14.2 Osteoarthritis, Rheumatoid Arthritis & Gout

Osteoarthritis, Rheumatoid Arthritis & Gout

Joint diseases are a frequent source of analgesic questions, immunosuppressant monitoring and serious drug interactions. The pharmacist's job differs for each: matching analgesic risk to comorbidities in osteoarthritis, safe disease-modifying therapy in rheumatoid arthritis, and a treat-to-target urate strategy in gout.

1. Osteoarthritis (OA)

• Foundations for everyone: exercise and strengthening, weight loss if overweight (each kilogram lost reduces knee load), walking aids, and education.
• Topical NSAIDs (diclofenac gel or solution) are first-line for knee and hand OA. Systemic exposure is only about 5 to 10% of oral dosing, which suits older adults and patients with GI or CV risk.
• Oral NSAIDs: the most effective oral option, at the lowest dose for the shortest time.
  • Add a PPI if the patient is 65 or older, has a past ulcer, or takes anticoagulants, antiplatelets or corticosteroids.
  • Avoid in CKD, heart failure, uncontrolled hypertension, or after recent CV events. In PRECISION, moderate-dose celecoxib was cardiovascularly noninferior to naproxen and ibuprofen (section 13.1).
• Acetaminophen gives only a small benefit in OA, but it remains reasonable when NSAIDs are unsafe, within the daily maximum.
• Duloxetine helps chronic OA pain, especially with coexisting depression or widespread pain.
• Intra-articular corticosteroid injections give short-term relief in flares.
• Opioids are generally avoided for OA because of harms without durable benefit. Glucosamine and chondroitin lack convincing evidence.

2. Rheumatoid Arthritis (RA)

RA is a systemic autoimmune polyarthritis. Early disease-modifying therapy within the first months prevents erosions, and treatment aims at remission or low disease activity ("treat to target").

Conventional Synthetic DMARDs

Biologic and Targeted Therapies

• Options when methotrexate is inadequate: TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab, golimumab), abatacept, tocilizumab, sarilumab and rituximab. Biosimilars exist for many, and provincial switching policies apply.
• Before starting: screen for latent TB and hepatitis B and C, and update vaccinations. Live vaccines are avoided during therapy, and the drug is held during serious infections.
• JAK inhibitors (tofacitinib, baricitinib, upadacitinib) are oral targeted agents. Health Canada warnings after the ORAL Surveillance trial: higher rates of serious cardiovascular events, cancer, thrombosis and death than with TNF inhibitors in patients 50 and older with a cardiovascular risk factor. Use them in older patients, smokers and those with CV or VTE risk only when no suitable alternative exists.
• Glucocorticoids bridge until DMARDs work (6 to 12 weeks), at the lowest dose for the shortest time, with bone protection if they are prolonged.

3. Gout

Acute Flare (Start Treatment as Early as Possible)

• NSAID at full anti-inflammatory dose (for example, naproxen 500 mg twice daily), unless contraindicated.
• Low-dose colchicine: 1.2 mg at onset, then 0.6 mg one hour later. It works best within 36 hours. High-dose regimens add toxicity without extra benefit.
• Corticosteroids: oral prednisone (for example, 30 to 35 mg daily for 5 days) or an intra-articular injection. Useful in CKD or when NSAIDs and colchicine are unsafe.
• Continue urate-lowering therapy (ULT) during a flare. Do not stop allopurinol.

Urate-Lowering Therapy

• Indications: 2 or more flares a year, tophi, or radiographic damage. It is also considered after a first flare with CKD stage 3 or higher, very high urate, or kidney stones.
• Allopurinol is first-line.
  • Start low: 100 mg daily or less, and 50 mg daily in moderate to severe CKD.
  • Titrate every 2 to 5 weeks to a serum urate below 360 µmol/L (below 300 µmol/L with tophi). The final dose can exceed renal-based "maximums" if titrated slowly and monitored.
  • HLA-B*5801 testing before starting is advised for patients of Han Chinese, Korean or Thai ancestry (and some guidelines add African ancestry). Carriers have a high risk of severe cutaneous reactions (SJS/TEN, DRESS).
• Flare prophylaxis when starting ULT: colchicine 0.6 mg once or twice daily (or a low-dose NSAID) for 3 to 6 months, because rapid urate lowering mobilizes crystals.
• Febuxostat is an alternative. It carries cardiovascular-death warnings, so it is avoided in established cardiovascular disease when alternatives exist.
• Drugs that raise urate: thiazide and loop diuretics, low-dose ASA, cyclosporine and niacin. Losartan modestly lowers urate, which helps when a hypertensive patient needs an alternative to a thiazide.