Optimal Steroid-Sparing Treatment for AIH with Polymyalgia Rheumatica
Azathioprine is the best steroid-sparing agent for patients with both autoimmune hepatitis and polymyalgia rheumatica, allowing reduction of corticosteroid doses to 10 mg/day or less while maintaining disease control for both conditions. 1
Why Azathioprine is First-Line
The combination of prednisolone plus azathioprine represents the established standard of care, achieving remission in 80-90% of AIH patients while dramatically reducing corticosteroid-related side effects compared to prednisone monotherapy (10% versus 44% incidence of side effects). 1, 2 This is particularly critical in patients with PMR who already require corticosteroids, as the dual autoimmune burden would otherwise necessitate prolonged high-dose steroid exposure with its attendant complications. 1
The steroid-sparing effect is substantial: azathioprine enables long-term maintenance at prednisolone doses ≤10 mg/day, the threshold below which severe corticosteroid complications typically do not develop even after 18 months of therapy. 1
Specific Dosing Algorithm
Initial Phase:
- Start prednisolone 30 mg/day, tapering to 10 mg/day over 4 weeks 1
- Initiate azathioprine at 50 mg/day when bilirubin is below 6 mg/dL, ideally two weeks after starting steroids 1, 2
- Increase azathioprine to maintenance dose of 1-2 mg/kg/day based on response and tolerability 1, 3
Maintenance Phase:
- Target prednisolone dose: ≤10 mg/day long-term 1
- Continue azathioprine at 1-2 mg/kg/day to maintain remission for both conditions 1
Critical Monitoring Requirements
Treatment goal is complete normalization of liver enzymes (AST, ALT) and IgG levels. 1, 2 Serum aminotransferases should improve within 2 weeks; most patients achieve biochemical remission within 6-12 months. 1
Before starting azathioprine, consider measuring thiopurine methyltransferase (TPMT) to exclude homozygote deficiency, especially if pre-existing leucopenia exists. 1, 2 This prevents life-threatening bone marrow toxicity in TPMT-deficient patients.
Monitor closely for azathioprine hepatotoxicity, which is more common in patients with advanced liver disease. 1, 3
Second-Line Options When Azathioprine Fails
If Azathioprine is Not Tolerated:
Mycophenolate mofetil (MMF) is the first choice, with a dose of 1 g daily initially, increased to 1.5-2 g daily for maintenance. 1, 2 Recent meta-analysis data from 2025 shows MMF achieves significantly higher complete biochemical response rates compared to azathioprine (RR = 1.44,95% CI = 1.03-2.01), particularly in patients over 50 years old. 4
Alternatively, 6-mercaptopurine may be effective in 75% of patients with azathioprine intolerance, as it bypasses some metabolic pathways causing azathioprine side effects. 5
If Azathioprine is Ineffective (Refractory Disease):
Tacrolimus is more effective for refractory disease not responding to standard therapy, with a starting dose of 0.075 mg/kg daily. 1, 2 Tacrolimus has shown superior efficacy compared to MMF in truly refractory cases. 2
Cyclosporine A (2-5 mg/kg daily) represents another option for corticosteroid-resistant patients. 6, 2
Critical Pitfalls to Avoid
Never use budesonide in patients with cirrhosis, as it carries significant risk of systemic side effects due to impaired first-pass metabolism. 1, 2 While budesonide may seem attractive as a steroid-sparing option, this contraindication is absolute in advanced liver disease.
Do not discontinue treatment before at least 2 years, as failure to achieve complete normalization of liver enzymes and IgG leads to almost universal relapse after treatment withdrawal. 1, 2
Avoid maintaining prednisolone doses >10 mg daily long-term, as severe corticosteroid complications typically develop after 18 months at higher doses. 1, 2 This is especially important in PMR patients who may be tempted to use higher steroid doses for symptom control.
Duration and Withdrawal Considerations
Treatment should continue for a minimum of 2 years before considering withdrawal. 1, 2 Persistent elevations of liver enzymes predict relapse, ongoing histologic activity, progression to cirrhosis, and poor outcomes. 3 In the context of dual autoimmune disease (AIH plus PMR), most patients will require lifelong immunosuppression with azathioprine to maintain low-dose corticosteroid therapy safely. 7