Methotrexate and Pegloticase Treatment Improves Uncontrolled Gout

John Botson, MD

More patients with uncontrolled gout maintain therapeutic response when treated concomitantly with methotrexate and pegloticase when compared to those who use pegloticase alone.

The findings were published as part of the European E-Congress of Rheumatology 2020 (EULAR 2020) meeting due to the cancellation of the in-person meeting.

John Botson, MD, and a team of US-based investigators assessed the efficacy and safety of concomitant pegloticase and methotrexate therapy in patients with uncontrolled gout. The colleagues considered adult patients with uncontrolled gout who were beginning pegloticase therapy for the ongoing multicenter, open-label, efficacy, and safety study of pegloticase with methotrexate co-treatment.

Botson and the team administered patients oral methotrexate 15 mg per week and folate 1 mg per day 4 weeks prior to the first pegloticase infusion and throughout the pegloticase treatment period. Patients had blood drawn before each infusion to measure serum urate level, monitor clinical parameters, and examine for anti-drug antibody development.

Each patient followed infusion reaction prophylaxis protocols including fexofenadine 1 day before and the morning of each infusion and acetaminophen and IV corticosteroid the morning of each infusion. Patients had gout flare prophylaxis with either nonsteroidal anti-inflammatory drugs, colchicine, or prednisone at least 1 week prior to day 1.

The main study outcome was the proportion of responders, which the investigators defined as a serum urate level <6 mg/dL for at least 80% of the time during month 6 (weeks 20, 22, and 24). The analyses were performed on a modified intent-to-treat population, which was defined as patients who received at least 1 pegloticase infusion.

Overall, 17 patients were screened, and 14 patients were enrolled. All of the patients were men and the average age was 49.3 ± 8.7 years old. On the first day of treatment, the mean serum urate level was 9.2 ± 2.5 mg/dL and 12 of the 14 patients had visible tophi. At 6 months, 11 of the 14 patients (78%; 95% CI, 49.2-95.3) met the definition of responder. Three patients discontinued after meeting stopping rules, which meant their pre-infusion serum urate values were >6 mg/dL at 2 consecutive scheduled visits.

While all patients tolerated methotrexate, there was 1 serious adverse event of bacterial sepsis occurred. The adverse event was ultimately resolved. Adverse events occurring in >1 patient during the co-treatment period were diarrhea and upper respiratory tract infection in 3 patients each, sinusitis, muscle strain, and hypertension in 2 patients each. There were gout flares in 12 of the 14 patients (85.7%) and no new safety concerns were identified.

Botson and the team of investigators found an increased number of patients maintained therapeutic response at 6 months when treated concomitantly with methotrexate and pegloticase (78.6%) when compared to the previously reported 42% using pegloticase alone. The results supported and reflected the improved response rates demonstrated in 2 prior cases.

The study, “Pegloticase Response Improvement By Co-Treatment With Methotrexate: Results From the Mirror Open-Label Clinical Trial in Patients With Uncontrolled Gout,” was published online on the EULAR 2020 website.