Canakinumab Prophylaxis Resolves Active Gout Flares Within 48 Hours

Canakinumab prophylaxis resolves active gout flares within 48 hours and prevents new gout flares among patients initiating pegloticase + methotrexate, according to a study presented at the 2024 European Alliance of Associations for Rheumatology (EULAR) in Vienna, Austria.

The US Food and Drug Administration (FDA) approved pegloticase + methotrexate in July 2022. Although the pivotal trial MIRROR supported the safety and efficacy of pegloticase + methotrexate with a response rate of 71% at month 6 (placebo: 39%), gout flares were the most common adverse event. More than half (54%) of the participants experienced gout flares, despite being on daily non-steroidal anti-inflammatory drugs (NSAIDs) or colchicine prophylaxis and pre-infusion IV methylprednisone 125 mg to tame gout flares.

“In [a 2021] trial, 75% of flares were observed in the first 3 months of pegloticase therapy, with a reduction in flares observed beyond the first 3 months of treatment,” wrote investigators.

Canakinumab is another FDA-approved treatment option for recurrent gout flares, intended for patients who do not respond to NSAIDs, colchicine, or repeated courses of corticosteroids. Studies have shown canakinumab can reduce flares during allopurinol initiation, which is thought to be through the IL-1 pathway. However, studies have yet to examine canakinumab as prophylaxis.

In a recent study, investigators, led by rheumatologist John Botson, MD, from the Orthopedic Physicians Alaska in Anchorage, sought to evaluate if canakinumab prophylaxis—without corticosteroids, NSAIDs, or colchicine—prevented gout flares caused by initiating pegloticase + methotrexate. The primary endpoint was monthly gout flares compared to published results from the MIRROR randomized controlled trial, particularly at week 12.

The team conducted a multicenter, open-label trial evaluating canakinumab prophylaxis on gout flares in 12 adult patients with uncontrolled gout who were scheduled to initiate pegloticase + methotrexate.

Participants were tuberculosis-negative and were able to take methotrexate for ≥ 4 weeks before starting pegloticase. They were excluded if they had a methotrexate or pegloticase contraindication, previous uricase exposure, an estimated glomerular filtration rate of < 25 mL/min/1.73 m 2, or dialysis.

The study gave participants canakinumab 150 mg subcutaneously 7 days before the first pegloticase infusion and ≥ 3 weeks after starting methotrexate. Participants received an infusion of pegloticase + methotrexate every 2 weeks without corticosteroids, NSAIDs, or colchicine.

Investigators assessed for gout flares with patient-reported criteria at the canakinumab injection and every 2 weeks at each pegloticase infusion for 6 months. If a participant discontinued pegloticase, gout flares were assessed during an appointment every 2 weeks). They also collected data on preinfusion serum acid and pegloticase response rates.

Twelve patients from 3 separate sites met inclusion criteria, but only 11 received canakinumab prophylaxis and ≥ 1 pegloticase infusion. Throughout the study, 5 participants discontinued: 1 was lost to follow-up after infusion, 2 discontinued pegloticase, 1 due to the rise in serum uric acid, and 1 by choice.

After canakinumab, no patients reported gout flares, and all active gout flares resolved within 48 hours of administration. The 82% response rate of pegloticase + methotrexate was comparable to previous MIRROR results, and this study found no new safety concerns.

“Prophylaxis using a single dose of canakinumab 150 mg prevented gout flares in all patients initiating pegloticase + [methotrexate] for uncontrolled gout without [corticosteroids] and did not compromise efficacy or safety,” investigators concluded. “Although additional studies are needed to corroborate these results, this data supports prophylaxis with canakinumab instead of [corticosteroids] when initiating pegloticase + [methotrexate] treatment.

References

1. ^{Botson J, Peterson J POS0277 CANAKINUMAB PROPHYLAXIS WITHOUT CORTICOSTEROIDS, PREVENTED FLARES IN PATIENTS INITIATING PEGLOTICASE WITH METHOTREXATE FOR UNCONTROLLED GOUT: A PROSPECTIVE, MULTICENTER, OPEN LABEL, PROOF-OF-CONCEPT, PHASE IV, CLINICAL TRIAL Annals of the Rheumatic Diseases 2024;83:410-411.}
2. ^{Botson JK, Tesser JRP, Bennett R, et al. Pegloticase in Combination With Methotrexate in Patients With Uncontrolled Gout: A Multicenter, Open-label Study (MIRROR). J Rheumatol. 2021;48(5):767-774. doi:10.3899/jrheum.200460}