Should a patient tolerating 200mg Plaquenil (hydroxychloroquine) daily without retinal toxicity be switched to Arava (leflunomide)?

Should a Patient Tolerating Plaquenil Without Retinal Toxicity Be Switched to Arava?

No, a patient tolerating 200mg Plaquenil daily without retinal toxicity should not be switched to Arava (leflunomide), as hydroxychloroquine is recommended for all patients with rheumatic diseases and should not be discontinued without adequate cause, particularly when the patient is tolerating it well and showing no signs of toxicity. 1

Rationale for Continuing Hydroxychloroquine

Critical Benefits of Hydroxychloroquine

• Hydroxychloroquine is recommended for all patients with SLE and other rheumatic diseases due to multiple beneficial effects including reduction in disease flares, prevention of organ damage accrual, decreased thrombotic events, and improved long-term survival 1, 2
• The drug reduces the risk of lupus flares by 2.5-fold compared to discontinuation, including prevention of renal flares 2
• It allows for reduction of corticosteroid doses, minimizing their harmful effects and preventing irreversible organ damage 1, 2
• The medication improves cardiovascular outcomes, lipid profiles, and bone preservation 2

Safety Profile at Current Dose

• At 200mg daily, the patient is likely well below the recommended maximum dose of 5.0 mg/kg real body weight (unless the patient weighs less than 40kg), which correlates with very low toxicity risk 1
• The risk of retinopathy at recommended doses is under 1% up to 5 years and under 2% up to 10 years 1
• Even after 20 years of use at proper dosing, a patient without toxicity has only a 4% risk of converting to toxicity in the subsequent year 1

When Hydroxychloroquine Should Be Discontinued

Definitive Indications for Stopping

• The drug should not be stopped until evidence of retinopathy is definitive, particularly in patients with active rheumatic or cutaneous disease 1
• Questionable or borderline screening findings should be rechecked after a few months or validated with additional procedures (multifocal electroretinography or fundus autofluorescence) before discontinuation 1
• The decision to discontinue must involve shared decision-making between patient, prescribing physician, and eye care provider, considering disease severity and estimated risk of visual loss 1

Appropriate Screening Protocol

• Annual screening should begin after 5 years of therapy for patients on acceptable doses without major risk factors 1
• Primary screening tests are spectral-domain OCT and automated visual fields (10-2 protocols), which can detect damage before it becomes visible on fundoscopy 1
• Modern screening should detect retinopathy at an early stage (before RPE loss) when damage can stabilize without serious visual loss if the drug is discontinued 1

Role of Leflunomide (Arava)

When to Consider Leflunomide

• Leflunomide is an alternative immunosuppressive agent that may be considered when hydroxychloroquine is contraindicated or when additional disease control is needed 1
• It has shown efficacy in controlling attacks in palindromic rheumatism when hydroxychloroquine and methotrexate are inadequate 3
• However, leflunomide is not a replacement for hydroxychloroquine but rather an adjunctive therapy 1

Important Distinction

• The choice of immunosuppressive agents depends on prevailing disease manifestations, but hydroxychloroquine should be continued as background therapy unless there is definitive evidence of toxicity or true contraindication 1
• Consequent initiation of additional immunosuppressive drugs facilitates more rapid glucocorticoid tapering but does not replace the fundamental role of hydroxychloroquine 1

Common Pitfalls to Avoid

• Do not discontinue hydroxychloroquine prematurely based on borderline or questionable screening findings, as the earliest changes can be subtle and hard to distinguish from normal variation 1
• Do not calculate dose using ideal body weight in patients, as actual body weight correlates better with risk and prevents overdosing 1
• Do not assume that absence of symptoms means the drug can be stopped, as hydroxychloroquine provides long-term disease modification and damage prevention even in stable patients 1, 2
• Recognize that retinopathy develops slowly over several years, providing time for suspicious findings to be validated before making irreversible treatment decisions 1

Recommended Management

• Continue hydroxychloroquine 200mg daily with appropriate annual ophthalmologic screening after 5 years of therapy (or earlier if risk factors present) 1, 4
• Ensure screening includes spectral-domain OCT and automated visual fields performed by practitioners experienced in detecting hydroxychloroquine toxicity 1
• Consider adding leflunomide or other immunosuppressive agents only if disease activity is inadequately controlled, not as a replacement for hydroxychloroquine 1
• Maintain open communication between ophthalmology and rheumatology to ensure coordinated care and appropriate interpretation of screening results 1