Corticosteroid Sparing Therapy

Corticosteroid sparing therapy uses disease-modifying or immunosuppressive drugs to allow steroid doses to be reduced to the lowest effective level or stopped, because long-term steroids cause diabetes, osteoporosis, infection, cataract, hypertension, myopathy and adrenal suppression. It is started early in any condition expected to need steroids for more than 3 months.

Triggers for a sparing agent. Prednisolone 7.5 mg or more daily for over 3 months; two or more relapses on tapering; high cumulative steroid dose; steroid adverse effects; or a disease where early disease-modifying treatment improves outcome.

Steroid equivalence (anti-inflammatory). Prednisolone 5 mg equals hydrocortisone 20 mg, methylprednisolone 4 mg and dexamethasone 0.75 mg.

Choice by disease.

• Rheumatoid arthritis and polymyalgia rheumatica: methotrexate 10 to 25 mg weekly.
• Giant cell arteritis: methotrexate 10 to 20 mg weekly, or tocilizumab 162 mg subcutaneously weekly (or every 2 weeks), with a prednisolone taper over 26 weeks or less.
• Lupus: hydroxychloroquine 200 to 400 mg daily, azathioprine 1 to 2.5 mg/kg daily, mycophenolate 1 to 1.5 g twice daily, belimumab 10 mg/kg IV at weeks 0, 2 and 4 then every 4 weeks.
• Vasculitis (ANCA-associated): rituximab 375 mg/m2 weekly for 4 doses (or 1 g twice 2 weeks apart), or cyclophosphamide, then azathioprine 2 mg/kg daily or methotrexate for maintenance.
• Eosinophilic granulomatosis with polyangiitis and eosinophilic asthma: mepolizumab 300 mg subcutaneously every 4 weeks (100 mg every 4 weeks for asthma alone).
• Inflammatory bowel disease: azathioprine 2 to 2.5 mg/kg daily or mercaptopurine 1 to 1.5 mg/kg daily, with thiopurine methyltransferase testing.
• Autoimmune hepatitis: azathioprine 1 to 2 mg/kg daily (50 to 100 mg), after steroid induction.
• Myasthenia gravis, nephrotic syndrome and uveitis: azathioprine 2 to 3 mg/kg daily, mycophenolate, ciclosporin or tacrolimus.
• Still disease and autoinflammatory disease: anakinra 100 mg subcutaneously daily.

Steroid taper principles.

• Polymyalgia rheumatica: prednisolone 15 to 25 mg daily, taper by 1 mg each month once controlled over 12 to 24 months.
• Giant cell arteritis: prednisolone 40 to 60 mg daily, taper to 15 to 20 mg by 3 months and to 5 mg by 12 months; use methylprednisolone 500 mg to 1 g IV daily for 3 days if visual symptoms.
• Other diseases: reduce by 10% every 1 to 2 weeks to 20 mg, then by 1 to 2.5 mg every 2 to 4 weeks, with slower steps under 7.5 mg.

Azathioprine and mercaptopurine. Start 25 to 50 mg daily (mercaptopurine 25 mg daily) and increase by 25 mg every 1 to 2 weeks to target; reduce to a quarter or a third of the dose with allopurinol or febuxostat.

Bone protection (prednisolone 7.5 mg or more daily for 3 months or more). Calcium 1000 mg and vitamin D 800 to 1000 units daily; alendronate 70 mg once weekly (or risedronate 35 mg weekly, zoledronic acid 5 mg IV once yearly if intolerant), after dental and renal checks; assess fracture risk.

Infection. Pneumocystis prophylaxis (co-trimoxazole 480 mg daily) when prednisolone 20 mg or more daily for over 4 weeks is combined with another immunosuppressant; screen for latent tuberculosis, hepatitis B and strongyloides before long courses in endemic areas.

Glucose and blood pressure. Check at each visit; treat steroid-induced diabetes with insulin or metformin.

Adrenal suppression. After more than 3 weeks at 5 mg or more of prednisolone, taper under 5 mg slowly and consider a morning cortisol or a short tetracosactide stimulation test before stopping. Stress dosing: double or triple the dose for fever, and give hydrocortisone 100 mg IV for surgery, vomiting or shock.

Kidney and liver impairment. Apply the kidney and liver limits of the sparing agent chosen (methotrexate eGFR limits, azathioprine reduction in severe impairment).

Pregnancy and breastfeeding. Prefer azathioprine, hydroxychloroquine, tacrolimus or ciclosporin; avoid methotrexate, mycophenolate and leflunomide.

Regional. Tuberculosis, HIV, hepatitis B and strongyloidiasis make steroid sparing especially valuable; treat strongyloides empirically with ivermectin 200 micrograms/kg orally for 2 days before prolonged high-dose steroids in endemic areas.

Monitoring. Disease activity and steroid dose at every visit; the monitoring schedule of each sparing agent; weight, blood pressure, glucose, eye checks for cataract and glaucoma each year; bone density at baseline and every 2 to 3 years.

Adjustment. Do not taper faster than the disease allows; if there is a flare, return to the last effective dose and add or optimise the sparing agent.

Stopping. Stop the sparing agent only after at least 1 to 2 years of remission (longer for lupus nephritis, vasculitis and transplant). Do not stop steroids abruptly after more than 3 weeks of treatment.

Escalation. Refer for relapse on 2 sparing agents, steroid complications (fracture, severe infection, psychosis) or when a biologic is needed.