What are the treatment options for inflammation?

Treatment Options for Inflammation

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for inflammation due to their effective inhibition of the cyclooxygenase pathway, which is central to the generation of inflammatory mediators. 1

First-Line Treatments

NSAIDs

• NSAIDs work by inhibiting cytokines, prostaglandins, and leukotriene synthesis, as well as leukocyte migration 2
• First-line choice for inflammatory conditions, particularly for acute inflammation 2
• Options include:
  • Ibuprofen: Effective for mild to moderate inflammatory pain 3
  • Naproxen: Provides longer-lasting anti-inflammatory effects 4
  • Celecoxib (Celebrex): COX-2 selective NSAID with potentially fewer gastrointestinal side effects 5

NSAID Administration Strategies

• For persistent inflammatory conditions like ankylosing spondylitis (AS), continuous NSAID treatment is preferred 2
• 75% of patients with AS show good or very good response to full-dose NSAIDs within 48 hours 2
• For long-term treatment, COX-2 selective NSAIDs may be preferred due to fewer gastric side effects 2

Important NSAID Safety Considerations

• NSAIDs carry risks of:
  • Gastrointestinal ulceration and bleeding 4, 3
  • Cardiovascular events, especially with long-term use 3
  • Renal complications 4
• Risk factors for complications include:
  • Older age
  • Concomitant corticosteroid or anticoagulant use
  • History of GI bleeding
  • Cardiovascular disease 4, 3

Second-Line and Adjunctive Treatments

Corticosteroids

• Effective for rapid control of moderate to severe inflammation 2
• Administration options:
  • Local injection for localized inflammation (e.g., peripheral oligoarthritis) 2
  • Systemic administration for widespread inflammation 2
• Should be used short-term as a bridge to steroid-free maintenance therapies 2
• Long-term systemic steroid use should be avoided due to adverse effects 2

Disease-Modifying Antirheumatic Drugs (DMARDs)

• For chronic inflammatory conditions when NSAIDs are insufficient 2
• Options include:
  • Methotrexate: Effective for peripheral arthritis in Crohn's disease and rheumatoid arthritis 2
  • Sulfasalazine: Useful for peripheral arthritis in ulcerative colitis 2

Biologic Therapies

• For moderate-to-severe inflammation unresponsive to conventional treatments 2
• TNF inhibitors (infliximab, adalimumab, golimumab):
  • First-line biologics for inflammatory bowel disease with associated spondyloarthritis 2
  • Effective for both intestinal and joint inflammation 2
• JAK inhibitors (tofacitinib, filgotinib, upadacitinib):
  • Alternative option for TNF inhibitor failures 2
  • Effective for rheumatoid arthritis and psoriatic arthritis 2
• Ustekinumab:
  • IL-12/23 inhibitor effective for psoriasis, psoriatic arthritis, and inflammatory bowel disease 2
  • Can be considered after TNF inhibitor failure 2

Topical Anti-inflammatory Agents

• For localized inflammation, especially in ophthalmologic conditions 2
• Topical corticosteroids (e.g., loteprednol 0.5%):
  • Recommended dosing: four times daily for two weeks, then twice daily for two weeks, then once daily for 6-12 weeks 2
  • Lower rates of side effects compared to systemic administration 2
• Steroid-sparing topical options:
  • Calcineurin inhibitors (cyclosporine A 0.05%, tacrolimus 0.03%) 2
  • IL-1 receptor antagonists (Anakinra 2.5%) 2

Novel and Emerging Approaches

Specialized Pro-resolving Mediators (SPMs)

• Endogenous mediators that actively promote resolution of inflammation 6
• Include resolvins, protectins, maresins, and lipoxins 6
• Potential advantages:
  • Promote clearance of microbes
  • Reduce pain
  • Support tissue regeneration 6

Combination Approaches

• NSAIDs combined with protective mediators to reduce toxicity 7
• Targeting multiple enzymes in the arachidonic acid cascade 7
• Phosphatidylcholine-associated NSAIDs show improved safety profiles 7

Treatment Algorithm Based on Inflammatory Condition

1. For mild to moderate inflammation:

   • Begin with NSAIDs at appropriate dosing 2, 1
   • Monitor for GI, cardiovascular, and renal side effects 4, 3

2. For moderate to severe inflammation or inadequate response to NSAIDs:

   • Consider short-term corticosteroids for rapid symptom control 2
   • Transition to steroid-sparing maintenance therapy 2

3. For chronic inflammatory conditions:

   • Add DMARDs based on specific condition:
     • Methotrexate for peripheral arthritis in Crohn's disease 2
     • Sulfasalazine for peripheral arthritis in ulcerative colitis 2

4. For refractory inflammation:

   • Consider biologic therapy:
     • TNF inhibitors as first-line biologics 2
     • JAK inhibitors or IL-12/23 inhibitors for TNF failures 2

5. For localized inflammation:

   • Consider local corticosteroid injections 2
   • For ocular inflammation, use topical anti-inflammatory agents 2

Common Pitfalls and Caveats

• Avoid long-term systemic corticosteroid use due to significant adverse effects 2
• NSAIDs may mask signs of infection, potentially leading to delayed diagnosis of serious conditions like necrotizing fasciitis 8
• Anti-IL-17 agents should be used with caution in patients with inflammatory bowel disease due to risk of disease exacerbation 2
• Vedolizumab, while effective for intestinal inflammation, has limited efficacy for extra-intestinal manifestations and may occasionally worsen joint symptoms 2
• Regular monitoring for NSAID complications is essential, especially in high-risk patients (elderly, history of GI bleeding, cardiovascular disease) 4, 3