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ID PMID Title PublicationDate abstract
34074100 Rheumatoid arthritis and metabolic disorders. 2021 Spring Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with multiple metabolic alterations and increased cardiovascular risk. It is supposed that visceral obesity seems to be a connection between rheumatoid arthritis and cardiovascular diseases. Obesity is not only associated with increased disease activity and worsened quality of life in this group of patients, but also determines the effectiveness of treatment. Biological therapy interferes with metabolic changes, too. Therefore, there is a tendency to select the right anticytokine preparation in the first line of treatment to reduce not only disease activity but also affect aspects of metabolic syndrome and comorbidites, thereby reducing cardiovascular risk and patients mortality. This work offers a basic overview of the associations between rheumatoid arthritis and metabolic disorders, describes the impact of biological therapy on individual components of the metabolic syndrome.
34473167 Treatment of rheumatoid arthritis by phototherapy: advances and perspectives. 2021 Sep 17 Rheumatoid arthritis (RA) is an inflammatory disease that is prevalent worldwide and seriously threatens human health. Though traditional drug therapy can alleviate RA symptoms and slow progression, high dosage and frequent administration would cause unfavorable side effects. Phototherapy including photodynamic therapy (PDT) and photothermal therapy (PTT) has demonstrated distinctive potential in RA treatment. Under light irradiation, phototherapy can convert light into heat, or generate ROS, to promote necrosis or apoptosis of RA inflammatory cells, thus reducing the concentration of related inflammatory factors and relieving the symptoms of RA. In this review, we will summarize the development in the application of phototherapy in the treatment of rheumatoid arthritis.
33932572 Rheumatoid arthritis and depression. 2021 Oct Depression constitutes the most frequent comorbid condition associated with rheumatoid arthritis (RA), with prevalence rates ranging from 14% to 48%. This wide range can be explained by several factors including subtypes of depression considered, instrument of measure (i.e. self-questionnaires versus clinical interview), threshold applied but also the overlap of symptoms between the two conditions. Despite being a frequent comorbid condition in RA, depressive states are repeatedly underdiagnosed and thus, often remain untreated. Consequences are dramatic as conclusive evidence show that depression deleteriously impacts just about all outcomes of RA, including disease activity, arthritis-related complications, level of pain, chance of remission, quality of life and mortality. Importantly, links between depression and RA appear to be bidirectional as if RA patients show increased prevalence of depression. Conversely, patients with depression compared to the general population have higher risk to develop RA. Among the factors explaining this strong association between depression and RA, recent advances have underlined the putative role of models based on the inflammatory hypothesis. Pro-inflammatory cytokines such as tumor necrosis factor, interleukin (IL)-1, IL-6, and IL-18 are involved in RA pathogenesis, but also in depression. Furthermore, the connections between the central nervous system, the peripheral system and the immune system are now better understood. As a consequence of the strong comorbidity and the aggravate prognostic, the management of patient showing this dual diagnosis should be carefully monitor. The common physiopathology also opens the path to utilization of RA treatment in severe depression or treatment-resistant depression.
33331946 Difficult-to-treat rheumatoid arthritis: contributing factors and burden of disease. 2021 Aug 2 OBJECTIVES: Treatment of difficult-to-treat (D2T) RA patients is generally based on trial-and-error and can be challenging due to a myriad of contributing factors. We aimed to identify risk factors at RA onset, contributing factors and the burden of disease. METHODS: Consecutive RA patients were enrolled and categorized as D2T, according to the EULAR definition, or not (controls). Factors potentially contributing to D2T RA and burden of disease were assessed. Risk factors at RA onset and factors independently associated with D2T RA were identified by logistic regression. D2T RA subgroups were explored by cluster analysis. RESULTS: Fifty-two RA patients were classified as D2T and 100 as non-D2T. Lower socioeconomic status at RA onset was found as an independent risk factor for developing D2T RA [odds ratio (OR) 1.97 (95%CI 1.08-3.61)]. Several contributing factors were independently associated with D2T RA, occurring more frequently in D2T than in non-D2T patients: limited drug options because of adverse events (94% vs 57%) or comorbidities (69% vs 37%), mismatch in patient's and rheumatologist's wish to intensify treatment (37% vs 6%), concomitant fibromyalgia (38% vs 9%) and poorer coping (worse levels). Burden of disease was significantly higher in D2T RA patients. Three subgroups of D2T RA patients were identified: (i) 'non-adherent dissatisfied patients'; (ii) patients with 'pain syndromes and obesity'; (iii) patients closest to the concept of 'true refractory RA'. CONCLUSIONS: This comprehensive study on D2T RA shows multiple contributing factors, a high burden of disease and the heterogeneity of D2T RA. These findings suggest that these factors should be identified in daily practice in order to tailor therapeutic strategies further to the individual patient.
33346109 Risk of venous thromboembolism in rheumatoid arthritis. 2021 May Rheumatoid arthritis (RA) is a chronic autoimmune joint disease with persistent systemic inflammation. Patients with RA suffer from joint pain and physical disability, but have their prognosis mostly driven by cardiovascular events, including venous thromboembolism (VTE). The risk of VTE is more than double in patients with RA compared with the general population. The incidence rate in patients with RA is estimated around 4 cases per 1000 person-years. The etiology of thrombotic tendency in RA is linked to various mechanisms and causal factors (antiphsolpholid antibodies, hyperhomocyteinemia, inflammation…): vascular injury, hypercoagulation, and venous stasis, the three components of the Virchow's triad, are activated in patients with RA. In clinical practice, situations that put patients for VTE should be identified (e.g., surgery, first year after RA diagnosis, hospitalization for acute illness…). Patients with RA are exposed to reversible risk factors, such as major surgery (knee or hip surgery) or hospitalization with immobilization. Similarly, uncontrolled RA, which is defined by the necessity to switch a biological disease-modifying anti-rheumatic drugs (DMARD), increases the incidence of VTE in observational studies. Moreover, DMARDs may impact the risk of VTE, especially in the time window after first prescription. Several biological DMARDs like tofacitinib have been associated with an increased risk of VTE. Therefore, patients with RA may require specific measures in terms of VTE diagnosis and management. In this review, we provide current insights into the pathophysiology, epidemiology, clinical considerations, and treatment strategies of VTE highlighting gaps in evidence and perspectives in patients with RA.
34197960 Traditional herbal medicine: Therapeutic potential in rheumatoid arthritis. 2021 Oct 28 ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by diverse endogenous and exogenous factors. It is characterized by cartilage and bone destruction. The current conventional allopathic therapy is expensive and carries adverse side effects. Recently, there were some ethnopharmacological studies on RA including anti-RA effects and therapeutic targets of distinct dosage forms of traditional herbal medicines (THMs). AIM OF THE REVIEW: This review provides a brief overview of the current understanding of the potential pharmacological mechanisms of THMs (active constituents, extracts and prescriptions) in RA. This study is intended to provide comprehensive information and reference for exploring new therapeutic strategies of THMs in the RA treatment. MATERIALS AND METHODS: This review captured scientific literatures invivo and vitro experiments on effects of anti-RA THMs published between 2016 and 2021 from journals and electronic databases (e.g. PubMed, Elsevier, Science Direct, Web of Science and Google Scholar). Relevant literatures were searched and analyzed by using keywords such as 'rheumatoid arthritis AND traditional herbal medicines', 'rheumatoid arthritis AND immune cells', 'rheumatoid arthritis AND inflammation', 'rheumatoid arthritis AND miRNA', 'rheumatoid arthritis AND Angiogenesis', 'rheumatoid arthritis AND oxidative stress', 'rheumatoid arthritis AND osteoclasts', 'rheumatoid arthritis AND CIA model', 'rheumatoid arthritis AND AA model' AND 'rheumatoid arthritis herbal prescription'. RESULTS: Experiments in vitro and in vivo jointly demonstrated the potential of THMs in the RA treatment. There are plentiful therapeutic targets in RA. THMs and active ingredients could alleviate RA symptoms through different therapeutic targets, such as immunoregulation, inflammation, fibroblast-like synoviocytes (FLSs), microRNAs (miRNAs), angiogenesis, oxidative stress, osteoclasts and multiple targets interaction. Anti-RA THMs, active ingredients and prescriptions through corresponding therapeutic targets were summarized and classified. CONCLUSIONS: Flavonoids, phenolic acids, alkaloids and triterpenes of THMs are identified as the main components to ameliorate RA. Regulation of different and multiple related therapeutic targets by THMs and their active ingredients were associated with greater therapeutic benefits, among which inflammation is the main therapeutic target. Nonetheless, further studies are required to unravel the complexities and in-depth mechanisms of THMs in alleviating RA.
33394602 Racial, ethnic, and healthcare disparities in rheumatoid arthritis. 2021 Mar 1 PURPOSE OF REVIEW: This review highlights the available data describing racial and ethnic health disparities among patients with rheumatoid arthritis in the United States from an epidemiological, disease activity, and wider socioeconomic standpoint. RECENT FINDINGS: Despite centralized government initiatives to include more underrepresentative minority populations into research, many of the studies that examined rheumatoid arthritis still fail to include sizeable cohorts of races or ethnic groups other than whites. Evidence is slowly mounting that individual, provider, and system-level barriers exist and contribute to unequal care that leads to poorer outcomes amongst patients with rheumatoid arthritis. As rheumatoid arthritis is a progressive disease, early treatment is crucial to delay functional decline - a narrow window for many minority patients who are disproportionality affected by disability. SUMMARY: To combat the inequality that exists amongst rheumatoid arthritis patients we must focus on why discrepancies exist on every level, system, physician, patient, and illness. Further research is needed to tease the complex interplay between race, social economic status, medical access, and outcomes to explain the disparities found in rheumatoid arthritis.
33787585 Effectiveness of resistance exercises in the treatment of rheumatoid arthritis: A meta-ana 2021 Apr 2 BACKGROUND: We aimed to assess the efficacy of resistance exercise in rheumatoid arthritis (RA) in randomized controlled trials (RCTs). METHOD: PubMed, the Cochrane Library, and Embase were searched according to the index words to identify eligible RCTs, and relevant literature sources were also searched. The latest search was done in August 2019. Odds ratios (OR), mean difference (MD), and 95% confidence interval (95% CI) were used to analyze the main outcomes. RESULT: Seventeen RCTs were included in the meta-analysis with 512 patients in the resistance exercise group and 498 patients in the control group. The results showed that compared with the control group, resistance exercise significantly decreased disease activity score in 28 joints (DAS-28) scores (standard mean difference [SMD]: -0.69, 95% CI: -1.26 to -0.11), reduced erythrocyte sedimentation rate (ESR) (SMD: -0.86, 95% CI: -1.65 to -0.07), and shortened the time of 50 ft. walking (SMD: -0.64, 95% CI: -0.99 to -0.28). No significant difference was observed in visual analog scale (VAS) scores (SMD: -0.61, 95% CI: -1.49-0.27) and health assessment questionnaire (HAQ) scores (weighted mean difference: -0.10, 95% CI: -0.26-0.06). CONCLUSION: Resistance exercise showed reducing DAS-28 score, ESR score, and the time of 50 ft. walking in RA patients compared with the control group. However, high quality multicenter RCTs with larger sample sizes to confirm the conclusion.
34899757 Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Impl 2021 Rheumatoid arthritis is an autoimmune disease that exhibits significant clinical heterogeneity. There are various treatments for rheumatoid arthritis, including disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and inflammatory cytokine inhibitors (ICI), typically associated with differentiated clinical effects and characteristics. Personalized responsiveness is observed to the standard treatment due to the pathophysiological heterogeneity in rheumatoid arthritis, resulting in an overall poor prognosis. Understanding the role of individual variation in cellular and molecular mechanisms related to rheumatoid arthritis will considerably improve clinical care and patient outcomes. In this review, we discuss the source of pathophysiological heterogeneity derived from genetic, molecular, and cellular heterogeneity and their possible impact on precision medicine and personalized treatment of rheumatoid arthritis. We provide emphasized description of the heterogeneity derived from mast cells, monocyte cell, macrophage fibroblast-like synoviocytes and, interactions within immune cells and with inflammatory cytokines, as well as the potential as a new therapeutic target to develop a novel treatment approach. Finally, we summarize the latest clinical trials of treatment options for rheumatoid arthritis and provide a suggestive framework for implementing preclinical and clinical experimental results into clinical practice.
35003139 Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death 2021 Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that can lead to clinical manifestations of systemic diseases. Its leading features include chronic synovial inflammation and degeneration of the bones and joints. In the past decades, multiple susceptibilities for rheumatoid arthritis have been identified along with the development of a remarkable variety of drugs for its treatment; which include analgesics, glucocorticoids, nonsteroidal anti-inflammatory medications (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and biologic response modifiers (bDMARDs). Despite the existence of many clinical treatment options, the prognosis of some patients remains poor due to complex mechanism of the disease. Programmed cell death (PCD) has been extensively studied and ascertained to be one of the essential pathological mechanisms of RA. Its dysregulation in various associated cell types contributes to the development of RA. In this review, we summarize the role of apoptosis, cell death-associated neutrophil extracellular trap formation, necroptosis, pyroptosis, and autophagy in the pathophysiology of RA to provide a theoretical reference and insightful direction to the discovery and development of novel therapeutic targets for RA.
33919365 Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis. 2021 Apr 21 The CCN family of matricellular proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1-2-3/CCN4-5-6) are essential players in the key pathophysiological processes of angiogenesis, wound healing and inflammation. These proteins are well recognized for their important roles in many cellular processes, including cell proliferation, adhesion, migration and differentiation, as well as the regulation of extracellular matrix differentiation. Substantial evidence implicates four of the proteins (CCN1, CCN2, CCN3 and CCN4) in the inflammatory pathologies of rheumatoid arthritis (RA) and osteoarthritis (OA). A smaller evidence base supports the involvement of CCN5 and CCN6 in the development of these diseases. This review focuses on evidence providing insights into the involvement of the CCN family in RA and OA, as well as the potential of the CCN proteins as therapeutic targets in these diseases.
34630412 N(6) -Methyladenosine and Rheumatoid Arthritis: A Comprehensive Review. 2021 Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N (6)-methyladenosine (m(6)A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m(6)A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m(6)A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m(6)A enzymes. The relationship between m(6)A enzymes, immune cells, and RA suggests that m(6)A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.
35229787 Microscopic Hematuria Associated with Rheumatoid Arthritis: Review of Literature. 2021 Jul Microscopic hematuria is common manifestation in patients with mild rheumatoid arthritis (RA). It has not been extensively addressed, to our knowledge, by scholars. In this review, we discussed in detail the epidemiological aspect of this problem from the clinical point of view. We reviewed many articles from different electronic databases on the web such as PubMed, LILACS, CINAHL, and PSYCH INFO to get up with a narrative review. Twenty-eight studies entailed the issue regarding etiology, pathology, clinical picture, prognosis complications, and treatment. This clinical sign must be addressed by clinical staff treating patients with RA. Also, further studies should be done to discover the hidden areas in this topic.
34343257 The JAK-STAT pathway: an emerging target for cardiovascular disease in rheumatoid arthriti 2021 Nov 7 Inflammation contributes centrally to cardiovascular diseases, and anti-inflammatory treatments can reduce cardiovascular events. The JAK-STAT pathway is an emerging target in inflammation, mainly in rheumatoid arthritis (RA) and chronic myeloproliferative neoplasms (MPNs), disorders that heighten cardiovascular risk. The aim of this study was to review the international literature on the relationship between dysregulation of the JAK-STAT pathway in RA/MPNs and cardiovascular risk and on the potential cardiovascular effects of JAK-STAT inhibitors. The JAK-STAT pathway sustains inflammatory and thrombotic events in autoimmune disorders such as RA and MPNs. Here, an imbalance exists between pro- and anti-inflammatory cytokines [increased levels of interleukin (IL)-6, IL-1-β, tumour necrosis factor-α, decreased levels of IL-10] and the over-expression of some prothrombotic proteins, such as protein kinase Cε, on the surface of activated platelets. This pathway also operates in atherosclerotic cardiovascular disease. JAK-STAT inhibitors may reduce cardiovascular events and related deaths in such conditions, but the potential of these agents requires more studies, especially with regard to cardiovascular safety, and particularly for potential prothrombotic effects. JAK-STAT inhibitors merit consideration to curb heightened cardiovascular risk in patients with RA and MPNs, with rigorous assessment of the potential benefits and risks.
33037539 Cervical spine manifestations of rheumatoid arthritis: a review. 2021 Aug Rheumatoid arthritis (RA) is a progressive autoimmune inflammatory disease affecting 1% of the population with three times as many women as men. As many as 86% of patients suffering from RA have cervical spine involvement. Synovial inflammation in the cervical spine causes instability and injuries including atlantoaxial subluxation, retroodontoid pannus formation, cranial settling, and subaxial subluxation. While many patients with cervical spine involvement are asymptomatic, symptomatic patients often present with nonspecific symptoms resulting from inflammation and additional secondary symptoms that are due to compression of the brainstem, cranial nerves, vertebral artery, and spinal cord. Radiographs are the imaging modality used most often, while MRI and CT are used for assessment of neural element involvement and surgical planning. Multiple classification systems exist. Early diagnosis and treatment of cervical spine involvement is critical. Surgical management is indicated when patients experience symptoms from cervical involvement that result in biomechanical instability and, or a neurological deficit. Atlantoaxial instability managed with atlantoaxial fusion, retroodontoid pannus with neural element compression is managed with posterior decompression and atlantoaxial fusion or occipitocervical fusion. Cranial settling is managed can be managed with anterior decompression and posterior fusion or with dorsal only approaches. Subaxial subluxation is managed with circumferential fusion or posterior only decompression and fusion. Patients with atlantoaxial instability have better functional and neurologic outcomes. RA patients have higher complication rates and more frequent need for revision surgery than the general population of spine surgery patients.
33529910 Fibroblast-like synoviocytes in rheumatoid arthritis: Surface markers and phenotypes. 2021 Apr Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly affects synovial joints. During the course of RA, the synovium transforms into hyperplastic invasive tissue, leading to cartilage and bone destruction. Fibroblast-like synoviocytes (FLS) in the synovial lining develop aggressive phenotypes and produce pathogenic mediators that lead to the occurrence and progression of disease, playing a major role in RA pathophysiology. Therefore, research on FLS has become the main focus within the RA field. With technical advances and the development of multi-omics comprehensive analysis approaches, it has become possible to identify different FLS subsets via high-throughput sequencing and investigate differences between FLS phenotypes, allowing for the detailed study of RA pathogenesis. This review summarizes recent works on FLS subtypes and the surface marker proteins identified for different subtypes, providing a theoretical basis and reference for future studies on FLS in RA. The current work also addresses the clinical potential of FLS surface markers in RA based on related research from other fields.
33060323 The Prevalence of Rheumatoid Arthritis: A Systematic Review of Population-based Studies. 2021 May OBJECTIVE: To estimate the prevalence of rheumatoid arthritis (RA) from international population-based studies and investigate the influence of prevalence definition, data sources, classification criteria, and geographical area on RA prevalence. METHODS: A search of ProQuest, MEDLINE, Web of Science, and EMBASE was undertaken to identify population-based studies investigating RA prevalence between 1980 and 2019. Studies were reviewed using the Joanna Briggs Institute approach for the systematic review and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Sixty studies met the inclusion criteria. There was a wide range of point prevalence reported (0.00-2.70%) with a mean of 0.56% (SD 0.51) between 1986 and 2014, and a mean period prevalence of 0.51% (SD 0.35) between 1955 and 2015. RA point and period prevalence was higher in urban settings (0.69% vs 0.48%) than in rural settings (0.54% vs 0.25%). An RA diagnosis validated by rheumatologists yielded the highest period prevalence of RA and was observed in linked databases (0.80%, SD 0.1). CONCLUSION: The literature reports a wide range of point and period prevalence based on population and method of data collection, but average point and period prevalence of RA were 51 in 10,000 and 56 in 10,000, respectively. Higher urban vs rural prevalence may be biased due to poor case findings in areas with less healthcare or differences in risk environment. The population database studies were more consistent than sampling studies, and linked databases in different continents appeared to provide a consistent estimate of RA period prevalence, confirming the high value of rheumatologist diagnosis as classification criteria.
33070253 RANKL as a therapeutic target of rheumatoid arthritis. 2021 Jan Rheumatoid arthritis (RA) is an inflammatory disorder characterized by progressive joint destruction. Recent studies have demonstrated that osteoclasts are responsible for bone destruction in RA. Receptor activator of nuclear factor kappa B ligand (RANKL), an osteoclast differentiation factor, belongs to the tumor necrosis factor superfamily and plays a critical role in osteoclast differentiation. RANKL is highly expressed in the synovial tissues in patients with RA and is involved in osteoclast development and thus bone destruction in RA. Denosumab, a specific antibody to human RANKL, efficiently suppressed the progression of bone destruction in patients with RA in a randomized controlled study and is considered a putative therapeutic option for RA.
33677948 Efficacy of gluten-free diet in patients with rheumatoid arthritis. 2021 Jan 18 Recent research has increasingly shown that depending on the foods we eat, gut flora may be affected by an inflammatory or anti-inflammatory response, thus playing an important role in inflammatory autoimmune diseases, such as rheumatoid arthritis or gastroenterological disorders. Gluten seems to be a glycoprotein with a clinically relevant inflammatory effect. Several observational studies and anecdotal cases reported a correlation between gluten and various diseases, including autoimmune diseases, such as rheumatoid arthritis. This study aimed to evaluate whether gluten-free diet could be effective in controlling inflammation and ongoing rheumatoid arthritis symptoms. We report 4 cases of patients with long-standing rheumatoid arthritis with no response to several conventional and biotechnological drugs, treated with a gluten-free diet concurrently with the drug therapy. Our patients presented different degrees of response to the diet, in terms of disease remission and improvement of symptoms. Our cases confirm that a gluten-free diet may improve symptoms of rheumatoid arthritis, even in patients resistant to conventional drug therapies.
33609791 Risk factors for hypertension in rheumatoid arthritis patients-A systematic review. 2021 Apr INTRODUCTION: Rheumatoid arthritis is frequently associated with hypertension, which has been shown to increase the risk of cardiovascular disease in these patients. The aim of this systematic review was to explore demographic, behavioural or clinical factors including medication use, associated with incident hypertension in rheumatoid arthritis. METHODS: MEDLINE and Scopus were searched for eligible studies that longitudinally investigated incident hypertension or changes in blood pressure (BP) in rheumatoid arthritis patients. Publications were screened by two reviewers according to predetermined inclusion and exclusion criteria. The quality of included studies was assessed via the Newcastle Ottawa Scale and Cochrane Risk of Bias Tool. RESULTS: Fourteen studies were deemed eligible and included in this review. The proportion of female subjects ranged from 12 to 87% and the mean age ranged from 47 to 61 years. Regular exercise was associated with a decrease in systolic BP, p = 0.021. Methotrexate was associated with decreased risk of hypertension in two studies. LEF was associated with increased BP in two studies. COX-2 inhibitors were associated with systolic BP and diastolic BP variability (p = 0.009, 0.039, respectively) in one study. Prednisone was found to increase BP and risk of hypertension in three studies. The risk of hypertension in patients taking biologic disease modifying anti-rheumatic drugs (DMARDs) is unclear as some studies report increased BP while others report no difference for biologic compared to conventional DMARDs. CONCLUSION: Despite limited longitudinal studies exploring this topic, methotrexate and exercise were shown to protect against risk of hypertension in RA patients, while prednisone and COX-2 inhibitors may increase risk of hypertension.