Recommended First-Line Prednisone Regimen for IgG4-Related Disease
Begin oral prednisone at 0.6 mg/kg/day (approximately 40 mg daily for most adults) for 2–4 weeks, then taper by 5 mg weekly over 8–12 weeks to reach a maintenance dose of 2.5–5 mg/day within 2–3 months. 1, 2
Initial Induction Phase
- Start with prednisone 0.6 mg/kg/day (≈40 mg daily) for the first 2–4 weeks to induce remission 1, 3
- This dose represents the international consensus from American, European, and Japanese guidelines for systemic IgG4-related disease 4, 1
- Assess treatment response after 2–4 weeks (before beginning the taper) using clinical improvement, normalization of liver biochemistry, and radiological evidence of lesion reduction 4, 1
Important Caveat for Elderly or High-Risk Patients
- For elderly patients or those with contraindications to high-dose steroids (insulin-dependent diabetes, severe osteoporosis), lower initial doses of 10–20 mg daily may be equally effective based on retrospective Dutch data, though this is less well-established 4
Tapering Schedule
- Reduce by 5 mg each week over 8–12 weeks until reaching the maintenance range 1, 2
- Target a maintenance dose of 2.5–5 mg/day achieved within 2–3 months from initiation 1, 3
- The taper should be gradual to minimize relapse risk while limiting steroid toxicity 1
Maintenance Therapy to Prevent Relapse
Add a steroid-sparing immunosuppressant during the prednisone taper for most patients, as at least 60% will relapse after steroid cessation. 1, 2
- Initiate azathioprine (≈2 mg/kg/day), 6-mercaptopurine, or mycophenolate mofetil as the steroid dose is being reduced 4, 1
- Continue immunosuppressive therapy for up to 3 years (potentially longer for multiorgan involvement) 4, 1
- Alternatively, maintain low-dose prednisone 5–7.5 mg/day long-term, which reduces 3-year relapse rates to 23% versus 58% with complete steroid withdrawal 1, 2
Rationale for Maintenance Therapy
- The high relapse rate (≥60%) after stopping steroids makes maintenance immunosuppression essential for most patients 1, 2
- Patients with perihilar or intrahepatic bile duct involvement have particularly high relapse rates and warrant sustained therapy 4, 1
Monitoring Treatment Response
- Evaluate response at weeks 4–8 through resolution of symptoms (e.g., jaundice), biochemical normalization, and objective radiological improvement 1, 2
- Absence of radiological improvement by weeks 4–8 suggests either misdiagnosis or a fibrotic (non-inflammatory) disease phase rather than true steroid failure 1
- Do not use serum IgG4 levels to guide treatment decisions or monitor response, though decreasing levels may parallel clinical improvement 1, 2
Management of Refractory or Relapsing Disease
For patients who fail first-line steroids or relapse during/after taper, rituximab is the preferred second-line agent with >95% response rates. 1, 5
- Standard rituximab regimen: two infusions of 1,000 mg given 15 days apart, repeated every 6 months for maintenance 4, 1, 2
- Premedicate with methylprednisolone and antihistamines to reduce infusion reactions 4, 1
- Rituximab is particularly indicated for multisystem disease or steroid-dependent patients 1, 5
Alternative Relapse Management
- If relapse occurs during taper, options include: (1) high-dose steroids tapered to low-dose maintenance (2.5–10 mg/day) plus a steroid-sparing agent, (2) high-dose steroids without maintenance, or (3) rituximab with or without maintenance rituximab 4
Critical Pitfalls to Avoid
- Do not taper steroids before 2–4 weeks of initial therapy, as premature tapering increases relapse risk 4, 1
- Do not stop all immunosuppression after initial response—relapse rates exceed 60% without maintenance therapy 1, 2
- Do not rely on serum IgG4 levels alone for diagnosis or treatment monitoring, as they do not reliably correlate with disease activity 1, 2
- Do not assume treatment failure if radiological improvement is absent by 4–8 weeks—consider fibrotic phase or incorrect diagnosis instead 1