Why do we titrate steroid therapy?

Why We Titrate Steroid Therapy

Steroid therapy is titrated to achieve the optimal balance between therapeutic efficacy and minimizing adverse effects, with dosage adapted to the activity of the disease and gradually reduced once remission is achieved.

Principles of Steroid Titration

• Steroid dosing should be adapted to the activity of the disease to maximize therapeutic benefit while minimizing side effects 1
• Titration allows for finding the lowest effective dose that maintains remission without causing major adverse effects 1
• The initial dosage should be maintained or adjusted until a satisfactory response is noted, then gradually decreased in small increments at appropriate intervals 2
• Dosage requirements are variable and must be individualized based on the disease being treated and the patient's response 2

Benefits of Steroid Titration

Minimizing Adverse Effects

• Combination therapy (e.g., prednisolone with azathioprine) is associated with fewer side effects (10% vs 44%) compared to high-dose steroid monotherapy 1
• Titrating to the lowest effective dose helps reduce the risk of:
  • Cushingoid features and weight gain 2
  • Osteoporosis and bone loss 1
  • Adrenal suppression 2
  • Diabetes mellitus and hypertension 2
  • Edema (dose and duration of treatment directly relate to risk) 3

Optimizing Therapeutic Response

• Titration allows for rapid initial control of disease activity followed by maintenance at the lowest effective dose 1
• For autoimmune hepatitis, combination therapy with prednisolone and azathioprine provides the best profile combining high efficacy with minimal side effects 1
• In inflammatory bowel disease, decisive treatment with an appropriate initial dose followed by a standard weaning strategy helps identify patients who relapse rapidly or do not respond 1

Specific Titration Approaches

Alternate Day Therapy

• Alternate day therapy involves administering twice the usual daily dose every other morning 2
• This approach provides therapeutic benefits while minimizing:
  • Pituitary-adrenal suppression
  • Cushingoid state
  • Corticoid withdrawal symptoms
  • Growth suppression in children 2
• The rationale is based on two premises:
  • The anti-inflammatory effect of corticosteroids persists longer than their physical presence
  • The off-steroid day allows for more normal hypothalamic-pituitary-adrenal activity 2

Tapering Strategies

• After a favorable response, the initial drug dosage should be decreased in small increments at appropriate time intervals 2
• For chronic asthma, a one to three month period of stability should be shown before stepwise reduction in inhaled steroids, decreasing the dose by 25-50% at each step 1
• In nephrotic syndrome, prednisone should be given on alternate days in the lowest dose to maintain remission without major adverse effects 1
• If long-term therapy is to be stopped, it's recommended to withdraw gradually rather than abruptly to avoid withdrawal symptoms 2

Disease-Specific Titration Approaches

Multiple Sclerosis

• For acute exacerbations, high-dose corticosteroid treatment (200 mg prednisolone daily for a week followed by 80 mg every other day for 1 month) has been shown to be effective 2
• A three to four-month slowly tapered course of oral therapy is often needed and usually well tolerated with few serious side effects when given once daily in the morning 4

Autoimmune Hepatitis

• A combination regimen of prednisolone (starting at 30 mg/day reducing to 10 mg/day maintenance) with azathioprine (50 mg/day) provides optimal efficacy with minimal side effects 1
• Histological remission was achieved in 75% of patients after 18 months of active prednisolone-based treatment 1

Nephrotic Syndrome

• For children with steroid-sensitive nephrotic syndrome, prednisone should be given on alternate days in the lowest dose to maintain remission without major adverse effects 1
• For frequently relapsing or steroid-dependent nephrotic syndrome, relapses should be treated with daily prednisone until remission for at least 3 days, followed by alternate-day prednisone for at least 3 months 1

Temporal Arteritis

• A regimen starting with 30-40 mg/day of prednisone and tapering to 10 mg/day within 6 months and to 5-7.5 mg/day within 1 year has been shown to be effective and less toxic than higher dose regimens 5
• Lower initial doses (30-40 mg/day) resulted in significantly fewer steroid side effects (36%) compared to higher doses of 40-60 mg/day (78%) or >60 mg/day (88%) 5

Practical Considerations for Titration

• Administer oral steroids in the morning prior to 9 am to minimize adrenal suppression, as maximal adrenal cortex activity is between 2 am and 8 am 2
• Constant monitoring is needed for dosage adjustments in response to:
  • Changes in clinical status due to remissions or exacerbations
  • Individual drug responsiveness
  • Patient exposure to stressful situations 2
• For pediatric patients, growth velocity may be a more sensitive indicator of systemic corticosteroid exposure than commonly used tests of HPA axis function 2

Common Pitfalls and Caveats

• Abrupt withdrawal of steroid therapy can lead to adrenal insufficiency and should be avoided 2
• Once-daily application of topical steroids is often as effective as three-times-daily application, reducing the risk of local and systemic effects 6
• For inhaled steroids in asthma, if symptoms are not controlled with standard doses, higher doses should be used up to a daily equivalent of 2000 μg beclomethasone before adding other medications 1
• Azathioprine monotherapy is not recommended as induction therapy for autoimmune hepatitis due to higher mortality rates compared to prednisone (36% vs 5-6%) 1