Rheumatoid Arthritis

Question 1

What is arthritis, and who is more likely to get it?

Answer 1

Arthritis is inflammation of the joints and surrounding tissues, affecting bones, muscles, and joints. It’s an umbrella term for over 100 different conditions. It’s more common in the elderly, women, and individuals with increased weight.

Question 2

Describe the primary manifestation of rheumatoid arthritis (RA).

Answer 2

The primary manifestation of RA is synovitis, which involves inflammation of the synovial lining of joints, leading to erosion of bone, cartilage, and periarticular structures.

Question 3

What are the articular clinical features of RA?

Answer 3

Include morning stiffness of ≥30 minutes, pain, swelling, fatigue, weakness, and characteristic joint deformities like boutonniere, swan neck, Z thumb, MCP subluxation, and ulnar deviation.

Question 4

What are the extra-articular clinical features of RA?

Answer 4

Include nodules (subcutaneous, pulmonary, cardiac), pulmonary complications (interstitial lung disease, pleuritis), ocular manifestations (scleritis, episcleritis), vasculitis, neurological issues, cardiovascular complications, cutaneous manifestations, hematologic abnormalities, malignancies, and renal complications.

Question 5

How is pyoderma gangrenosum present in patients with RA?

Answer 5

Pyoderma gangrenosum in RA starts as a small pimple, red bump, or blood blister, which rapidly enlarges into a painful ulcer with purple or blue edges. It commonly occurs on the legs and heals after treatment with medications like methotrexate and high-dose oral prednisolone.

Question 6

What are the differences in joint involvement between rheumatoid arthritis (RA) and osteoarthritis (OA) according to Goldman’s Cecil Medicine?

Answer 6

RA typically shows symmetric joint involvement affecting the wrist, MCP, and PIP joints, with soft tissue swelling. OA, on the other hand, tends to exhibit asymmetric joint involvement affecting the DIP joints and the base of the thumb, with no soft tissue swelling.

Question 7

What are some of the extra-articular manifestations of rheumatoid arthritis (RA)?

Answer 7

Extra-articular manifestations of RA include nodules (subcutaneous, pulmonary, cardiac), pulmonary complications (interstitial lung disease, pleuritis), ocular manifestations (scleritis, episcleritis), vasculitis, neurological issues, cardiovascular complications, cutaneous manifestations, hematologic abnormalities, malignancies, and renal complications.

Question 8

How does RA differ from osteoarthritis (OA) in terms of joint involvement

Answer 8

RA typically involves symmetric joint inflammation, affecting the wrist, metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints with soft tissue swelling. In contrast, OA tends to involve asymmetric joint inflammation, affecting distal interphalangeal (DIP) joints and the base of the thumb, with marginal osteophytes and joint space narrowing.

Question 9

Explain the prevalence and burden of arthritis in Australia.

Answer 9

In Australia, around 3.7 million people have arthritis, with prevalence increasing with age and being higher in females, individuals with increased waist circumference, and First Nations populations. Arthritis accounts for 13% of the total burden of disease, with significant healthcare expenditure and socioeconomic costs.

Question 10

What are some of the radiographic features of rheumatoid arthritis (RA) in the wrist?

Answer 10

Typical radiographic features of RA in the wrist include osseous erosion at sites like the triquetrum, pisiform, scaphoid, distal radius, ulnar styloid process, and radiocarpal joint. Diffuse cartilage loss and erosion are also observed.

Question 11

Describe the clinical presentation and symptoms of atlantoaxial (AA) subluxation in RA.

Answer 11

AA subluxation in RA can lead to symptoms such as pain radiating up to the occiput, slowly progressive spastic quadriparesis, transient medullary dysfunction (altered conscious state, syncope, loss of sphincter control, dysphagia, vertigo), and neurological deficits.

Question 12

Describe synovium

Answer 12

A thin membrane lining the joint capsule in diarthrodial joints, extending from skeletal tissue and covering the joint cavity.

Question 13

Describe cell types and their normal function

Answer 13

• Cell Types: It consists of synoviocytes, mainly fibroblast-like synoviocytes (FLS) and macrophages.
• Normal Function: Synoviocytes facilitate joint movement, with FLS producing lubricants like hyaluronan and collagen, while macrophages clean debris and maintain immune balance.

Question 14

Describe the changes that happen to healthy synovial tissue in RA.

Answer 14

• In RA, synovial tissue undergoes proliferation, infiltration by inflammatory cells (neutrophils, lymphocytes), and neovascularization.
• Proliferation: Synovial lining layer thickens, forming pannus.
• Infiltration: Inflammatory cells invade, leading to inflammation and joint damage.

Question 15

Describe the cell types present and their functions within the inflamed synovium in RA.

Answer 15

• Cell Types: In RA synovium, various cells are present, including activated fibroblast-like synoviocytes (FLS), inflammatory macrophages, T cells, and B cells.
• Functions: FLS produce pro-inflammatory cytokines and enzymes causing cartilage destruction, while macrophages clean debris and initiate immune responses.

Question 16

Explain what TNF is what it does in RA

Answer 16

A cytokine produced by various cells in RA synovium, promoting inflammation, leukocyte accumulation, and bone resorption.

Question 17

Explain IL-1 and what is does in RA.

Answer 17

Pro-inflammatory cytokine inducing chemokine production, metalloproteinase release, and osteoclast differentiation.

Question 18

Explain what IL-6 is what it does in RA

Answer 18

Stimulates acute phase response, immunoglobulin production, and promotes TH17 cell differentiation, contributing to inflammation and bone resorption.

Question 19

Explain how JAK-STAT signalling contributes to synovial inflammation.

Answer 19

• JAK-STAT Signalling: Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathways mediate inflammatory responses in RA.
• Contribution: Activated by cytokines like IL-6, JAK-STAT signalling enhances cytokine expression, promotes T cell survival, and induces antibody production, exacerbating synovial inflammation and joint damage.

Question 20

Explain why animal models are used for pre-clinical studies of RA pathogenesis and treatment.

Answer 20

• Purpose: Animal models, like rodent CIA and hTNF.Tg mice, mimic RA pathogenesis, aiding in understanding disease mechanisms and testing potential therapies.
• Advantages: They allow controlled studies, testing various interventions, and evaluating treatment responses before human trials.

Question 21

What are two pre-clinical models of RA

Answer 21

1. Collagen-Induced Arthritis (CIA)
2. hTNF.Tg mice

Question 22

Describe CIA and how it has helped understand RA and its limitations

Answer 22

• Utility: Mimics synovial inflammation, cartilage, and bone erosion seen in RA.
• Limitations: Dependent on specific mouse strains and collagen antibodies, not perfectly representing human RA.

Question 23

Describe hTNF.Tg and how it has helped understand RA and its limitations

Answer 23

• Utility: Offers chronic, TNF-driven arthritis model, reflecting RA’s chronic nature and responsiveness to TNF inhibition.
• Limitations: Limited to TNF-driven mechanisms, not reflecting the multifactorial nature of human RA.

Question 24

Describe how TNF was identified and developed as a therapeutic target for RA treatment

Answer 24

• Identification: TNF, discovered as a factor killing fibrosarcoma cells, was later found elevated in RA synovium, driving inflammation and joint damage.
• Development: Monoclonal antibodies like Infliximab and Adalimumab were developed, targeting TNF and reducing synovial inflammation and bone erosion in RA patients.

Question 25

Describe the anatomical and molecular structure of bone

Answer 25

Bone comprises trabecular (spongy) and cortical structures. Trabecular bone is found at the ends of long bones and in the vertebrae, while cortical bone forms the outer shell of most bones. Bone contains bone marrow cells, adipocytes, blood vessels, and extracellular components such as osteoid (organic matrix) and mineral salts (hydroxyapatite).

Question 26

Describe the function of bone

Answer 26

Bones provide mechanical support for movement and protection for internal organs. They also serve as a metabolic store for minerals like calcium and phosphate, regulate hematopoiesis, and produce hormones and cytokines.

Question 27

Explain the process of bone remodelling

Answer 27

Bone remodeling involves the coordinated action of osteoclasts, which resorb bone, and osteoblasts, which form bone. It is initiated asynchronously throughout the skeleton and is essential for skeletal adaptation and renewal.

Question 28

Explain how bone remodelling contributes to bone homeostasis

Answer 28

Remodeling removes regions of micro-damage, responds to calcium homeostatic needs by releasing calcium into the bloodstream, and adapts to changes in mechanical needs by redistributing bone. It helps maintain bone density and strength.

Question 29

Describe osteoclasts and how they resorb bone

Answer 29

Osteoclasts are multinucleated cells derived from hematopoietic precursors. They attach to bone surfaces and resorb bone mineral and collagenous matrix. Osteoclasts create an acidified microenvironment that aids in bone resorption and possess a characteristic “ruffled border” to increase surface area for ion exchange.

Question 30

Describe osteoblasts and how they form bone

Answer 30

Osteoblasts are specialized stromal cells responsible for bone formation. They produce type I collagen (osteoid) and non-collagenous proteins, which form the organic matrix of bone. Osteoblasts mineralize this matrix, leading to the formation of new bone.

Question 31

Describe osteocytes and their role in the skeleton

Answer 31

Osteocytes are terminally differentiated osteoblasts embedded within the bone matrix. They act as mechanosensors, detecting changes in mechanical load, and regulating osteoblast and osteoclast activity accordingly. Osteocytes play a crucial role in bone remodeling and adaptation to mechanical stress.

Question 32

Explain the RANKL / OPG system in osteoclast differentiation

Answer 32

RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand) produced by osteoblast-lineage cells stimulates osteoclast formation, while OPG (Osteoprotegerin) inhibits RANKL’s action by acting as a decoy receptor. This system regulates osteoclast differentiation and activity.

Question 33

Explain how the RANKL / OPG system in osteoclast differentiation is regulated in RA.

Answer 33

In rheumatoid arthritis (RA), there is an overproduction of RANKL, leading to excessive osteoclast activity and bone resorption. Cytokines such as TNF, IL-1, and IL-6 promote osteoclast differentiation and bone destruction indirectly by inducing RANKL expression in various cell types within the inflamed joint.

Question 34

Define focal bone loss in RA and explain how osteoclasts contribute.

Answer 34

Focal bone loss in RA refers to bone erosion within the arthritic joint, particularly at the junction of cartilage and bone. Osteoclasts contribute to focal bone loss by resorbing cortical bone within the affected joint.

Question 35

Define systemic bone loss in RA and explain how osteoclasts contribute.

Answer 35

Systemic bone loss in RA involves thinning of trabecular and cortical bone at sites remote from affected joints, increasing susceptibility to fractures. Osteoclasts contribute to systemic bone loss by releasing cytokines into the bloodstream, leading to increased RANKL production and bone resorption throughout the skeleton.

Question 36

Describe how anti-resorptive therapies protect bone in RA.

Answer 36

Anti-resorptive therapies in RA aim to inhibit osteoclast activity and bone resorption. Examples include bisphosphonates, which induce osteoclast apoptosis, and denosumab, a RANKL antibody that blocks osteoclast formation. By reducing bone resorption, these therapies protect against bone damage and loss associated with RA.

Question 37

Describe how the inflamed synovium, via TNF, IL-1 and IL-6, causes bone destruction in RA.

Answer 37

In RA, the inflamed synovium produces pro-inflammatory cytokines such as TNF, IL-1, and IL-6. These cytokines promote osteoclast differentiation and bone destruction indirectly by inducing RANKL expression in synovial fibroblasts, T cells, and osteoblast-lineage cells.

Question 38

What are the risk factors associated with rheumatoid arthritis (RA)?

Answer 38

Risk factors for RA include genetic predisposition (HLA-DRB1 alleles), epigenetic modifications, hormonal influences (e.g., estrogen), environmental triggers (e.g., smoking, infections), and emerging factors such as microbiome alterations.

Question 39

How does genetic susceptibility contribute to the development of RA?

Answer 39

Genetic factors, particularly HLA-DRB1 alleles like *0401 and *0404, play a significant role in RA susceptibility. The presence of the shared epitope (SE) within these alleles increases the risk of developing RA and is associated with more severe disease outcomes.

Question 40

What is the role of citrullination in the pathogenesis of RA?

Answer 40

Citrullination, a post-translational modification catalyzed by PADI enzymes, leads to the generation of neoepitopes, triggering autoimmunity in RA. Citrullinated peptides bind more avidly to the shared epitope, contributing to the production of anti-citrullinated protein antibodies (ACPA) and proinflammatory cytokines.

Question 41

How do epigenetic mechanisms contribute to RA?

Answer 41

Epigenetic modifications, including histone modifications, DNA methylation, and microRNA expression, can alter gene expression without changing DNA sequences. In RA, these mechanisms affect synovitis, immune cell proliferation, and inflammation, influencing disease development and progression.

Question 42

What hormonal factors are associated with RA, particularly in females?

Answer 42

Female preponderance in RA suggests a potential role for hormones like estrogen. Estrogen affects immune function, apoptosis resistance in B cells, and production of inflammatory mediators by synoviocytes and macrophages. Pregnancy is associated with temporary remission, likely due to hormonal changes.

Question 43

How do environmental factors such as smoking contribute to RA risk?

Answer 43

Smoking is a potent environmental risk factor for RA, particularly in individuals with genetic susceptibility (e.g., HLA-DRB1 alleles). It increases the risk of developing RA and accelerates disease progression by promoting citrullination and immune dysregulation.

Question 44

What emerging theories propose additional mechanisms underlying RA pathogenesis?

Answer 44

Emerging theories suggest the involvement of the microbiome and altered vascular permeability in RA. Dysbiosis in the gut microbiota and altered vascular integrity may contribute to immune dysregulation and joint inflammation in susceptible individuals.

Question 45

How can lifestyle modifications help prevent RA?

Answer 45

Lifestyle modifications, including smoking cessation, maintaining a healthy weight, regular physical activity, good dental hygiene, breastfeeding, and dietary changes (e.g., omega-3 fatty acids), may reduce the risk of RA by addressing behavioral risk factors and promoting overall health.

Question 46

What autoantibodies are used in the diagnosis of RA, and how do they contribute to disease classification and prognosis

Answer 46

Rheumatoid Factor (RF) and Anti-Citrullinated Protein Antibodies (ACPA) are key autoantibodies used in RA diagnosis. Their presence helps classify RA and predict disease progression, severity, and extra-articular manifestations, providing valuable prognostic information.

Question 47

How is disease activity assessed in RA patients, and what are the components of disease activity measurement?

Answer 47

Disease activity in RA is assessed through joint counts (tender/swollen), global assessment, pain scores, morning stiffness duration, laboratory tests (ESR, CRP), disability assessment, fatigue evaluation, and radiological imaging to monitor erosive changes. These components help guide treatment decisions and evaluate therapeutic response.

Question 48

Risk factors for rheumatoid arthritis (RA): Genetic

Answer 48

Genetic predisposition, particularly HLA-DRB1 alleles like *0401 and *0404, contributes significantly to RA susceptibility. The presence of the shared epitope within these alleles increases the risk of developing RA and is associated with more severe disease outcomes.

Question 49

Risk factors for rheumatoid arthritis (RA): Epigenetic

Answer 49

Epigenetic modifications, including histone modifications, DNA methylation, and microRNA expression, can alter gene expression without changing DNA sequences. These mechanisms affect synovitis, immune cell proliferation, and inflammation, influencing RA development and progression.

Question 50

Risk factors for rheumatoid arthritis (RA): Environmental

Answer 50

Environmental factors such as smoking, infections, and exposure to pollutants play a significant role in RA development. Smoking, in particular, is a potent risk factor that accelerates disease progression by promoting citrullination and immune dysregulation.

Question 51

Risk factors for rheumatoid arthritis (RA): Hormonal

Answer 51

Female preponderance in RA suggests a potential role for hormones like estrogen. Estrogen affects immune function, apoptosis resistance in B cells, and production of inflammatory mediators by synoviocytes and macrophages. Pregnancy is associated with temporary remission, likely due to hormonal changes.

Question 52

Risk factors for rheumatoid arthritis (RA): Emerging factors

Answer 52

Emerging theories propose additional mechanisms underlying RA pathogenesis, including dysbiosis in the gut microbiota and altered vascular integrity. These factors may contribute to immune dysregulation and joint inflammation in susceptible individuals.

Question 53

Risk factors for rheumatoid arthritis (RA): Preventing RA

Answer 53

Lifestyle modifications, including smoking cessation, maintaining a healthy weight, regular physical activity, good dental hygiene, breastfeeding, and dietary changes (e.g., omega-3 fatty acids), may reduce the risk of RA by addressing behavioral risk factors and promoting overall health.

Question 54

Diagnosis: Role of autoantibodies

Answer 54

Autoantibodies, particularly Rheumatoid Factor (RF) and Anti-Citrullinated Protein Antibodies (ACPA), play a crucial role in the diagnosis of RA. Their presence helps classify RA and predict disease progression, severity, and extra-articular manifestations, providing valuable prognostic information.

Question 55

Diagnosis: Classification criteria

Answer 55

The 2010 ACR/EULAR classification criteria for RA help identify patients who should be tested for autoantibodies and diagnosed with RA. These criteria include the presence of definite clinical synovitis in one or more joints and synovitis not better explained by another disease. Sensitivity and specificity of these criteria are essential for accurate diagnosis and treatment initiation.

Question 56

What are the principles of rheumatoid arthritis (RA) treatment regarding the timing of intervention?

Answer 56

RA treatment should begin early, within the first three months of symptom onset, during the therapeutic “window of opportunity.”

Question 57

Describe the therapeutic approach recommended for RA management.

Answer 57

The therapeutic approach for RA emphasizes early treatment initiation, aiming for remission or low disease activity through a treat-to-target strategy, and employing intensive therapeutic regimens.

Question 58

What is the significance of the “window of opportunity” in RA treatment?

Answer 58

The “window of opportunity” refers to the early phase of RA when intervention can significantly impact disease progression, reduce chronicity, and minimize joint damage, leading to improved long-term outcomes.

Question 59

What medications are used in RA treatment, and what are the categories of disease-modifying anti-rheumatic drugs (DMARDs)?

Answer 59

RA treatment includes analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, conventional synthetic DMARDs (csDMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs). DMARDs are categorized into csDMARDs and bDMARDs.

Question 60

How are conventional synthetic DMARDs (csDMARDs) typically initiated in RA management?

Answer 60

After an RA diagnosis, csDMARDs, such as methotrexate, are usually started early, either as monotherapy or in combination therapy, with methotrexate being the first-line choice for the majority of patients.

Question 61

What evidence supports the use of intensive therapeutic regimens in RA management?

Answer 61

Studies like TICORA (tight intensive control of RA) and triple therapy trials provide evidence for the effectiveness of intensive therapeutic regimens, emphasizing the importance of tight disease control and combination therapy.

Question 62

How are biological DMARDs (bDMARDs) typically used in RA treatment, and what are the available classes?

Answer 62

bDMARDs are reserved for RA patients who do not respond adequately to csDMARDs. There are five classes of bDMARDs: TNF-α inhibitors, IL-1 antagonists, IL-6 receptor antagonists, CTLA4 ligands, and B-cell depleting agents.

Question 63

Explain the eligibility criteria for receiving bDMARDs under the Pharmaceutical Benefits Scheme (PBS) in Australia.

Answer 63

To be eligible for bDMARDs under the PBS, patients must have failed intensive csDMARD therapy, meet specific disease activity criteria (ESR, CRP, and active joint count), and fulfill other clinical requirements.

Question 63

What is the role of the PBS in providing access to medications for RA patients in Australia?

Answer 63

The PBS subsidizes the cost of medications for various medical conditions, including RA, ensuring affordable access to necessary treatments for patients.

Question 64

Summarise the key principles of RA treatment and the significance of early intervention.

Answer 64

RA treatment involves early initiation of therapy within the “window of opportunity,” employing a treat-to-target approach with intensive regimens. Medications include csDMARDs and bDMARDs, with PBS criteria guiding access to subsidized treatments in Australia.

Question 65

What are the principles of RA treatment?

Answer 65

The principles include treating early and aiming for a target of low disease activity or remission.

Question 66

Define the “window of opportunity” in RA treatment.

Answer 66

The “window of opportunity” refers to the first three months after symptom onset, during which early intervention may significantly reduce disease progression and the burden of RA.

Question 67

What is the main goal of Phase I clinical trials?

Answer 67

Phase I trials aim to evaluate the safety of a new intervention, typically involving a small group of people to assess pharmacokinetics, pharmacodynamics, and toxicity.

Question 68

What is the primary purpose of Phase III clinical trials?

Answer 68

Phase III trials compare the new intervention to the current standard of treatment in large groups of patients to confirm efficacy and safety.

Question 69

List the classes of biological DMARDs (bDMARDs) for RA treatment.

Answer 69

1. Tumor necrosis factor alpha (TNF-α) inhibitors
2. Interleukin one (IL-1) antagonists
3. Interleukin six (IL-6) receptor antagonists
4. Cytotoxic T-lymphocyte antigen 4 (CTLA4) ligand (co-stimulation modifier)
5. B-cell depleting agents (anti-CD20)

Question 70

What are the eligibility criteria for bDMARDs under the Pharmaceutical Benefits Scheme (PBS) in Australia?

Answer 70

Patients must have failed six months of intensive DMARD therapy, with specific clinical criteria such as active joint counts and elevated inflammatory markers.

Question 71

Describe the mechanism of action of Methotrexate (MTX) in RA treatment.

Answer 71

Methotrexate is the first-line csDMARD choice for RA and is believed to exert its effects through mechanisms that are not fully understood. It is typically used as an anchor drug to which other medications may be added.

Question 72

What are the common adverse effects associated with TNF inhibitors in RA treatment?

Answer 72

Common adverse effects include injection site reactions, infusion reactions, cytopenias (neutropenia), and increased susceptibility to infections.

Question 73

What is the American College of Rheumatology 20% improvement criteria (ACR20)?

Answer 73

ACR20 is used to evaluate treatment response in clinical trials and requires at least a 20% improvement in swollen and tender joint counts, along with improvements in additional disease-related variables.

Question 74

Name three emerging therapies for RA treatment.

Answer 74

Mavrilimumab (GM-CSF inhibition), Rheumavax (autologous dendritic cell therapy), and cholinergic neurostimulation are emerging therapies being explored for RA treatment.

Question 75

Human Clinical Trials of TNFi:

Answer 75

Human clinical trials of TNFi (Tumor Necrosis Factor inhibitors) have demonstrated their efficacy in the treatment of various autoimmune diseases, including rheumatoid arthritis (RA). These trials typically involve different phases, starting from Phase I trials to evaluate safety and escalating to Phase III trials to assess efficacy in larger patient populations.

Question 76

Principles of Clinical Trial Design:

Answer 76

1. Ethical considerations: Trials must adhere to ethical guidelines to ensure the safety and well-being of participants.
2. Randomization: Random assignment of participants to treatment groups helps minimize bias and ensures comparability between groups.
3. Placebo/control: Utilization of placebos or active controls allows researchers to assess the true effect of the intervention being studied.
4. Blinding (masking): Blinding helps prevent bias by ensuring that participants and/or researchers are unaware of which treatment is being administered.
5. Adequate power (sample size): Trials need to enroll a sufficient number of participants to detect clinically meaningful differences between treatment groups.

Question 77

TNF-Inhibitors (TNFi):

Answer 77

TNFi comprises different classes of biologic agents that target tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine implicated in various autoimmune diseases. These classes include:

• Monoclonal anti-TNF antibodies: Examples include Infliximab, Adalimumab, Certolizumab pegol, and Golimumab.
• TNF receptor fusion proteins: Etanercept is an example of this class.
• Efficacy: TNFi have demonstrated efficacy in reducing disease activity, improving symptoms, and inhibiting joint damage in RA and other autoimmune conditions.
• Failure: Despite their efficacy, some patients may experience primary or secondary failure with TNFi therapy. Primary failure occurs when patients do not respond to TNFi due to factors such as different inflammatory pathways driving the disease. Secondary failure may occur over time due to the development of neutralizing antibodies or other mechanisms leading to loss of efficacy.

Question 78

Future of RA Treatment:

Answer 78

The future of RA treatment is evolving with the development of new therapeutic agents and treatment paradigms. Some aspects of the future of RA treatment include:

1. Evolving treatment paradigms: There is a shift towards “head-to-head” trials comparing different biologic DMARDs (bDMARDs) and biosimilars to assess their relative efficacy and safety.
2. Introduction of biosimilars: Biosimilars, which are lower-cost alternatives to biologic drugs, are becoming increasingly available, potentially reducing the economic burden of RA treatment.
3. New therapeutic agents: Small molecule inhibitors targeting Janus Kinase (JAK) pathways, such as tofacitinib, baricitinib, and upadacitinib, offer alternative treatment options for RA patients.
4. Emerging therapies: Novel agents targeting pathways involved in RA pathogenesis, such as GM-CSF inhibition and cholinergic neurostimulation, are being investigated for their potential in RA treatment.