Effective Treatment For Rheumatoid Arthritis Research Articles

The steroid-sparing effect of JAK inhibitors across multiple patient populations.

JAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. We prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment. In all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. Chronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.

Ionic Liquid Transdermal Patches of Two Active Ingredients Based on Semi-Ionic Hydrogen Bonding for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to deformities and disabilities in patients. Conventional treatment focuses on delaying progression; therefore, new treatments are necessary. The present study reported a novel ionic liquid transdermal platform for efficient RA treatment, and the underlying mechanism was elucidated using FTIR, 1H-NMR, Raman, XPS, and molecular simulations. The results showed that the reversibility of the semi-ionic hydrogen bonding facilitated high drug loading and enhanced drug permeability. Actarit's drug loading had an approximately 11.34-times increase. The in vitro permeability of actarit and ketoprofen was improved by 5.46 and 2.39 times, respectively. And they had the same significant effect in vivo. Furthermore, through the integration of network pharmacology, Western blotting (WB), and radiology analyses, the significant osteoprotective effects of SIHDD-PSA (semi-ionic H-bond double-drug pressure-sensitive adhesive transdermal patch) were revealed through the modulation of the JAK-STAT pathway. The SIHDD-PSA significantly reduced paw swelling and inflammation in the rat model, and stimulatory properties evaluation confirmed the safety of SIHDD-PSA. In conclusion, these findings provide a novel approach for the effective treatment of RA, and the semi-ionic hydrogen bonding strategy contributes a new theoretical basis for developing TDDS.

Liposomes: An Emerging Strategy for the Effective Treatment of Rheumatoid Arthritis.

A Liposomal delivery system is a novel and distinguishing way of organized medicine administration. The advancements in liposomal technology allow for controlled drug distribution to treat rheumatoid arthritis effectively. Liposomes are microscopic lipid-based vesicles that have shown promise in transporting substances, such as superoxide dismutase, hemoglobin, erythrocyte interleukin-2, gamma interferon, and smaller compounds. Liposomes are biocompatible, nontoxic, biodegradable, non-immunogenic, and flexible, with sizes ranging from 0.025 to 2.5 micrometers. LDS is normally employed to distribute drugs through topical conduits, but fresh investigation has shown that it offers promise for oral, ocular, and parenteral administration. Our major objective is to gather information about liposomes, focusing on their applicability in rheumatoid arthritis treatment. In the current review, we have tried to cover the preparation techniques, clinical trials, patents, marketed formulations, vesicle types, formulations used to treat rheumatoid arthritis and other ailments, and layered liposomal formulations with improved characteristics. Research has established LDS as a biocompatible, sustainable, non-toxic, adaptable material. Researchers working on LDS technology in rheumatoid arthritis will find this review particularly useful as it may unclutter novel ways for therapeutic intercessions in treating the disease.

Inflammation-Responsive Nanoagents for Activatable Photoacoustic Molecular Imaging and Tandem Therapies in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, representing a pressing public health concern. The pathogenesis of RA includes the excessive production of proinflammatory cytokines and harmful oxygen-derived free radicals, such as nitric oxide (NO), which constitute vital targets for precise diagnosis and effective treatment of RA. In this study, we introduce an advanced nanoagent that integrates the RA microenvironment-activatable photoacoustic (PA) imaging with multitarget synergistic treatment for RA. A highly sensitive organic probe with NO-tunable energy transformation and molecular geometry is developed, which enables strong near-infrared absorption with a turn-on PA signal, and the active intramolecular motion could further boost PA conversion. The probe is coassembled with an inflammation-responsive prodrug to construct the theranostic nanoagent, on which a macrophage-derived cell membrane with natural tropism to the inflammatory sites is camouflaged to improve the targeting ability to inflamed joints. The nanoagent could not only sensitively detect RA and differentiate the severity but also efficiently alleviate RA symptoms and improve joint function. The combination of activatable probe-mediated NO scavenging and on-demand activation of anti-inflammatory prodrug significantly inhibits the proinflammatory factors and promotes macrophage repolarization from M1 to M2 phenotype. This meticulously designed nanoagent ingeniously integrates RA-specific PA molecular imaging with synergistic multitarget therapy, rendering tremendous promise for precise intervention of RA-related diseases.

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by chronic synovitis and the progressive destruction of cartilage and bone. RA is commonly accompanied by extra-articular comorbidities. The pathogenesis of RA and its comorbidities is complex and not completely elucidated. The assembly of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activates caspase-1, which induces the maturation of interleukin (IL)-1β and IL-18 and leads to the cleavage of gasdermin D with promoting pyroptosis. Accumulative evidence indicates the pathogenic role of NLRP3 inflammasome signaling in RA and its comorbidities, including atherosclerotic cardiovascular disease, osteoporosis, and interstitial lung diseases. Although the available therapeutic agents are effective for RA treatment, their high cost and increased infection rate are causes for concern. Recent evidence revealed the components of the NLRP3 inflammasome as potential therapeutic targets in RA and its comorbidities. In this review, we searched the MEDLINE database using the PubMed interface and reviewed English-language literature on the NLRP3 inflammasome in RA and its comorbidities from 2000 to 2023. The current evidence reveals that the NLRP3 inflammasome contributes to the pathogenesis of RA and its comorbidities. Consequently, the components of the NLRP3 inflammasome signaling pathway represent promising therapeutic targets, and ongoing research might lead to the development of new, effective treatments for RA and its comorbidities.

A Peripheral Blood Signature of Increased Th1 and Myeloid Cells Combined with Serum Inflammatory Mediators Is Associated with Response to Abatacept in Rheumatoid Arthritis Patients.

Abatacept (CTLA4-Ig)-a monoclonal antibody which restricts T cell activation-is an effective treatment for rheumatoid arthritis (RA). Nevertheless, only 50% of RA patients attain clinical responses, while predictors of response are rather limited. Herein, we aimed to investigate for early biomarkers of response to abatacept, based on a detailed immunological profiling of peripheral blood (PB) cells and serum proteins. We applied flow cytometry and proteomics analysis on PB immune cells and serum respectively, of RA patients starting abatacept as the first biologic agent. After 6 months of treatment, 34.5% of patients attained response. At baseline, Th1 and FoxP3+ T cell populations were positively correlated with tender joint counts (p-value = 0.047 and p-value = 0.022, respectively). Upon treatment, CTLA4-Ig effectively reduced the percentages of Th1 and Th17 only in responders (p-value = 0.0277 and p-value = 0.0042, respectively). Notably, baseline levels of Th1 and myeloid cell populations were significantly increased in PB of responders compared to non-responders (p-value = 0.009 and p-value = 0.03, respectively). Proteomics analysis revealed that several inflammatory mediators were present in serum of responders before therapy initiation and strikingly 10 amongst 303 serum proteins were associated with clinical responses. Finally, a composite index based on selected baseline cellular and proteomics' analysis could predict response to abatacept with a high sensitivity (90%) and specificity (88.24%).

Mannose-modified celastrol liposomes targeted activated macrophages for rheumatoid arthritis treatment in vitro and in vivo evaluation

Rheumatoid arthritis (RA) is an autoimmune illness characterized by symmetrical polyarthritis as the primary clinical symptom. A substantial number of synovial macrophages are activated in RA patients, resulting in synovial inflammation, joint inflammation, and cartilage degradation. The goal of this study is to develop a novel therapy for the effective treatment of RA. We prepared mannose-modified celastrol liposomes (MAN-CSL-lips) by thin-film hydration method. The particle size of the prepared liposomes was (95.37 ± 0.16) nm, and the zeta potential was (−5.4 ± 0.40) mV. The experimental results showed that MAN-CSL-lips had low cytotoxicity and could be efficiently taken up by macrophages, suppress osteoclast formation, and reduce the level of inflammatory factors. In addition, in vivo animal experiments, liposomes can prolong the systemic circulation time of drugs, reduce the joint score and serum inflammatory factor expression in arthritic rats, and have significant cartilage protection and anti-inflammatory effects, making it a promising therapeutic method for treating RA.

Nano-based therapeutics for Rheumatoid arthritis: Recent patents and development.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease marked by inflammation of synovium and generation of autoantibodies. Bone and cartilage are frequently damaged along with weakening of tendons and ligaments resulting in disability. An effective RA treatment needs a multi-disciplinary approach which relies upon pathophysiology that is still partially understood. In RA patients, inflammation was induced by pro-inflammatory cytokines including IL-1, IL-6 & IL-10. The conventional dosage regimens for treating RA have drawbacks such as ineffectiveness, greater doses, frequent dosing, relatively expensive and serious adverse effects. To formulate an effective treatment plan for RA, research teams have recently focused on producing several nanoformulations containing anti-inflammatory APIs with an aim to target the inflamed area. Nanomedicines have recently gained popularity in the treatment of RA. Interestingly, unbelievable improvements have been observed in current years in diagnosis and management of RA utilizing nanotechnology.

Infection incidence, timing, and dose dependency in rheumatoid arthritis patients treated with rituximab: a retrospective cohort study.

Rituximab (RTX) is a safe and effective treatment for rheumatoid arthritis (RA). However, there are some concerns about infection risk and preliminary data suggest dose and time dependency. This study aims to determine the infection incidence in a large real-life population of RA patients using RTX, with special focus on (ultra-)low dosing and time since last infusion. RA patients treated with 1000, 500 or 200 mg RTX per cycle between 2012 and 2021 at the Sint Maartenskliniek were included in a retrospective cohort study. Patient-, disease-, treatment- and infection characteristics were retrieved from electronic health records. Infection incidence rates, dose and time relations with RTX infusion were analysed using mixed-effects Poisson regression. Among 490 patients, we identified 819 infections in 1254 patient years. Most infections were mild and respiratory tract infections were most common. Infection incidence rates were 41, 54 and 71 per 100 patient years for doses of 200, 500 and 1000 mg. Incidence rate ratio (IRR) was significantly lower for 200 mg compared to 1000 mg (adjusted IRR 0.35, 95% CI 0.17-0.72, p = 0.004). In patients receiving 1000 or 500 mg RTX, infections seemed to occur more frequently within the first two months after infusion compared to later on in the treatment cycle, suggesting an association with peak concentration. Ultra-low dosing (200 mg) of RTX is associated with a lower risk of infections in RA. Future interventions focusing on ultra-low dosing and slow release of RTX (e.g. by subcutaneous administration) may lower infection risk.

Effect of autologous bone marrow derived mesenchymal stem cells in treatment of rheumatoid arthritis

IntroductionChronic inflammation causes articular bone and cartilage degeneration in people with rheumatoid arthritis (RA). Despite recent advancements in the management of RA, adverse side effects and ineffective treatments remain a problem. Effective treatment is usually hampered by financial issues. As a result, less expensive medications that reduce both inflammation and bone resorption are required. Mesenchymal stem cells (MSCs) have recently been identified as a potential therapy for RA. Aim of the studyThis study aimed to examine the anti-arthritic effect of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides (Os), and human placental extract (HPE), individually and combined, on an RA model, using Complete Freund's adjuvant (CFA)-induced arthritis in rats. Materials and methodsIn female rats, RA was induced by injecting CFA in the paw of the hind limb. Rat bone marrow-MSCs, oligosaccharides, and human placental extract (HPE) were given individually and in combination via the intraperitoneal route. A complete blood count (CBC), erythrocyte sedimentation rate (ESR), serum cortisol, urea, uric acid, and other biochemical parameters were measured to determine the safety and efficacy of the different treatments. Histopathological analysis of bone sections was carried out. ResultsCombining oligosaccharides and HPE therapy with the infusion of rat-bone marrow MSCs had beneficial antiarthritic and anti-inflammatory effects in CFA-induced arthritis in rats: overall such triple therapy significantly reduced serum levels of IL-6, IL-10, and TNF-alpha in comparison with all other combinations (all P > 0.05). Meanwhile, the triple therapy did not have negative effects on levels of CBC, serum cortisol, ESR, and liver enzymes (all NS) as well as on renal functions (NS). Also, the histopathological analysis showed significant improvements in the healing and remodelling of osteoporotic lesions in arthritic rats. As shown by counting apoptotic cells as a histopathological substitute for measuring apoptotic or regeneration markers, the lowest count was found in the group treated with a triple therapy of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides, and HPE. ConclusionThe combination of rat MSCs, oligosaccharides, and HPE has the potential to be an effective treatment for rheumatoid arthritis.

TNFipred: a classification model to predict TNF-α inhibitors.

Rheumatoid arthritis (RA), characterized by severe inflammation in the joint lining, is a progressive, chronic, autoimmune disorder with high morbidity and mortality rates. There are several mechanisms responsible for joint damage, but overproduction of TNF-α is a significant mechanism that results in excess swelling and pain. Drugs acting on TNF-α are known to significantly reduce the disease progression and improve the quality of life in many RA patients. Hence, inhibiting TNF-α is considered one of the most effective treatments for RA. Currently, there are only a few FDA-approved TNF-α inhibitors, which are mainly monoclonal antibodies, fusion proteins, or biosimilars with disadvantages such as poor stability, difficulty in route of administration (often given as injection or infusion), cost-prohibitive large-scale production, and increased side effects. There are just a handful of small compounds known to have TNF- inhibitory capabilities. Thus, there is a dire need for new drugs, especially small molecules in the market, such as TNF-α inhibitors. The conventional method of identifying TNF-α inhibitors is expensive, labor, and time intensive. Machine learning (ML) can be used to solve existing drug discovery and development problems. In this study, four classification algorithms-naïve Bayes (NB), random forest (RF), k-nearest neighbor (kNN), and support vector machine (SVM)-were used to train ML models for classifying TNF-α inhibitors based on three sets of features. The performance of the RF model was found to be best when using 1D, 2D, and fingerprints as features, with an accuracy of 87.96 and a sensitivity of 86.17. To our knowledge, this is the first ML model for TNF-α inhibitor prediction. The model is available at http://14.139.57.41/tnfipred/.

Biomimetic Epigallocatechin Gallate-Cerium Assemblies for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease that is so far incurable with long-term health risks. The high doses and frequent administration for the available RA drug always lead to adverse side effects. Aiming at the obstacles to achieving effective RA treatment, we prepared macrophage cell membrane-camouflaged nanoparticles (M-EC), which were assembled from epigallocatechin gallate (EGCG) and cerium(IV) ions. Due to its geometrical similarity to the active metal sites of a natural antioxidant enzyme, the EC possessed a high scavenge efficiency to various types of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The macrophage cell membrane assisted M-EC in escaping from the immune system, being uptaken by inflammatory cells, and specifically binding IL-1β. After tail vein injection to the collagen-induced arthritis (CIA) mouse model, the M-EC accumulated at inflamed joints and effectively repaired the bone erosion and cartilage damage of rheumatoid arthritis by relieving synovial inflammation and cartilage erosion. It is expected that the M-EC can not only pave a new way for designing metal-phenolic networks with better biological activity but also provide a more biocompatible therapeutic strategy for effective treatment of RA.

Tubson-2 decoction ameliorates rheumatoid arthritis complicated with osteoporosis in CIA rats involving isochlorogenic acid A regulating IL-17/MAPK pathway

BackgroundOsteoporosis (OP) is considered as one of the major comorbidities of rheumatoid arthritis (RA), and is responsible for fragility fracture. However, there is currently no effective treatment for RA complicated with OP. Tubson-2 decoction (TBD), a Mongolian medicine also known as Erwei Duzhong Decoction, has been shown to exert a preventive effect on post-menopausal osteoporosis (PMOP). The preventive effects of TBD on RA-induced OP, as well as the bioactive compound responsible and the underlying mechanisms, remain to be elucidated. ObjectiveTo explore the effects of TBD on RA-induced OP in vivo, and to elucidate the mechanism of isochlorogenic acid A (ICA), the effective component of TBD, in vitro. MethodsTo evaluate the anti-arthritic and anti-osteoporotic effects of TBD, we conducted H&E straining and safranine O/fast green, TEM, immunohistochemistry (IHC), bone histomorphometry, micro-CT imaging, and biomechanical testing in collagen induced arthritis (CIA) rats. The active ingredient in TBD was identified using network pharmacology and molecular docking. The identification was supported by in vivo IHC assay, and further confirmed using qRT-PCR, Western blot, and SEM analysis in TNF-α-treated MH7A cells and/or in LPS-exposed RAW264.7 cells. ResultsOral administration of TBD attenuated the severity of arthritis and osteopenia as well as poor bone quality, in CIA rats. Additionally, TBD and the positive control, tripterygium glycosides (TG), exhibited similar effects in reducing inflammation in both the synovium and ankle joint. They also were both effective in improving bone loss, microarchitecture, and overall bone quality. TBD reduced the expression of MMP13, IL-17, and p-JNK protein in the synovium of CIA rats. ICA, which was screened, suppressed TNF-α or LPS-triggered inflammatory responses via down-regulating IL-17 signaling, involving in MMP13, IL-1β, IL-23, and IL-17, and the MAPK pathway including p-ERK, p-JNK, and p-P38, both in MH7A cells and in RAW264.7 cells. Furthermore, ICA prevented osteoclasts from differentiating and bone resoprtion in a dose-dependent manner in vitro. ConclusionThis study provides the first evidence that TBD exerts intervening effects on RA-induced OP, possibly through the downregulation of the IL-17/MAPK signaling pathway by ICA. The findings of our study provides valuable insights for further research in this area.

A Non-targeted Metabolomics Reveals Therapeutical Effect and Mechanism of Sanmiao Pill on Adjuvant-induced Arthritis Rats.

Rheumatoid arthritis (RA) is an increasingly serious disease worldwide that can damage the joints and bones of sufferers. Sanmiao Pill (SMP), a classical traditional Chinese medicine (TCM) prescription, has been used for effective treatments for RA in the clinic. To comprehensively illuminate the therapeutic mechanism of SMP in the treatment of RA, the effects of SMP on biomarkers and metabolic pathways in rats with adjuvant-induced arthritis (AIA) were examined. > Methods: Sprague Dawley rats were randomly divided into two control (CC, Control) groups, two model (MM, Model) groups, a methotrexate group (MTX, 7.6 mg/kg body weight per week), and two SMP groups (San-L, 28.7 mg/kg body weight per day and San-H, 57.4 mg/kg body weight per day). Rats' body weight, paw swelling, arthritis scores, biochemical parameters, histopathology, and so on were used to evaluate the success of the model and the therapeutic effects of SMP. The metabolic techniques were used to characterize the metabolic profile and biomarkers of the serum and urine samples of rats to reveal the metabolic changes that occurred after SMP treatment. > Results: After 21 days of treatment, SMP improved weight gain, reduced the severity of paw swelling, lowered the levels of biochemical indicators (CCP-Ab, IL-6, TNF-α, RF), decreased destruction of articular cartilage and bone erosion, and protected the affected joints.Additionally, 17 and 19 potential biomarkers associated with RA were identified in the serum and urine, respectively. SMP significantly reversed 14 potential biomarkers, such as arachidonic acid, lysoPC(20:4(5Z,8Z,11Z,14Z)), L-tryptophan, 9-cis-Retinoic acid, hippuric acid, pyridoxine, and pantothenic acid. These metabolites are associated with arachidonic acid metabolism, glycerophospholipid catabolism, tryptophan metabolism, phenylalanine metabolism, vitamin B6 metabolism, etc. > Conclusion: These results indicated that RA-related biomarkers reflected the metabolic profile of AIA rats. Meanwhile, SMP could effectively treat RA mainly by reducing inflammation and regulating abnormal lipid metabolic pathways and amino acid metabolisms. It showed that metabolomics could be used to analyze the metabolic profiles involved in RA and reveal the mechanism of SMP treatment of RA.>.

Current Remedial Strategies for the Treatment of Rheumatoid Arthritis through the Oral Route with Janus Kinase Inhibitors

Abstract: Rheumatoid arthritis (RA) is a well-known chronic inflammatory disease that results in articular degradation, comorbidities, and body part functional loss. In the last two decades, the development of effective biologics and small compounds, such as Janus kinase inhibitors (Jakinibs), has significantly improved clinical outcomes. Low-molecular-weight chemicals known as jakinibs are currently used for effective treatment of RA. Jakinibs are a new class of drugs being developed to treat RA, and several of them are now in different phases of clinical trials to establish their safety and efficacy in humans. Jakinibs can be very different in their selectivity against JAK inhibitors. For an efficient therapy of RA, it is critical to fully comprehend the properties of JAK inhibitors as well as their mechanism of action. Tofacitinib, Baricitinib, Upadacitinib, Peficitinib, Filgotinib, Decernotinib, Itacitinib, Ruxolitinib, and PF-06651600 are a few selective orally active Jakinibs that have entered clinical trials to treat RA. This review aims to elaborate on Jakinibs for the treatment of Rheumatoid Arthritis (RH), including their mechanism of action (MOA), efficacy and safety profiles, clinical trials of adverse effects (AEs) associated with Jakinibs and combination therapy with other DMARDs.

Differentiating between Seronegative Elderly-Onset Rheumatoid Arthritis and Polymyalgia Rheumatica: A Qualitative Synthesis of Narrative Reviews.

Elderly-onset rheumatoid arthritis (EORA) is prevalent among older patients, and its incidence is increasing due to aging societies. However, differentiating between EORA and polymyalgia rheumatica (PMR) is challenging for clinicians and hinders the initiation of effective treatment for rheumatoid arthritis among older generations, thereby allowing its progression. Therefore, we conducted a qualitative synthesis of narrative reviews via meta-ethnography regarding seronegative EORA diagnosis to clarify the methods to differentiate seronegative EORA from PMR. Three databases (PubMed, EMBASE, and Web of Science) were searched for relevant reviews published between January 2011 and October 2022. The extracted articles were synthesized using meta-ethnography, and 185 studies were selected following the protocol. Seven reviews were analyzed, and four themes and nine concepts were identified. The four themes included difficulty in differentiation, mandatory follow-up, and factors favoring rheumatoid arthritis and those favoring PMR. Factors favoring seronegative EORA and PMR should be considered for effective diagnosis and prompt initiation of disease-modifying anti-rheumatic drugs. Mandatory and long follow-ups of suspected patients are essential for differentiating the two diseases. The attitude of rheumatologists toward tentatively diagnosing seronegative EORA and flexibly modifying their hypotheses based on new or altered symptoms can aid in effective management and avoiding misdiagnosis.

DESIGN, DEVELOPMENT AND EVALUATION OF NOVEL MOUTH DISSOLVING FILM OF TOFACITINIB CITRATE

Objective: The aim of the present study was to design and evaluation of mouth dissolving oral films of tofacitinib citrate allowing fast reproducible drug dissolution in oral cavity thus bypassing the first-pass metabolism to enhance the patient convenience and effective treatment for rheumatoid arthritis. Methods: Films have been prepared by way of solvent casting technique by using Hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose, sodium alginate, and gelatin had been used as the hydrophilic film-forming polymeric bases and glycerol as plasticizer. The prepared film evaluated for in vitro disintegration time, tensile strength, content uniformity, folding endurance, swelling index, and in vitro drug release. Results: The results of prepared film pH of all the selected formulation were ranging between 6.1 to 7.5. Thickness of the films was found in the range of 0.07 to 0.19 mm. The folding endurance was found to vary between 95.7 to 105.4-fold, Disintegration time was found 25 to 35, Drug content was found to be for F3 and F6 formulation i.e., 99.035±1.37 and 99.014±0.79. Conclusion: Thus, the current study successfully designed, developed an optimized Tofacitinib citrate formulation.

Design and Development of Etoricoxib Loaded Nanoparticles for the Effective Treatment of Rheumatoid Arthritis

Design and Development of Etoricoxib Loaded Nanoparticles for the Effective Treatment of Rheumatoid Arthritis

Chemically modified small interfering RNA targeting Hedgehog signaling pathway for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is an inflammatory disease that leads to disability; however, existing therapies are still unsatisfactory. Activated fibroblast-like synoviocytes (FLSs) play an essential role in synovitis formation and joint destruction in RA. The Hedgehog signaling pathway is aberrantly activated and contributes to the aggressive phenotype of RA-FLSs. However, it remains uncertain whether inhibiting Smoothened (SMO), a critical component of the Hedgehog signaling pathway, is an effective treatment for RA. Here, we design a series of small interfering RNAs (siRNAs) that specifically target the SMO gene. With precise chemical modifications, siRNAs' efficacy and stability are significantly improved, and the off-target effects are minimized. The optimized chemically modified siRNA (si-S1A3-Chol) decreases RA-FLS proliferation and invasiveness without the transfection reagent. Furthermore, si-S1A3-Chol injected intra-articularly effectively alleviates joint destruction and improves motor function in collagen-induced arthritis mouse models. Consequently, our results demonstrate that chemically modified siRNA targeting the Hedgehog signaling pathway may be a potential therapy for RA.

Research in Brief

Olokizumab, a humanised monoclonal antibody against interleukin-6, might be a safe and effective treatment for rheumatoid arthritis, according to a multicentre, double-blind, phase 3 trial by Josef Smolen and colleagues. 1648 patients with rheumatoid arthritis and an inadequate response to methotrexate were randomly assigned (2:2:2:1) to olokizumab (64 mg subcutaneously) every 2 weeks (n=464) or every 4 weeks (n=479), adalimumab every 2 weeks (40 mg; n=462), or placebo (n=243), alongside maintenance methotrexate. At week 12, 108 (44·4%) patients on placebo had an American College of Rheumatology 20 response (primary outcome) versus 326 (70·3%) on olokizumab every 2 weeks (difference 25·9%, 97·5% CI 17·1–34·1; p<0·001), 342 (71·4%) receiving olokizumab every 4 weeks (27·0%, 18·3–35·2; p<0·001), and 309 (66·9%) on adalimumab (22·5%, 14·8–29·8; p<0·001). 154 (63·4%) patients on placebo had at least one adverse event, versus 324 (70·0%) on olokizumab every 2 weeks, 338 (70·9%) on olokizumab every 4 weeks, and 302 (65·4%) on adalimumab. Seven deaths occurred: three on olokizumab every 2 weeks, two on olokizumab every 4 weeks, one on adalimumab, and one on placebo. Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UKThese findings warrant targeted cardiovascular prevention measures, in particular in younger patients with autoimmune diseases, and further research into pathophysiological mechanisms underlying these complications. Full-Text PDF