Intravoxel Incoherent Motion Diffusion-Weighted MRI, Fat Quantification, and Electromyography: Correlation in Polymyositis and Dermatomyositis.

(1) Background: The intravoxel incoherent motion (IVIM) model can provide information about both molecular diffusion and blood flow for the evaluation of skeletal muscle inflammation. MRI-based fat quantification is advantageous for assessing fat infiltration in skeletal muscle. (2) Purpose: We aimed to quantitatively measure various parameters associated with IVIM diffusion-weighted imaging (DWI) and fat quantification in the muscles of patients with polymyositis and dermatomyositis using magnetic resonance imaging and to investigate the relationship between these parameters and electromyography (EMG) findings. (3) Material and methods: Data were retrospectively evaluated for 12 patients with polymyositis and dermatomyositis who underwent thigh MRI, including IVIM-DWI and fat quantification. The IVIM-derived parameters included the pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f). Fat fraction values were assessed using the six-point Dixon technique. Needle EMG was performed within 9 days of the MRI. (4) Results: The f values (19.02 ± 4.87%) in muscles with pathological spontaneous activity on EMG were significantly higher than those (14.60 ± 5.31) in muscles without pathological spontaneous activity (p < 0.027). There were no significant differences in D, D*, ADC, or fat fraction between muscles with and without pathologic spontaneous activity. Significant negative correlations were observed between fat fraction and amplitude (r = -0.402, p < 0.015) and between fat fraction and duration (r = -0.360, p < 0.031). (5) Conclusion: The current study demonstrates that IVIM-DWI and fat quantification using 3.0 T MRI may aid in predicting EMG findings in patients with polymyositis and dermatomyositis and promote the pathophysiological study of idiopathic inflammatory myopathies.

Biosimilars in the treatment of rheumatoid arthritis: a pharmacokinetic overview.

INTRODUCTION: As of May 2023, 19 and 18 biosimilars have been approved for the treatment of rheumatoid arthritis (RA) by the European Medicines Agency (EMA) and United States Food and Drug Administration (US FDA) respectively. AREA COVERED: Pharmacokinetic results of phase 1 studies of approved biosimilars were reviewed by systematic literature search. The impact of immunogenicity on the pharmacokinetic data and clinical response was assessed, and the potential benefit of monitoring serum concentrations of biologic drugs is discussed. The advantage of subcutaneous CT-P13 (an infliximab biosimilar) in clinical practice is reviewed. EXPERT OPINION: Biosimilars are approved based on the totality of evidence including comparable physiochemical properties, PK / PD profiles, and clinical efficacy and safety to the originator. To utilize biosimilars more effectively, physicians should be aware of the utility of combination DMARD therapy to reduce immunogenicity and maintain efficacy and PK profile. PK monitoring, however, is not currently recommended in clinical practice. CT-P13 subcutaneous (SC) is the first SC infliximab used for treatment of RA patients. Based on data from clinical studies and the real world, SC-infliximab is an attractive therapeutic option compared to IV formulations of infliximab based on its efficacy, pharmacokinetics, patient-reported outcomes, and safety profile.

Induction and Maintenance Treatment of Lupus Nephritis: A Comprehensive Review of Meta-Analyses.

BACKGROUND: Lupus nephritis (LN) is present in over 50% of patients with systemic lupus erythematosus (SLE) which is managed with immunosuppressive and immunomodulatory therapies. However, several novel therapeutic approaches for LN are under investigation due to the adverse effects spectrum of conventional therapy; Methods: We performed a comprehensive review of meta-analyses aggregating the comparative efficacies of various pharmacotherapies for LN. We conducted a literature search and retrieved a total of 23 meta-analyses and network meta-analyses for summarization. Pharmacotherapies were evaluated across six major outcomes: remission, relapse, mortality, end stage kidney disease (ESKD) progression, infection, and malignancy. RESULT: Calcineurin inhibitors (CNI), particularly tacrolimus (TAC), in combination with glucocorticoids (GC) outperformed cyclophosphamide (CPA) with GC in the rate of remission, either complete or partial remission, and in terms of infectious complications. In maintenance therapy, MMF was superior to azathioprine (AZA) as the MMF-treated patients had lower relapse rate. INTERPRETATION: This review aggregates evidence of therapy for clinicians and sheds light on comparative efficacies of alternative LN treatments. As more promising agents are entering the market, such as voclosporin, belimumab, and obinutuzumab, LN management might undergo significant changes during the next years.

Gender differences in factors associated with low quality of life and depression in Korean patients with ankylosing spondylitis.

PURPOSE: To identify predictors of low health-related quality of life (HRQoL) and depression in ankylosing spondylitis (AS) patients with a focus on gender differences. METHODS: We conducted a cross-sectional cohort study. Both AS-related clinical data and contextual factors were obtained. HRQoL and depressive mood were assessed by EuroQol-5 dimension (EQ-5D) and the Center for Epidemiological Studies Depression Scale (CES-D), respectively. Gender-stratified multivariable logistic regression analyses were performed. RESULTS: Among 211 patients, 161 were males. Males had similar disease activity and higher radiographic damage compared with females. There was no significant difference in EQ-5D index score between genders. CES-D score was higher in females. Higher ASDAS-C-reactive protein (CRP) was associated with low HRQoL in both males (Odds ratio [OR] 4.25, 95% confidence interval [CI] 2.42-7.46) and females (OR 2.94, 95% CI 1.02-8.48). Being employed was associated with decreased possibility of having low HRQoL in males (OR 0.39, 95% CI 0.16-0.95). Regarding depression, higher ASDAS-CRP (OR 1.87, 95% CI 1.03-3.40), current smoking (OR 2.98, 95% CI 1.09-8.15), and being employed (OR 0.17, 95% CI 0.06-0.46) were associated with depression in males. For females, living with a partner was related to depression (OR 0.08, 95% CI 0.01-0.93). CONCLUSION: AS patients with high disease activity are likely to be suffering from low HRQoL. Both disease-related factors and contextual factors were associated with depression, and predictors showed some differences between genders. Awareness of gender differences in comprehensive assessment can lead us to better personalized management in AS patients.

Different Features of Interleukin-37 and Interleukin-18 as Disase Activity Markers of Adult-Onset Still's Disease.

The aim of this study was to evaluate the usefulness of serum interleukin (IL)-37 and IL-18 as disease activity markers of adult-onset Still's disease (AOSD) and to compare their related clinical features. Forty-five patients with a set of high and subsequent low disease activity status of AOSD were enrolled. Modified Pouchot (mPouchot) score and serologic disease activity markers including levels of IL-37 and IL-18 were compared between high and low disease activity status. The relationships between disease activity parameters and differences in levels of cytokines according to each disease manifestation were evaluated in high disease activity status. mPouchot score and all disease activity markers including IL-37 and IL-18 significantly declined after treatment. Though both cytokines positively correlated with mPouchot score, the two did not correlate with each other in high disease activity status. IL-18 positively correlated with ferritin, AST, and LDH while IL-37 correlated better with CRP. The expression level of IL-37 was related to leukocytosis while IL-18 was related to pleuritis, pneumonitis, abnormal LFT, and hyperferritinemia. In addition, patients in the IL-18 dominant group presented with higher LDH levels and required a higher mean corticosteroid dose. In conclusion, IL-37 and IL-18 are disease activity markers reflecting different aspects of AOSD that can complement each other.

Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of in vitro, in vivo, and clinical trials.

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-ß1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.

A Pragmatic Application of Ultrasonography for the Assessment of Disease Activity in Patients with Early Inflammatory Arthritis.

The aim of the study was to examine the usefulness of targeted musculoskeletal ultrasonography (MSUS) in assessing the disease activity of patients with early inflammatory arthritis (EIA). Twenty-eight patients with EIA were enrolled. The MSUS examination of joints with arthritic signs (tenderness or swelling), measurement of 28-joint Disease Activity Score (DAS28), and its components were performed at four-week interval visits until power doppler (PD) US remission was achieved. Various MSUS parameters of grey scale (GS) and PD synovitis were measured. Pearson or Spearman correlation coefficients were determined for the purpose of the study. Data were gathered from a total of 85 visits. The Sum of GS grade correlated better with physical examination findings, while the Sum of PD grade correlated better with serum inflammatory markers and patient global health. However, Global OMERACT-EULAR Synovitis Score (GLOESS), which reflected both PD and GS grades, correlated evenly well with each clinical parameter. In addition, GLOESS correlated best with DAS28 in the overall study population (p < 0.01). Conclusively, our targeted MSUS parameters of arthritic joints, especially sums of semi-quantitative grades of synovitis, could be useful in monitoring patients with EIA.

The usefulness of trabecular bone score in patients with ankylosing spondylitis.

BACKGROUNDS/AIMS: This study was performed to reveal the usefulness of the trabecular bone score (TBS) in assessing bone strength in patients with ankylosing spondylitis (AS) in comparison with dual-energy X-ray absorptiometry (DXA) methods. METHODS: A total of 215 AS patients (75.8% male) were enrolled from a single university hospital in Korea. Demographic and clinical information were assessed. Patients completed X-rays of the cervical and lumbar spine (L-spine), and spinal ankyloses were quantified using the modified Stoke AS Spine Score (mSASSS). Hip, anteroposterior and lateral L-spine bone mineral density (BMD) and TBS were assessed by DXA methods. Clinical characteristics and bone strength measurement results were compared between male and female AS patients. The accuracy of each bone strength evaluation method in predicting Fracture Risk Assessment Tool (FRAX) scores indicating moderate or higher fracture risk was compared by receiver operating characteristic curves in patients aged ≥ 40 years. Correlations between each bone strength measurement method and mSASSS were examined. RESULTS: Male patients showed higher mSASSS and less prevalent peripheral joint involvement compared to female patients (p < 0.05). TBS, hip BMD, and L-spine lateral BMD showed comparably high areas under the curve (AUCs) for predicting FRAX-major osteoporotic fractures (MOF) ≥ 10% (AUC ranged 0.72 to 0.76). TBS negatively correlated with mSASSS in both male and female patients (p < 0.01). CONCLUSION: TBS could predict the risk of MOF and is not influenced by spinal osteoproliferation in AS patients, even in those with advanced spinal changes.

Understanding the genetics of systemic lupus erythematosus using Bayesian statistics and gene network analysis.

The publication of genetic epidemiology meta-analyses has increased rapidly, but it has been suggested that many of the statistically significant results are false positive. In addition, most such meta-analyses have been redundant, duplicate, and erroneous, leading to research waste. In addition, since most claimed candidate gene associations were false-positives, correctly interpreting the published results is important. In this review, we emphasize the importance of interpreting the results of genetic epidemiology meta-analyses using Bayesian statistics and gene network analysis, which could be applied in other diseases.

Sarcopenia in Autoimmune and Rheumatic Diseases: A Comprehensive Review.

Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia.

Comparative effectiveness of oral pharmacologic interventions for knee osteoarthritis: A network meta-analysis.

OBJECTIVES: To explore the relative efficacy of oral pharmacologic interventions in the treatment of knee OA. METHODS: A systematic literature review was conducted using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases to identify trials conducted in patients with knee OA with a minimum 6 weeks of follow-up. The standardized mean differences of the change from baseline to week 6 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain between the treatment groups were estimated using Bayesian random-effects network meta-analyses. Subgroup analyses of baseline pain status (high, pain score ≥60 mm; low, pain score <60 mm) were performed. RESULTS: Of 4067 manuscripts, 44 were included in the evidence synthesis. Etoricoxib had the highest ranking for improving WOMAC pain (probability of being top ranked, p (best) = .43) followed by naproxen (p (best) = .12), acetaminophen (AAP) (p (best) = .04), and celecoxib (p (best) = .02). The top three ranked interventions were etoricoxib, celecoxib and aceclofenac in the higher pain group, and tramadol, celecoxib, and diclofenac in the lower pain group. CONCLUSION: In the overall analysis, etoricoxib, celecoxib, and aceclofenac had the highest rankings for improving WOMAC pain. The ability to improve knee OA symptoms may differ depending on baseline pain and radiologic features.