Treatment Options for Steroid-Resistant Sarcoidosis
For patients with steroid-resistant sarcoidosis, methotrexate should be the first-line alternative treatment, followed by infliximab for those who continue to have disease progression or toxicity despite methotrexate therapy. 1
Treatment Algorithm for Steroid-Resistant Sarcoidosis
First-Line Approach (After Steroid Failure)
- Methotrexate is the preferred second-line agent for patients with inadequate response to steroid therapy or those experiencing steroid toxicity 1
- Oral administration is generally favored (over subcutaneous) for most patients 1
- Allow 3-6 months to assess therapeutic response to methotrexate before considering further treatment escalation 1
- Consider folic acid supplementation to reduce methotrexate-associated side effects, though this did not reach full consensus in guidelines 1
Second-Line Approach (After Methotrexate Failure)
- For patients who have been treated with glucocorticoids and methotrexate with continued disease, anti-TNF therapy with infliximab is recommended 1
- Infliximab is the preferred biologic agent with the strongest evidence base 1, 2
- The recommended loading dose is 5 mg/kg at weeks 0,2, and 6, followed by maintenance therapy 1
- Consider combining infliximab with low-dose methotrexate to reduce the risk of autoantibody formation 1
Third-Line Options
- For patients with continued disease progression after infliximab, consider:
- Alternative TNF inhibitors such as adalimumab (though evidence is less robust than for infliximab) 1, 2
- Repository corticotrophin injection (RCI) or antimicrobial therapy (CLEAR: concomitant levofloxacin, ethambutol, azithromycin, and rifampin), though consensus on these approaches was not reached 1
- Rituximab may be considered in highly refractory cases 2
Alternative Second-Line Agents
- If methotrexate is not tolerated or contraindicated, consider:
Organ-Specific Considerations
Pulmonary Sarcoidosis
- For symptomatic pulmonary sarcoidosis with high risk of mortality or permanent disability, methotrexate followed by infliximab is recommended to improve/preserve forced vital capacity and quality of life 1
- Inhaled corticosteroids may provide symptomatic relief for cough and asthma-like symptoms but should be discontinued if ineffective 1
Cutaneous Sarcoidosis
- For patients with cutaneous sarcoidosis who have failed glucocorticoids, infliximab is recommended to reduce skin lesions 1, 4
- Hydroxychloroquine is particularly effective for skin manifestations 1, 4
- Maximum dosages of hydroxychloroquine should not exceed 6.5 mg/kg/day to avoid ocular toxicity 4
Neurosarcoidosis
- For neurosarcoidosis patients who have failed glucocorticoids and methotrexate, infliximab is recommended 1
- The treatment approach is more aggressive due to the high morbidity associated with neurological involvement 1
Monitoring and Management
- Regular monitoring for drug toxicity is essential, particularly:
- Consider Pneumocystis pneumonia prophylaxis for patients receiving multiple immunosuppressive agents 1
- Ensure pneumococcal and influenza vaccination 1
Treatment Duration
- For biologic agents like infliximab, consider continuation for 2-3 years in patients who respond 1
- Consider discontinuation of biologics after demonstration of disease stability for at least 2-3 years 1
- The goal remains to taper all immunosuppressive medications to the lowest effective dose or discontinue if possible 1
Pitfalls and Caveats
- Avoid prolonged corticosteroid monotherapy, as it fails to adequately address disease progression and causes significant toxicity 1
- Allow sufficient time (3-6 months) to assess response to each new therapy before escalating treatment 1
- Anti-TNF agents other than infliximab and adalimumab (such as etanercept) have not shown efficacy in sarcoidosis 1
- Consider lung transplantation for patients with severe disease unresponsive to therapy, worsening pulmonary function, or pulmonary hypertension 1