What type of medication is hydroxychloroquine (Disease-Modifying Antirheumatic Drug, DMARD)?

Hydroxychloroquine is a Disease-Modifying Antirheumatic Drug (DMARD)

Hydroxychloroquine is classified as a conventional synthetic disease-modifying antirheumatic drug (csDMARD) used primarily in the treatment of autoimmune and inflammatory conditions. 1, 2, 3

Classification and Mechanism of Action

Hydroxychloroquine functions as a disease-modifying antirheumatic drug through several mechanisms:

• Immunomodulatory effects: It accumulates in intracellular vesicles like endosomes and lysosomes where it increases vesicular pH, inhibiting pH-dependent proteases involved in processing secretory proteins 1
• Anti-inflammatory properties: Reduces production of inflammatory cytokines including tumor necrosis factor α and interleukin 6 1
• Cellular effects: Changes intracellular pH, which downregulates numerous immune functions 4
• Antiviral properties: Acts on entry and post-entry stages of certain viral infections by affecting endosomal pH 1

Clinical Applications

Hydroxychloroquine is FDA-approved for several conditions:

1. Rheumatoid arthritis in adults 3
2. Systemic lupus erythematosus in adults 3
3. Chronic discoid lupus erythematosus in adults 3
4. Malaria (treatment and prophylaxis) 3

It's also used in various other rheumatic conditions as evidenced by clinical guidelines:

• Recommended as a DMARD option in juvenile idiopathic arthritis 1
• Used in combination therapy with other DMARDs (e.g., methotrexate + hydroxychloroquine, or triple therapy with methotrexate + hydroxychloroquine + sulfasalazine) 1

Positioning in Treatment Algorithms

In rheumatoid arthritis treatment:

• Often used as part of initial therapy or in combination with other DMARDs 1
• While not the most effective DMARD, it has the advantage of being the least toxic 4
• May be used as monotherapy in mild disease or when other DMARDs are contraindicated 1

In treatment algorithms:

• For patients with well-controlled disease on hydroxychloroquine, it should be continued when available 1
• When hydroxychloroquine is unavailable, switching to a different conventional synthetic DMARD (either as monotherapy or combination therapy) should be considered 1

Safety Profile

Hydroxychloroquine has a favorable safety profile compared to other DMARDs:

• Lower toxicity profile than most other DMARDs 4
• Can be continued during COVID-19 exposure or infection, unlike many other immunosuppressive medications 1

Monitoring Requirements

Due to potential side effects, monitoring is required:

• Regular ophthalmologic examinations (every 6-12 months) to detect retinopathy, which is the most significant dose-limiting toxicity 2
• Monitoring for QT prolongation, especially when combined with other QT-prolonging medications 1
• Baseline and periodic liver function tests, complete blood count, and renal function tests 2

Key Differences from Other DMARDs

• Mechanism: Unlike biologics that target specific cytokines or immune pathways, hydroxychloroquine has broader immunomodulatory effects
• Safety: Better safety profile than most other DMARDs, particularly regarding serious infections 4
• Onset of action: Slower onset of action (may take 2-3 months) compared to glucocorticoids but faster than some other DMARDs
• Structural protection: Less effective at preventing structural damage compared to methotrexate and biologics 1

In summary, hydroxychloroquine is a conventional synthetic disease-modifying antirheumatic drug with immunomodulatory and anti-inflammatory properties, used primarily in rheumatoid arthritis, lupus, and other inflammatory conditions, with a favorable safety profile compared to other DMARDs.