Drugs In Rheumatoid Arthritis Research Articles

Comparison of Liver Injury in Patients Taking Methotrexate and Leflunamide in Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints, leading to inflammation and potential joint damage. Methotrexate (MTX) and Leflunomide (LEF) are commonly used disease-modifying antirheumatic drugs (DMARDs) for RA, but their hepatotoxic effects require careful monitoring. Objective: This study aimed to compare the incidence of liver injury in RA patients treated with Methotrexate versus Leflunomide. Methods: This prospective study was conducted from January 2023 to June 2023 and included 80 RA patients aged 20 years or older, who reported to the Medicine Department at Combined Military Hospital (CMH) Lahore. Patients were divided into two groups: Group A received 20 mg/day Methotrexate (n=40), and Group B received 20 mg/day Leflunomide (n=40). Exclusion criteria included pregnant females, patients with hepatitis B or C, those with known allergies to Methotrexate or Leflunomide, and alcoholics. Baseline investigations, including liver enzyme levels (ALT/AST), were performed, and patients were monitored every three months. Hepatotoxicity was defined as an increase in ALT/AST levels to at least twice the upper limit of normal (ULN). Data were analyzed using SPSS version 25.0, with mean and standard deviation for quantitative data and frequency and percentage for qualitative data. The Chi-square test was used to compare variables, with p<0.05 considered statistically significant. Results: Out of 80 patients, 43 (53.75%) were female, and 37 (46.25%) were male. In Group A, 7 patients (17.5%) had elevated ALT/AST levels, while 6 patients (15%) in Group B exhibited elevated liver enzymes. The mean age was 52.4 ± 8.3 years in Group A and 50.6 ± 9.1 years in Group B. The mean BMI was 26.7 ± 3.5 kg/m² in Group A and 27.1 ± 3.8 kg/m² in Group B. No statistically significant difference in hepatotoxicity was observed between the two groups (p>0.05). Conclusion: Methotrexate and Leflunomide were equally effective in treating RA, with no significant difference in liver toxicity observed between the two groups. Both medications have comparable risks for hepatotoxicity, necessitating regular liver function monitoring during treatment.

Energy landscape analysis and time-series clustering analysis of patient state multistability related to rheumatoid arthritis drug treatment: The KURAMA cohort study.

Rheumatoid arthritis causes joint inflammation due to immune abnormalities, resulting in joint pain and swelling. In recent years, there have been considerable advancements in the treatment of this disease. However, only approximately 60% of patients achieve remission. Patients with multifactorial diseases shift between states from day to day. Patients may remain in a good or poor state with few or no transitions, or they may switch between states frequently. The visualization of time-dependent state transitions, based on the evaluation axis of stable/unstable states, may provide useful information for achieving rheumatoid arthritis treatment goals. Energy landscape analysis can be used to quantitatively determine the stability/instability of each state in terms of energy. Time-series clustering is another method used to classify transitions into different groups to identify potential patterns within a time-series dataset. The objective of this study was to utilize energy landscape analysis and time-series clustering to evaluate multidimensional time-series data in terms of multistability. We profiled each patient's state transitions during treatment using energy landscape analysis and time-series clustering. Energy landscape analysis divided state transitions into two patterns: "good stability leading to remission" and "poor stability leading to treatment dead-end." The number of patients whose disease status improved increased markedly until approximately 6 months after treatment initiation and then plateaued after 1 year. Time-series clustering grouped patients into three clusters: "toward good stability," "toward poor stability," and "unstable." Patients in the "unstable" cluster are considered to have clinical courses that are difficult to predict; therefore, these patients should be treated with more care. Early disease detection and treatment initiation are important. The evaluation of state multistability enables us to understand a patient's current state in the context of overall state transitions related to rheumatoid arthritis drug treatment and to predict future state transitions.

Towards Personalized Medicine in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, incurable, multisystem, inflammatory disease characterized by synovitis and extra-articular features. Although several advanced therapies targeting inflammatory mechanisms underlying the disease are available, no advanced therapy is universally effective. Therefore, a ceiling of treatment response is currently accepted where no advanced therapy is superior to another. The current challenge for medical research is the discovery and integration of predictive markers of drug response that can be used to personalize medicine so that the patient is started on "the right drug at the right time". This review article summarizes our current understanding of predicting response to anti-rheumatic drugs in RA, obstacles impeding the development of personalized medicine approaches and future research priorities to overcome these barriers.

QbD-guided phospholipid-tagged nanonized boswellic acid naturosomal delivery for effective rheumatoid arthritis treatment

Studies have reported the potential role of Boswellic acids (BAs), bioactive pentacyclic triterpenes from Boswellia serrata, in treating rheumatoid arthritis (RA). However, poor water solubility and limited oral absorption are restricting factors for its better therapeutic efficacy. Based on these assumptions, the current study set out to develop naturosomal delivery of BAs to boost their extremely low bioavailability, colloidal stability, and water solubility. Nanonized naturosomes were developed and subsequently analyzed to show their physicochemical and functional features employing the quality-by-design approach. The solubility analysis of Boswellic acid naturosomes (BSENs) revealed a 16 times improvement in aqueous solubility compared to BS extract (BSE). The zeta potential and dynamic light scattering findings of BSENs have demonstrated their colloidal stability with regulated nano-size particles. Additionally, compared to BSE (⁓31%), in-vitro dissolution experiments showed that >99% of pentacyclic triterpenes were released from BSENs. Studies on ex-vivo permeation showed that BSENs' permeation (>79%) significantly improved over BSE's (⁓20%). In-vivo efficacy studies using CFA-prompted arthritis in rodents showed a critical expansion in body wt and an undeniable reduction in paw thickness, paw volume, and TNF-α treated with BSEN compared to the arthritis control and BSE-treated group. These findings suggest that BSENs can help treat RA drugs by demonstrating their efficacy in further clinical research to validate the significant improvements.

P122 Secular trends in prescription of biologic and targeted synthetic disease-modifying anti-rheumatic drugs in rheumatoid arthritis: Experience from a UK regional centre (2016-2022)

Abstract Background/Aims In the past two decades, biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) have substantially transformed the treatment landscape for rheumatoid arthritis (RA). With the emergence of new molecules, the introduction of cost-effective biosimilars, and the impact of the COVID pandemic, the treatment preferences might have shifted over time. We aim to explore the evolving trends in the prescription of biologic and targeted synthetic DMARDs in RA patients whose disease was refractory to conventional DMARDs. Methods A biologic registry was set up sourcing data from pharmacy and departmental records. Data of RA patients who were commenced on biologics or targeted synthetic DMARDs between January 2016 and December 2022 are presented descriptively without formal statistical assessments. Line plots depict prescription trends over the years. Data visualization done using R studio (v 2023.06). Results We have 1504 out of the 2345 patients in our biologic registry with RA; 827 of these patients commenced the treatment in the 7-year study period. Over the years, biosimilars are increasingly being preferred as the first-line agents. If a biosimilar for a biologic drug was available, all prescriptions were for the biosimilar in 2022. There was a significant drop (43.7%) in biologic prescriptions during the pandemic in 2020 compared to the previous year. However, by the next year, prescriptions rebounded to 91% of their pre-pandemic levels. TNF inhibitors and Janus kinase (JAK) inhibitors were the most common treatments initiated. There was a steady increase in the prescription of JAK inhibitors since their introduction in 2017. During the pandemic, JAK inhibitors were the most preferred agents for RA. However, a decline in their prescriptions was noted in 2022, down 36% from the previous year, possibly due to emerging concerns about their cardiovascular safety. While there was reduction in prescription of all biologics during pandemic, anti B cell therapy had the steepest decline (74.1% reduction in 2020 compared to previous year). This may be due to the increased risk of SARS-CoV-2 infection and impaired response to the vaccine with Rituximab. This trend is gradually reversing. Rates of prescription of abatacept and anti-IL6 agents remained fairly stable across the seven years. Conclusion Significant fluctuations are evident in the trend of prescription of biologic and targeted synthetic DMARDs in patients with rheumatoid arthritis in a regional centre in UK. We conclude that availability of biosimilars, safety data on JAK inhibitors and impact of the COVID pandemic had influenced the prescription trends. Disclosure H. Muhammed: None. H. Osborn: None. K. Hughes: None. A. Yau: None. G. Hirsch: None. S. Raizada: None. T. Sheeran: None. S. Venkatachalam: None.

Visualization of polarity changes in endoplasmic reticulum (ER) autophagy and rheumatoid arthritis mice with near-infrared ER-targeted fluorescent probe

The crucial cellular activities for maintaining normal cell functions heavily rely on the polarity of the endoplasmic reticulum (ER). Understanding how the polarity shifts, particularly in the context of ER autophagy (ER-phagy), holds significant promise for advancing knowledge of disorders associated with ER stress. Herein, a polarity-sensitive fluorescent probe CDI was easily synthesized from the condensation reaction of coumarin and dicyanoisophorone. CDI was composed of coumarin as the electron-donating moiety (D), ethylene and phenyl ring as the π-conjugation bridge, and malononitrile as the electron-accepting moiety (A), forming a typical D-π-A molecular configuration that recognition in the near-infrared (NIR) region. The findings suggested that as the polarity increased, the fluorescence intensity of CDI decreased, and it was accompanied by a redshift of emission wavelength at the excitation wavelength of 524 nm, shifting from 641 nm to 721 nm. Significantly, CDI exhibited a notable ability to effectively target ER and enabled real-time monitoring of ER-phagy induced by starvation or drugs. Most importantly, alterations in polarity can be discerned through in vivo imaging in mice model of rheumatoid arthritis (RA). CDI has been proven effective in evaluating the therapeutic efficacy of drugs for RA. ER fluorescent probe CDI can be optically activated in lysosomes, providing a sensitive tool for studying ER-phagy in biology and diseases.

A Machine Learning Approach for Prediction of CDAI Remission with TNF Inhibitors: A Concept of Precision Medicine from the FIRST Registry.

This study aimed to develop low-cost models using machine learning approaches predicting the achievement of Clinical Disease Activity Index (CDAI) remission 6months after initiation of tumor necrosis factor inhibitors (TNFi) as primary biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatoid arthritis (RA). Data of patients with RA initiating TNFi as first b/tsDMARD after unsuccessful methotrexate treatment were collected from the FIRST registry (August 2003 to October 2022). Baseline characteristics and 6-month CDAI were collected. The analysis used various machine learning approaches including logistic regression with stepwise variable selection, decision tree, support vector machine, and lasso logistic regression (Lasso), with 48 factors accessible in routine clinical practice for the prediction model. Robustness was ensured by k-fold cross validation. Among the approaches tested, Lasso showed the advantages in predicting CDAI remission: with a mean area under the curve 0.704, sensitivity 61.7%, and specificity 69.9%. Predicted TNFi responders achieved CDAI remission at an average rate of 53.2%, while only 26.4% of predicted TNFi non-responders achieved remission. Encouragingly, the models generated relied solely on patient-reported outcomes and quantitative parameters, excluding subjective physician input. While external cohort validation is warranted for broader applicability, this study highlights the potential for a low-cost predictive model to predict CDAI remission following TNFi treatment. The approach of the study using only baseline data and 6-month CDAI measures, suggests the feasibility of establishing regional cohorts to generate low-cost models tailored to specific regions or institutions. This may facilitate the application of regional/in-house precision medicine strategies in RA management.

Microenvironmental Enzyme-Responsive Methotrexate Modified Quercetin Micelles for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients. Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed. The developed micelles had a particle size of (89.62 ±1.33) nm and a zeta potential of (-4.9 ±0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ±6.98) μmol/L was significantly lower than that of free Que (141.10 ±6.39) μmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats. The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.

Medical Ozone: A Redox Regulator with Selectivity for Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common arthritic diseases. Medical ozone has demonstrated its effectiveness in combination therapy with methotrexate or non-steroidal anti-inflammatory drugs for RA and OA, respectively. Although RA and OA have been compared from different points of view, few studies have considered their redox status in spite of the oxidative processes that are involved in both diseases. The aim of this study was to compare RA with OA, evaluating their redox status and the effects of ozone on their clinical response to combined therapy with ozone. The redox status of 80 patients was determined: antioxidant defenses, injury markers, two subjective variables (pain and disability), and levels of antibodies against cyclic citrullinated peptides were evaluated. Oxidative stress and clinical response to combined therapy with ozone was higher than in the case of RA. After medical ozone treatment, there was an increase in antioxidant defense and a decrease in injury markers as well as pain, disability, and autoantibody concentrations. Redox biomarkers were able to differentiate between both arthritic diseases and combined therapy with ozone (methotrexate + ozone), showing a therapeutic selectivity for RA in comparison with OA.

In-situ GSH-responsive gas nanogenerator for active NIR-II FL/PA imaging and synergistic restoration the macrophage niche in rheumatoid arthritis

Rheumatoid arthritis (RA) is currently one of the most common systemic autoimmune disorders, with no clinically effective theranostics. Therapeutic manipulation of the gasotransmitter hydrogen sulfide (H2S) has exhibited promising potential as an innovative strategy in RA, whereas limited with non-targeting, low solubility, and systemic toxicity. In this work, based on the physicochemical and structural advantages of stimulus-responsive nanotechnology, we develop multifunctional glutathione (GSH)-responsive H2S nanogenerators (BDMA NGs), achieving activatable precise second near-infrared fluorescence (NIR-II FL)/photoacoustic (PA) bimodal imaging-guided gas/chemotherapy synergistic therapy. Contributed to the suitable size and excellent biocompatibility, the BDMA NGs accumulate passively in the RA region and then feature a responsive deformation reaction with GSH to release functional small molecules: H2S and methotrexate (MTX). The H2S undergoes a mineralization process with Ag+ ions in situ, resulting in the rapid formation of Ag2S to “turn on” the NIR-II FL/PA signals. Remarkably, the effective generation of H2S downregulates hypoxia-inducible factor-1α (HIF-1α) and promotes nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, thereby restoring homeostasis in the RA microenvironment and facilitating the reprogramming of pro-inflammatory macrophages (M1) into anti-inflammatory phenotype (M2). Moreover, the controlled release of MTX, clinically approved drug for RA, synergistically promotes repolarization to further suppress local inflammation. Overall, the H2S-based nanogenerators BDMA NGs present a sophisticated and versatile strategy for implementing stimuli-responsive imaging and M1-to-M2 repolarization, demonstrating significant potential in the theranostics of RA and clinical transformation.

Use of Analgesic and Anti-Inflammatory Medicines before and after Initiation of Biological Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis

Background. Rheumatoid arthritis (RA) is an inflammatory condition that causes joint damage and is associated with pain. The biological disease-modifying antirheumatic drugs (bDMARDs) for RA are linked to additional therapeutic benefits as they suppress the inflammatory process, which in turn prevents joint erosion and reduces pain. Thus, the use of bDMARDs has the potential to reduce the need for other analgesic and anti-inflammatory therapies for RA. The aim of this study was to examine the analgesic and anti-inflammatory use around the initiation of bDMARDs. Methods. A cohort study was conducted using a 10% random sample of the population dispensing medicines under the Australian Pharmaceutical Benefits Scheme. People who initiated the first bDMARD for RA between 2014 and 2018 were included. The proportion who received any analgesic or anti-inflammatory, including nonsteroidal anti-inflammatory drugs, opioids, or glucocorticoids, in the twelve months prior to and post-bDMARD initiation was determined and compared using regression models. Results. There were 18,360 persons in the cohort, with a mean age of 55 years, and 69% were women. The use of any analgesic or anti-inflammatory in both tumor necrosis factor inhibitor (TNFi) and non-TNF initiators increased prior to initiation of bDMARD–from 43% to 52% in TNFi and from 52% to 63% in non-TNF initiators. In both groups, overall use decreased significantly post initiation to 37% and 42% in TNFi and non-TNF initiators, respectively (p<0.0001). bDMARD initiation was associated with lower use of glucocorticoid therapy, but there was no decreasing effect on opioid use. Conclusion. While the use of any analgesic or anti-inflammatories decreased post-initiation of bDMARDs for RA, more than one-third of people were dispensed analgesic or anti-inflammatory agents twelve months post initiation. Ongoing review of the need for analgesic and glucocorticoids appears warranted, with assessment of nonpharmacological approaches to support pain management.

The impact of autoantibodies on the efficacy of biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis: meta-analysis of randomized controlled trials.

To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies. Previous systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF + vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses. Data from 28 eligible RCTs were analyzed, pooling 23 studies in three subgroups: 6 including csDMARD-naïve patients, 14 csDMARD-IR, and 3 TNFi-IR patients. In csDMARD-naïve and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88-1.18) and 1.09 (0.90-1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on 3 trials, the 6-month ACR20 RRR was 2.28 (1.31-3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs. The effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used.

Co-stimulatory pathway competitive assay development using Liquid chromatography–tandem mass spectrometry (LC-MS/MS)

T-cells play a significant role in the development of autoimmune diseases. The CD28-B7 costimulatory pathway is crucial for activating T-cells, and blocking this pathway is essential for treating autoimmune diseases. Therapeutic antibodies and fusion proteins that target costimulatory molecules like CD80, CD86, CTLA-4, and CD28 have been developed to explore the costimulation process and as targeted treatments. To advance our understanding of costimulation in autoimmunity and the inhibition of the costimulatory pathway, it is crucial to have an accurate, precise, and direct method for detecting and quantifying the soluble form of these molecules in body fluids and various biological systems. Herein, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying the four costimulatory proteins depending on the signature peptides derived from the soluble isoform of these proteins in multiple reaction monitoring (MRM) mode. The method was validated using the US FDA guidelines. The LOQ was determined as ∼0.5 nM for the four analytes, with quantification extended to 20 nM with a correlation coefficient of R2>0.998. The developed MRM method was used to analyze on-bead digested protein mixtures to establish a competitive assay for the CD28-B7 costimulatory pathway using CTLA4-Ig (Abatacept ™) as an FDA-approved drug for rheumatoid arthritis. The IC50 was determined to be 2.99 and 159.8 nM for sCD80 and sCD86, respectively. A straightforward MRM-based competitive assay will advance the knowledge about the costimulatory role in autoimmunity and the autoimmune therapeutic drug discovery, with the need for broad application on different in vitro and in vivo models to discover new targeted inhibitors.

Potential mechanisms and drug prediction of Rheumatoid Arthritis and primary Sjögren's Syndrome: A public databases-based study.

Rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) are the most common systemic autoimmune diseases, and they are increasingly being recognized as occurring in the same patient population. These two diseases share several clinical features and laboratory parameters, but the exact mechanism of their co-pathogenesis remains unclear. The intention of this study was to investigate the common molecular mechanisms involved in RA and pSS using integrated bioinformatic analysis. RNA-seq data for RA and pSS were picked up from the Gene Expression Omnibus (GEO) database. Co-expression genes linked with RA and pSS were recognized using weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. Then, we screened two public disease-gene interaction databases (GeneCards and Comparative Toxicogenomics Database) for common targets associated with RA and pSS. The DGIdb database was used to predict therapeutic drugs for RA and pSS. The Human microRNA Disease Database (HMDD) was used to screen out the common microRNAs associated with RA and pSS. Finally, a common miRNA-gene network was created using Cytoscape. Four hub genes (CXCL10, GZMA, ITGA4, and PSMB9) were obtained from the intersection of common genes from WGCNA, differential gene analysis and public databases. Twenty-four drugs corresponding to hub gene targets were predicted in the DGIdb database. Among the 24 drugs, five drugs had already been reported for the treatment of RA and pSS. Other drugs, such as bortezomib, carfilzomib, oprozomib, cyclosporine and zidovudine, may be ideal drugs for the future treatment of RA patients with pSS. According to the miRNA-gene network, hsa-mir-21 may play a significant role in the mechanisms shared by RA and pSS. In conclusion, we identified commom targets as potential biomarkers in RA and pSS from publicly available databases and predicted potential drugs based on the targets. A new understanding of the molecular mechanisms associated with RA and pSS is provided according to the miRNA-gene network.

Identification of Hub Genes and Prediction of Targeted Drugs for Rheumatoid Arthritis and Idiopathic Pulmonary Fibrosis

Identification of Hub Genes and Prediction of Targeted Drugs for Rheumatoid Arthritis and Idiopathic Pulmonary Fibrosis

Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis

BackgroundDysregulation of several inflammatory cytokines including tumour necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed...

Approval status of essential therapeutic drugs for systemic sclerosis versus that of drugs for rheumatoid arthritis

Objective: Systemic sclerosis, a rare disease characterized by chronic multisystem fibrosis, requires lifelong management, necessitating enough insurance coverage for the patient. Official drug approval is the first step to ensuring that the drug is covered by insurance. In this study, we investigated the approval status of essential therapeutic drugs for systemic sclerosis across eight countries and compared it with that of drugs for rheumatoid arthritis. Methods: The essential therapeutic drug lists for systemic sclerosis and rheumatoid arthritis were taken from the guidelines of the American College of Rheumatology and the European Alliance of Associations for Rheumatology. Official drug approval status for the selected drugs was confirmed by searching representative Internet databases from eight countries: the United States, the United Kingdom, Germany, France, Italy, Switzerland, Japan, and the Republic of Korea. Results: A total of 21 and 16 drugs were selected for systemic sclerosis and rheumatoid arthritis, respectively. The drug approval rates of the 21 drugs for systemic sclerosis varied among countries. Most drugs used to treat pulmonary arterial hypertension, which were developed recently and are expensive, are approved by most countries; however, most older drugs—which are still essential for management of Raynaud’s phenomenon, digital ulcers, interstitial lung disease, and skin fibrosis—are not approved by most countries. By contrast, almost all of the 16 drugs used to treat rheumatoid arthritis, whether old or new, are approved by most countries. Conclusion: Approval rates for drugs used to treat systemic sclerosis, a rare disease, are much lower than those for drugs used to treat rheumatoid arthritis. Thus, approval rates of essential therapeutic drugs for systemic sclerosis need to improve, which will benefit patients by increasing the number of drugs covered by insurance.

Rheumatoid arthritis: remission without biotherapy? The experience of Burkina Faso (West Africa)

the objective of this study was to evaluate the therapeutic response of patients treated with disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA). descriptive and analytical single-center cross-sectional study conducted in Burkina Faso from January 2019 to December 2021 in patients with RA meeting American Rheumatism Association/European League against rheumatism criteria. Therapeutic response was assessed according to the criteria of the European League Against Rheumatism, the clinical disease activity index and the simplified disease activity Index after at least six months of treatment. one hundred and three patients, including 85 women were included. The average age of the patients was 50.14 years ± 15.04 years. Eighty-seven patients (84.47%) were ACPA positive and 50 patients (48.54%) had radiological damage at inclusion. The mean DAS28-CRP, CDAI and SDAI were 5.17, respectively; 32.16 and 35.48 at inclusion compared to 2.53; 7.83 and 8.76 after at least six months of treatment (p<0.0001). Ninety-six patients (93.20%) were treated with methotrexate. According to the criteria of the European League Against Rheumatism, 89 patients (86.41%) were good responders, 62 patients (60.19%) were in remission. Major improvement was observed in 53 patients (51.46%) as assessed by the Clinical Disease Activity Index and the Simplified Disease Activity Index. despite the unavailability of biotherapies in sub-Saharan Africa, remission of RA can be obtained by optimizing treatment with DMARDs and "tight control".

Analysis of survival rate and persistence predictors of baricitinib in real-world data from a large cohort of rheumatoid arthritis patients

ObjectivesThe persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate. MethodsThis is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan–Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence. ResultsOverall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07–1.49, p = 0.006. ConclusionReal-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.

Spirulina as a promising agent in rheumatoid arthritis with no observed hepatic injury

Aim of the workTo examine early mitigation and conservative effects of low-dose gamma radiation (LDR) or spirulina (SPR) algae on inflammation, oxidative stress and liver function in experimentally-induced arthritis in rats, and comparing such effects to conventionally used rheumatoid arthritis (RA) drugs; methotrexate (MTX) and hydroxychloroquine (HCQ) in an attempt to unleash a safer remedy/therapeutic modality for RA management. Materials and methodsMale Wister albino rats were rendered arthritic by sub-plantar injection of 0.1 ml Freund's complete adjuvant (FCA). Adjuvant-induced arthritis (AIA) rats were treated with each of LDR (0.5 Gy at day 0 of arthritis induction), MTX (1 mg/kg/week, intra-peritoneal), HCQ sulphate (15 mg/kg/day, orally), MTX + HCQ, and SPR (1 g/kg/day, orally) for 28 days. ResultsSub-plantar injection of FCA led to marked increase in paw volume accompanied with increased serum level of C-reactive protein (CRP) and oxidative stress markers including malondialdehyde (MDA) and nitric oxide (NO) levels. Exposure to LDR did not induce any significant alteration in the estimated parameters. Treatment with MTX and HCQ alone or combined induced deterioration in liver function (transaminases), insignificantly reduced paw edema, yet failed to attenuate CRP, MDA and NO levels. Instead, treatment with SPR significantly guarded against changes in nearly all measured parameters and kept liver function at normal level. ConclusionThis is a leading work showing the hepato-preservative impact of spirulina as a promising alternative therapy during the course management of RA. It could thus be considered as a potential option in the management armamentarium of RA.