What is the role of IL-1 (Interleukin-1) blockers, such as anakinra, canakinumab, and rilonacept, in treating patients with pseudogout?

IL-1 Blockers in Pseudogout

IL-1 blockers, particularly anakinra, are effective treatment options for pseudogout when conventional therapies (NSAIDs, colchicine, corticosteroids) are contraindicated, ineffective, or poorly tolerated, based on case series demonstrating rapid resolution of symptoms within 2 weeks. 1, 2

Evidence for IL-1 Blockade in Pseudogout

The rationale for using IL-1 inhibitors in pseudogout stems from the shared inflammatory pathway with gout—both calcium pyrophosphate dihydrate (CPPD) crystals and monosodium urate crystals trigger IL-1β production through the NALP3 inflammasome. 3

Anakinra (IL-1 Receptor Antagonist)

Anakinra at 100 mg subcutaneously daily is the most studied IL-1 blocker for pseudogout, with documented success in resistant cases. 1, 2

• A 63-year-old patient with multi-joint pseudogout resistant to allopurinol, steroids, and NSAIDs achieved complete resolution of symptoms within 2 weeks of anakinra treatment, with normalization of inflammatory markers. 1

• In patients with end-stage renal failure (where NSAIDs are contraindicated and corticosteroids failed), anakinra successfully treated acute attacks and prevented recurrence when given 3 days per week after hemodialysis sessions, with 8 months of follow-up showing no severe arthritis episodes. 2

Dosing Regimen

• Acute treatment: 100 mg subcutaneously daily for 3 consecutive days 4
• Prophylaxis in high-risk patients: 100 mg subcutaneously 3 times weekly (particularly useful in dialysis patients) 2

Other IL-1 Inhibitors

Canakinumab (Anti-IL-1β Monoclonal Antibody)

• Canakinumab 150 mg subcutaneously has FDA approval in Europe for gout but not for pseudogout specifically. 5
• While effective in gout trials, there is no published evidence for its use in pseudogout. 6, 5

Rilonacept (IL-1 Trap)

• Rilonacept showed no benefit over indomethacin in gout trials and lacks evidence for pseudogout treatment. 4
• Not recommended based on available data. 6

Clinical Indications for IL-1 Blockers in Pseudogout

Consider IL-1 inhibitors when:

• Severe renal impairment (GFR <30 mL/min) precludes NSAIDs and colchicine 2
• Corticosteroids are contraindicated or ineffective 1
• Multi-joint involvement resistant to conventional therapy 1
• Recurrent attacks requiring prophylaxis in patients unable to use standard options 2

Critical Safety Considerations

Screen for active infection before initiating IL-1 blockade—current infection is an absolute contraindication. 4

• Risk of serious infections, including sepsis, requires vigilant monitoring 4
• Generally well-tolerated in case series with no reported adverse effects in short-term use 1, 2, 3

Practical Limitations

• Lack of FDA approval: None of the IL-1 inhibitors have regulatory approval specifically for pseudogout in the United States 4
• Cost: Substantially higher than conventional therapies, limiting access 4
• Evidence quality: Based primarily on case reports and small case series rather than randomized controlled trials 1, 2

Treatment Algorithm for Pseudogout

1. First-line: NSAIDs, colchicine (dose-adjusted for renal function), or corticosteroids (oral, intra-articular, or parenteral) 7, 8

2. Second-line: Switch to alternative first-line agent or combine therapies 4

3. Third-line (refractory cases): Anakinra 100 mg subcutaneously daily for 3 days, particularly when:

   • Severe renal impairment exists 2
   • Multiple conventional therapies have failed 1
   • Patient requires prophylaxis and cannot use standard options 2

4. Ensure infection screening before initiating IL-1 blockade 4