For people living with IgG4-Related Disease (IgG4-RD), treatment can be complicated. The disease is rare, often misdiagnosed, and can affect many different organs. When it affects the pancreas, it is called Type 1 Autoimmune Pancreatitis (AIP).
Steroids are usually the first treatment doctors prescribe because they quickly reduce inflammation, improve symptoms, and induce remission, and as a result, are considered effective. For many patients, they provide relief when little else works. To learn more about Type 1 Autoimmune Pancreatitis and Treatment options, including steroid use, watch our webinar on the topic here. However, long-term use of steroids carries serious risks, and patients can often relapse after stopping them.
A new study looked at real-world data from 295 U.S. patients with IgG4-RD and confirmed that people who required higher daily steroid doses experienced significantly more harmful side effects. These findings highlight the need for safer and more sustainable treatment options.
What is IgG4-RD?
- Abdominal pain
- Sudden unexplained weight loss
- Painless jaundice (yellowing of skin or eyes)
- Exocrine Pancreatic Insufficiency (EPI): inability to digest food properly due to a lack of pancreatic enzymes
- Type 3c Diabetes: diabetes caused by pancreatic disease
How is IgG4-RD Treated?
Treatment for IgG4-RD aims to reduce inflammation, manage symptoms, and prevent relapses. Options include:
- Steroids (like prednisone): First-line therapy to quickly reduce inflammation
- Immunomodulators: Drugs that adjust the immune system’s response
- B-cell depletion therapy: Immunotherapy that targets the overactive B-cells driving IgG4-RD
Why are steroids widely used?
Steroids are effective in the short term, with over 90% of patients experiencing initial improvement. Typically, a high dose is administered for 2–4 weeks and then tapered over 3 to 6 months under the supervision of a physician, based on assessment.
The challenge with steroids
- Most patients relapse within 3 years.
- Many require repeated or long-term courses.
- Over time, steroids can cause widespread harm to the body.
- Risks associated with long-term steroid use
Well-known steroid risks include:
- High blood pressure and heart problems
- Diabetes or worsening blood sugar control
- Bone loss and osteoporosis
- Infections, including severe infections such as sepsis
- Cataracts and glaucoma
- Gastrointestinal ulcers and bleeding
- Mood changes, anxiety, and sleep problems
- Weight gain and muscle weakness
What the New Research Found
Researchers analyzed U.S. insurance records for 295 people with IgG4-RD in the year following diagnosis.
Patients were divided into two groups:
- Low-dose: less than 5 mg/day prednisone equivalent
- High-dose: 5 mg/day or more
Key findings:
- High-dose patients had significantly more side effects.
- Nearly 30 percent of high-dose patients experienced three or more complications in one year.
- Complications included infections (including sepsis), gastrointestinal problems, and cardiovascular problems.
- Patients with autoimmune pancreatitis were more likely to receive high-dose steroids and were observed to have more comorbidities, including type 2 diabetes and EPI, in this analysis.
Notably, the use of other non-steroidal immunosuppressants (Azathioprine, Methotrexate Mycophenolate mofetil, Mycophenolic acid, and Rituximab) was similar between patients on low-dose and high-dose steroids (Prednisone, Dexamethasone, Methylprednisolone, and Prednisolone). Effective and well-tolerated steroid-sparing treatments can reduce steroid exposure, improve patient outcomes, and lessen the overall burden of IgG4-RD.
Limitations
This study only covered the first year after diagnosis. Some complications, such as bone loss and cataracts, often take longer to appear, meaning the true long-term burden of steroids is likely greater.
What Does This Mean for Patients?
This research shows the risks of long-term, high-dose steroid use, especially for people with Autoimmune Type 1 Pancreatitis. It highlights a genuine need for improved treatment options.
Patients with Autoimmune Type 1 Pancreatitis are already at a higher risk of developing diabetes, bone disease, and EPI. They are at greater risk while on high-dose steroids over long periods of time. For patients with AIP Type 1 pancreatitis, having more treatment options would reduce their chances of facing more complications.
There are also tools that can help AIP Type 1 patients track their steroid-related symptoms if they’ve been on steroid therapy. Apps like Steroids and Me (SAM) help track side effects, mood, and concerns as they occur, making it easier for patients to discuss these issues with their doctor and take more control over their health. SAM can serve as a valuable resource for patients undergoing steroid treatment.
Alternative to Steroids: A New FDA-Approved Treatment Option for IgG4-RD
Does Uplizna report any side effects?
Uplizna risks include:- Most common: Urinary tract infections, low white blood cell counts, headaches, joint pain
- Infusion reactions: 7 to 9 percent of patients, usually mild but rarely severe allergic responses
- Infections: Higher risk of respiratory or urinary infections
- Screening required: For hepatitis B and tuberculosis before starting treatment; no live vaccines while on therapy
- Rare but serious: Progressive Multifocal Leukoencephalopathy (PML), a severe brain infection, requires careful monitoring
- Long-term immune effects: Some patients develop low immunoglobulin levels, which may increase infection risk; not recommended during pregnancy or for six months after
Limitations
Long-term safety data are still being collected, and ongoing research will continue to evaluate risks and benefits over many years.Key Takeaways
- Type 1 autoimmune pancreatitis can be treated with steroids, immunomodulators, or biologic therapy after weighing the best treatment approach based on the patient’s needs.
- Steroids remain an important treatment but carry serious risks when used long-term or at high doses.
- Patients with autoimmune pancreatitis are especially vulnerable to steroid complications.
- Uplizna, now FDA approved, offers a new option that reduces dependence on steroids.
- Both steroids and Uplizna have risks, but the safety profiles are different and should be weighed carefully with your doctor, considering the benefits
References
Wallace ZS, Park JY, Serra E, et al. Burden of Glucocorticoid Use and Risk of Toxicities Among Patients with Immunoglobulin-G4-Related Disease: A Retrospective US-Based Claims Study. Rheumatol Ther. 2025. doi: 10.1007/s40744-025-00763-9
Stone JH, Khosroshahi A, Zhang W, et al. Inebilizumab for Treatment of IgG4-Related Disease (MITIGATE Trial). N Engl J Med. 2024;391:XXX–XXX. doi: 10.1056/NEJMoa2409712
Amgen. Uplizna (inebilizumab-cdon) approved by FDA as first treatment for IgG4-RD. Press Release. April 3, 2025. Amgen Newsroom
Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015;385(9976):1460–1471. doi: 10.1016/S0140-6736(14)60720-0
Khosroshahi A, Wallace ZS, Crowe JL, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol. 2015;67(7):1688–1699. doi: 10.1002/art.39132Â
About Mission: Cure
At Mission: Cure, we are dedicated to finding effective treatments and, ultimately, a cure for pancreatitis. Through patient education, research, and advocacy, we strive to improve the lives of those affected by this condition.
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