What is the role of hydrochloroquine (HCQ) in the treatment of Systemic Lupus Erythematosus (SLE)?

Role of Hydroxychloroquine in Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine is recommended for all patients with SLE regardless of disease severity or organ involvement, as it reduces disease flares, prevents organ damage, and improves long-term survival. 1, 2

Core Benefits of Hydroxychloroquine in SLE

• Reduces disease activity and prevents flares, including renal flares, with patients who discontinue treatment having 2.5 times higher risk of experiencing flares 2
• Decreases damage accrual in multiple organ systems, including renal damage progression 2, 3
• Improves long-term survival rates in SLE patients 3, 4
• Allows for reduction in glucocorticoid dosage, minimizing steroid-related adverse effects 1, 2
• Provides cardioprotective effects by improving lipid profiles and reducing thrombotic events, particularly in patients with antiphospholipid antibodies 1, 2
• Safe during pregnancy and breastfeeding, associated with decreased lupus activity without fetal harm 2

Dosing Recommendations

• The daily dose should not exceed 5 mg/kg real body weight to minimize risk of retinal toxicity 1, 2
• Patients with chronic kidney disease (GFR <30 ml/min) should have dose reduced by approximately 25% 2
• Blood levels of hydroxychloroquine >0.6 mg/L may be associated with better control of disease activity, particularly for preventing renal flares 2, 5
• Patients in long-standing remission may have their dose lowered, though no formal studies have addressed this strategy 1

Monitoring and Safety Considerations

• Ophthalmological screening should be performed at baseline, after 5 years of treatment, and yearly thereafter in patients without risk factors for retinal toxicity 1, 2
• More frequent monitoring is recommended for patients with risk factors for retinopathy (long duration of treatment, high cumulative dose, chronic kidney disease, pre-existing retinal disease) 1, 2
• Retinal toxicity risk increases with treatment duration, with prevalence exceeding 10% after 20 years of continuous use 1, 2
• Consider measuring glucose-6-phosphate dehydrogenase (G6PD) levels in men from African, Asian, or Middle Eastern descent before initiating treatment 2

Use in Special Populations

Lupus Nephritis

• Hydroxychloroquine is specifically recommended for all patients with lupus nephritis, as it improves renal outcomes 1, 2
• Contributes to higher rates of renal response, fewer renal flares, and reduced accrual of renal damage 2, 6

Pediatric SLE

• Recommended for all pediatric SLE patients with the same dosing principles as adults 6
• Should be continued indefinitely due to its beneficial effects on reducing renal flares, limiting organ damage, and improving long-term outcomes 6

Pregnancy

• Safe during pregnancy and should be continued to prevent disease flares 2
• Discontinuation during pregnancy increases risk of disease exacerbation 2, 4

Clinical Pitfalls and Practical Considerations

• Never discontinue hydroxychloroquine abruptly as this may trigger disease flares 6, 7
• Poor adherence to hydroxychloroquine is common and associated with worse outcomes; measuring blood levels can help assess compliance 1, 5
• Quinacrine can be considered as an alternative antimalarial in patients who develop HCQ-induced retinal toxicity but still need antimalarial therapy 1
• Treatment continuation rates are significantly higher in SLE compared to rheumatoid arthritis, reflecting its greater efficacy in lupus 7
• Hydroxychloroquine may rarely cause cardiotoxicity (cardiomyopathy or conduction abnormalities) in patients with high cumulative exposure 2

Treatment Algorithm for SLE

1. Initial diagnosis of SLE: Start hydroxychloroquine at ≤5 mg/kg real body weight per day for all patients unless contraindicated 1, 3
2. Mild to moderate disease: Hydroxychloroquine may be sufficient as monotherapy or combined with low-dose glucocorticoids 1
3. Moderate to severe disease: Continue hydroxychloroquine while adding appropriate immunosuppressants based on organ involvement 1
4. Refractory disease: Maintain hydroxychloroquine while escalating to biologics like belimumab or rituximab 1, 3
5. Long-term management: Continue hydroxychloroquine indefinitely, even during remission, with possible dose reduction after sustained remission 1, 2

The evidence strongly supports that hydroxychloroquine should be considered a cornerstone therapy for all SLE patients, regardless of disease severity or organ involvement, due to its proven benefits on disease activity, organ damage prevention, and mortality reduction 1, 3, 4.