I. Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that primarily affects joints but can also impact other systems in the body, including the skin, eyes, lungs, heart, and blood vessels. (Lee, 2001) Joint damgage occurs in RA when the immune system mistakenly attacks the body's tissues, leading to inflammation. According the World Health Organization just over 0.2% of the global population was affected by RA in 2019, (WHO, 2013) with women being three times more likely than men to develop this disease (NIAMS, 2023). The cause of RA remains unknown, but genetic, environmental, and hormonal factors are believed to play significant roles in its development. (Deane, 2017) (Alpízar-Rodríguez, 2017)

A range of symptoms including joint pain, stiffness, swelling, and a decreased range of motion are caused by RA. If left untreated, it can lead to joint deformity and disability. Early diagnosis and treatment are crucial in managing the disease and preventing irreversible damage. (Cush, 2021)

II. Rheumatoid Arthritis Pathophysiology

RA involves an abnormal immune response that leads to the production of autoantibodies and inflammatory cytokines, resulting in chronic inflammation of the synovium—the lining of the membranes that surround joints. Over time, this inflammation can cause the synovium to thicken, eventually destroying the cartilage and bone within the joint. (Zhang, 2023)

The exact mechanism that triggers this autoimmune response is not fully understood. However, it is believed that a combination of genetic predisposition and environmental factors, such as smoking or infections, may contribute to the onset of RA (Mayo Clinic, 2023). 

III. Common Treatments for Rheumatoid Arthritis 

The primary goals of RA treatment are to reduce inflammation, alleviate symptoms, prevent joint and organ damage, improve physical function and overall well-being, and reduce long-term complications. Treatment typically involves a combination of medications, lifestyle changes, and sometimes surgery. The choice of treatment depends on the severity of the disease, the patient’s overall health, and how well they respond to specific therapies. (Smolen, 2020)

IV. Disease-Modifying Antirheumatic Drugs (DMARDs)

DMARDs are a cornerstone of RA treatment. They work by slowing the progression of the disease and preventing joint damage. Traditional DMARDs include methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine. Methotrexate is often the first-line treatment due to its effectiveness and relatively favorable side effect profile. However, it can cause side effects such as liver toxicity and bone marrow suppression, necessitating regular monitoring (NIAMS, 2023) (Roodenrijs, 2022).

V. Biologic DMARDs

Biologic DMARDs are a newer class of drugs that target specific components of the immune system. These include tumor necrosis factor (TNF) inhibitors (e.g., adalimumab, etanercept, infliximab), interleukin-6 (IL-6) inhibitors (e.g., tocilizumab), B-cell depleting agents (e.g., rituximab), and T-cell activation inhibitors (e.g., abatacept). Biologics are usually prescribed for patients who do not respond adequately to traditional DMARDs. (Singh, 2016)  

Biologics can be very effective but are associated with an increased risk of infections due to their immunosuppressive effects. They are also expensive and may not be accessible to all patients. (Ruffing, 2020)

VI. Jakinibs - Janus Kinase (JAK) Inhibitors

JAK inhibitors are an emerging class of medications for RA that work by interfering with the JAK-STAT signaling pathway, which is involved in the immune response. Baricitinib, tofacitinib, and upadacitinib are examples of JAK inhibitors that have been approved for the treatment of RA.

An important side effect of these "Jakinibs" is the risk of serious infections, including bacterial, mycobacterial, fungal, and viral infections. In phase III trials of tofacitinib, three cases of pulmonary tuberculosis (TB) were reported among opportunistic infections, despite all patients initially testing negative for TB during screening. (O'Shea, 2013)

VII. Baricitinib

Baricitinib is an oral JAK inhibitor that has shown efficacy in treating moderate to severe RA. It works by blocking the activity of Janus kinase enzymes, which play a key role in the inflammatory process. Baricitinib is often prescribed for patients who have not responded well to other DMARDs such as methotrexate or biologics such as adalimumab. (Taylor, 2017)

In clinical trials, Baricitinib has demonstrated significant improvements in RA symptoms, including reduced joint pain and swelling, improved physical function, and slowed progression of joint damage (Taylor, 2017). Common side effects include upper respiratory tract infections, nausea, and increased liver enzymes. Serious side effects can include blood clots, serious infections, and an increased risk of cancer.

Baricitinib is usually taken once daily in combination with methotrexate, and patients need to be monitored regularly for potential side effects. It is important to balance the benefits of Baricitinib with its risks, and it should be used under the guidance of a healthcare professional. (Lilly, 2022)

VIII. Lifestyle and Supportive Therapies 

In addition to medication, lifestyle changes and supportive therapies play a vital role in managing RA. Regular exercise, a balanced diet, maintaining a healthy weight, and avoiding smoking are essential for overall health and can help alleviate RA symptoms. (Chehade, 2019)

Physical therapy can improve joint function and flexibility, while occupational therapy can help patients adapt their daily activities to minimize joint strain. Assistive devices, such as splints and braces, can also provide support and reduce pain. (Peter, 2021)

IX. Surgical Interventions

In cases where joint damage is severe and does not respond to medication, surgical intervention may be necessary. Surgical options include synovectomy (removal of the inflamed synovium), tendon repair, joint fusion, and total joint replacement. Surgery can significantly improve pain and function, but it is usually considered a last resort after other treatments have failed. (Johns Hopkins Medicine, 2020)

X. Conclusion

Rheumatoid arthritis is a complex autoimmune disease that requires a multifaceted approach to treatment. Early diagnosis and aggressive management are crucial to prevent joint damage and improve quality of life. A combination of medications, including DMARDs, biologics, and JAK inhibitors like baricitinib, along with lifestyle changes and supportive therapies, can help manage symptoms and slow disease progression.

While advancements in RA treatment have significantly improved outcomes for many patients, ongoing research is essential to develop more effective and safer therapies. Regular monitoring and a personalized treatment plan, tailored to the individual patient’s needs, are key to successfully managing RA.

XI. References

Alpízar-Rodríguez, D., Pluchino, N., Canny, G., Gabay, C., & Finckh, A. (2017). The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology (Oxford), 56(8), 1254-1263. https://doi.org/10.1093/rheumatology/kew318

Chehade, L., Jaafar, Z. A., El Masri, D., Zmerly, H., Kreidieh, D., Tannir, H., Itani, L., & El Ghoch, M. (2019). Lifestyle modification in rheumatoid arthritis: Dietary and physical activity recommendations based on evidence. Current Rheumatology Reviews, 15(3), 209-214. https://doi.org/10.2174/1573397115666190121135940

Cush, J. J. (2021). Rheumatoid arthritis: Early diagnosis and treatment. Medical Clinics of North America, 105(2), 355-365. https://doi.org/10.1016/j.mcna.2020.10.006

Deane, K. D., Demoruelle, M. K., Kelmenson, L. B., Kuhn, K. A., Norris, J. M., & Holers, V. M. (2017). Genetic and environmental risk factors for rheumatoid arthritis. Best Practice & Research Clinical Rheumatology, 31(1), 3-18. https://doi.org/10.1016/j.berh.2017.08.003

Johns Hopkins Medicine. Rheumatoid arthritis treatment options. (2020). Retrieved from https://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/#surg#surg:~:text=in%20the%20course.-,Surgical%20Approaches,-Although%20rheumatoid%20arthritis 

Lee, D. M., & Weinblatt, M. E. (2001). Rheumatoid arthritis. The Lancet, 358(9285), 903-911. https://doi.org/10.1016/S0140-6736(01)06075-5

Mayo Clinic Staff. (2023). Rheumatoid arthritis. Retrieved from https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648 

Lilly. (2022). OLUMIANT- baricitinib tablet, film coated. Retrieved from https://uspl.lilly.com/olumiant/olumiant.html#pi 

NIAMS - National Institute of Arthritis and Musculoskeletal and Skin Diseases. (2023). Rheumatoid Arthritis. https://www.niams.nih.gov/health-topics/rheumatoid-arthritis

O'Shea, J. J., Kontzias, A., Yamaoka, K., Tanaka, Y., & Laurence, A. (2013). Janus kinase inhibitors in autoimmune diseases. Annals of the Rheumatic Diseases, 72 (Suppl 2), ii111-ii115. https://doi.org/10.1136/annrheumdis-2012-202576

Peter, W. F., Swart, N. M., Meerhoff, G. A., & Vliet Vlieland, T. P. M. (2021). Clinical practice guideline for physical therapist management of people with rheumatoid arthritis. Physical Therapy, 101(8), pzab127. https://doi.org/10.1093/ptj/pzab127

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Ruffing, V. (2020). Side effects of biologic medications. Retrieved from https://www.hopkinsarthritis.org/arthritis-news/side-effects-of-biologic-medications/ 

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Smolen, J. S. (2020). Insights into the treatment of rheumatoid arthritis: A paradigm in medicine. Journal of Autoimmunity, 110, 102425. https://doi.org/10.1016/j.jaut.2020.102425

Taylor, P. C., Keystone, E. C., van der Heijde, D., Weinblatt, M. E., Del Carmen Morales, L., Reyes Gonzaga, J., Yakushin, S., Ishii, T., Emoto, K., Beattie, S., Arora, V., Gaich, C., Rooney, T., Schlichting, D., Macias, W. L., de Bono, S., & Tanaka, Y. (2017). Baricitinib versus placebo or adalimumab in rheumatoid arthritis. The New England Journal of Medicine, 376(7), 652-662. https://doi.org/10.1056/NEJMoa1608345

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Zhang, F., Jonsson, A. H., Nathan, A., Millard, N., Curtis, M., Xiao, Q., Gutierrez-Arcelus, M., Apruzzese, W., Watts, G. F. M., Weisenfeld, D., Nayar, S., Rangel-Moreno, J., Meednu, N., Marks, K. E., Mantel, I., Kang, J. B., Rumker, L., Mears, J., Slowikowski, K., Weinand, K., ... Raychaudhuri, S. (2023). Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature, 623(7987), 616-624. https://doi.org/10.1038/s41586-023-06708-y

About the Author:

David Orchard-Webb

David  Orchard-Webb, Ph.D., is a technical writer with broad interests including health & technology writing, plus extensive training and knowledge of  biomedicine and microbiology. My Ph.D. and postdoc were in oncology and  developing cancer medicines. I provide technical medical and other writing  services for projects ranging from “knowledge automation” to pure pharma, to  food safety, to the history of science, and everything in between. I also provide white papers, ebooks, meta-analysis reviews, editing, consulting,  business, and market research-related activities in biomedicine, technology,  and health. In addition to its well-known role in the development of  medicines, I am a big believer in biotechnology’s ability to revolutionize industries such as food-tech, agtech, textiles & fashion.