What is rheumatoid arthritis?

Rheumatoid arthritis is a chronic autoimmune inflammatory disease — where the immune system attacks the synovial lining of joints, causing inflammation, pain, swelling and stiffness. Untreated, it causes progressive joint destruction (erosions, deformity), disability and shortened life expectancy from cardiovascular disease. It affects 18 million people globally (0.5-1% of adults), with a 3:1 female predominance, typically presenting between ages 40-60.

RA is multifactorial — genetic predisposition (HLA-DRB1 "shared epitope" alleles are the strongest genetic risk factor; contributing approximately 30-50% of genetic risk) plus environmental triggers. Smoking is the most important modifiable risk factor — doubles RA risk and worsens severity. Other factors: female sex hormones; gut microbiome alterations; periodontal disease (Porphyromonas gingivalis may initiate citrullination triggering anti-CCP antibody production); and prior respiratory infections. The "pre-RA" period — when anti-CCP antibodies are present without clinical arthritis — may last years.

The 2022 EULAR RA management recommendations: (1) Initiate methotrexate (MTX) immediately at diagnosis ± short-term glucocorticoids (rapid bridging). (2) Target remission (DAS28 <2.6) or low disease activity within 3-6 months. (3) If target not achieved with MTX: add or switch to biologic DMARD (TNF inhibitor, IL-6 inhibitor, abatacept, rituximab) or JAK inhibitor in combination with MTX. (4) If bDMARD fails: switch to a different bDMARD class or JAKi. (5) Continue at lowest effective dose when sustained remission achieved.

What are JAK inhibitors?

JAK inhibitors (JAKi) — tofacitinib (Xeljanz, JAK1/3), baricitinib (Olumiant, JAK1/2), upadacitinib (Rinvoq, JAK1-selective), filgotinib (Jyseleca, JAK1) — are oral small molecule drugs blocking JAK-STAT intracellular signalling pathways that mediate cytokine-driven inflammation. Advantages: oral; rapid onset; no immunogenicity; comparable efficacy to TNF inhibitors. Safety considerations: increased risk of serious infections, herpes zoster; FDA boxed warning for cardiovascular events, malignancy and thrombosis (derived primarily from tofacitinib in high-CV-risk patients — the CLASS of concern applies to all JAKi per FDA).

What extra-articular manifestations does RA cause?

RA is a systemic disease with extra-articular manifestations: cardiovascular disease (2x elevated risk — inflammation-driven atherosclerosis; the leading cause of premature death); interstitial lung disease (a major cause of morbidity and mortality in RA); rheumatoid nodules (firm subcutaneous nodules over pressure points); episcleritis/scleritis; Sjögren's syndrome overlap; Felty syndrome (splenomegaly + neutropenia); and anaemia of chronic disease. Cardiovascular risk reduction is an integral part of RA management.

What is the treat-to-target approach?

Treat-to-target (T2T) in RA means: defining a clear target (remission — DAS28 <2.6 — or low disease activity); measuring disease activity objectively with validated composite scores (DAS28, CDAI, SDAI) at every visit; and intensifying therapy until the target is reached. T2T has been shown in multiple RCTs (TICORA, BeSt, CAMERA, COBRA) to produce significantly better structural and functional outcomes than conventional management. EULAR and ACR recommend T2T as standard of care.

RA is not fully preventable — but modifiable risk factors can reduce risk: smoking cessation (the most important modifiable factor — smoking doubles RA risk and should be actively addressed); optimal weight; treatment of periodontal disease (may reduce citrullinated antigen exposure); and potentially strategies to modify gut microbiome. In individuals with high anti-CCP antibodies detected during the pre-RA phase (e.g. blood relatives of RA patients), trials are examining whether early methotrexate or abatacept can prevent progression to clinical RA.

How does GMJ News cover RA?

GMJ News covers WHO RA burden data, TNF inhibitor and JAK inhibitor evidence, treat-to-target implementation, cardiovascular risk management in RA, anti-CCP testing and biologic access in LMICs. RA is a significant inflammatory condition in Georgia — directly relevant to PHIG's rheumatology and healthcare quality priorities.

Home › Topics › Rheumatoid Arthritis

Rheumatoid Arthritis

Q: What are JAK inhibitors?

JAK inhibitors (JAKi) — tofacitinib (Xeljanz, JAK1/3), baricitinib (Olumiant, JAK1/2), upadacitinib (Rinvoq, JAK1-selective), filgotinib (Jyseleca, JAK1) — are oral small molecule drugs blocking JAK-STAT intracellular signalling pathways that mediate cytokine-driven inflammation. Advantages: oral; rapid onset; no immunogenicity; comparable efficacy to TNF inhibitors. Safety considerations: increased risk of serious infections, herpes zoster; FDA boxed warning for cardiovascular events, malignancy and thrombosis (derived primarily from tofacitinib in high-CV-risk patients — the CLASS of concern applies to all JAKi per FDA).

Q: What extra-articular manifestations does RA cause?

RA is a systemic disease with extra-articular manifestations: cardiovascular disease (2x elevated risk — inflammation-driven atherosclerosis; the leading cause of premature death); interstitial lung disease (a major cause of morbidity and mortality in RA); rheumatoid nodules (firm subcutaneous nodules over pressure points); episcleritis/scleritis; Sjögren's syndrome overlap; Felty syndrome (splenomegaly + neutropenia); and anaemia of chronic disease. Cardiovascular risk reduction is an integral part of RA management.

Q: What is the treat-to-target approach?

Treat-to-target (T2T) in RA means: defining a clear target (remission — DAS28 <2.6 — or low disease activity); measuring disease activity objectively with validated composite scores (DAS28, CDAI, SDAI) at every visit; and intensifying therapy until the target is reached. T2T has been shown in multiple RCTs (TICORA, BeSt, CAMERA, COBRA) to produce significantly better structural and functional outcomes than conventional management. EULAR and ACR recommend T2T as standard of care.

Q: Is RA preventable?

RA is not fully preventable — but modifiable risk factors can reduce risk: smoking cessation (the most important modifiable factor — smoking doubles RA risk and should be actively addressed); optimal weight; treatment of periodontal disease (may reduce citrullinated antigen exposure); and potentially strategies to modify gut microbiome. In individuals with high anti-CCP antibodies detected during the pre-RA phase (e.g. blood relatives of RA patients), trials are examining whether early methotrexate or abatacept can prevent progression to clinical RA.

Q: How does GMJ News cover RA?

GMJ News covers WHO RA burden data, TNF inhibitor and JAK inhibitor evidence, treat-to-target implementation, cardiovascular risk management in RA, anti-CCP testing and biologic access in LMICs. RA is a significant inflammatory condition in Georgia — directly relevant to PHIG's rheumatology and healthcare quality priorities.

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Rheumatoid arthritis (RA) — a chronic immune-mediated inflammatory arthritis destroying joint cartilage and bone — affects approximately 18 million people globally (0.5-1% of adults), causing pain, progressive disability, cardiovascular disease and premature mortality (WHO). The treat-to-target revolution — achieving remission or low disease activity through escalating therapy — combined with the biological and targeted synthetic DMARD era (TNF inhibitors, IL-6 inhibitors, JAK inhibitors) has transformed RA from a disease of inevitable disability to one where near-normal function and life expectancy is achievable with modern treatment.

Key messages

18 million people globally

Rheumatoid arthritis (RA) — a chronic immune-mediated inflammatory arthritis — affects approximately 18 million people globally (0.5-1% of adults), causing progressive joint destruction, disability and elevated cardiovascular mortality (WHO).

Treat-to-target — the care revolution

The treat-to-target (T2T) approach — defining remission or low disease activity as the treatment target, monitoring objectively with validated scores (DAS28, CDAI), and escalating therapy until the target is achieved — has transformed RA outcomes.

TNF inhibitors changed everything

TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab, golimumab) — the first biologic DMARDs — transformed RA management in the late 1990s, achieving remission in patients who previously progressed to disability. Combined with methotrexate, they remain first-line biologic therapy.

JAK inhibitors — latest advance

JAK inhibitors (baricitinib, tofacitinib, upadacitinib, filgotinib) — oral small molecules blocking Janus kinase signalling — offer comparable efficacy to TNF inhibitors and are increasingly used after methotrexate failure or as alternatives to biologics.

Cardiovascular risk doubled

RA doubles cardiovascular risk — driven by systemic inflammation, dyslipidaemia and physical inactivity. Cardiovascular disease is the leading cause of premature death in RA. Aggressive inflammation control and cardiovascular risk factor management are both essential.

Anti-CCP antibodies — a revolution in diagnosis

Anti-citrullinated protein antibodies (anti-CCP) are highly specific for RA (approximately 95-98%) and appear years before clinical disease onset — enabling early diagnosis and identifying patients at risk for development.

Key statistics

18M

people with RA globally

WHO

0.5-1%

of adults affected globally

WHO

3:1

female to male ratio

WHO/EULAR

cardiovascular mortality risk vs general population

EULAR

95-98%

specificity of anti-CCP antibodies for RA

EULAR/ACR

50%

of RA patients achieve remission with optimal T2T

EULAR

RA treatment response rates (ACR50) — comparative clinical trial data

Source: Published RCTs. All bDMARDs and JAKi show similar efficacy in TNF-naive patients.

Glossary of key terms

Anti-CCP antibodies
WHO/EULAR/ACRAnti-citrullinated protein/peptide antibodies — the most disease-specific laboratory marker for RA (95-98% specificity). Appear years before clinical RA onset. Together with rheumatoid factor (RF), define "seropositive" RA — associated with more severe, erosive disease. Used in the 2010 ACR/EULAR classification criteria.

DMARDs (Disease-modifying antirheumatic drugs)
WHO/EULARA class of drugs that slow or halt RA progression. Conventional synthetic DMARDs (csDMARDs): methotrexate (anchor drug, first-line); leflunomide; sulfasalazine; hydroxychloroquine. Biologic DMARDs (bDMARDs): TNF inhibitors, IL-6 inhibitors, CTLA4-Ig (abatacept), anti-CD20 (rituximab). Targeted synthetic DMARDs (tsDMARDs): JAK inhibitors.

Methotrexate (MTX)
WHO EML/EULARThe anchor drug for RA — first-line DMARD used as monotherapy or in combination with biologics/JAKi. Weekly oral or SC dose (15-25mg/week) with folic acid supplementation to reduce side effects. Inexpensive, effective and on the WHO Essential Medicines List.

TNF inhibitors (bDMARDs)
EULAR/ACRMonoclonal antibodies or fusion proteins targeting TNF-alpha — the first and most widely used biologic class for RA: adalimumab (SC biweekly), etanercept (SC weekly), infliximab (IV), certolizumab (SC), golimumab (SC or IV). Combined with methotrexate, achieve ACR50 response in approximately 55-60%.

JAK inhibitors (JAKi)
EULAR/FDAOral targeted synthetic DMARDs blocking Janus kinase signalling — tofacitinib (JAK1/3), baricitinib (JAK1/2), upadacitinib (JAK1-selective), filgotinib (JAK1). Comparable efficacy to TNF inhibitors in MTX-inadequate responders. FDA boxed warning for cardiovascular events, malignancy, thrombosis (based on tofacitinib data in high-CV-risk patients — extrapolated to class).

DAS28 (Disease Activity Score)
EULARA validated composite disease activity measure — incorporating 28-joint tender and swollen joint counts, patient global assessment and ESR or CRP. DAS28 <2.6 = remission; 2.6-3.2 = low disease activity; 3.2-5.1 = moderate; >5.1 = high disease activity. Used in treat-to-target monitoring.