Rheumatoid Arthritis (RA) — Management

Principles of Treatment

RA has no known cure; the overriding goals are remission (achievable in >50% of patients treated early) or low disease activity in all patients. Key principles:

Key	Detail
Early diagnosis + early DMARD	Erosions begin in the first 1–2 years — irreversible once established
Treat-to-target (T2T)	Reassess every 1–3 months; escalate until target is met
Multidisciplinary	Rheumatologist, nurse specialist, physio, OT, orthopedic surgeon
Comorbidities	CVD, infection risk, osteoporosis must be actively managed

— Goldman-Cecil Medicine, p. 2794

Three Drug Categories

1. NSAIDs

Provide symptomatic relief only — do not alter disease course
Never use as sole therapy — always pair with a DMARD
Prefer naproxen/ibuprofen over COX-2 inhibitors given CV risk in RA; if COX-2 used, keep at lowest dose
Add PPI for all RA patients on NSAIDs
Doses: Celecoxib 100 mg BD | Naproxen 500 mg BD | Ibuprofen 400 mg QID

2. Glucocorticoids

Rapid onset — used as bridge while DMARDs take effect
Prednisone ≤10 mg/day; taper to lowest effective dose
Shown to reduce erosive damage and disability when added at start of MTX-based therapy
Can use intra-articular or IM depot for flares
Goal: wean off, or very low dose, once DMARDs are effective
Risk: 25% ↑ serious infection even at 5 mg/day; doubling at 5–10 mg/day

3. DMARDs (cornerstone of therapy)

Conventional (csDMARDs)

Drug	Dose	Notes
Methotrexate	7.5–25 mg PO/SQ once weekly	First-line anchor drug
Hydroxychloroquine	200–400 mg daily (5 mg/kg)	Mild disease; retinal monitoring
Leflunomide	10–20 mg daily	Alternative to MTX
Sulfasalazine	500 mg BD → 2 g/day	Often used in combination
Azathioprine	1–2.5 mg/kg/day	Steroid-sparing
Minocycline	100 mg BD	Mild, seropositive disease

Triple therapy (MTX + hydroxychloroquine + sulfasalazine) has efficacy comparable to MTX + biologic in some trials.

Biologic DMARDs (bDMARDs)

Class	Agents	Route
TNF inhibitors	Etanercept, Infliximab, Adalimumab, Certolizumab, Golimumab	SC / IV
IL-6 inhibitors	Tocilizumab, Sarilumab	SC / IV
T-cell costimulation blocker	Abatacept (500–1000 mg IV q4wk)	IV / SC
B-cell depletion	Rituximab (1000 mg IV × 2, 2 wks apart)	IV
IL-1 inhibitor	Anakinra	SC daily

Note: Tocilizumab and JAK inhibitors raise serum cholesterol; TNF inhibitors and MTX reduce cardiovascular mortality.

Targeted Synthetic DMARDs (tsDMARDs) — JAK Inhibitors

Drug	Dose
Tofacitinib	5 mg PO BD or 11 mg XR daily
Baricitinib	2 mg PO daily
Upadacitinib	15 mg PO daily

JAK inhibitors carry FDA black-box warnings for thrombosis, serious infections, and malignancy risk (particularly in patients >65, smokers, or with CVD). Use after failure of at least one csDMARD.

Treatment Algorithm (ACR Guidelines)

ACR RA Treatment Algorithm — Early DMARD-Naïve RA

Early RA (DMARD-naïve):

Low disease activity → DMARD monotherapy (MTX preferred)
Moderate/high disease activity → DMARD monotherapy (conditional) → if still moderate/high → Combination csDMARDs or TNF inhibitor ± MTX or non-TNF biologic ± MTX

Established RA (inadequate response):

Escalate to combination DMARDs, add biologic, or switch biologic class
If TNF inhibitor fails → try non-TNF biologic (e.g., abatacept, tocilizumab, rituximab) or JAK inhibitor

— Swanson's Family Medicine Review, Fig. 49.2

Monitoring & Safety

Drug	Key Monitoring
MTX	LFTs, CBC, renal function; folic acid 1 mg/day to reduce toxicity
Hydroxychloroquine	Annual ophthalmology (retinal toxicity)
Leflunomide	LFTs, blood pressure
Biologics/JAK inhibitors	TB screening (LTBI), hepatitis B serology before starting; annual influenza vaccine; pneumococcal vaccine; avoid live vaccines
Glucocorticoids	Bone density (DEXA); calcium + vitamin D; BP; glucose

Comorbidity Management

Cardiovascular: Aggressive risk factor treatment; MTX + TNF inhibitors reduce CV mortality
Osteoporosis: Screen all RA patients; treat early
Infections: Heightened risk (disease + therapy); vaccinate (pneumococcal, influenza, zoster); prompt treatment of infections
Lymphoma: Increased risk — monitor; some B-cell lymphomas regress on reducing immunosuppression
Cervical spine: C1–C2 instability in 30–40% of established RA; 5% develop myelopathy — screen before procedures

Surgical Management

Considered when medical therapy fails to control joint damage
Procedures: synovectomy, tendon repair, joint replacement (hip/knee most common)
Pre-op cervical spine X-ray mandatory (atlanto-axial instability)

Prognosis

RF+, anti-CCP+, and shared epitope (HLA-DRB1) → worse prognosis (more erosions, extra-articular disease)
With modern aggressive DMARD/biologic therapy, all-cause mortality now approaches that of the general population

— Goldman-Cecil Medicine, p. 2795

Recent evidence note: A 2024 systematic review/meta-analysis supporting JAK inhibitors in RA-associated ILD (PMID: 39270812) and the 2024 Japan College of Rheumatology updated guidelines (PMID: 38814660) are available for reference. CAR-T cell therapy is under early investigation for refractory autoimmune disease (PMID: 39754644).

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