What are the best intravenous (IV) anti-inflammatory medications?

Best Intravenous Anti-Inflammatory Medications

For severe inflammatory conditions requiring IV therapy, high-dose corticosteroids—specifically methylprednisolone 1-2 mg/kg/day IV or hydrocortisone 100 mg every 6 hours—represent the cornerstone first-line treatment, with methylprednisolone preferred due to significantly less mineralocorticoid effects and reduced hypokalemia. 1

First-Line IV Corticosteroids

Methylprednisolone vs Hydrocortisone

• Methylprednisolone 60 mg daily (or 1-2 mg/kg/day) is the preferred IV corticosteroid because it causes significantly less hypokalaemia compared to hydrocortisone at equivalent doses, while maintaining equal efficacy 1
• Hydrocortisone 100 mg every 6 hours (400 mg total daily) is an alternative, though it has stronger mineralocorticoid effects 1
• No advantage exists from giving higher corticosteroid doses above methylprednisolone 60 mg equivalent, and bolus injection is as effective as continuous infusion 1
• In acute severe ulcerative colitis, both regimens achieve approximately 67% response rates with 29% requiring colectomy 1

Dosing by Severity

• Moderate disease (grade 2): Methylprednisolone 1 mg/kg/day IV or prednisone 0.5-1 mg/kg/day 1
• Severe disease (grade 3) or organ-threatening: Methylprednisolone 1-2 mg/kg/day IV 1
• Life-threatening manifestations: High-dose pulse methylprednisolone 10-30 mg/kg/day IV for refractory cases 1

Second-Line IV Biologics for Refractory Disease

When Corticosteroids Fail (within 72 hours)

• Tocilizumab (IL-6 receptor inhibitor) 8 mg/kg IV is the preferred biologic for corticosteroid-refractory inflammatory conditions, given every 2 weeks if needed 1, 2
• Infliximab (TNF-α inhibitor) 5 mg/kg IV is an alternative, particularly if fasciitis is present, given every 2 weeks if needed 1
• Anakinra (IL-1 receptor antagonist) >4 mg/kg/day IV or SC for refractory disease, especially with macrophage activation syndrome features 1

IVIG for Specific Conditions

• IVIG 2 g/kg IV (based on ideal body weight) is first-line for multisystem inflammatory syndrome in children (MIS-C), often combined with low-dose corticosteroids 1
• For immune-mediated myositis with life-threatening features (dysphagia, dyspnea, myocarditis), add IVIG 2 g/kg over 2-5 days to high-dose corticosteroids 1, 3
• Cardiac function and fluid status must be assessed before IVIG administration; divided doses (1 g/kg daily over 2 days) may be necessary with cardiac dysfunction 1

Treatment Algorithm by Clinical Scenario

Acute Severe Inflammatory Bowel Disease

1. Start methylprednisolone 60 mg IV daily or hydrocortisone 100 mg IV every 6 hours immediately 1
2. Do not delay treatment pending stool cultures or C. difficile results 1
3. Assess response after 3 days; if no improvement, escalate to rescue therapy 1
4. Add prophylactic low-molecular-weight heparin for VTE prevention 1

Immune-Related Adverse Events from Checkpoint Inhibitors

1. Grade 2 (moderate): Discontinue checkpoint inhibitor, start prednisone 0.5-1 mg/kg/day 1
2. Grade 3-4 or life-threatening: Methylprednisolone IV pulses then 1-2 mg/kg/day, add IVIG and/or plasma exchange for myocarditis, bulbar symptoms, or respiratory failure 1, 3
3. If no improvement within 72 hours, add tocilizumab 8 mg/kg IV (preferred) or infliximab 5 mg/kg IV 1, 3

Multisystem Inflammatory Syndrome (MIS-C)

1. First-line: IVIG 2 g/kg IV AND methylprednisolone 1-2 mg/kg/day IV for shock or organ-threatening disease 1
2. Intensification: Methylprednisolone 10-30 mg/kg/day IV for patients requiring multiple inotropes/vasopressors 1
3. Do not give a second IVIG dose due to volume overload and hemolytic anemia risk 1
4. Consider high-dose anakinra >4 mg/kg/day IV for refractory disease 1

Critical Pitfalls to Avoid

• Never extend IV corticosteroid therapy beyond 7-10 days as this carries no additional benefit and increases toxicity 1
• Do not use methylprednisolone pulse therapy (1000 mg/day for 3 days) for COVID-19 ARDS, as it increases bacterial pneumonia risk without improving outcomes 4
• Methylprednisolone causes significantly more requirement for rescue therapy compared to hydrocortisone in IBD (36.4% vs 19.6%), though with less hypokalemia 5
• Do not delay corticosteroid treatment while awaiting diagnostic confirmation in suspected severe inflammatory conditions 1, 3
• Monitor for hypokalemia with hydrocortisone (67% incidence) versus methylprednisolone (55.8% incidence) 5

Monitoring Requirements

• Assess clinical and biochemical response after 3 days of IV corticosteroid therapy 1
• Serial laboratory testing (CRP, ESR, CK if myositis suspected) and cardiac assessment should guide treatment response and tapering 1
• Taper immunomodulatory medications over 2-3 weeks or longer to avoid rebound inflammation 1
• For tocilizumab, monitor liver enzymes (ALT/AST elevations ≥3× ULN occur in 4% of patients) and lipids 2