Rheumatoid Arthritis Research News & Progress

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. It is a complex disease with a range of clinical manifestations and can cause significant pain, disability, and reduced quality of life. While there is currently no cure for RA, significant progress has been made in understanding the disease's pathophysiology and developing effective treatments. In this article, we will explore the latest research directions and frontiers of scientific research on rheumatoid arthritis.

Early diagnosis and intervention

One of the most critical areas of research in RA is early diagnosis and intervention. Early diagnosis and treatment of RA are critical in preventing joint damage and disability. The main RA diagnostic markers that have been widely used are?rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and autoantibodies against citrullinated proteins (ACPA). Amongst ACPAs, the assay for anti-cyclic citrullinated peptide (anti-CCP) is widely clinically available?and has excellent diagnostic and prognostic value.?Researchers are working on identifying biomarkers that can predict the development of RA before clinical symptoms appear. Novel RA biomarkers of many types (eg. serum, tissue-specific, genetic factors) are?under active investigation for both diagnosis and disease activity monitoring[1].?Better biomarkers could lead to earlier diagnosis, treatment, and outcomes. Once a better biomarker is identified, the cost and feasibility of testing will need to be considered in order to ensure clinical utility on a worldwide scale.?

Personalized medicine

Another exciting area of research in RA is personalized medicine. We have come to understand that RA is a heterogeneous disease on a clinical as well as a pathophysiological level. Despite this heterogeneity, current management recommendations still adopt a “one-size-fits-all”?treatment approach, where ideally individualised treatment, or personalised medicine, is preferred. The following three principles are the foundation of the modern management of RA: (1) early recognition of the disease, (2) early initiation of intensive therapy and (3) a treat-to-target approach. Within this approach, rheumatologists should strive for clinical remission, or low disease activity when remission is not achievable. Early recognition and initiation of intensive therapy prevents disease progression and joint destruction.?The first step towards personalised medicine in RA would be to designate different treatment strategies to distinct clinical or molecular phenotypes of patients.?Clinical trials aimed at personalised medicine as well as translational research targeted at finding molecular biomarkers are needed to identify subgroups that will or will not respond to a certain treatment strategy[2].

Biological therapies

Previously, therapeutic options for RA were limited with non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Later expanded to include what are now known as conventional

synthetic disease modifying anti-rheumatic drugs (csDMARDs) such as methotrexate, hydroxychloroquine and sulfasalazine. ?One of the most significant shifts in the RA therapeutic landscape has occurred with the introduction of biological disease modifying anti-rheumatic drugs (bDMARDs).?The classes of bDMARDs currently available for use in RA include tumour necrosis factor-alpha (TNF) inhibitors, the CD80/CD86 costimulation inhibitor abatacept, the interleukin-6 (IL-6) inhibitors, the CD-20 depleting agent rituximab and an anti-IL1 antibody[3].?

Furthermore, targeted synthetic DMARDs (tsDMARDs) inhibiting Janus kinase (JAK) and biosimilars also are approved for RA.?Currently, five TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) and two tsDMARDs inhibiting JAK (tofacitinib and baricitinib) are approved for therapy in RA[4].?In general, bDMARDs or tsDMARDs should be considered if the first csDMARD does not achieve treatment target in the presence of negative prognostic factors or if response to two conventional synthetic DMARDs (csDMARDs) is insufficient in the absence of negative prognostic factors.

Non-pharmacological therapies

With the new biological and targeted therapies, complete remission has become an attainable goal in rheumatoid arthritis, nevertheless a part of RA patients are still not meeting treatment goals according to treat to target principles, and can be defined as difficult-to-treat RA. The different non-pharmacological therapies (NPT) cover a wide range of interventions, including many exercise modalities, psychological interventions, physio- and balneotherapy, dietary interventions, education etc. NPTs with their complex action can have a synergistic, additive effect with targeted pharmacological therapies, which is highly needed in D2TRA patients, where pharmacological treatment options are often limited.?Researchers suggest that simultaneously with pharmacotherapy, a complex non-pharmacological treatment program should be offered to all D2TRA patients, including regular assessment by a psychologist and a physiotherapist in parallel with the rheumatologist’s investigations, and obligatory and optional NPT elements[5].?

Gut microbiome

Recent research has suggested that the gut microbiome may play a role in the development and progression of RA. The gut microbiome is the collection of microorganisms that live in the digestive tract. Studies have shown that RA patients have a different gut microbiome composition than healthy individuals. Understanding the gut microbiome's role in RA could lead to new therapeutic approaches. Furthermore, multiple therapies commonly used to treat RA may alter gut microbiota diversity, suggesting that modulating the gut microbiota may help prevent or treat RA. Hence, a better understanding of the changes in the gut microbiota that accompany RA should aid the development of novel therapeutic approaches. Mounting evidence indicating that targeted modulation of the gut microbiota may alleviate RA suggests that personalized treatment approaches based on patient microbiome profiles may increase drug efficacy, lower toxicity risk, and improve clinical outcome[6].

Artificial intelligence

Artificial intelligence?is an emerging field with the potential to transform many areas of healthcare, including the management of RA. Machine learning algorithms can analyze large amounts of data to identify patterns and make predictions. Artificial intelligence models are used to assess RA development risk, diagnose RA using omics, imaging, clinical, and sensor data, detect RA patients within EHR, predict treatment response, monitor disease course, determine prognosis, discover novel drugs, and enhance basic science research. A growing body of evidence supports the potential role of artificial intelligence in revolutionizing the screening, diagnosis, and management of patients with RA.[7]

Nanotechnology

Nanotechnology is another area of research that shows promise in the treatment of RA. Nanoparticles can be designed to deliver drugs directly to affected joints, reducing the risk of systemic side effects. With the development of nanotechnology, more and more nano-drugs have been applied in the treatment of RA?due to the unique physical and chemical properties of nanomaterials. Treatment of RA with nanomaterials can improve bioavailability and selectively target damaged joint tissue.?Although nanomaterials have achieved good therapeutic effects in the treatment of rheumatoid arthritis, their potential therapeutic mechanisms are still unclear, and there are still certain limitations in application. We need to further explore and research the biocompatibility of the nanometer carrier and metabolic pathways in the body. Precise control of drug release rate and retention time is the direction that we should strive for next. At present, most researches are only for single-targeted therapy. We can consider targeting multiple targets to treat arthritis, using multiple drugs to synergistically block multiple pathways in the pathogenesis of RA, alleviate the disease process, and improve the therapeutic effect. Perhaps it can become a new direction for the treatment of RA in the future[8].

Gene therapy

Gene therapy is a rapidly evolving field that has the potential to revolutionize the treatment of RA. Gene therapy involves introducing genetic material into cells to modify their function. Researchers are exploring the use of gene therapy to target cells involved in the inflammatory response in RA. The arsenal of gene therapy tools keeps growing. Currently, both viral and nonviral delivery systems are used for RA therapy[10].

Conclusion

In conclusion, significant progress has been made in understanding the pathophysiology of RA and developing effective treatments. However, there is still much to be learned about the disease, and researchers are actively exploring new directions and frontiers in RA research. Advances in personalized medicine, biologic drugs, biosimilars, non-pharmacological therapies, the gut microbiome, artificial intelligence, nanotechnology, and gene therapy offer new opportunities for improving the lives of RA patients. With continued research, it is hoped that RA can be effectively managed, and ultimately cured.

References

1.?Shapiro S C. Biomarkers in rheumatoid arthritis[J]. Cureus, 2021, 13(5).

2.?Heutz J, De Jong P H P. Possibilities for personalised medicine in rheumatoid arthritis: hype or hope[J]. RMD open, 2021, 7(3): e001653.

3.?Findeisen K E, Sewell J, Ostor A J K. Biological therapies for rheumatoid arthritis: an overview for the clinician[J]. Biologics: Targets and Therapy, 2021: 343-352.

4.?Rein P, Mueller R B. Treatment with biologicals in rheumatoid arthritis: an overview[J]. Rheumatology and therapy, 2017, 4(2): 247-261.

5.?Majnik J, Császár-Nagy N, B?cskei G, et al. Non-pharmacological treatment in difficult-to-treat rheumatoid arthritis[J]. Frontiers in Medicine, 2022, 9.

6.?Zhao T, Wei Y, Zhu Y, et al. Gut microbiota and rheumatoid arthritis: From pathogenesis to novel therapeutic opportunities[J].?Frontiers in Immunology, 2022, 13.

7.?Momtazmanesh S, Nowroozi A, Rezaei N. Artificial Intelligence in Rheumatoid Arthritis: Current Status and Future Perspectives: A State-of-the-Art Review[J]. Rheumatology and Therapy, 2022, 9(5): 1249-1304.

8.?Zheng M, Jia H, Wang H, et al. Application of nanomaterials in the treatment of rheumatoid arthritis[J]. RSC advances, 2021, 11(13): 7129-7137.

9.?Gao F, Yuan Q, Cai P, et al. Au clusters treat rheumatoid arthritis with uniquely reversing cartilage/bone destruction[J]. Advanced Science, 2019, 6(7): 1801671.

10.?Deviatkin A A, Vakulenko Y A, Akhmadishina L V, et al. Emerging concepts and challenges in rheumatoid arthritis gene therapy[J]. Biomedicines, 2020, 8(1): 9.