022 Jan 24 Adropin is a secretory protein that mainly modulates metabolic homeostasis and endothelial function. There is growing evidence supporting association of adropin with various inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to compare serum adropin levels between 70 patients with RA and 70 matched healthy controls. Furthermore, we explored adropin correlations with RA disease activity, glucose metabolism parameters and inflammatory biomarkers. Serum adropin levels were determined by a competitive enzyme-linked immunosorbent assay. Serum adropin levels were significantly lower in RA patients than in the control group (2.85 ± 0.91 vs. 4.02 ± 0.99 ng/mL, p < 0.001). In the RA group, serum adropin levels had a significant negative correlation with total cholesterol (r = -0.172, p = 0.043), HbA1c (r = -0.406, p < 0.001), fasting glucose (r = -0.377, p < 0.001) and HOMA-IR (the homeostasis model assessment-estimated insulin resistance; (r = -0.315, p = 0.008)). Multiple linear regression analysis showed that serum adropin levels retained a significant association with levels of fasting glucose (β ± SE, -0.450 ± 0.140, p = 0.002) and HbA1c (-0.528 ± 0.223, p = 0.021) after model adjustments. These findings imply that adropin could have an impact on metabolic homeostasis in RA, although further well-designed studies are warranted in order to establish this.
35069829 Silencing CoREST inhibits the viability and migration of fibroblast-like synoviocytes in T 2022 Feb Fibroblast-like synoviocytes (FLSs) have functions in the pathogenesis of rheumatoid arthritis (RA) through the onset of synovitis, the growth of pannus and the destruction of cartilage and bone. The significant increase in the proliferation, migration and invasion of FLSs induces the onset and advancement of RA. To date, the exact function of corepressor element-1 silencing transcription factor (CoREST) in RA remains unclear, but its expression has been determined in RA synovial tissues. In this study, the effects of CoREST were investigated in a TNF-α-induced FLS activation model. Following the silencing of CoREST expression with small interfering (si)RNA, the viability and migration of FLSs were evaluated. Furthermore, the possible molecular mechanisms were explored by detecting the expression of key factors, including matrix metalloproteinases (MMPs), lysine-specific histone demethylase 1 (LSD1) and associated cytokines, via reverse transcription-quantitative PCR and western blotting. CoREST expression increased not only in the RA synovial tissues, but also in the TNF-α-induced FLS activation model. Following the silencing of CoREST in the FLSs treated with TNF-α, cell viability was inhibited, and the migratory capacity of FLSs was suppressed, which was accompanied by the reduced expression of MMP-3 and MMP-9. The expression of LSD1 was also downregulated. There was a notable decrease in the synthesis of interferon-γ and interleukin (IL)-17, while IL-10 expression was increased. The knockdown of CoREST inhibited the viability and migration of FLSs stimulated with TNF-α. Thus, the suppression of CoREST may have crucial roles in the occurrence and development of RA.
35410410 Clinical characteristics and variants that predict prognosis of difficult-to-treat rheumat 2022 Apr 11 Factors influencing prognosis after administration of the last biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) to patients with difficult-to-treat rheumatoid arthritis (D2T_RA) were evaluated in a clinical setting. RA patients who met the EULAR definition of D2T_RA were recruited. These patients were grouped according to success/failure. Success was defined as sustained within light disease activity or discontinued after clinical remission, and all of the following were met, including glucocorticoid (GCS) < 7.5 mg/day, no rapid radiographic progression, and improved quality of life from the beginning of the b/tsDMARD (baseline). Failure was defined as any other condition from success. The primary endpoint of the study was success or failure at 12 months after baseline. Factors influencing success/failure were statistically evaluated. A total of 71 D2T_RA patients were selected, 22 were in the success group and 49 in the failure group. For patients taking GCS and methotrexate (MTX) ≤ 8.6 mg/week, only one was included in the success group and the other 24 were included in the failure group (p < 0.001). Of the 18 patients without GCS and with MTX ≥ 8.7 mg, 12 patients whose 28-joint disease activity score ≤ 1.90 at 3 months or ≤ 2.54 at 6 months were in the success group (p < 0.01). D2T_RA patients with GCS or MTX ≤ 8.6 mg at baseline are considered to be at high risk of repeat D2T_RA. Patients with no GCS and MTX ≥ 8.7 mg are more likely to withdraw from D2T_RA if their disease activity is tightly controlled.
35218177 Factors influencing methotrexate and methotrexate polyglutamate in patients with rheumatoi 2022 Feb 24 Low dose methotrexate (MTX) is commonly used in the treatment of rheumatoid arthritis. The clinical effect is mediated by its metabolite, methotrexate polyglutamate (MTX-PGn). The drug exhibits high interindividual pharmacokinetic variability and the optimal MTX dose is different among individuals. Thus, several MTX population pharmacokinetic (PopPK) models were developed to characterize factors affecting MTX pharmacokinetic variability. This review summarizes significant predictors for MTX pharmacokinetics and identifies knowledge gaps to be further examined. A total of 359 articles were identified from a systematic search of four databases: PubMed, Science Direct, and CINAHL Complete. Of these eight studies were included. Most studies investigated influential factors on MTX pharmacokinetics, but information on MTX-PGn is limited, with only one study performing a parent-metabolite (MTX-PG3) model. MTX pharmacokinetics was described using a two-compartment model with first-order elimination in most studies, with the MTX clearance ranging from 6.94 to 12.39 L/h. Significant predictors influencing MTX clearance included weight, creatinine clearance, sex, OATP1B3 polymorphism, and MTX multiple dosing. While body mass index and red blood cell counts were significant predictors for MTX-PG3 clearance. Providing that MTX-PGn plays a crucial role in clinical effect, further studies should determine other factors affecting MTX-PGn as well as its relationship with clinical response.
34636022 Impact of smoking habit on adult-onset Still's disease prognosis, findings from a multicen 2022 Mar The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still's disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45-14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46-15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43-11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36-11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33-13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis. Key points • Smoking habit resulted to be a negative prognostic factor on AOSD. • Smokers were characterised by an increased frequency of serositis and higher values of systemic score. • Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD.