Treatment Options For Rheumatoid Arthritis Research Articles

Novel RP-HPLC method for estimation of a newly developed combination of tizanidine and etoricoxib in rat plasma: Eight criteria for greens evaluation.

A novel environmentally friendly reversed-phase high-performance liquid chromatography (RP-HPLC) method has been effectively validated for simultaneously measuring a prospective conjunction of tizanidine (TIZ) and etoricoxib (ETC), the combined medicine, in rat plasma. The technique employs diclofenac potassium as the internal standard, guaranteeing dependable and precise outcomes. This study aimed to assess the impact of the suggested combination therapy on treating inflammation resulting from rheumatoid arthritis (RA) in a rat model. The procedure was performed using an Agilent series 1200 model HPLC apparatus. The chromatographic conditions consist of isocratic elution mode, C18 column with dimensions of 150 mm × 4.6 mm × 5 µm, flow rate of 1.5 mL/min, wavelength of 230 nm, temperature of 50°C, and injection volume of 10 µL. The elution was performed using a mobile phase consisting of a phosphate buffer with a pH of 3.5 and acetonitrile in a ratio of 80:20 v/v. Calibration curves were conducted for TIZ and ETC within the 1-50 µg/mL range, demonstrating linear trends with R2 values over 0.999. The effectiveness and eco-friendliness of the proposed method were evaluated using eight separate environmentally conscious metrics. The addition of TIZ and ETC to arthritic rodents amplified these effects significantly. Furthermore, TIZ and ETC significantly reduced serum levels in arthritic rodents, and safety investigations revealed normal complete blood count, liver, and renal functions. TIZ and ETC appear to have antiarthritic, anti-inflammatory, and safe combinations, making them viable future treatment options for RA that are also safe and efficacious. Following validation by United States Food and Drug Administration(US-FDA) rules, all goods met the criteria.

The Role of Semaphorins in the Pathogenesis of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Inflammation of the synovial fluid propagates the pathological process of angiogenesis. Semaphorins play a crucial role in the context of endothelial cell function, and their pleiotropic nature has various effects on the further development of RA. This narrative review summarises the various roles of semaphorins in the pathology of RA and whether they could play a role in developing novel RA treatment options.

A Review of Proposed Mechanisms in Rheumatoid Arthritis and Therapeutic Strategies for the Disease.

Rheumatoid arthritis (RA) is characterized by synovial edema, inflammation, bone and cartilage loss, and joint degradation. Patients experience swelling, stiffness, pain, limited joint movement, and decreased mobility as the condition worsens. RA treatment regimens often come with various side effects, including an increased risk of developing cancer and organ failure, potentially leading to mortality. However, researchers have proposed mechanistic hypotheses to explain the underlying causes of synovitis and joint damage in RA patients. This review article focuses on the role of synoviocytes and synoviocytes resembling fibroblasts in the RA synovium. Additionally, it explores the involvement of epigenetic regulatory systems, such as microRNA pathways, silent information regulator 1 (SIRT1), Peroxisome proliferatoractivated receptor-gamma coactivator (PGC1-α), and protein phosphatase 1A (PPM1A)/high mobility group box 1 (HMGB1) regulators. These mechanisms are believed to modulate the function of receptors, cytokines, and growth factors associated with RA. The review article includes data from preclinical and clinical trials that provide insights into potential treatment options for RA.

Isoliquiritigenin inhibits apoptosis and ameliorates oxidative stress in rheumatoid arthritis chondrocytes through the Nrf2/HO-1-mediated pathway

Rheumatoid arthritis (RA) is a chronic inflammatory condition known for its irreversible destructive impact on the joints. Chondrocytes play a pivotal role in the production and maintenance of the cartilage matrix. However, the presence of inflammatory cytokines can hinder chondrocyte proliferation and promote apoptosis. Isoliquiritigenin (ISL), a flavonoid, potentially exerts protective effects against various inflammatory diseases. However, its specific role in regulating the nuclear factor E2-associated factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in chondrocytes in RA remains unclear. To investigate this, this study used human chondrocytes and Sprague-Dawley rats to construct in vitro and in vivo RA models, respectively. The study findings reveal that cytokines markedly induced oxidative stress, the activation of matrix metalloproteinases, and apoptosis both in vitro and in vivo. Notably, ISL treatment significantly mitigated these effects. Moreover, Nrf2 or HO-1 inhibitors reversed the protective effects of ISL, attenuated the expression of Nrf2/HO-1 and peroxisome proliferator-activated receptor gamma-coactivator-1α, and promoted chondrocyte apoptosis. This finding indicates that ISL primarily targets the Nrf2/HO-1 pathway in RA chondrocytes. Moreover, ISL treatment led to improved behavior scores, reduced paw thickness, and mitigated joint damage as well as ameliorated oxidative stress in skeletal muscles in an RA rat model. In conclusion, this study highlights the pivotal role of the Nrf2/HO-1 pathway in the protective effects of ISL and demonstrates the potential of ISL as a treatment option for RA.

Challenges and insights in managing difficult-to-treat rheumatoid arthritis: real-world clinical perspectives.

The treatment options for rheumatoid arthritis (RA) have expanded with the availability of biological and targeted synthetic disease-modifying anti-rheumatic drugs. Despite all these developments and treatments, an important group of patients remain symptomatic and have not achieved clinical remission. The terminology "difficult-to-treat" (D2T) has been developed to describe this group. This study aimed to determine the frequency of D2T RA among our patients according to the EULAR 2021 definition of D2T RA and to identify the differences in demographic and disease characteristics, contributing factors, and disease burden. The study included 302 consecutive patients diagnosed with RA according to the 2010 ACR criteria. These patients were categorised into the D2T and non-D2T RA groups. Risk factors independently associated with D2T RA were identified using logistic regression analysis. Of the 302 patients (mean age, 56.5 years, 80.1% female, 75% seropositive), 27 (8.9%) had D2T RA. Those with D2T RA had a lower age at diagnosis and longer disease duration and showed significantly higher rates of peripheral erosion, Sjögren's syndrome, extra-articular manifestations, and PtGA-PhGA discordance, together with high disease activity scores. Furthermore, the median number of comorbidities and concomitant fibromyalgia was significantly higher in the D2T RA group. In the multiple regression analysis, D2T RA was independently associated with higher HAQ-DI, RF levels, and concomitant fibromyalgia. D2T RA requires more intensive management, and patients with D2T RA have higher disease activity, poorer functional status, and quality of life than those without D2T RA.

The newly engineered monoclonal antibody ON104, targeting the oxidized Macrophage Migration Inhibitory Factor (oxMIF), ameliorates clinical and histopathological signs of collagen-induced arthritis

Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic inflammatory cytokine that emerged as a pivotal regulator in the pathogenesis of several autoimmune diseases including rheumatoid arthritis (RA). MIF occurs in two immunologically distinct conformational isoforms, indicated as reduced (redMIF) and oxidized MIF (oxMIF) where the latter exerts disease-related activities. In this study we demonstrate the presence of circulating oxMIF in RA patients and investigate the in vivo effects of an oxMIF-neutralizing antibody in a murine model of RA.By advanced antibody engineering we generated the fully human anti-oxMIF antibody ON104 with abolished effector functions. The therapeutic potential of ON104 was tested in a model of Collagen-Induced Arthritis (CIA) in DBA/1j mice. At disease onset, the mice received ON104 twice a week for three weeks. Clinical symptoms were assessed daily, and histological examinations of the joints were performed at the end of the study.Antibody ON104, specifically targeting human and murine oxMIF, is highly affine and does not elicit effector functions in vitro. The treatment of CIA mice with ON104 profoundly modulated disease progression with marked amelioration of clinical signs of arthritis that was associated with reduced synovial and cartilage damage and reduced F4/80-positive macrophages in the joints.These data prove that oxMIF is a relevant target in a well-known model of human RA and its specific neutralization by the antibody ON104 ameliorates clinical and histological signs of the disease in the so-treated mice. Thus, ON104 represents a new and promising treatment option for RA and possibly other autoimmune diseases.

In silico screening of a series of 1,6-disubstituted 1H-pyrazolo[3,4-d]pyrimidines as potential selective inhibitors of the Janus kinase 3

Rheumatoid arthritis is a common chronic disabling inflammatory disease that is characterized by inflammation of the synovial membrane and leads to discomfort. In the current study, twenty-seven 1,6-disubstituted 1H-pyrazolo[3,4-d]pyrimidines were tested as potential selective inhibitors of the tyrosine-protein kinase JAK3 using a number of molecular modeling methods. The activity of the screened derivatives was statistically quantified using multiple linear regression and artificial neural networks. To assess the quality, robustness, and predictability of the generated models, the leave-one-out cross-validation method was applied with favorable results (Q2 = 0.75) and Y-randomization. In addition, the evaluation of the predictive ability of the established model was confirmed by means of an external validation using a composite test set and an applicability domain approach. The covalent docking indicated that the tested 1H-pyrazolo[3,4-d]pyrimidines containing the acrylic aldehyde moiety had irreversible interaction with the residue Cys909 in the active sites of the tyrosine-protein kinase JAK3 by Michael addition. The molecular dynamics for three selected derivatives (compounds 9, 12, and 18) were used to verify the covalent docking by determining the stability of hydrogen bonding interactions with active sites, which are needed to stop tyrosine-protein kinase JAK3. The results obtained showed that the tested compounds containing acrylic aldehyde moiety had favorable binding free energies, indicating a strong affinity for the JAK3 enzyme. Overall, this current study suggests that the tested compounds containing the acrylic aldehyde moiety have the potential to act as anti-JAK3 inhibitors. They could be explored further to be used as treatment options for rheumatoid arthritis. Communicated by Ramaswamy H. Sarma.

Impact of upadacitinib on the risk of digestive events in patients with rheumatoid arthritis: A systematic review and meta-analysis of randomized controlled trials

BackgroundUpadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, is an effective treatment option for rheumatoid arthritis (RA), but its use has been associated with an increased risk of digestive events. This systematic review aimed to investigate the risk of digestive events in RA patients treated with UPA. MethodsSystematic searches of electronic databases (PubMed, Cochrane Library, and EMBASE) from inception to September 2022 were conducted to locate randomized controlled trials (RCTs) that compared UPA with control treatment and reported digestive events in RA patients. We pooled data using the random-effects model and meta-analysis was conducted by Stata software. ResultsTen RCTs met the inclusion criteria and were analyzed, with a total of 6103 patients. Compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), pooled analysis of 8 trials revealed no statistical difference in hepatic disorder (HD) risk and gastrointestinal (GI) perforation (GIP) risk ((OR = 1.16, 95% CI 0.86 to 1.56, I2 = 0.00%); OR = 4.49, 95% CI 0.56 to 35.93, I2 = 0.00%)). When we considered the influence of UPA on the grade of liver enzymes, the data indicated that grade 3 and 4 elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were infrequent. Additionally, a dose-dependent impact of UPA on the risks of HD was not observed. The results suggested no interaction by dose of drug, or indication for treatment of GIP risk. ConclusionOur results showed that RA patients receiving UPA compared with csDMARDs had no significant increased risk associated with digestive events. Further long-term research of emerging data is urgently needed to gain a better understanding of the association between UPA and digestive events in the RA population.

A bioinformatics system for exploring potential targets and therapies in rheumatoid arthritis

Rheumatoid arthritis (RA), one of the most common chronic inflammatory diseases, is an autoimmune disease that causes cartilage, bone damage, and disability. RA has become a concern, affecting more than 1.5% of the global population. Immunomodulatory or anti-inflammatory targets are the lead candidates in existing clinical trials to develop RA drugs. These targets were reported to be ineffective in reducing symptoms, slowing disease progression, and causing adverse side effects. Therefore, this study focuses on addressing the continuing need for safer, more selective, and more effective treatment options for RA by identifying novel targets and therapeutic approaches. The study involves six important steps: retrieving a dataset from the Gene Expression Omnibus (GEO) database, file conversion, gene differentiation (up-regulated and downregulated), Entrez gene ID retrieval for Search Tool for the Retrieval of Interacting Genes (STRING), protein–protein interaction (PPI) network delineation via STRING, drugs identification via Drug Bank, and relationship establishment between networks and drugs via The Drug–Gene​ Interaction Database (DGIdb). Nine protein hubs, three up-regulated and six down-regulated were identified as interacting with 8 and 18 drugs, respectively. Seven protein sites have never been directly associated with RA and could serve as potential therapeutic targets. Eleven drugs were shown to interact with these seven selected protein hubs as potential therapeutics for RA. These new targets and therapies will help researchers improve the RA treatment pipeline by adding these into the pipeline and bringing successful treatment options for RA patients.

Hydrogel Encapsulation of Genome-Engineered Stem Cells for Long-Term Self-Regulating Anti-Cytokine Therapy.

Biologic therapies have revolutionized treatment options for rheumatoid arthritis (RA) but their continuous administration at high doses may lead to adverse events. Thus, the development of improved drug delivery systems that can sense and respond commensurately to disease flares represents an unmet medical need. Toward this end, we generated induced pluripotent stem cells (iPSCs) that express interleukin-1 receptor antagonist (IL-1Ra, an inhibitor of IL-1) in a feedback-controlled manner driven by the macrophage chemoattractant protein-1 (Ccl2) promoter. Cells were seeded in agarose hydrogel constructs made from 3D printed molds that can be injected subcutaneously via a blunt needle, thus simplifying implantation of the constructs, and the translational potential. We demonstrated that the subcutaneously injected agarose hydrogels containing genome-edited Ccl2-IL1Ra iPSCs showed significant therapeutic efficacy in the K/BxN model of inflammatory arthritis, with nearly complete abolishment of disease severity in the front paws. These implants also exhibited improved implant longevity as compared to the previous studies using 3D woven scaffolds, which require surgical implantation. This minimally invasive cell-based drug delivery strategy may be adapted for the treatment of other autoimmune or chronic diseases, potentially accelerating translation to the clinic.

The Pet-Pain Study: How Caring for a Dog Affects Quality of Life, Pain, and Depression in Patients With Inflammatory Arthritis.

Treatment options for rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) have improved with the introduction of biologic and targeted synthetic disease-modifying antirheumatic drugs. Although a good clinical response and even remission can be achieved in most cases, a low quality of life (QOL), depression, and chronic pain often persist and lead to an increased disease burden.

Folate receptor-mediated targeted therapy for rheumatoid arthritis by methotrexate-phospholipid complex nano-emulsions

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease. Activated macrophages in arthritic joints play a prominent role in the initiation and persistence of RA. Despite great progress in the clinical treatment of RA, poor response and high discontinuation due to systemic toxicity remain unsolved issues, especially the well-known methotrexate (MTX). Therefore, active targeted delivery of therapeutic drugs to pathogenic cells in arthritic joints is essential to increase in situ activity and decrease systemic toxicity. Here, we developed an MTX-loaded macrophage-targeted nano-emulsion (NE) based on the overexpression of folate receptor (FR) on activated macrophages, the inherent high affinity of FR for folate (FA), as well as the property of MTX and phospholipids to form complexes (MTX@PC). Intravenous injection of DID-labelled MTX@PC-FA NEs into adjuvant-induced arthritis (AIA) mice, in vivo images and flow cytometry results revealed that the NEs were highly targeted to inflamed joints and macrophages, respectively. Therapeutic studies suggested that this strategy was conducive to achieve high efficacy and low toxicity of MTX in the treatment of RA. Our research highlights MTX@PC-FA NEs as a potential treatment option for RA targeting the FR-expressed activated macrophages.

Preparation and physical characterization of Methotrexate encapsulated poly (n-methyl glycine) microspheres for the Rheumatoid arthritis treatment option

AimsThis research aimed to prepare and physically characterize methotrexate-encapsulated poly (n-methyl glycine) microspheres as a treatment option for rheumatoid arthritis. BackgroundRheumatoid arthritis is an autoimmune disease that leads to cartilage destruction, synovial joint inflammation, and bacterial joint/bone infections. Methotrexate (MTX), commonly used in rheumatoid arthritis (RA), has severe adverse effects. Therefore, a reliable drug delivery system is required to control the release of Methotrexate during the treatment of Rheumatoid arthritis. ObjectiveThe primary goal of this study was to develop and characterise methotrexate-loaded polysarcosine microspheres (MTX-PSar Microspheres), as well as to examine their physical characteristics, pharmacodynamics, and anti-rheumatic study effects. MethodMethotrexate (MTX) loaded Polysarcosine (PSar) Microsphere was developed using Mannitol, Magnesium hydroxide, Dichloromethane, Aqueous polyvinyl alcohol and Chitosan hydrochloride. The MTX-PSar Microsphere was developed by w/o/w multiple emulsions method in the current study to reduce inflammation and disease progression/joint stiffness caused by Rheumatoid Arthritis. FTIR, HPLC, XRD, DSC, and SEM were used to evaluate the physical properties of MTX-PSar Microspheres. ResultThe physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and X-Ray Diffraction have shown that drug encapsulated in the microparticles and lost its crystalline nature. The particle size, entrapment efficacy, reported in the range of 10–20 µm, 86.37 ± 0.65 %. Even after one month, the microsphere’s particle size maintained its spherical shape In-vitro drug release, pharmacodynamics study shows good anti-rheumatic study effects. ConclusionThe MTX-PSar Microsphere is a good option for treating RA despite the lack of in vivo action. OtherIt is hoped that in future studies, Methotrexate-loaded polysarcosine microspheres (MTX-PSar Microsphere) will be used to conjugate ligands, and hence active targeting in rheumatoid arthritis would be possible.

Rituximab, a Safer Option for Rheumatoid Arthritis: A Comparison of the Reported Adverse Events of Approved Monoclonal Antibodies

Monoclonal antibodies (mAbs), which are commonly used to treat rheumatoid arthritis (RA), have been linked to a variety of adverse events (AEs). The objective of the study was to compare the safety profiles of six FDA approved mAbs (sarilumab, tocilizumab, adalimumab, golimumab, infliximab, and rituximab) marketed for the treatment of RA. A systematic review of the literature was conducted using the databases PubMed, Cochrane Library, and Science Direct. The manuscript comprised a total of 23 clinical studies. The percentage of patients who had AEs was calculated and presented using box-whisker and forest plots. Infections and infestations were found to be the most common AEs in RA patients treated with mAbs. Raised alanine aminotransferase (ALT), aspartate aminotransferase (AST), upper respiratory tract infection (URTI), and nasopharyngitis were frequently reported. The most common AEs were reported with adalimumab. The highest percentage of patients reporting AEs was associated with golimumab (52%), while rituximab had the fewest AEs (4.9%). In conclusion, rituximab appears to be a safer treatment option for RA as it is found to be associated with a lower risk of AEs, particularly respiratory infections.

The economic burden of biologic disease-modifying antirheumatic drugs in rheumatoid arthritis patients in the United States

Background Previous U.S. economic burden estimates for rheumatoid arthritis (RA) varied from $85.6 to 148.1 billion annually. However, these estimates do not reflect comparative amounts spent on RA treatment options in addition to other medical expenditures. Therefore, this study’s goal was to comparatively analyze the overall economic burden of U.S. patients treated for RA using conventional disease-modifying antirheumatic drugs (DMARDs) versus TNF alpha biologic DMARDs. Research Design and Methods This retrospective observational study analyzed Medical Expenditure Panel Survey Household Component data from 2016 to 2018. Healthcare utilization, total medical expenditures, and out-of-pocket expenditures were compared between RA medication groups. Results Three hundred twenty-five adult RA patients experiencing 603 RA-related events, including at least one medical visit, between 2016 and 2018 were identified. Rheumatic arthritis-attributable medical expenditures among patients prescribed DMARDs were $11.4 billion. Average total medical expenditures were significantly higher for the TNF alpha biologic group $26,216.67 (95% CI: $19,502.84–$32,930.5) versus $5,388.52 (95% CI: $2,768.25–$8,008.79) for the conventional DMARD group (p<0.001). Conclusions RA patients receiving TNF alpha biologics experienced significantly higher total medical and out-of-pocket expenditures; however, they have experienced fewer or no occurrences of high-cost drivers of healthcare utilization compared to patients receiving conventional DMARDs.

Bone-Targeted Delivery of Novokinin as an Alternative Treatment Option for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune inflammatory bone destructive disorder that is orchestrated by multiple systems in the body, including Renin-Angiotensin System (RAS) and arachidonic acid (ArA) pathway. Current therapeutic options are not highly effective and are associated with severe side effects, including cardiovascular complications. Therefore, new safe and effective disease modulators are seriously needed. In this study, we investigate the anti-inflammatory effects of a synthetic peptide, novokinin, through Angiotensin Type (II) receptor (AT2R). Peptide drugs like novokinin suffer from plasma instability and short half-life. Thus, we developed a novel bone targeting novokinin conjugate (Novo Conj). It uses the bone as a reservoir for sustained release and protection from systemic degradation, improving stability and enhancing pharmacological efficacy. We tested Novo Conj’s anti-inflammatory effects in adjuvant-induced arthritis (AIA) rat model to prove our hypothesis by measuring various RAS and ArA pathway components. We observed that inflammation causes a significant imbalance in cardioprotective RAS components like ACE2, AT2R, and Ang 1-7 and increases the ArA inflammatory metabolites like hydroxyeicosatetraenoic acids (HETEs). Treatment with novokinin or Novo Conj restores balance in the RAS and favors the production of different epoxyeicosatrienoic acids (EETs), which are anti-inflammatory mediators. This study demonstrated that the bone-targeted delivery improved the stability and enhanced the anti-inflammatory effects of the parent peptide novokinin in AIA. These observations offer an efficacious alternative therapy for managing RA.

Novel Treatment Option for Rheumatoid Arthritis through Bone‐Targeted Delivery of Novokinin

ObjectiveRheumatoid arthritis (RA) is an autoimmune inflammatory disorder affecting about 1‐2% of the world population. RA is known to be a major cause of disability which progresses eventually to systemic complexities with high chances of early morbidity. This complex dynamic situation of inflammation is orchestrated by multiple systems in the body, including the Renin‐Angiotensin System (RAS). Angiotensin II (Ang II), a main effector peptide in the RAS, predominantly binds to Angiotensin II Type (I) receptor (AT1R). When it overproduced can result in inflammation, vasoconstriction, and oxidative stress. Ang II also binds to Angiotensin II Type (II) receptor (AT2R), which provides functional antagonism to AT1R activation. Novokinin, a synthetic peptide, promotes beneficial effects through activation of AT2R, and can be considered a potential drug candidate for alternative therapy in RA if its plasma stability and half‐life could be improved. Here, we developed a novel bone‐targeting novokinin Conjugate (Novo Conj), which binds to the bone, utilizes it as a reservoir while protecting it from enzymatic and hydrolytic degradation. We hypothesized that this delivery approach would extend the peptide half‐life and provide sustained plasma levels to elicit anti‐inflammatory activity.MethodHealthy male, Sprague Dawley rats, were induced adjuvant arthritis (AA) by administering 0.2mL of 50mg/mL of Mycobacterium butyricum through the tail base injection. Arthritic rats were divided into three groups (n=5/group) and dosed with saline (Inflamed), novokinin of 400 µg/kg (Novokinin), or an equivalent dose of 400 µg/kg of novokinin (Novo Conj). A group of healthy rats (n=5) received saline and was taken as a healthy control (Control) group. After the emergence of arthritis (i.e., 10‐12 days after adjuvant arthritis induction), animals were dosed with assigned treatment every other day for two weeks. Animals were monitored three times a week for their body weight, paw, and joint diameters. At the end of the experiment, rats were euthanized, plasma/tissues were harvested and analyzed for plasma nitric oxide (NO) and the RAS components by western blot.ResultsThe induction of AA led to a significant reduction in percent body weight gain over time, increased paws and joints swelling, and elevated plasma NO levels. AA brought an imbalance in the RAS enzymatic inflammatory axis indicator, i.e., Angiotensin‐Converting Enzyme (ACE) and ACE2 causing a reduction in ACE2/ACE and AT2R/AT1R ratio. The treatment of arthritic rats by novokinin and Novo Conj restored their body weight gain, reduced paws and joints' swelling, lowered the plasma NO level, and reinstated the imbalanced ratios of enzymes and receptors. These observed anti‐inflammatory effects were significantly higher in the Novo Conj group.ConclusionThis result indicates that the novokinin and its bone‐targeted conjugate shows anti‐inflammatory effects through the RAS. The observed enhanced impacts could be attributed to improved stability and extension of the half‐life of novokinin through its conjugation and binding to the bone. Our novel bone‐targeting delivery of novokinin offers effective alternative therapy for managing RA signs and symptoms and could be further utilized for various RAS disorders.

P189 A longitudinal study of psychological predictors of response to adalimumab in patients with rheumatoid arthritis

Abstract Background/Aims The treatment of rheumatoid arthritis (RA) has improved since the introduction of targeted biological disease-modifying antirheumatic drugs (bDMARDs), such as adalimumab. However, no treatment options for RA are universally effective. Psychological factors may have an important role in treatment response. Published data reported that pre-treatment psychological variables such as an increased treatment necessity belief correlated with better adherence to adalimumab in RA patients. This current study aimed to investigate whether psychological factors correlate with change in 4V-DAS28-CRP as well as subcomponents of the score in adalimumab-treated RA patients. Methods Psychological, clinical and demographic data and DAS28 scores were collected pre-treatment, and at 3,6, and 12-months post-treatment, as part of a prospective national study, BRAGGSS. Sixteen pre-treatment clinical and psychological variables were tested for association with treatment response at 3 and 12 months. Multiple linear regression models were analysed and a Bonferroni corrected p-value of &amp;lt; 0.003 was applied at each interval to assess significance. Results Data was available for 501 patients at 3 months follow up. Pre-treatment Beliefs about Medicine Questionnaire (BMQ) scores with regards to treatment necessity (P = 0.001), and two domains of the Illness Perception Questionnaire (IPQ), which were treatment belief and treatment control (P = 0.0001), correlated with the change in DAS28 by 3 months (Table 1). At 12 months, data were available for 362 patients. The treatment belief domain of the pre-treatment Illness Perception Questionnaire correlated with the change in tender joint count (P = 0.001) (Table 1). At 12 months no other sub-components correlated with the psychological variables. Conclusion Pre-treatment scores with regards to Illness Perception and Beliefs about Medicine correlated with 4V-DAS28-CRP response at 3 months. Of the subcomponents of DAS28, the psychological variables showed the highest correlation with tender joint count; as the tender joint count receives the highest weighting in the 4 variable DAS28 score, this may confound the assessment of treatment response. It will be necessary to undertake further analyses to assess the predictive value of these potentially modifiable psychological variables identified, but to also understand factors contributing to these psychological scores, such as the role of severe disease itself on psychological beliefs. Disclosure N. Raza: None. N. Nair: None. D. Plant: None. K. Hyrich: None. A.W. Morgan: None. J. Isaacs: None. A.G. Wilson: None. A. Barton: None.

Postoperative outcomes after degenerative lumbar spine surgery in rheumatoid arthritis patients -a propensity score-matched analysis

BackgroundAlthough treatment options for rheumatoid arthritis (RA) have evolved significantly since the introduction of biologic agents, degenerative lumbar disease in RA patients remains a major challenge. Well-controlled comparisons between RA patients and their non-RA counterparts have not yet been reported. The objective of the present study was to compare postoperative outcomes of lumbar spine surgery between RA and non-RA patients by a retrospective propensity score-matched analysis.MethodsPatients who underwent primary posterior spine surgery for degenerative lumbar disease in our prospective multicenter study group between 2017 and 2020 were enrolled. Demographic data including age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, diabetes mellitus, smoking, steroid usage, number of spinal levels involved, and preoperative patient-reported outcome (PRO) scores (numerical rating scale [NRS] for back pain and leg pain, Short Form-12 physical component summary [PCS], EuroQOL 5-dimension [EQ-5D], and Oswestry Disability Index [ODI]) were used to calculate a propensity score for RA diagnosis. One-to-one matching was performed and 1-year postoperative outcomes were compared between groups.ResultsAmong the 4567 patients included, 90 had RA (2.0%). RA patients in our cohort were more likely to be female, with lower BMI, higher ASA grade and lower current smoking rate than non-RA patients. Preoperative NRS scores for leg pain, PCS, EQ-5D, and ODI were worse in RA patients. Propensity score matching generated 61 pairs of RA and non-RA patients who underwent posterior lumbar surgery. After background adjustment, RA patients reported worse postoperative PCS (28.4 vs. 37.2, p = 0.008) and EQ-5D (0.640 vs. 0.738, p = 0.03), although these differences were not significant between RA and non-RA patients not on steroids.ConclusionsRA patients showed worse postoperative quality of life outcomes after posterior surgery for degenerative lumbar disease, while steroid-independent RA cases showed equivalent outcomes to non-RA patients.

Rheumatoid Arthritis and JAK-STAT Inhibitors: Prospects of Topical Delivery

Abstract:Rheumatoid arthritis (RA) is the most common musculoskeletal disease in the world. The clinical prospects have increased tremendously since the advent of biological agents as therapy options. NSAIDs such as indomethacin, celecoxib, and etoricoxib are used often in the treatment of RA but off-target effects decreased their use. DMARDs such as methotrexate and etanercept were also effective in the treatment of RA, but tolerance to methotrexate developed in many cases. Janus kinase inhibitors (JAKi) have also gained popularity as a treatment option for rheumatoid arthritis. Tofacitinib is the foremost JAK inhibitor that is used to treat RA as an individual agent or in combination with other DMARDs. The most frequently used route of administration for JAKi is oral. Since oral formulations of JAK inhibitors have a number of health hazards, such as systemic toxicity and patient noncompliance, topical formulations of JAK inhibitors have emerged as a preferable alternative for administering JAK inhibitors. Tofacitinib delivered topically, seems to have the potential to eliminate or reduce the occurrences of negative effects when compared to tofacitinib taken orally. Given the scarcity of knowledge on the techniques for topical distribution of JAKi, more effort will be required to develop a stable topical formulation of JAKi to address the limitations of oral route. The current review looks at JAK inhibitors and the ways that have been used to generate topical formulations of them.