Upward Titration of Anakinra Effective in Auto-Inflammatory Disease

SAN DIEGO, CA—In patients with auto-inflammatory disease who have inadequate disease suppression on anakinra 100mg daily, an upward titration to 600mg/day is relatively safe and well-tolerated, without a substantial increase in adverse events, reported Amanda K. Ombrello, MD, of the National Human Genome Research Institute, National Institutes of Health (NIH), Bethesda, MD, at the 2013 ACR/ARHP Annual Meeting.

Anakinra, an IL-1 antagonist that approved for use in rheumatoid arthritis and neonatal onset multisystem inflammatory disease (NOMID), is also frequently used in other auto-inflammatory diseases, including the tumor necrosis factor–associated periodic syndrome, familial Mediterranean fever, familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and pyogenic arthritis with pyoderma gangrenosum and acne syndrome. “Anakinra is often used in patients with undiagnosed auto-inflammatory syndromes,” she reported.

Many patients continue to have frequent disease flares and documented inflammation at the approved daily dose of 100mg.

“We have found that aggressive titration of anakinra can help to better control disease and that higher doses have not been found to have increased adverse events,” stated Dr. Ombrello. She, along with her team, conducted a retrospective chart review of adults seen in the NIH Autoinflammatory Disease Clinic. They assessed what dose of anakinra provided adequate disease control for patients taking anakinra daily.

Twenty-nine patients were on 100mg anakinra daily and the remaining 38 patients were on 150mg (n=3), 200mg (n=16), 250mg (n=2), 300mg (n=7), 400mg (n=5), 500mg (n=3), and 600mg (n=2) daily. Comparing patients on 100mg daily with those on higher doses, local site reactions were the most common adverse event in both groups but resolve with continued administration of the agent.

“Only 2 of 38 patients did not achieve disease suppression on anakinra >100mg/day (5%),” the investigators reported. “In the remaining 36 patients inflammation was suppressed although, at times of disease flare, 7 patients required brief periods of 100-200mg additional daily anakinra (18%).”

Of particular interest, Dr. Ombrello noted, were 4 patients who underwent organ transplantation secondary to AA amyloidosis (3 kidney and 1 liver) and had viable transplants at 7, 9, 13, and 16 years post-transplant on 300mg, 600mg, 300mg, and 200mg anakinra daily, respectively.

Serious adverse events (SAEs) on anakinra included facial abscess, viral meningitis, Clostridium difficile infection, S. epidermidis bacteremia and osteomyelitis, and Serratia bacteremia. Most SAEs “had additional explanations for their increased risk (two with indwelling central venous lines and one with repeated antibiotic exposure due to a misdiagnosis of cellulitis), and all infections were able to be managed successfully without additional sequelae,” she reported.

“Although apparently well-tolerated and safe, additional long-term follow-up of patients on high dose anakinra is needed to assess for any additional complications,” she concluded.
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