What are the treatment options for sarcoidosis?

Sarcoidosis Treatment Options

The treatment of sarcoidosis follows a stepped approach, starting with prednisone 20-40 mg daily for 3-6 months for symptomatic disease, followed by methotrexate as the preferred second-line agent if disease continues or steroid side effects become unacceptable, and infliximab as the third-line agent for refractory cases. 1, 2

First-Line Treatment: Glucocorticoids

• Prednisone 20-40 mg daily is the standard initial treatment for symptomatic sarcoidosis with risk of mortality or permanent disability 3, 1
• For acute exacerbations of pulmonary sarcoidosis, even short-course, low-dose therapy (20 mg daily for approximately 21 days) can improve spirometry and clinical symptoms 4
• After initial treatment for 2-6 weeks, maintenance with 5-10 mg daily or every other day is recommended 1
• Nearly half of patients with sarcoidosis never require systemic treatment, as asymptomatic pulmonary sarcoidosis often doesn't benefit from corticosteroid treatment 3
• Prolonged prednisone may be required to stabilize disease, with at least half of patients remaining on treatment 2 years later 2

Second-Line Treatment: Steroid-Sparing Agents

• Methotrexate (10-15 mg weekly) is the most common and preferred second-line agent when there is:
  • Disease progression despite adequate glucocorticoid treatment
  • Unacceptable side effects from glucocorticoids
  • Need for prolonged treatment with prednisone >10 mg daily 3, 1, 2
• Methotrexate is the most widely studied drug for sarcoidosis, including a placebo-controlled randomized trial, and is better tolerated than other cytotoxic agents 3
• Alternative second-line agents include:
  • Azathioprine
  • Mycophenolate mofetil
  • Leflunomide 3, 1, 2

Third-Line Treatment: Biologics

• Infliximab is the first choice as a biologic agent for patients with continued disease despite glucocorticoids and second-line agents 3, 1, 2
• This anti-TNF-α monoclonal antibody has multiple clinical trials supporting its use in various manifestations of sarcoidosis 3
• Discontinuation of infliximab after 6-12 months is associated with disease relapse in more than half of cases 2
• Adalimumab has been found effective in some patients, but other anti-TNF agents such as golimumab and etanercept are generally not effective in most sarcoidosis patients 3

Organ-Specific Treatment Considerations

Pulmonary Sarcoidosis

• For symptomatic pulmonary disease with parenchymal infiltrates and abnormal pulmonary function, start with prednisone 20-40 mg daily 5
• Taper prednisone over 6-18 months if symptoms, spirometry, and radiographs improve 5
• Relapse rates range from 13% to 75% depending on disease stage, organs involved, and other factors 5

Cardiac Sarcoidosis

• Glucocorticoids with or without immunosuppressives are strongly recommended for patients with functional cardiac abnormalities 1, 2
• Consider early initiation of steroid-sparing medications due to significant morbidity of long-term glucocorticoid use 1

Neurosarcoidosis

• First-line treatment is glucocorticoids
• Second-line treatment is methotrexate
• Third-line treatment is infliximab 1, 2

Cutaneous Sarcoidosis

• Oral glucocorticoids for cosmetically important active skin lesions not controlled by local treatment 2
• Hydroxychloroquine (200-400 mg once daily) can be considered as an alternative treatment, with periodic ocular exams 1, 2
• Infliximab for patients with continued active skin disease despite glucocorticoids/immunosuppressives 1

Sarcoidosis-Associated Fatigue

• First-line treatment is a pulmonary rehabilitation program and/or inspiratory muscle strength training for 6-12 weeks
• Second-line treatment is consideration of D-methylphenidate or armodafinil for 8 weeks to test effect on fatigue and tolerability 1

Treatment Duration and Monitoring

• Continue therapy for at least 3-6 months if there is improvement in symptoms, pulmonary function tests, and radiographic findings 2
• Re-evaluate the need for continued successful treatment every 1-2 years 2
• Monitor for steroid-induced complications including weight gain and reduced quality of life 3
• For cardiac sarcoidosis, monitor left ventricular ejection fraction and brain natriuretic peptide 1
• For fatigue, evaluate functional improvement with 6-minute walk test 1

Advanced Treatment Options

• For refractory cases, repository corticotrophin injection or concomitant levofloxacin, ethambutol, azithromycin, rifampin (CLEAR) therapy may be considered, although consensus on these therapies is limited 3
• Rituximab has shown some effectiveness in treating sarcoidosis in limited studies 3

Risk Stratification

• Prioritize treatment for patients at risk for mortality or permanent disability 1
• Risk factors for cardiac sarcoidosis include age >50 years, left ventricular ejection fraction <40%, ventricular tachycardia, and cardiac inflammation on imaging 1
• Risk factors for pulmonary sarcoidosis include pulmonary hypertension, reduced lung function, and pulmonary fibrosis 1, 5
• Stage IV fibrocystic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT, or pre-capillary pulmonary hypertension have the highest risk of mortality (>40% at 5 years) 5