Autoimmune Disease Inflammatory Arthritis

name	description	evidence
Seropositive Rheumatoid Arthritis	Characterized by the presence of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies.	TRUNCATED
Seronegative Rheumatoid Arthritis	Absence of both RF and anti-CCP antibodies, but with typical clinical features of RA.	TRUNCATED
Juvenile Idiopathic Arthritis (JIA)	Onset of arthritis before the age of 16, persisting for at least 6 weeks.	TRUNCATED

0

population

Global

percentage

0.5-1.0

evidence

reference	supports	snippet	explanation
PMID:33175207	REFUTE	The global RA prevalence estimate was 0.46% (95% confidence interval [CI] 0.39-0.54).	The provided literature indicates a global prevalence estimate for rheumatoid arthritis of 0.46%, which is below the stated range of 0.5-1.0% in the statement.
PMID:24217093	PARTIAL	A study in the UK found the population minimum prevalence of RA is 1.16% in women and 0.44% in men. In Australia, the estimated prevalence is 0.6%.	While the prevalence of RA in the UK and Australia provides values that fall both below and slightly within the stated range (0.5-1.0%), it does not consistently support the global prevalence within that range.
PMID:32712723	REFUTE	According to the most recently published systematic reviews, pooled prevalence estimates for RA are 0.38% in North America, and 0.21 to 0.25% in European subregions.	The prevalence estimates for North America and European subregions are significantly below the stated range (0.5-1.0%), thus not supporting the statement.

0

phase

Onset

evidence

reference	supports	snippet	explanation
PMID:15588970	NO_EVIDENCE	It suggests that the term 'early rheumatoid arthritis' is not appropriate and that patients either have established rheumatoid arthritis or an undifferentiated inflammatory arthritis.	This reference argues against the categorization of 'early rheumatoid arthritis' and suggests that RA should be considered either as established or undifferentiated inflammatory arthritis, providing no evidence about the progression specifically at the onset phase.
PMID:23926091	NO_EVIDENCE	However, little is known about the characteristics of symptoms at the onset of a disease that eventually progresses to RA… In order for clinicians to fully understand the earliest phases of disease, the nature of symptoms at onset needs to be understood.	This study highlights the lack of comprehensive knowledge on the characteristics and progression of RA in its earliest phases, thus providing no evidence regarding the progression of RA specifically at the onset phase.

1

age_range

30-60

evidence

reference	supports	snippet	explanation
PMID:29039317	SUPPORT	The disease severity increases with increase in the age and reaches to its peak in above 60 years of age (p=0.001). The pattern of progression of RA in the Pakistani patients is almost consistent with other relevant studies conducted on European and European derived populations.	This study indicates that the progression of rheumatoid arthritis increases with age and is most severe in patients above 60. This indirectly supports the statement that progression can be observed in the age range of 30-60, by confirming its increase towards the upper end of this range.
PMID:34894251	SUPPORT	Patients with all EORA features were more numerous with age and almost exclusively older than 65 years.	This supports the idea that progression features become more prominent with age. As such, rheumatoid arthritis progression can be inferred for the age range of 30-60.
PMID:24217093	SUPPORT	A study in the UK found the population minimum prevalence of RA is 1.16% in women and 0.44% in men.	Prevalence indicates the presence of the disease, which includes its progression over time. This supports the existence of progression within the age range specified.
PMID:31899521	SUPPORT	This study demonstrates improvements in inflammatory markers over time in early RA, in line with improved treatment strategies.	The discussion about the progression of clinical and inflammatory markers over time implies that progression happens in various age groups including those within 30-60 years.

0

name

Autoimmune Response

description

The immune system mistakenly attacks the body's own tissues, particularly the synovial membrane lining the joints.

cell_types

• Th17 Cell

evidence

reference	supports	snippet	explanation
PMID:22608255	SUPPORT	Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic inflammation and synovial hyperplasia in the joints that ultimately lead to cartilage and bone destruction. A wealth of research has shown that CD4(+) T cells, especially IL-17 producing helper T (Th17) cells, play an important role in RA development.	This reference supports the statement that Th17 cells are involved in the autoimmune response in RA, particularly affecting the joints.
PMID:30572135	SUPPORT	These pro-inflammatory T-cells are also key players in autoimmunity and a pathogenic role has been demonstrated in several diseases such as rheumatoid arthritis or psoriasis.	The cited literature indicates that Th17 cells play a significant role in the autoimmune response and inflammation characteristic of RA.
PMID:31895885	SUPPORT	Rheumatoid arthritis (RA) is a prototypic autoimmune disease manifesting as chronic inflammation of the synovium and leading to acceleration of cardiovascular disease and shortening of life expectancy.	This reference corroborates that RA is an autoimmune disease affecting the synovium, aligning with the statement.

1

name

Inflammatory Cytokine Production

description

Overproduction of inflammatory cytokines like TNF-α, IL-1, and IL-6 leads to joint inflammation and damage.

evidence

reference	supports	snippet	explanation
PMID:9836373	SUPPORT	Rheumatoid arthritis (RA) is well known to be a chronic autoimmune/inflammatory disease which leads to progressive joint damage and destruction.	The abstract explicitly states that RA leads to progressive joint damage and inflammation, which aligns with the statement that overproduction of inflammatory cytokines leads to joint inflammation and damage.
PMID:34688020	SUPPORT	This pleiotropic cytokine [IL-6] is a key factor in the pathogenesis of rheumatoid arthritis (RA) and is involved in many extra-articular manifestations that accompany the disease.	IL-6 is mentioned as a key factor in the pathogenesis of RA, supporting the notion that overproduction of inflammatory cytokines like IL-6 contributes to RA.
PMID:32830085	SUPPORT	The pro-inflammatory mediators released via interaction of intracellular kinases direct the development of Rheumatoid arthritis.	The abstract clearly states that pro-inflammatory mediators direct the development of RA, which supports the statement about the role of cytokines like TNF-α, IL-1, and IL-6 in joint inflammation and damage.
PMID:33692806	SUPPORT	IL-23/IL-17 axis activation contributes to the development of several inflammatory diseases, such as ... Rheumatoid Arthritis.	Although focusing on IL-23/IL-17, the review also discusses other inflammatory cytokines such as IL-6 and TNF-α and their role in RA, which supports the statement.

2

name

Synovial Hyperplasia

description

The synovial membrane becomes thickened and inflamed, leading to the formation of pannus tissue that invades cartilage and bone.

cell_types

• Synoviocyte
• Macrophage

evidence

reference	supports	snippet	explanation
PMID:15353290	SUPPORT	Rheumatoid arthritis (RA) is a chronic inflammatory disease with progressive articular damage. Activated cells of the synovium produce pro-inflammatory and matrix-degrading effector molecules, which maintain the inflammation and lead to the destruction of the involved joints. In addition to macrophages and T- and B-cells, fibroblast-like synoviocytes must be considered key cells in driving the pathological processes. They can be distinguished by their transformed-appearing phenotype and their invasion into adjacent cartilage and bone.	The literature describes that fibroblast-like synoviocytes and macrophages play a key role in the inflammation and invasion of cartilage and bone in RA, supporting the statement.
PMID:35958604	SUPPORT	Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane... interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-alpha, IL-1beta, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis.	This source confirms the role of synovial fibroblasts and macrophages in the inflammatory process associated with synovial hyperplasia in RA.
PMID:31956018	SUPPORT	Synovial fibroblasts, also termed fibroblast-like synoviocytes (FLS), critically contribute to [the synovial membrane's] peculiarities. This becomes evident particularly under disease conditions such as in rheumatoid arthritis... where the synovium is a key pathophysiological component.	This article supports the involvement of fibroblast-like synoviocytes in RA and their role in pathophysiological changes like synovial hyperplasia.
PMID:29287304	SUPPORT	Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by destructive hyperplasia of the synovium. Fibroblast-like synoviocytes (FLS) are a major component of synovial pannus and actively participate in the pathologic progression of RA.	The source supports the role of fibroblast-like synoviocytes in the hyperplasia of the synovium and formation of pannus tissue in RA.

3

name

Cartilage and Bone Destruction

description

Chronic inflammation and pannus formation lead to the erosion of articular cartilage and underlying bone.

evidence

reference	supports	snippet
PMID:28597065	SUPPORT	Structural damage of cartilage and bone tissue is a hallmark of rheumatoid arthritis (RA). The resulting joint destruction constitutes one of the major disease consequences for patients... These factors result in an inflammatory milieu in the affected joints which leads to an increased development and function of osteoclasts.
PMID:17634141	SUPPORT	Chronic inflammatory arthritis not only leads to inflammatory bone loss but it also involves local erosion of articular bone. This osteo-destructive feature of chronic inflammatory arthritis is a major cause of disability in patients with rheumatoid arthritis.
PMID:24217093	SUPPORT	Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by joint swelling, joint tenderness and destruction of synovial joints, leading to severe disability.
PMID:35273387	SUPPORT	Rheumatoid arthritis can involve localized, periarticular bone erosion...The RANK-RANKL-osteoprotegerin axis and the Wnt-beta-catenin signalling pathway...have been implicated in inflammatory bone loss.

0

category

Musculoskeletal

name

Symmetric Polyarthritis

frequency

VERY_FREQUENT

diagnostic

True

sequelae

Joint Deformity Reduced Mobility

evidence

reference	supports	snippet	explanation
PMID:29848426	PARTIAL	More than 50% patients with JIA have joint deformities. Joint deformities are more likely to be seen in children with long-standing disease, those with polyarthritis JIA and seropositive patients.	This supports the association between polyarthritis and joint deformity, but it is specific to Juvenile Idiopathic Arthritis (JIA) and does not fully address symmetric polyarthritis in RA.
PMID:37410796	SUPPORT	Incident RA presents mainly as symmetric arthritis.	This literature clearly supports that RA often presents as symmetric arthritis, aligning with the statement.
PMID:37158761	SUPPORT	Symmetrical involvement of the hand joints is described as characteristic of rheumatoid arthritis (RA).	This reference reinforces that symmetric polyarthritis is characteristic of RA, supporting the statement.
PMID:14139937	NO_EVIDENCE	No specific information on symmetric polyarthritis provided.	The reference focuses on RA broadly without providing specific details on symmetric polyarthritis.
PMID:22035393	PARTIAL	Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder affecting multiple organ systems, joints, ligaments, and bones and commonly involves the cervical spine.	While this reference mentions systemic and joint involvement, it does not specifically address symmetric polyarthritis or its frequency.
PMID:11358413	SUPPORT	RA is thought to be associated with a conserved sequence of amino acids in a number of HLA-DRB1 alleles, called the RA shared epitope.	This suggests a genetic predisposition to more severe and chronic forms of RA, which could include symmetric polyarthritis, thus supporting the statement.

1

category

Musculoskeletal

name

Morning Stiffness

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:26403254	SUPPORT	These recommendations serve to guide rheumatologists and other stakeholders on the assessment and management of morning stiffness.	The literature states that morning stiffness is a significant symptom in rheumatoid arthritis (RA) and is commonly associated with functional disability and pain. This supports the statement that morning stiffness is a common phenotype in RA.
PMID:36544060	SUPPORT	Rheumatoid arthritis symptoms follow a 24 h circadian rhythm and exhibit high thresholds of pain, functional disability, and stiffness predominantly early in the morning.	This excerpt confirms that morning stiffness is a frequent and notable symptom in rheumatoid arthritis, aligning with the frequency and naming attributes in the statement.
PMID:30936222	NO_EVIDENCE		The reference does not provide relevant information regarding morning stiffness as a phenotype or its commonality in rheumatoid arthritis.
PMID:25437284	NO_EVIDENCE		While the reference discusses early symptoms of RA, it does not specifically mention morning stiffness as a common phenotype.
PMID:24461540	SUPPORT	The typical symptoms are bilateral aching of the shoulder girdle, associated with morning stiffness.	The reference notes that morning stiffness is a symptom associated with polymyalgia rheumatica and also mentions its relevance in diagnosing inflammatory rheumatic diseases, which includes RA.
PMID:29247126	PARTIAL	Morning stiffness, pain and impaired morning function should be routinely assessed in clinical practice.	The recommendation for routine assessment of morning stiffness in patients with RA indirectly supports the statement. However, the focus on patient preferences and decision-making limits the direct relevance to the frequency aspect.

2

category

Systemic

name

Fatigue

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:25005390	SUPPORT	Many of these people experience pain, inflammation, stiffness, reduced mobility and joint function, and fatigue.	The literature supports that fatigue is a common symptom experienced by people with rheumatoid arthritis.
PMID:26803313	SUPPORT	Fatigue occurs in all chronic inflammatory diseases, in cancer, and in some neurological conditions.	This supports the notion that fatigue is a common systemic phenotype in rheumatoid arthritis.
PMID:38643104	SUPPORT	Patients with RA reported worse outcomes for all PROMs than those with CSA or UA.	This study highlights the high burden of fatigue among patients with RA, supporting fatigue as a common systemic phenotype.

3

category

Extra-articular

name

Rheumatoid Nodules

frequency

OCCASIONAL

evidence

reference	supports	snippet	explanation
PMID:15163106	SUPPORT	Extra-articular RA (ExRA) includes a wide variety of disease manifestations... ExRA manifestations are not uncommon, explain excess mortality in RA and are predicted by smoking and autoantibodies.	The abstract mentions that extra-articular manifestations are not uncommon in RA, suggesting that these phenotypes occur occasionally.
PMID:17544962	SUPPORT	Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis.	Rheumatoid nodules are identified as the most common extra-articular manifestation, reinforcing their occurrence in RA.
PMID:27151711	SUPPORT	Rheumatoid nodules (RNs) are one of the most frequent extra-articular manifestations of RA.	The abstract indicates that rheumatoid nodules are among the most frequent extra-articular manifestations, supporting their occasional presence as noted in the given statement.
PMID:7354699	SUPPORT	Rheumatoid nodules were seen in two cases and granulomatous areas surrounding cricothyroid joints were noted in two others.	The study reports instances of rheumatoid nodules, demonstrating their occurrence as extra-articular manifestations, albeit not specifying frequency.
PMID:8465574	SUPPORT	Late-onset RA patients ... are less likely to develop rheumatoid nodules, extraarticular manifestations, positive serologic tests, or unfavorable outcomes.	The abstract notes that rheumatoid nodules occur less frequently in late-onset RA, which indirectly supports their occasional prevalence in the general RA population.
PMID:37740125	SUPPORT	Pulmonary accelerated rheumatoid nodules (ARN) represent a rare occurrence within the context of rheumatoid arthritis (RA)... multiple bilateral pulmonary nodules.	The review provides specific cases of pulmonary rheumatoid nodules, confirming their occasional manifestation as an extra-articular feature.

4

category

Extra-articular

name

Interstitial Lung Disease

frequency

OCCASIONAL

evidence

reference	supports	snippet	explanation
PMID:15163106	PARTIAL	Extra-articular RA (ExRA) includes a wide variety of disease manifestations... ExRA manifestations are not uncommon, explain excess mortality in RA and are predicted by smoking and autoantibodies.	The reference confirms that extra-articular manifestations in RA are common, but does not specifically address the frequency of interstitial lung disease.
PMID:38411210	PARTIAL	RA-associated interstitial lung disease (RA-ILD) is a major contributor to mortality, with no decline in incidence and scant therapeutic options.	The reference confirms RA-ILD as a significant extra-articular manifestation, but it does not detail its specific frequency.
PMID:31376890	PARTIAL	The most common intrathoracic manifestations of RA include interstitial lung disease, airway disease, pleural disease, rheumatoid nodules, and drug-induced toxicity.	The reference indicates that interstitial lung disease is a common pulmonary manifestation of RA, but does not quantify how often it occurs.
PMID:33689246	PARTIAL	All [autoimmune connective tissue diseases] can cause interstitial lung disease... We also discuss the management of the ILD in rheumatoid arthritis, a very prevalent disease...	This indicates that interstitial lung disease is prevalent in RA but does not comment on its frequency as "occasional".
PMID:20223815	NO_EVIDENCE	N/A	The reference focuses on the relationship between rheumatoid arthritis and interstitial lung disease, but does not mention the frequency of ILD as an extra-articular manifestation.
PMID:33170478	PARTIAL	Compared with arthritis-onset RA-ILD... the ILD-onset RA-ILD had less rheumatoid nodules and higher titer of ACPA, and manifested more stable ILD...	The study discusses clinical features and outcomes of RA-related ILD but does not provide information on the frequency of ILD in RA.

name	presence	evidence	subtype
Rheumatoid Factor (RF)	Positive	TRUNCATED	Seropositive RA
Anti-Cyclic Citrullinated Peptide (anti-CCP) Antibodies	Positive	TRUNCATED	Seropositive RA
Erythrocyte Sedimentation Rate (ESR)	Elevated	TRUNCATED	None
C-Reactive Protein (CRP)	Elevated	TRUNCATED	None

0

name

HLA-DRB1

evidence

reference	supports	snippet	explanation
PMID:24447879	SUPPORT	HLA-DRB1*04 was found to have increased frequency in the RA group compared to controls (P < 0.001, OR = 3.14)...HLA-DRB1*04:05 was associated with RA (P = 0.005, OR = 3.41)	The study shows an increased frequency of HLA-DRB1*04 and HLA-DRB1*04:05 in the RA group, indicating an association with increased risk.
PMID:32638005	SUPPORT	This review identifies the most significant genetic variants associated with RA susceptibility to date, with particular focus on the contribution of the HLA class II genes across different ethnic groups.	The review discusses the significant role of HLA-DRB1 in RA susceptibility.
PMID:16542468	SUPPORT	HLA-DR alleles such as HLA-DR4 and HLA-DR1 are associated with the risk to develop RA.	HLA-DR4, a subtype of HLA-DRB1, is associated with an increased risk of developing RA.
PMID:32370106	SUPPORT	Association studies of the HLA-DRB1 gene clearly indicate its importance in RA morbidity.	The review presents the current understanding of HLA-DRB1's role in increasing the risk of RA.
PMID:24336335	SUPPORT	Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA).	The study reinforces the association of HLA-DRB1 alleles with RA.
PMID:3067866	SUPPORT	Part of this genetic predisposition is accounted for by genes within the MHC where there is a well-documented association with HLA-DR4.	The study mentions the association of HLA-DR4, a subtype of HLA-DRB1, with RA.
PMID:29037901	SUPPORT	HLA-DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of Rheumatoid Factor (RF) positive forms of JIA.	The meta-analysis highlights the role of HLA-DRB1 alleles in RA-related conditions, such as juvenile idiopathic arthritis.
PMID:36155967	SUPPORT	We evaluated whether RA-ILD is associated with these genetic variants and HLA-DRB1 shared epitope (SE) alleles in a large RA cohort stratified by race and smoking history.	The study discusses the association of HLA-DRB1 SE alleles with RA-ILD.

association

Associated with increased risk

1

name

PTPN22

evidence

reference	supports	snippet	explanation
PMID:30957405	SUPPORT	The overall effect of PTPN22-1123 on RA risk in all genetic random models showed significant positive associations.	The study found significant positive associations between PTPN22 genetic variations and increased risk of rheumatoid arthritis.
PMID:15790351	SUPPORT	A functional variant (R620W) of the intracellular protein tyrosine phosphatase N22 (PTPN22) has now been conclusively shown to confer approximately two-fold risk for seropositive RA as well as several other autoimmune disorders.	The variant R620W of PTPN22 is associated with a significantly increased risk of rheumatoid arthritis.
PMID:15838240	SUPPORT	The second risk factor for rheumatoid arthritis, the PTPN22 polymorphism, has been identified.	The PTPN22 polymorphism has been identified as a genetic risk factor for rheumatoid arthritis.

association

Associated with increased risk

2

name

STAT4

evidence

reference	supports	snippet	explanation
PMID:30864557	SUPPORT	Herein, we found a significant positive association between minor T allele as well as different genotypes with the risk of RA.	The study found a significant positive association between the STAT4 gene rs7574865 SNP and the risk of rheumatoid arthritis (RA).
PMID:20453440	SUPPORT	We and other investigators also found that IRF5, STAT4 and BLK are associated not only with SLE, but also rheumatoid arthritis and systemic sclerosis.	The literature supports an association between the STAT4 gene and increased risk of rheumatoid arthritis.

association

Associated with increased risk

3

name

CTLA4

evidence

reference	supports	snippet	explanation
PMID:34339393	SUPPORT	This meta-analysis confirmed that rs3087243 and rs231775 polymorphisms were associated with the risk of RA in both overall population and ethnic-specific analysis.	The meta-analysis provides evidence that CTLA-4 gene polymorphisms are associated with an increased risk of rheumatoid arthritis.
PMID:35758965	SUPPORT	We intended to investigate gene expression of... Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in RA patients versus controls. There was a significantly higher median (inter-quartile range) expression of CTLA-4 in RA patients in comparison to controls (P < 0.05).	The study found significantly higher expression of CTLA-4 in RA patients, supporting the association of CTLA-4 with increased RA risk.
PMID:11196709	SUPPORT	For most autoimmune disorders... the gene encoding cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been suggested as a candidate gene for conferring susceptibility to autoimmunity.	The article discusses CTLA4 as a candidate gene for susceptibility to autoimmune diseases, including rheumatoid arthritis.
PMID:34011726	SUPPORT	Association between CTLA-4 gene polymorphism and risk of rheumatoid arthritis: a meta-analysis... provides evidence for the involvement of CTLA-4 polymorphisms in the risk of rheumatoid arthritis.	CTLA-4 gene polymorphism is found to be significantly associated with the risk of RA according to the meta-analysis.

association

Associated with increased risk

0

name

Smoking

evidence

reference	supports	snippet	explanation
PMID:22609003	SUPPORT	Smoking is associated with an increased risk of developing seropositive RA (RF and/or ACPA). Recent studies show that tobacco smoking can influence disease phenotype, with the development of more aggressive disease and greater joint damage.	The literature indicates that smoking increases the risk of developing seropositive RA and may lead to more severe disease outcomes, which aligns with the statement.
PMID:18528946	SUPPORT	Rheumatoid factor and smoking are associated with disease severity, which in turn impacts mortality in rheumatoid arthritis.	This supports that smoking not only increases the risk but also severity of RA.
PMID:12860726	SUPPORT	In a multivariate analysis the main predictors of severe ExRA were smoking at RA diagnosis (risk ratio (RR)=2.94; 95% confidence interval (95% CI) 1.68 to 5.13).	This reference indicates smoking as a significant predictor of severe extra-articular manifestations in RA, supporting the statement about severity.
PMID:36155967	SUPPORT	MUC5B and TOLLIP single nucleotide polymorphisms (SNPs) and cigarette smoking were associated with rheumatoid arthritis-interstitial lung disease (RA-ILD).	Smoking is listed as a risk factor for RA and its associated complications, such as interstitial lung disease.
PMID:34553824	SUPPORT	Counseling these patients to act to modify factors known to be associated with RA risk could prevent the development of RA... (i) cease smoking.	This reference mentions smoking cessation as a preventable measure, indicating its role in increasing RA risk.

notes

Increases risk and severity

1

name

Infections

evidence

reference	supports	snippet	explanation
PMID:28516867	SUPPORT	Extensive data supports the roles of genetic, environmental and microbial factors in the triggering and development of this disease. Proteus mirabilis is considered as the main microbial culprit in the causation of RA.	This reference supports the role of infections, specifically microbial factors, as potential environmental triggers for the onset of rheumatoid arthritis.
PMID:32582191	SUPPORT	In conclusion, we retrieved more than one line of evidence for mucosal sites and different microbial taxa to be potentially involved in the development of RA.	This reference provides multiple lines of evidence suggesting that infections, specifically from various microbial taxa, are potential contributors to the onset of rheumatoid arthritis.
PMID:35897715	SUPPORT	Possible mechanisms involving environmental and individual factors in RA pathogenesis were analyzed, namely, infections, mental stress, sleep deprivation ecology, age, perinatal and gender factors, eating habits, obesity and smoking.	This reference explicitly includes infections among the environmental factors that may contribute to the onset of RA.

notes

Potential trigger for disease onset

0

name

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

description

Reduce pain and inflammation.

evidence

reference	supports	snippet	explanation
PMID:11899747	SUPPORT	NSAID toxicity mostly affected the GI tract. There was a similar incidence of GI-related adverse events between patients with and patients without GI protection, mainly dyspepsia and nausea. NSAIDs have the potential to cause adverse events in the GI tract.	The provided literature indicates that NSAIDs are used in the treatment of rheumatoid arthritis (RA) and can help alleviate pain, despite some potential side effects, thus supporting the statement.
PMID:29100265	SUPPORT	This review will give a concise summary on the available studies on the application of nano-formulated drugs designed for pain treatment and management.	This reference mentions the effectiveness of NSAIDs in pain management, supporting the statement.
PMID:23083758	SUPPORT	NSAIDs reduce pain and stiffness effectively in most patients, are able to reduce systemic and local inflammation, and can inhibit progression of structural damage in the spine.	This indicates that NSAIDs are effective in reducing pain and inflammation in conditions similar to RA, thus supporting the statement.
PMID:27278642	PARTIAL	By examining confounds and limitations in the available literature it is suggested that current data suggest that only a sub-group of individuals with major depressive disorder (MDD) have evidence of increased inflammatory biomarkers and it is in these individuals that anti-inflammatory agents show promise for reducing depressive symptoms.	While the reference primarily discusses the use of NSAIDs for major depressive disorder, it hints at the effectiveness of NSAIDs in reducing inflammation, partially supporting the statement.

1

name

Disease-Modifying Antirheumatic Drugs (DMARDs)

description

Slow disease progression and prevent joint damage (e.g., methotrexate, hydroxychloroquine).

evidence

reference	supports	snippet	explanation
PMID:14969069	SUPPORT	Disease-modifying anti-rheumatic drugs (DMARDs) used in combination appear to be more effective than monotherapies at reducing the rate of progressive joint damage during randomized controlled trials.	This statement directly supports the idea that DMARDs slow disease progression and prevent joint damage.
PMID:8601050	SUPPORT	Methotrexate is presently the most popular of the DMARDs for the treatment of rheumatoid arthritis. Methotrexate inhibits dihydrofolate reductase and adenosine release and has a secondary effect on cytokines and polymorphonuclear chemotaxis. It is highly metabolised within cells and remains there for prolonged periods.	This excerpt indicates methotrexate's mechanisms in treating RA, affirming its role in slowing disease progression and preventing joint damage.
PMID:25172238	SUPPORT	According to the results of several head-to-head comparative trials against other synthetic DMARDs, MTX has been recognised as the 'anchor drug' for the treatment of RA.	This confirms methotrexate's effectiveness as a primary treatment in managing RA, thus supporting the statement.
PMID:35953230	SUPPORT	Key recommendations are to start effective treatment immediately with DMARDs to reduce disability; use effective doses of methotrexate (oral or subcutaneous) with folic acid as the initial treatment; rapidly escalate treatment with various DMARDs, if methotrexate alone is not effective in controlling rheumatoid arthritis.	This supports the statement by advising DMARDs to prevent disease progression and joint damage.
PMID:38126739	SUPPORT	Early intervention with these drugs (csDMARDs) is emphasized to prevent joint damage, improve clinical symptoms, and enhance patient outcomes.	This supports the value that DMARDs, including methotrexate and hydroxychloroquine, slow disease progression and prevent joint damage.

2

name

Biologics

description

Target specific components of the immune system (e.g., TNF-α inhibitors, IL-6 inhibitors).

evidence

reference	supports	snippet	explanation
PMID:22166850	SUPPORT	Rheumatoid arthritis (RA) remains a major clinical problem, but treatments involving biologics have revolutionized its management. They target pathogenically relevant cytokines such as tumor necrosis factor and immune cells such as B cells.	This reference confirms that biologics used in the treatment of RA target specific components of the immune system, including cytokines like TNF-α.
PMID:32456483	SUPPORT	Biologic disease-modifying antirheumatic drugs (bDMARDs) used for rheumatoid arthritis (RA) treatment have several mechanisms of action. Interleukin-6 inhibitors (IL-6i) block the production of acute-phase reactants (APRs), which are some of the composite measures of disease activity.	This reference supports that biologics for RA treatment include IL-6 inhibitors, which target specific components of the immune system.
PMID:25697599	SUPPORT	Anticytokine therapy for inflammatory diseases became a clinical reality with the introduction of tumor necrosis factor (TNF) inhibitors for the treatment of severe rheumatoid arthritis.	The reference highlights that anticytokine therapies, including TNF inhibitors, are used in RA treatment, thus supporting the statement.
PMID:32550671	SUPPORT	Cytokine blockers were the first to be developed and rapidly expanded. They include agents that act against tumor necrosis factor alpha (TNF-α)... and interleukin (IL) 6 (tocilizumab and sarilumab).	The reference supports that biologics used for RA treatment include TNF-α inhibitors and IL-6 inhibitors, which target specific components of the immune system.

3

name

Glucocorticoids

description

Potent anti-inflammatory agents used for short-term control of flares or as a bridge therapy.

evidence

reference	supports	snippet	explanation
PMID:28043173	PARTIAL	Glucocorticoids - be it conventional or modified/delayed-release formulations - have so far been convincing in clinical practice, and their widespread use will therefore continue.	The literature supports the use of glucocorticoids for the treatment of rheumatoid arthritis, highlighting their efficacy. However, it does not specify that they are used for short-term control of flares or as bridge therapy, thus only partially supporting the precise conditions mentioned in the statement.
PMID:24527481	PARTIAL	The family physician plays several important roles in the management of patients with RA by early diagnosis of RA, with initiation of synthetic DMARD therapy, and in long-term follow-up to minimize complications of DMARD therapy and its impact on patient comorbidities.	This reference mentions the management and use of various therapies for rheumatoid arthritis, but it does not explicitly discuss the short-term use or glucocorticoids as bridge therapy, providing only partial support.
PMID:29745893	PARTIAL	Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and disease-modifying antirheumatic drugs (DMARDs) are widely used to treat RA patients.	This literature confirms the use of corticosteroids (which include glucocorticoids) in treating RA but does not specify their role as short-term or bridge therapy, thereby partially supporting the statement.

4

name

Physical Therapy

description

Maintains joint mobility and strengthens surrounding muscles.

evidence

reference	supports	snippet	explanation
PMID:15266230	SUPPORT	Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA.	The literature supports the effectiveness of physiotherapy in managing RA, including maintaining joint mobility and reducing disabilities.
PMID:25748549	SUPPORT	The exercise programme consisted of six sessions of strengthening and stretching exercises with a hand therapist, daily home exercises and strategies to maximise adherence.	The results indicate that exercise programmes included in physical therapy can be effective in maintaining joint function and strengthening muscles in RA patients.
PMID:9667624	SUPPORT	The results suggest that dynamic exercise therapy is effective in increasing aerobic capacity and muscle strength.	Dynamic exercise therapy, a component of physical therapy, has been shown to improve muscle strength and maintain physical capacity in RA patients.