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Frontiers in Immunology 2022Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease. Despite the wide use of conventional synthetic, targeted and biologic disease modifying... (Review)
Review
Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease. Despite the wide use of conventional synthetic, targeted and biologic disease modifying anti-rheumatic drugs (DMARDs) to control its radiological progress, nearly all DMARDs are immunologically non-selective and do not address the underlying immunological mechanisms of RA. Patients with RA often need to take various DMARDs long-term or even lifelong and thus, face increased risks of infection, tumor and other adverse reactions. It is logical to modulate the immune disorders and restore immune balance in patients with RA by restoring immune tolerance. Indeed, approaches based on stem cell transplantation, tolerogenic dendritic cells (tolDCs), and antigen-based tolerogenic vaccination are under active investigation, and some have already transformed from wet bench research to clinical investigation during the last decade. Among them, clinical trials on stem cell therapy, especially mesenchymal stem cells (MSCs) transplantation are most investigated and followed by tolDCs in RA patients. On the other hand, despite active laboratory investigations on the use of RA-specific peptide-/protein-based tolerogenic vaccines for T cell, clinical studies on RA patients are much limited. Overall, the preliminary results of these clinical studies are promising and encouraging, demonstrating their safety and effectiveness in the rebalancing of T cell subsets; particular, the recovery of RA-specific Treg with increasing anti-inflammatory cytokines and reduced proinflammatory cytokines. Future studies should focus on the optimization of transplanted stem cells, the preparation of tolDCs, and tolerogenic vaccines with RA-specific protein or peptide, including their dosage, course, and route of administration with well-coordinated multi-center randomized clinical control researches. With the progress of experimental and clinical studies, generating and restoring RA-specific immune tolerance may bring revolutionary changes to the clinical management of RA in the near future.
Topics: Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Cytokines; Humans; Immune Tolerance
PubMed: 36248797
DOI: 10.3389/fimmu.2022.1012868 -
Clinical Rheumatology Nov 2020The outbreak of coronavirus in the world has led to an uncertainty about treatment of patients with autoimmune disorders because of their weakened immune system coupled... (Review)
Review
The outbreak of coronavirus in the world has led to an uncertainty about treatment of patients with autoimmune disorders because of their weakened immune system coupled with immunosuppressive agents they take which predisposes them to a host of infections. Data on COVID-19 patients with underlying rheumatological diseases has been emerging mostly in the form of small case series and one global registry. From these data, it seems like our patients, although immunosuppressed, are not particularly susceptible to the coronavirus infection and if infected, do not have significantly worse outcomes than other patients. In fact, drugs like hydroxychloroquine, dexamethasone, and tocilizumab have been studied for treatment of COVID-19. However, this is only preliminary data, and since a few parts of the world are still grappling with the pandemic at its peak, we need to be equipped on how to protect and manage our immunosuppressed patients. Published evidence to guide treatment decisions are lacking and doubts regarding continuation and initiation of immunosuppressants remain. Rheumatoid arthritis (RA) is the most common immune-mediated disorder in COVID-19 patients, and in this review, we discuss how the commonly used drugs in RA alter the patients' susceptibility to this infection. The review also summarizes the recommendations from the major bodies on how to manage this disease in these times. Key Points • Patients on immunosuppressive medications are not found to be at a greatly increased risk of acquiring COVID-19 infection. • Patients doing well on a stable dose of steroid and/or Disease-Modifying Antirheumatic Drugs (DMARDs) should be allowed to continue the same unless they get infected in which case, temporary stoppage of methotrexate and leflunomide may be considered. • Initiation of high-dose steroids, DMARDs, and biologics, if the clinical situation demands so, can be done. • Maintenance biologic therapy for stable patients should be individualized by the treating physician.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Betacoronavirus; Biological Products; COVID-19; Coronavirus Infections; Deprescriptions; Disease Management; Glucocorticoids; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tumor Necrosis Factor Inhibitors
PubMed: 32892311
DOI: 10.1007/s10067-020-05358-z -
Calcified Tissue International Nov 2022The therapeutic armamentarium for rheumatoid arthritis has increased substantially over the last 20 years. Historically antirheumatic treatment was started late in the... (Review)
Review
The therapeutic armamentarium for rheumatoid arthritis has increased substantially over the last 20 years. Historically antirheumatic treatment was started late in the disease course and frequently included prolonged high-dose glucocorticoid treatment which was associated with accelerated generalised bone loss and increased vertebral and non-vertebral fracture risk. Newer biologic and targeted synthetic treatments and a combination of conventional synthetic DMARDs prevent accelerated systemic bone loss and may even allow repair of cortical bone erosions. Emerging data also gives new insight on the impact of long-term conventional synthetic DMARDs on bone health and fracture risk and highlights the need for ongoing studies for better understanding of "established therapeutics". An interesting new antirheumatic treatment effect is the potential of erosion repair with the use of biologic DMARDs and janus kinase inhibitors. Although several newer anti-rheumatic drugs seem to have favorable effects on bone mineral density in RA patients, these effects are modest and do not seem to influence the fracture risk thus far. We summarize recent developments and findings of the impact of anti-rheumatic treatments on localized and systemic bone integrity and health.
Topics: Antirheumatic Agents; Biological Products; Bone Diseases, Metabolic; Bone and Bones; Glucocorticoids; Humans; Janus Kinase Inhibitors
PubMed: 35771255
DOI: 10.1007/s00223-022-01001-y -
International Immunopharmacology Sep 2023In recent years, difficult-to-treat rheumatoid arthritis (D2T RA) has attracted significant attention from rheumatologists due to its poor treatment response and the... (Review)
Review
In recent years, difficult-to-treat rheumatoid arthritis (D2T RA) has attracted significant attention from rheumatologists due to its poor treatment response and the persistent symptoms or signs experienced by patients. The therapeutic demands of patients with D2T RA are not properly met due to unclear pathogenic causes and a lack of high-quality data for current treatment options, creating considerable management difficulties with this patient population. This review describes the clinical challenges associated with disease-modifying antirheumatic drugs (DMARDs) and explores contributing factors associated with inappropriate response to DMARDs that may lead to D2T RA and related immunological dysregulation. It is now understood that D2T RA is a highly heterogeneous pathological status that involves multiple factors. These factors include but are not limited to genetics, environment, immunogenicity, comorbidities, adverse drug reactions, inappropriate drug application, poor adherence, and socioeconomic status. Besides, these factors may manifest in the selection and utilization of specific DMARDs, either individually or in combination, thereby contributing to inadequate treatment response. Finding these variables may offer hints for enhancing DMARD therapy plans and bettering the condition of D2T RA patients.
Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products
PubMed: 37481847
DOI: 10.1016/j.intimp.2023.110655 -
Frontiers in Immunology 2021Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation and bone erosion. The exact mechanism of RA is still unknown, but various immune... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation and bone erosion. The exact mechanism of RA is still unknown, but various immune cytokines, signaling pathways and effector cells are involved. Disease-modifying antirheumatic drugs (DMARDs) are commonly used in RA treatment and classified into different categories. Nevertheless, RA treatment is based on a "trial-and-error" approach, and a substantial proportion of patients show failed therapy for each DMARD. Over the past decades, great efforts have been made to overcome treatment failure, including identification of biomarkers, exploration of the reasons for loss of efficacy, development of sequential or combinational DMARDs strategies and approval of new DMARDs. Here, we summarize these efforts, which would provide valuable insights for accurate RA clinical medication. While gratifying, researchers realize that these efforts are still far from enough to recommend specific DMARDs for individual patients. Precision medicine is an emerging medical model that proposes a highly individualized and tailored approach for disease management. In this review, we also discuss the potential of precision medicine for overcoming RA treatment failure, with the introduction of various cutting-edge technologies and big data.
Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Treatment Failure
PubMed: 35003068
DOI: 10.3389/fimmu.2021.755844 -
Best Practice & Research. Clinical... Dec 2022Psoriatic arthritis (PsA) is a common immune-mediated inflammatory disease (IMID) that can present with a heterogenous clinical phenotype. The advent of advanced... (Review)
Review
Psoriatic arthritis (PsA) is a common immune-mediated inflammatory disease (IMID) that can present with a heterogenous clinical phenotype. The advent of advanced therapies has substantially improved patient outcomes, but many patients still have suboptimal or unsustained response, resulting in morbidity, structural damage and functional impairment. There remains a need for better therapeutic options and precision medicine approaches to improve outcomes for patients with PsA. This review synthesises recently approved the state-of-the-art therapeutics for PsA, including inhibitors of IL-23, Janus kinase (JAK), tyrosine kinase 2 (TYK2) and dual-target IL-17A/F. The evidence base for emerging therapeutics, including MK-2 inhibitors, nano-IL-17 inhibitors, nanobodies and other dual-target therapies for PsA is also reviewed. Potential future therapeutic strategies and unmet research needs are discussed.
Topics: Humans; Arthritis, Psoriatic; Precision Medicine; Antirheumatic Agents
PubMed: 36567224
DOI: 10.1016/j.berh.2022.101809 -
Eye (London, England) Jul 2020
Topics: Antirheumatic Agents; Humans; Hydroxychloroquine; Retina; Retinal Diseases; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32427967
DOI: 10.1038/s41433-020-0934-9 -
Seminars in Arthritis and Rheumatism Oct 2023To assess real-world comparative effectiveness studies of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) in adults with... (Review)
Review
OBJECTIVE
To assess real-world comparative effectiveness studies of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA) through a systematic review.
METHODS
We searched Medline for journal articles (2001-2021) and Embase® for abstracts presented at the European Alliance of Associations for Rheumatology and American College of Rheumatology (ACR) 2020 and 2021 annual meetings on non-randomized studies comparing the effectiveness of b/tsDMARDs using ACR-recommended disease activity measures, measures of functional status, and patient-reported outcomes (HAQ, PROMIS PF, patient pain, Patient and Physician Global Assessment of disease activity). Methodological heterogeneity between studies precluded meta-analyses. Risk of bias was assessed using the Cochrane Risk Of Bias In Non-randomized Studies of Interventions-I tool.
RESULTS
Of 1283 records screened, 68 were selected for data extraction, of which 1 was excluded due to critical risk of bias. Most studies were multicenter observational cohort/registry studies (n = 60) and were published between 2011 and 2021 (n = 60). Mean or median reported RA duration was between 6 and 15 years. Disease Activity Score in 28 joints (46 studies), Clinical Disease Activity Index (37 studies), and Health Assessment Questionnaire-Disability Index (32 studies) were the most common outcomes used in clinical practice, with regional differences identified. The most common comparison was between tumor necrosis factor inhibitors (TNFis) and non-TNFi bDMARDs (35 studies). There were no evident differences between b/tsDMARDs in clinical effectiveness.
CONCLUSION
This systematic review summarizing real-world evidence from a very large number of global studies found there are many effective options for the treatment of RA, but relatively less evidence to support the use of any one b/tsDMARD or drug class over another. Treatment for patients with RA should be tailored to suit individual clinical profiles. Further research is needed to identify whether specific patient subgroups may benefit from specific drug classes.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Treatment Outcome; Biological Products; Multicenter Studies as Topic
PubMed: 37573754
DOI: 10.1016/j.semarthrit.2023.152249 -
Journal of Biomedical Materials... Apr 2021Osteoarthritis (OA) is a joint degenerative disease that has become one of the leading causes of disability in the world. It is estimated that OA affects 50 million... (Review)
Review
Osteoarthritis (OA) is a joint degenerative disease that has become one of the leading causes of disability in the world. It is estimated that OA affects 50 million adults in the United States. Currently, there are no FDA-approved treatments that slow OA progression and its treatment is limited to pain management strategies and life style changes. Despite the discovery of several disease-modifying OA drugs (DMOADs) and promising results in preclinical studies, their clinical translation has been significantly limited because of poor intra-articular (IA) bioavailability and challenges in delivering these compounds to tissues of interest within the joint. Here, we review current OA treatments and their effectiveness at reducing joint pain, as well as novel targets for OA treatment and the challenges related to their clinical translation. Moreover, we discuss intra-articular (IA) drug delivery as a promising route of administration, describe its inherent challenges, and review recent advances in biomaterial-based IA drug delivery for OA treatment. Finally, we highlight the potential of tissue targeting in the development of effective IA drug delivery systems.
Topics: Animals; Antirheumatic Agents; Biocompatible Materials; Drug Carriers; Drug Delivery Systems; Humans; Injections, Intra-Articular; Osteoarthritis
PubMed: 32780515
DOI: 10.1002/jbm.a.37074 -
Giornale Italiano Di Dermatologia E... Aug 2020Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis often observed in patients with skin psoriasis. Treatment of PsA, especially peripheral PsA, has... (Review)
Review
Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis often observed in patients with skin psoriasis. Treatment of PsA, especially peripheral PsA, has typically relied on disease-modifying anti-rheumatic agents (DMARDs); however, these agents have limited efficacy and considerable associated toxicity. More recently, monoclonal antibodies (biologic agents) have revolutionized management of immune-mediated diseases; however, these therapies carry a high cost and require parenteral administration. Apremilast, a novel oral DMARD, was approved by the European Union for psoriatic arthritis in 2015. Apremilast inhibits the function of phosphodiesterase-4, a regulator of cyclic adenosine monophosphate, leading to a broad inhibition of proinflammatory mediators and subsequent reduction in tumour necrosis factor-alpha (TNF-α) response. The PALACE and ACTIVE trials, phase III randomized controlled trials for apremilast, showed that apremilast is effective at improving various clinical and patient-reported outcome measures for psoriatic arthritis in both DMARD-naïve and DMARD-experienced PsA patients. Efficacy was limited in patients with previous biologic DMARD failure and the overall efficacy of apremilast appears to be less than biologics agents, though no head-to-head trials exist comparing apremilast to biologic DMARDs. Apremilast is generally well tolerated, with short-lived gastrointestinal side effects being the most commonly reported adverse events. Guidelines suggest a trial of apremilast in patients who have failed traditional oral DMARDs and for whom, biologics are contraindicated. More studies directly comparing apremilast to conventional DMARDs and biologic DMARDs are needed and will be crucial in informing clinical and economic decisions about apremilast role in management of PsA.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Humans; Phosphodiesterase 4 Inhibitors; Randomized Controlled Trials as Topic; Thalidomide
PubMed: 33050680
DOI: 10.23736/S0392-0488.20.06640-7