The study results presented at the American College of Rheumatology Convergence (held virtually from 5 to 9 November 2020) demonstrated that the combination therapy of methotrexate and pegloticase was found to lower the incidence of gout flares over a period of 12 months.

A multicenter open-label trial was performed to explore the safety and efficacy of pegloticase in patients having uncontrolled gout who were co-treated with oral methotrexate. The researchers incorporated adult patients from six sites. The key inclusion criteria was uncontrolled gout (defined as serum uric acid ≥6 mg/dL with ≥1 of the following: serum uric acid ≥6 mg/dL despite oral urate-lowering therapy, intolerance to urate-lowering therapy, or functionally limiting tophaceous deposits).

Participants were initiated with oral methotrexate (15 mg/week) and folic acid (1 mg/day) for four weeks before the first pegloticase infusion and were continued with pegloticase therapy (8 mg) every two weeks. The protocol initially consisted of 24 weeks of co-therapy but was modified to extend to 52 weeks.

The percentage of responders during month 6 (defined as serum uric acid < 6 mg/dL for ≥80% of the time) was the primary endpoint. The analyses were conducted on the modified intent-to-treat (mITT) population (subjects who were given ≥1 pegloticase infusion).

Of the total 14 patients (mean age 49.3 ± 8.7 yrs, all males) incorporated in the mITT population, 11 (78.6%) patients were considered 6-month pegloticase responders and 3 non-responders discontinued pegloticase after two consecutive serum uric acid levels >6 mg/dL.

Mean serum uric acid was about 9.2 ± 2.5 mg/dL prior to the first pegloticase infusion. 12 patients had visible tophi. Of the 11 subjects who were responders in the sixth month, one subject did not extend (pre-protocol amendment), two subjects discontinued pegloticase due to meeting their therapy goals (continued on allopurinol; one subject fulfilled responder definition during month 12), and 8 subjects continued receiving pegloticase/ methotrexate combination and remained responders at the 12th month.

The occurrence of gout flares in the first 12 weeks and weeks 36-52 is shown in the following table:

In the first 6 months, a serious adverse event of sepsis occurred in one patient. During co-treatment, the noxious adverse events that were found to occur in more than one patient were hypertension, nasopharyngitis, upper respiratory tract infection, diarrhea, sinusitis, muscle strain, and arthralgia. No novel safety issues were witnessed.

The six-month response rate of methotrexate/pegloticase co-therapy was found to be 78.6%. The responders at the sixth month who stayed on treatment continued to be responders at the 12th month with serum uric acid remaining below 1 mg/dL. Thus, the methotrexate/pegloticase co-therapy displayed good tolerability over this 12 month time period with minimized gout flares incidence over time.