What is the drug of choice for managing arthritis?

Drug of Choice for Arthritis

NSAIDs (non-steroidal anti-inflammatory drugs) are the drug of choice for initial symptomatic treatment of arthritis, with the specific type of arthritis determining whether disease-modifying therapy should be initiated concurrently or after NSAID trial. 1

Type-Specific First-Line Recommendations

Osteoarthritis

• Topical NSAIDs are strongly recommended as first-line pharmacological treatment for knee osteoarthritis, offering comparable efficacy to oral NSAIDs with superior safety profiles 2, 1
• For hand osteoarthritis, topical NSAIDs combined with hand orthoses (particularly for first carpometacarpal joint involvement) represent the optimal initial approach 2, 3
• Oral NSAIDs should be reserved for patients who fail topical therapy or have polyarticular involvement requiring systemic treatment 2
• Paracetamol (acetaminophen) received only conditional recommendations in recent guidelines due to modest efficacy, with patients preferring NSAIDs in real-world use 2, 4, 5

Rheumatoid Arthritis

• Methotrexate is the drug of choice for rheumatoid arthritis and should be initiated rapidly in patients with polyarthritis, with NSAIDs serving only as adjunctive symptomatic therapy 2, 6
• For patients with monoarthritis/oligoarthritis plus poor prognostic factors (structural damage, elevated acute phase reactants, dactylitis, nail involvement), methotrexate should also be started immediately 2
• NSAIDs provide symptomatic relief but do not alter disease progression or prevent joint destruction, making them inadequate as monotherapy beyond 2 months 1, 7

Psoriatic Arthritis

• Methotrexate is preferred as the first-line conventional synthetic DMARD, particularly when clinically relevant skin involvement is present 2
• NSAIDs may be used for symptomatic relief of musculoskeletal manifestations 2
• Rapid escalation to biologic DMARDs (IL-17 inhibitors or IL-12/23 inhibitors preferred with skin involvement) is indicated after inadequate response to one csDMARD 2

NSAID Selection Algorithm

Risk Assessment Required Before Prescribing

• Evaluate gastrointestinal risk factors: age >65, prior peptic ulcer disease, concurrent corticosteroid/anticoagulant use 2, 1, 8
• Assess cardiovascular risk: uncontrolled hypertension, heart failure, ischemic heart disease 2, 9, 8
• Check renal function: NSAIDs can worsen renal impairment 9, 8

NSAID Choice Based on Risk Profile

• Low GI/CV risk: Any oral NSAID at lowest effective dose 2, 8
• High GI risk: COX-2 inhibitor plus proton pump inhibitor, or topical NSAID 2, 8
• High CV risk: Avoid NSAIDs if possible; if necessary, use naproxen with PPI gastroprotection 2, 8
• Elderly patients (≥75 years): Topical NSAIDs strongly preferred over oral formulations 9

Adjunctive Glucocorticoid Use

• Intra-articular glucocorticoid injections are strongly recommended for moderate-to-severe pain in knee osteoarthritis, providing relief for up to 4 months with triamcinolone hexacetonide 2, 1, 3
• Local injections should be considered for oligoarticular involvement in any arthritis type 2, 1
• Systemic glucocorticoids may be used cautiously at <7.5 mg/day prednisone equivalent for the shortest duration possible (<6 months) to avoid cumulative toxicity 2, 1

Critical Pitfalls to Avoid

• Never continue NSAID monotherapy beyond 2 months in active rheumatoid arthritis—this represents inappropriate care and allows irreversible joint damage 1, 7
• Do not prescribe oral NSAIDs without assessing GI, cardiovascular, and renal risk factors—this is the most common prescribing error 1, 8
• Avoid combining aspirin with COX-2 inhibitors—this eliminates the GI safety advantage of selective inhibition 8
• Do not use glucosamine, chondroitin, or rubefacients—these lack evidence of efficacy and are not recommended 2

Treatment Escalation Pathway

For inflammatory arthritis (RA, PsA) with inadequate NSAID response:

1. Add methotrexate (or initiate if not already started) 2, 6
2. If inadequate response to csDMARD after 3-6 months: Add biologic DMARD (TNF inhibitor, IL-6 receptor inhibitor, or others depending on arthritis type) 2, 10
3. If inadequate response to first biologic: Switch to alternative biologic or consider JAK inhibitor with safety considerations 2

The treat-to-target strategy with regular monitoring (every 1-3 months) until remission or low disease activity is achieved represents the standard of care for inflammatory arthritis, where the treatment strategy matters more than the specific drug chosen 2, 11