May I discontinue hydroxychloroquine abruptly to initiate systemic corticosteroid therapy?

Hydroxychloroquine Discontinuation for Steroid Initiation

No, you should not stop hydroxychloroquine abruptly to start steroids—continue hydroxychloroquine while initiating corticosteroid therapy, as both medications serve complementary roles and abrupt discontinuation significantly increases the risk of disease flare. 1, 2

Evidence-Based Rationale

Why Hydroxychloroquine Should Be Continued

• Abrupt discontinuation carries a 2.5-fold increased risk of clinical flare compared to continuing therapy, with flares occurring significantly earlier in patients who stop the medication 2
• The risk of severe disease exacerbation requiring study withdrawal was 6.1 times higher in patients who discontinued hydroxychloroquine versus those who maintained therapy 2
• Long-term data demonstrates a 57% reduction in major flares (requiring ≥10 mg/day prednisone increase or immunosuppressive agents) when hydroxychloroquine is maintained over 42 months 3
• Gradual discontinuation is conditionally recommended over abrupt discontinuation for any DMARD, including hydroxychloroquine, according to the American College of Rheumatology 1

Complementary Mechanisms Support Concurrent Use

• Hydroxychloroquine serves as the "backbone therapy" for lupus and other rheumatic diseases, providing immunomodulation that is distinct from corticosteroid mechanisms 4, 5
• Combining hydroxychloroquine with corticosteroids increases achievement of Lupus Low Disease Activity State (LLDAS) from 10% at baseline to 80% at 104 weeks, while simultaneously allowing corticosteroid dose reduction 6
• Hydroxychloroquine demonstrates significant improvements in disease activity indices (SLEDAI, BILAG) during both remission induction and maintenance phases, whether used as monotherapy or combined with corticosteroids 7

Clinical Management Algorithm

For Non-Life-Threatening Disease

1. Continue hydroxychloroquine at current dose (typically 200-400 mg daily, maximum 5 mg/kg actual body weight) 4, 5
2. Initiate corticosteroids at the appropriate dose for your clinical indication 1
3. Use the lowest effective corticosteroid dose to control disease while maintaining hydroxychloroquine 1, 5
4. Target long-term corticosteroid doses ≤5-2.5 mg/day prednisolone equivalent for maintenance, with hydroxychloroquine providing the foundational disease control 5

For Life-Threatening or Organ-Threatening Disease

• Do not delay high-dose corticosteroids (≥2 mg/kg/day oral or ≥10 mg/kg/day IV methylprednisolone) when clinically indicated 1
• Continue hydroxychloroquine throughout unless there is a specific contraindication unrelated to steroid initiation 1, 4
• Hydroxychloroquine continuation during acute illness is recommended by multiple rheumatology societies, as it provides immunomodulation without compromising infection control 1, 4

Critical Pitfalls to Avoid

Common Misconception About Drug Interactions

• There is no pharmacologic reason to stop hydroxychloroquine before starting corticosteroids—these medications do not have clinically significant interactions and work through different mechanisms 4
• Hydroxychloroquine can be safely continued even during acute infections (including COVID-19) in patients with rheumatic diseases, as the immunomodulatory benefits outweigh theoretical risks 1, 4

Consequences of Unnecessary Discontinuation

• Disease flares from hydroxychloroquine withdrawal can be severe enough to require hospitalization, with relative risk of 0.58 for hospitalization when hydroxychloroquine is maintained 3
• Flares may include nephritis (relative risk 0.26 with continued therapy), vasculitis (relative risk 0.51), or other severe manifestations 3
• Abrupt discontinuation of DMARDs can lead to irreversible disease progression, making reinitiation more difficult 4

Only Valid Reason for Hydroxychloroquine Discontinuation

• Definitive evidence of retinal toxicity on OCT or visual field testing is the primary indication for stopping hydroxychloroquine, and this decision should involve shared decision-making between patient, prescribing physician, and ophthalmologist 1
• Questionable or borderline ophthalmologic findings should not prompt immediate discontinuation—the drug should be continued while further evaluation is pursued, especially in patients with active disease 1

Monitoring During Combined Therapy

• Baseline ophthalmologic examination is required before starting hydroxychloroquine, with annual screening after 5 years for low-risk patients 1, 4
• Monitor for corticosteroid-related adverse effects while maintaining hydroxychloroquine as the steroid-sparing agent 5, 6
• Aim for corticosteroid dose reduction over time as hydroxychloroquine provides sustained disease control, with studies showing significant corticosteroid dose reduction by 52-104 weeks 6, 7