Disease-modifying Agents Research Articles

Psychosocial Protective Factors in Cognitive Aging: A Targeted Review.

The lack of disease-modifying pharmacological agents for dementia highlights the critical importance of prevention, but known modifiable factors (e.g., education, physical health and health behaviors, depression, and social isolation) do not fully represent potential intervention targets. Positive psychosocial factors predict cognitive aging outcomes above and beyond known risk factors and may also correspond to upstream determinants that open up new avenues for prevention and intervention, as well as for reducing racial/ethnic inequalities in dementia. In this brief report, I summarize contemporary evidence for three positive psychosocial factors that appear to be particularly relevant to cognitive aging: perceived control, religious involvement, and social relations. Targeted review and synthesis of published studies. Each of the multidimensional constructs appears to contain "active ingredients" that could help to optimize cognitive aging through disparate mechanisms. Although historically marginalized racial/ethnic groups face disproportionate barriers to accessing certain psychosocial protective factors (e.g., perceived control), these same groups also exhibit naturally occurring sources of psychosocial resilience (e.g., religious involvement) that allow them to achieve better late-life cognitive health than would be otherwise expected. With regard to social relations, converging evidence from disparate studies shows that fostering late-life friendships in particular may have high potential for building cognitive reserve and promoting healthy cognitive aging. Positive psychosocial factors represent culturally relevant resources that, through careful research, could ultimately be harnessed to promote better cognitive aging for a growing and increasingly diverse population of older adults.

Multiple sclerosis in 2020

Recent developments in the management of multiple sclerosis (MS) are ushering in a new era in MS treatment. The novel therapeutic disease-modifying agents that have been recently approved for the treatment of MS are B-cell therapies and various sphingosine-1-phosphate inhibitors. The Bruton's tyrosine kinase inhibitor therapies provide a novel therapeutic approach in the treatment of MS. Numerous studies have demonstrated a high degree of efficacy with autologous hematopoietic stem cells. There are upcoming trials focusing on remyelination strategies in MS. In this yearly review, we will focus on all these latest developments which are leading to a promising change in the diagnosis, treatment, and prognosis of this disease.

Emerging role of integrated PET-MRI in osteoarthritis.

Osteoarthritis (OA) is a common degenerative disorder of the articular cartilage, which is associated with hypertrophic changes in the bone, synovial inflammation, subchondral sclerosis, and joint space narrowing (JSN). Radiography remains thefirst line of imaging till now. Due to the lack of soft-tissue depiction in radiography, researchers are exploring various imaging techniques to detect OA at an early stage and understand its pathophysiology to restrict its progression and discover disease-modifying agents in OA. As the OA relates to the degradation of articular cartilage and remodeling of the underlying bone, an optimal imaging tool must be sensitive to the bone and soft tissue health. In that line, many non-invasive imaging and minimally invasive techniques have been explored. Out of these, the non-invasive compositional magnetic resonance imaging (MRI) for evaluation of the integrity of articular cartilage and positron emission tomography (PET) scan with fluorodeoxyglucose (FDG) and more specific bone-seeking tracer like sodium fluoride (18F-NaF) for bone cartilage interface are some of the leading areas of ongoing work. Integrated PET-MRI system, a new hybrid modality that combines the virtues of the above two individual modalities, allows detailed imaging of the entire joint, including soft tissue cartilage and bone, and holds great potential to research complex disease processes of OA. This narrative review attempts to signify individual characteristics of MRI, PET, the fusion of these characteristics in PET-MRI, and the ongoing research on PET-MRI as a potential tool to understand the pathophysiology of OA.

Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management.

Rheumatoid arthritis (RA) is a systemic inflammatory disorder, with the most common extra-articular manifestation of RA being lung involvement. While essentially any of the lung compartments can be affected and manifest as interstitial lung disease (ILD), pleural effusion, cricoarytenoiditis, constrictive or follicular bronchiolitis, bronchiectasis, pulmonary vasculitis, and pulmonary hypertension, RA-ILD is a leading cause of death in patients with RA and is associated with significant morbidity and mortality. In this review, we focus on the common pulmonary manifestations of RA, RA-ILD and airway disease, and discuss evolving concepts in the pathogenesis of RA-associated pulmonary fibrosis, as well as therapeutic strategies, and have revised our previous review on the topic. A rational clinical approach for the diagnosis and management of RA-ILD, as well as an approach to patients with clinical worsening in the setting of treatment with disease-modifying agents, is included. Future directions for research and areas of unmet need in the realm of RA-associated lung disease are raised.

Genetic Basis and Novel Treatment Strategies in Parkinson's Disease – A Review

Parkinson's disease (PD) is the 2nd most common progressive neurodegenerative disorder after Alzheimer's disease. Approximately 60000 are diagnosed with Parkinson's disease each year and more than 10 million people are living with PD. PD is a neurodegenerative disorder in addition to the causes of PD are so many, it's not caused by a single pathophysiologic disturbance. So many drugs are available to treat PD but all are only for symptomatic relief no one drug is a disease-modifying agent. Although so many targets are available for targeting the Synuclein alpha, mitochondrial oxidative stress, autophagy, targeting glial cell inflammation, targeting metal ion homeostasis. But till now no one drug is successful in targeting these targets. In this review, we have summarized the genetic basis and novel targets available for the disease-modifying strategy for PD.

PND67 Factors Associated with Prescribing of Disease-Modifying Agents Among Older Adults with Multiple Sclerosis: A Real-World Analysis of Electronic Medical Records

The value of disease-modifying agents (DMA) for managing Multiple Sclerosis (MS) in older adults is highly debated as most older adults have progressive MS. Hence, this study examined the DMA prescribing and the factors associated with prescribing of DMAs in older adults with MS using electronic medical records (EMR) data. Retrospective longitudinal study was conducted using the TriNetX, a federated EMR network from the US, data from 2016–2019. The study included older adults (≥60 years) with MS diagnosis (ICD-9/10-CM codes: 340/G35) having any prescription record during the study period. Patients with DMA prescriptions were identified and further classified into injectable, oral, or infusion users based on their prescription on the last DMA prescription. Multivariable logistic regression model was used to evaluate factors associated with prescribing of DMAs using the Andersen Behavioral Model. The study cohort consisted of 12,922 older adults with MS with 2,455(18.99%) receiving DMA prescription. The frequently prescribed DMAs were injectable (10.46%), followed by oral (6.06%) and infusion (2.40%). Multivariable logistic regression revealed older adults between 60–64years [Adjusted Odds Ratio (aOR)=2.39] and 65-69 years (aOR=1.60) had higher odds of receiving DMA compared to older adults 70 years and above. African Americans (aOR=1.71) had higher odds of receiving DMA prescriptions compared to Caucasians. Presence of symptoms (general, speech, walking difficulty) and use of symptomatic drugs (anti-fatigue, bladder dysfunction medications, antispasmodics, antidepressants and relapse medications) had higher odds of being prescribed DMA. Further, certain comorbidities (hypertension, neurological disorders, congestive heart failure) and healthcare utilization (emergency room, inpatient, outpatient visit) were associated with lower odds of receiving a DMA prescription. Nearly one in five older adults with MS are prescribed DMAs. Predisposing and need factors are associated with DMA prescribing in older adults. Further studies are needed to understand the clinical outcomes associated with DMA use in older adults with MS.

CE2 Effect of Different Variance Estimation Methods with Inverse Probability Treatment Weights (IPTW) on Comparative Effectiveness Measure in Multiple Sclerosis

The Inverse Probability Treatment Weighting (IPTW) method provides marginal treatment effects that are more generalizable than other propensity score (PS) methods. The objective of this study was to compare the treatment effects from three different variance estimation methods with stabilized IPTWs on comparative effectiveness between oral fingolimod and injectable Disease Modifying Agents (DMA) users in Multiple Sclerosis (MS).

Mechanisms of disease-modifying effect of saracatinib (AZD0530), a Src/Fyn tyrosine kinase inhibitor, in the rat kainate model of temporal lobe epilepsy

We have recently demonstrated the role of the Fyn-PKCδ signaling pathway in status epilepticus (SE)-induced neuroinflammation and epileptogenesis in experimental models of temporal lobe epilepsy (TLE). In this study, we show a significant disease-modifying effect and the mechanisms of a Fyn/Src tyrosine kinase inhibitor, saracatinib (SAR, also known as AZD0530), in the rat kainate (KA) model of TLE. SAR treatment for a week, starting the first dose (25 mg/kg, oral) 4 h after the onset of SE, significantly reduced spontaneously recurring seizures and epileptiform spikes during the four months of continuous video-EEG monitoring. Immunohistochemistry of brain sections and Western blot analyses of hippocampal lysates at 8-day (8d) and 4-month post-SE revealed a significant reduction of SE-induced astrogliosis, microgliosis, neurodegeneration, phosphorylated Fyn/Src-419 and PKCδ-tyr311, in SAR-treated group when compared with the vehicle control. We also found the suppression of nitroxidative stress markers such as iNOS, 3-NT, 4-HNE, and gp91phox in the hippocampus, and nitrite and ROS levels in the serum of the SAR-treated group at 8d post-SE. The qRT-PCR (hippocampus) and ELISA (serum) revealed a significant reduction of key proinflammatory cytokines TNFα and IL-1β mRNA in the hippocampus and their protein levels in serum, in addition to IL-6 and IL-12, in the SAR-treated group at 8d in contrast to the vehicle-treated group. These findings suggest that SAR targets some of the key biomarkers of epileptogenesis and modulates neuroinflammatory and nitroxidative pathways that mediate the development of epilepsy. Therefore, SAR can be developed as a potential disease-modifying agent to prevent the development and progression of TLE.

Monomethyl Fumarate (MMF, Bafiertam) for the Treatment of Relapsing Forms of Multiple Sclerosis (MS).

Multiple sclerosis (MS) is a prevalent neurologic autoimmune disorder affecting two million people worldwide. Symptoms include gait abnormalities, perception and sensory losses, cranial nerve pathologies, pain, cognitive dysfunction, and emotional aberrancies. Traditional therapy includes corticosteroids for the suppression of relapses and injectable interferons. Recently, several modern therapies—including antibody therapy and oral agents—were approved as disease-modifying agents. Monomethyl fumarate (MMF, Bafiertam) is a recent addition to the arsenal available in the fight against MS and appears to be well-tolerated, safe, and effective. In this paper, we review the evidence available regarding the use of monomethyl fumarate (Bafiertam) in the treatment of relapsing-remitting MS.

Myricetin prevents high molecular weight Aβ1-42 oligomer-induced neurotoxicity through antioxidant effects in cell membranes and mitochondria

Excessive accumulation of amyloid β-protein (Aβ) is one of the primary mechanisms that leads to neuronal death with phosphorylated tau in the pathogenesis of Alzheimer's disease (AD). Protofibrils, one of the high-molecular-weight Aβ oligomers (HMW-Aβo), are implicated to be important targets of disease modifying therapy of AD.We previously reported that phenolic compounds such as myricetin inhibit Aβ1-40, Aβ1-42, and α-synuclein aggregations, including their oligomerizations, which may exert protective effects against AD and Parkinson's disease. The purpose of this study was to clarify the detailed mechanism of the protective effect of myricetin against the neurotoxicity of HMW-Aβo in SH-SY5Y cells.To assess the effect of myricetin on HMW-Aβo-induced oxidative stress, we systematically examined the level of membrane oxidative damage by measuring cell membrane lipid peroxidation, membrane fluidity, and cell membrane potential, and the mitochondrial oxidative damage was evaluated by mitochondrial permeability transition (MPT), mitochondrial reactive oxygen species (ROS), and manganese-superoxide dismutase (Mn-SOD), and adenosine triphosphate (ATP) assay in SH-SY5Y cells.Myricetin has been found to increased cell viability by suppression of HMW-Aβo-induced membrane disruption in SH-SY5Y cells, as shown in reducing membrane phospholipid peroxidation and increasing membrane fluidity and membrane resistance. Myricetin has also been found to suppress HMW-Aβo-induced mitochondria dysfunction, as demonstrated in decreasing MPT, Mn-SOD, and ATP generation, raising mitochondrial membrane potential, and increasing mitochondrial-ROS generation.These results suggest that myricetin preventing HMW-Aβo-induced neurotoxicity through multiple antioxidant functions may be developed as a disease-modifying agent against AD.

Synthesis, Structure-Activity Relationships, and In Vivo Evaluation of Novel Tetrahydropyran-Based Thiodisaccharide Mimics as Galectin-3 Inhibitors.

Galectin-3 is a member of a family of β-galactoside-binding proteins. A substantial body of literature reports that galectin-3 plays important roles in cancer, inflammation, and fibrosis. Small-molecule galectin-3 inhibitors, which are generally lactose or galactose-based derivatives, have the potential to be valuable disease-modifying agents. In our efforts to identify novel galectin-3 disaccharide mimics to improve drug-like properties, we found that one of the monosaccharide subunits can be replaced with a suitably functionalized tetrahydropyran ring. Optimization of the structure-activity relationships around the tetrahydropyran-based scaffold led to the discovery of potent galectin-3 inhibitors. Compounds 36, 40, and 45 were selected for further in vivo evaluation. The synthesis, structure-activity relationships, and in vivo evaluation of novel tetrahydropyran-based galectin-3 inhibitors are described.

Management of Autoimmune Liver Diseases after Liver Transplantation

Autoimmune liver diseases are characterized by immune-mediated inflammation and eventual destruction of the hepatocytes and the biliary epithelial cells. They can progress to irreversible liver damage requiring liver transplantation. The post-liver transplant goals of treatment include improving the recipient’s survival, preventing liver graft-failure, and decreasing the recurrence of the disease. The keystone in post-liver transplant management for autoimmune liver diseases relies on identifying which would be the most appropriate immunosuppressive maintenance therapy. The combination of a steroid and a calcineurin inhibitor is the current immunosuppressive regimen of choice for autoimmune hepatitis. A gradual withdrawal of glucocorticoids is also recommended. On the other hand, ursodeoxycholic acid should be initiated soon after liver transplant to prevent recurrence and improve graft and patient survival in primary biliary cholangitis recipients. Unlike the previously mentioned autoimmune diseases, there are not immunosuppressive or disease-modifying agents available for patients with primary sclerosing cholangitis. However, colectomy and annual colonoscopy are key components during the post-liver transplant period.

Huprine Y – Tryptophan heterodimers with potential implication to Alzheimer’s disease treatment

The search for novel and effective therapeutics for Alzheimer's disease (AD) is the main quest that remains to be resolved. The goal is to find a disease-modifying agent able to confront the multifactorial nature of the disease positively. Herewith, a family of huprineY-tryptophan heterodimers was prepared, resulting in inhibition of cholinesterase and neuronal nitric oxide synthase enzymes, with effect against amyloid-beta (Aβ) and potential ability to cross the blood–brain barrier. Their cholinesterase pattern of behavior was inspected using kinetic analysis in tandem with docking studies. These heterodimers exhibited a promising pharmacological profile with strong implication in AD.

Factors associated with oral fingolimod use over injectable disease- modifying agent use in multiple sclerosis

BackgroundFingolimod is the first approved oral disease-modifying agent (DMA) in 2010 to treat Multiple Sclerosis (MS). There is limited real-world evidence regarding the determinants associated with fingolimod use in the early years. ObjectiveThe objective of this study was to examine the factors associated with fingolimod prescribing in the initial years after the market approval. MethodsA retrospective, longitudinal study was conducted involving adults (≥18 years) with MS from the 2010–2012 IBM MarketScan. Individuals with MS were selected based on ICD-9-CM: 340 and a newly initiated DMA prescription. Based on the index/first DMA prescription, patients were classified as fingolimod or injectable users. All covariates were measured during the six months baseline period prior to the index date. Multivariable logistic regression was performed to determine the predisposing, enabling, and need factors, conceptualized as per the Andersen Behavioral Model (ABM), associated with prescribing of fingolimod versus injectable DMA for MS. ResultsThe study cohort consisted of 3118 MS patients receiving DMA treatment. Of which, 14.4% of patients with MS initiated treatment with fingolimod within two years after the market entry, while the remaining 85.6% initiated with injectable DMAs. Multivariable regression revealed that the likelihood of prescribing oral DMA increased by 2–3 fold during 2011 and 2012 compared to 2010. Patients with ophthalmic (adjusted odds ratio [aOR]-2.60), heart (aOR-2.21) and urinary diseases (aOR-1.37) were more likely to receive fingolimod. Patients with other neurological disorders (aOR-0.50) were less likely to receive fingolimod than those without neurological disorders. Use of symptomatic medication (for impaired walking (aOR-2.60), bladder dysfunction (aOR-1.54), antispasmodics (aOR-1.48), and neurologist consultation (aOR-1.81) were associated with higher odds of receiving fingolimod. However, patients with non-MS associated emergency visits (aOR-0.64) had lower odds of receiving fingolimod than those without emergency visits. ConclusionsDuring the initial years after market approval, patients with highly active MS were more likely to receive oral fingolimod than injectable DMAs. More research is needed to understand the determinants of newer oral DMAs.

Elicitation of Rheumatologist Preferences for the Treatment of Patients with Rheumatoid Arthritis After the Failure of a First Conventional Synthetic Disease-Modifying Anti-Rheumatic Agent.

IntroductionRheumatoid arthritis (RA) clinical guidelines do not provide strong recommendations for the choice of disease-modifying anti-rheumatic drugs (DMARD) in patients with an inadequate response to methotrexate (MTX), and only limited evidence is available on factors influencing rheumatologist treatment decisions. We aimed to describe therapeutic preferences after the failure of a first-line strategy of MTX in simulated cases of patients with RA.MethodsFictional but realistic case-vignettes (n = 64) of patients with RA and an inadequate response to MTX were developed with a combination of RA-poor prognostic factors and comorbidities. Physicians were presented with eight vignettes and chose the most and least appropriate therapeutic option from the following six options randomly proposed 3 by 3: (1) replacing MTX with another csDMARD; (2) combining MTX with one or more csDMARDs; (3) adding a bDMARD of either TNF inhibitors (TNFi), tocilizumab (TCZ), abatacept (ABA), or rituximab (RTZ). A total of 1605 complete case vignettes were produced and randomly assigned to a representative sample of French rheumatologists. For each vignette, whenever a treatment was preferred, one point was incremented for this treatment; if this treatment was the least desired, one point was removed. Preferences were elicited using a normalized best–worst score.ResultsTwo hundred and four French rheumatologists participated in the study with each vignette being assessed 20–28 times for a completion rate of 94%. TNFi was the first-choice strategy (80% of vignettes), except in cases with a history of infection and pulmonary comorbidity, where ABA was the first preference (85%). TCZ came third in 83% of the cases. Other options were never preferred and repeatedly yielded negative scores.ConclusionsWe observed a conservative trend with TNFi as the main therapeutic choice for patients with RA and inadequate response to MTX. Preference for bDMARD-based strategies increased with the number of RA-poor prognosis factors, whereas an increase in the number of comorbidities resulted in an increased preference for ABA. Understanding clinical decision-making will be particularly important as the therapeutic landscape for RA continues to evolve.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00311-1.

Antioxidative effects of silymarin on the reduction of liver complications of fingolimod in patients with relapsing-remitting multiple sclerosis: A clinical trial study.

Multiple sclerosis (MS) is a chronic disease that affects the central nervous system and is characterized by inflammation, demyelination, and degenerative changes. Relapsing-remitting MS (RRMS) is the most common form of MS. Fingolimod (FTY720) is a once-daily disease-modifying agent approved to treat RRMS, and it binds to sphingosine 1-phosphate receptors. Milk thistle (silybum marianum; SM) is an herb generally used to protect the liver with antioxidant and antifibrotic effects. The purpose of this study was to evaluate the effects of silymarin on reducing liver complications of FTY720 in patients with RRMS and decrease the oxidative stress that plays an important role in the pathogenesis of this disease. Forty-eight patients with RRMS were divided into two groups using random assignment:the placebo and drug-treated groups. Participants of intervention and control groups took FTY720 with silymarin and placebo without silymarin per day for six months. Findings showed a significant reduction in the level of ALT and AST, reduction of main pathogenic factors in MS containing malondialdehyde, and also a significant rise in total antioxidant capacity, and total thiol groups in the serum of patients treated with silymarin as compared with the placebo group. Our outcomes propose the practical effects of silymarin in multiple sclerosis and reduction of hepatic side effects of fingolimod.

Disease modifying agents of myeloproliferative neoplasms: a review.

The identification of driver mutations in Janus kinase (JAK) 2, calreticulin (CALR), and myeloproliferative leukemia (MPL) has contributed to a better understanding of disease pathogenesis by highlighting the importance of JAK signal transducer and activator of transcription (STAT) signaling in classical myeloproliferative neoplasms (MPNs). This has led to the therapeutic use of novel targeted treatments, such as JAK2 inhibitors. More recently, with the development of next-generation sequencing, additional somatic mutations, which are not restricted to MPNs, have been elucidated. Treatment decisions for MPN patients are influenced by the MPN subtype, symptom burden, and risk classification. Although prevention of vascular events is the main objective of therapy for essential thrombocythemia (ET) and polycythemia vera (PV) patients, disease-modifying drugs are needed to eradicate clonal hematopoiesis and prevent progression to more aggressive myeloid neoplasms. JAK inhibitors are a valuable therapeutic strategy for patients with myelofibrosis (MF) who have splenomegaly and/or disease-related symptoms, but intolerance, refractory, resistance, and disease progression still present challenges. Currently, allogeneic stem cell transplantation remains the only curative treatment for MF, but it is typically limited by age-related comorbidities and high treatment-related mortality. Therefore, a better understanding of the molecular pathogenesis and potential new therapies with the aim of modifying the natural history of the disease is important. In this article, I review the current understanding of the molecular basis of MPNs and clinical studies on potential disease-modifying agents.

Non-steroidal treatment of cardiac sarcoidosis: A systematic review.

The treatment of active cardiac sarcoidosis (CS) usually involves immunosuppressive therapy, with the goal of preventing inflammation-induced scar formation. In most cases, steroids remain the first-line treatment for CS. However, given the side effect profile of their long-term use, steroid-sparing therapies are increasingly used. There are no published randomized trials of steroid-sparing agents in CS. We sought to do a systematic review to evaluate the current published data on the use of non-steroidal treatments in the management of CS. We searched the Cochrane Library, Ovid Medline, Ovid Embase, PubMed, and Web of Science Core Collection databases from inception of database to August 2020 to identify the effectiveness of biological or synthetic disease-modifying antirheumatic agents (s- and bDMARDs). Secondary objectives include safety profile as well as the change in the average corticosteroid dose after treatment initiation. Twenty-three studies were ultimately selected for inclusion which included a total of 480 cases of CS treated with a range of both s- and bDMARDs. In all included studies, sDMARDs and bDMARDs were studied in combination with steroids or as second or higher-line treatments after therapeutic failure or intolerance to corticosteroid use. Methotrexate (MTX) and infliximab (IFX) were the most common synthetic and biologic DMARDs studied respectively, reported in about 35% of the studies reviewed. The use of steroid-sparing agents was associated with a reduction in the maintenance steroid dose used. In conclusion, steroids will remain as the cornerstone of anti-inflammatory management in patients with CS until trials on the use and safety profile of other immunosuppressive agents are completed and published.

Mitoprotective therapy reduces inflammation and prevents cartilage turnover in an in vivo model of posttraumatic osteoarthritis

Mitoprotective therapy reduces inflammation and prevents cartilage turnover in an in vivo model of posttraumatic osteoarthritis

Clinical characteristics of igG4-related disease in the United Arab Emirates: A retrospective single-center study

Background: Demographic and clinical data of IgG4-related disease affecting solely the native population of the UAE, known as Emiratis, does not exist in the literature. Aim: To explore the demographic and clinical characteristics of IgG4-related disease in a well-defined population of Emirati patients attending Cleveland Clinic Abu Dhabi, a large tertiary center in the Middle East. Patients and Methods: The data presented is part of a retrospective cohort study, in which 15 Emirati patients with IgG4-related disease (IgG4-RD) were evaluated over 5 years from April 2015 to September 2020 at the rheumatology outpatient clinic at Cleveland Clinic Abu Dhabi. The demographic and clinical data were recorded. Descriptive statistics of the variables were applied. Results: Fifteen Emirati patients with an established diagnosis of IgG4-RD were assessed. There was a male predominance (53%) with a median age at the time of diagnosis of 47 ± 11.2 years. A 6-year lag period was noted from the initial presentation until a diagnosis of IgG4-RD was established. The most frequent comorbidities observed were hematological conditions (63%), hypertension (47%), diabetes mellitus (40%), and gastroesophageal reflux disease (40%). An elevated serum IgG4 was observed in the majority of patients at the initial presentation. Rheumatoid factor was detected in 13% and low titer of immunofluorescence antinuclear antibody in 7%. 86% of patients had a tissue biopsy with marked lymphocytic and plasmacytic infiltration being the most reported finding in 86%. Methotrexate, azathioprine, and rituximab were the most frequently prescribed disease-modifying agents. Conclusion: We report the first comprehensive analysis on a small cohort of Emirati patients with IgG4-RD. We describe disease features unique to UAE patients and demonstrate that IgG4-RD has a significant disease burden. Our results underscore the need for the IgG4-RD UAE-wide national registry to improve the quality of care of these patients.