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

Background:

Pegloticase + methotrexate (MTX), FDA approval July 2022,[1] is effective at reducing signs/symptoms of uncontrolled gout.[2] The pivotal trial (MIRROR RCT) confirmed pegloticase + MTX superiority in safety and efficacy (mo 6 response rate: 71% vs. 39%; IR rate: 4% vs. 31%). Gout flare, the most common adverse event, occurred in 54% of patients in the pegloticase + MTX treatment group despite daily NSAID or colchicine prophylaxis and pre-infusion IV methylprednisone 125 mg.[3] Canakinumab is FDA approved for treatment of recurrent gout flares in patients who cannot be treated with NSAIDs, colchicine, or repeated courses of corticosteroids (CS)[4] and can reduce subsequent flares during allopurinol initiation, presumably through the IL-1 pathway,[5,6] but has not been studied as prophylaxis.

Objectives:

To determine if canakinumab prophylaxis (without CS, NSAIDs, or colchicine) prevents gout flares associated with initiating pegloticase + MTX (MIRROR-C).

Methods:

In this multicenter, open label trial, 12 sequential adult uncontrolled gout patients scheduled to initiate pegloticase + MTX treatment were consented. Patients were TB negative and able to take MTX for ≥ 4 wks prior to pegloticase initiation. Key exclusion criteria (similar to MIRROR RCT) included MTX or pegloticase contraindication, previous uricase exposure, eGFR < 25 mL/min/1.73 m² or dialysis. Canakinumab 150 mg was given subcutaneously 7 days prior to the first pegloticase infusion and ≥ 3 wks since starting MTX. Pegloticase every 2 wks + MTX was initiated without preinfusion CS, NSAIDs, or colchicine. Assessment for gout flares using validated, patient reported criteria published by Gaffo et al[7] was performed at canakinumab injection and every 2 wks at each pegloticase infusion (or appointment if pegloticase was discontinued) for 6 mos. The primary endpoint was monthly gout flares vs. previously published results from MIRROR RCT, with particular interest at 12 wks. Preinfusion serum uric acid (SUA) and pegloticase response rates (intention to observe – last observation carried forward) were also collected.

Results:

Twelve patients met inclusion criteria from 3 separate sites and 11 received canakinumab prophylaxis and ≥ 1 pegloticase infusion. One patient was lost to follow up after infusion 1. Two patients discontinued pegloticase, 1 due to a rise in SUA and 1 by patient choice. One patient experienced a rise in SUA but continued pegloticase. No new gout flares were reported in any patient receiving canakinumab prophylaxis. All active gout flares resolved within 48 hours of administration (Figure 1). Pegloticase + MTX response rate of 82% was comparable to previous MIRROR RCT results. No new safety signals.

Conclusion:

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

REFERENCES:

[1] Pegloticase PI 2022. [2] Sundy JS et al. Arthritis Rheum 2008;58(9):2882-91. [3] Botson JK et al. Arthritis Rheumatol 2023;75:293-304. [4] Canakinumab PI 2023. [5] Schlesinger N et al. Ann Rheum Dis 2011;70(7):1264-71. [6] Kingsbury SR et al. J Inflamm Res 2011;4:39-49. [7] Gaffo AL et al. Arthritis Rheumatol 2018;70(3):462-467.

Acknowledgements:

The Alaska and Washington rheumatology state societies for funding the clinical trial.

Disclosure of Interests:

John Botson Speaker bureau: Abbvie, Amgen, and Horizon Therapeutics (now Amgen, Inc.)., Consultant: Horizon Therapeutics (now Amgen, Inc.) and Novartis., Grant/research support: Study site and principal investigator: Horizon Therapeutics (now Amgen, Inc.) and Olatec., Jeff Peterson Speaker bureau: Eli Lilly, Horizon Therapeutics (now Amgen, Inc.), and Janssen., Consultant: GlaxoSmithKline, Horizon Therapeutics (now Amgen, Inc.), Novartis, and Union Chimique Belge., Grant/research support: Study site and principal investigator Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Horizon Therapeutics (now Amgen, Inc.), Olatec, and SetPoint Medical.