Is Acthar (Repository Corticotropin Injection) the Typical Treatment for Sarcoidosis?
No, Acthar (repository corticotropin injection, RCI) is not the typical first-line treatment for sarcoidosis—oral prednisone/prednisolone at 20-40 mg daily is the standard initial therapy. 1
First-Line Treatment: Oral Glucocorticoids
Systemic oral glucocorticoids (prednisone/prednisolone) are the established first-line treatment for symptomatic sarcoidosis requiring therapy. 1 The European Respiratory Society strongly recommends glucocorticoid treatment for patients at higher risk of mortality or permanent disability, with initial dosing of 20-40 mg daily for 3-6 months. 1, 2
Key points about first-line glucocorticoid therapy:
- Prednisone demonstrates clear short-term efficacy by improving symptoms, chest radiography, and achieving disease regression in many cases. 1
- Studies show no additional benefit for treating pulmonary disease with more than 20 mg prednisone daily. 1
- At least half of patients started on glucocorticoids remain on treatment 2 years later. 1, 2
- For patients with worsening quality of life but lower risk, initial low-to-medium dose (5-10 mg daily) may be considered through shared decision-making. 1, 2
Where Acthar Fits in the Treatment Algorithm
Repository corticotropin injection (Acthar) is listed as an alternative treatment option but is not positioned as typical or first-line therapy. 1 The 2021 European Respiratory Society guidelines include RCI in their treatment table with a usual dosage of 40-80 units twice weekly, noting major toxicities include diabetes, hypertension, edema, and anxiety, with most toxicity occurring on the day of injection. 1
Important context about Acthar:
- RCI is one of only two FDA-approved medications for symptomatic pulmonary sarcoidosis (the other being prednisone), but this approval status does not make it typical first-line therapy. 3, 4
- The European Respiratory Society guidelines recommend RCI use "on a case-by-case basis" rather than as standard treatment. 3
- RCI has demonstrated steroid-sparing properties and works through a unique mechanism activating melanocortin receptors. 3
- Recent publications have added information about RCI's use and efficacy, particularly in immunosuppressant contexts. 5
Standard Treatment Algorithm
The evidence-based treatment approach follows this hierarchy:
First-line: Oral prednisone 20-40 mg daily for 3-6 months, then taper to lowest effective dose. 1, 6, 2, 7
Second-line: Add methotrexate 10-15 mg weekly if disease progresses despite adequate glucocorticoid treatment or unacceptable glucocorticoid side effects develop. 6, 2, 7 Methotrexate is the most widely studied and best-tolerated second-line agent. 2
Third-line: Add infliximab 3-5 mg/kg for patients with continued disease despite glucocorticoids and second-line agents. 6, 2, 7
Clinical Decision-Making Framework
Treatment decisions should be based on three key factors:
- Risk of mortality or permanent disability - Strong indication for treatment. 2
- Significant impairment of quality of life - Consider treatment with shared decision-making. 1, 2
- Presence of symptoms - Asymptomatic patients without organ dysfunction risk should not be treated. 2, 7
Nearly half of sarcoidosis patients never require systemic treatment due to spontaneous disease resolution. 2, 7
Common Pitfalls to Avoid
- Do not use Acthar as first-line therapy when oral prednisone is the evidence-based standard with stronger guideline support. 1
- Avoid treating asymptomatic patients without risk factors for morbidity/mortality, as the high prevalence of glucocorticoid adverse events outweighs benefits. 1, 2
- Do not add inhaled glucocorticoids to oral glucocorticoids - three double-blind RCTs showed no significant benefit. 1, 2
- Recognize that prolonged use of even low-dose prednisone leads to significant toxicity including weight gain and reduced quality of life. 2
- Re-evaluate the need for continued treatment every 1-2 years rather than continuing indefinitely without reassessment. 6, 2