A total of 34 patients with uncontrolled gout were identified and included in the analyses. Most patients were male (79%) and Caucasian (74%) and mean age was 62.4 ± 16.3 years (Table 1). Comorbidities were common, with hypertension (76%), obesity (71%), osteoarthritis (68%), chronic kidney disease (CKD, 47%), and cardiovascular disease (35%) most frequently reported. Baseline eGFR averaged 65.4 ± 25.2 ml/min/1.73 m2 and 41% of patients had eGFR < 60 ml/min/1.73 m2. No kidney transplant or dialysis patients were included.

Gout duration averaged 14.7 ± 13.4 years and mean SU prior to pegloticase exposure was 9.1 ± 2.0 mg/dl. Subcutaneous (subQ) tophi were noted in 91% of patients and all had signs of severe gout, including chronic pain, frequent gout flares, and/or bone erosions on radiography. Thirty-one of 34 patients (91%) had documented oral ULT use prior to beginning pegloticase, with a history of allopurinol use in 28 patients (82%, mean dose: 270.8 ± 139.8 mg/day [n = 24]) and febuxostat use in three patients (9%, mean dose: 53.3 ± 23.1 mg/day [n = 3]). Of the three patients (9%) without oral ULT use noted, one patient was not on an oral ULT at first rheumatology office visit and two patients reported allopurinol intolerance.

A total of 498 pegloticase doses were administered (14.6 ± 7.1 infusions/patient) over a mean of 28.5 ± 14.9 weeks. Immunomodulator use included subQ methotrexate (MTX; 20 patients [59%], 10−25 mg/week), oral MTX (9 patients [26%], 7.5−20 mg/week), oral mycophenolate mofetil (MMF; 3 patients [9%], 1000 mg/day), and oral azathioprine (AZA; 2 patients [6%], 100 mg/day; Table 2). Immunomodulation co-therapy was initiated prior to pegloticase in 32 patients (94%) 5.3 ± 3.0 weeks before the first pegloticase infusion. The remaining two patients (6%) initiated immunomodulation (both subQ MTX) and pegloticase on the same day (Fig. 1).

Schematic of study design showing pegloticase and immunomodulation co-therapy. Patients were considered to have sustained urate-lowering efficacy (treatment responder) if they had received at least 12 pegloticase infusions and had SU < 6 mg/dl just prior to infusion 12. MTX methotrexate, LEF leflunomide, MMF mycophenolate mofetil, AZA azathioprine

At data collection, 11 patients (32%) remained on therapy, 17 patients (50%) had met treatment goals and discontinued therapy, and six patients (18%) had prematurely discontinued therapy. Of the 11 patients who remained on therapy, six had not yet reached infusion 12 and were excluded from responder rate analyses. Premature therapy discontinuation occurred because of loss of follow-up (n = 2), urate-lowering efficacy loss (n = 1), patient choice (n = 1), COVID concerns (n = 1), and adverse event (n = 1; stroke [further described below]). Therefore, 28 patients were included in responder rate analyses. Twenty-five of 28 patients (89%) met treatment response criteria (Fig. 2). On average, SU fell to 1.0 ± 0.6 mg/dl following pegloticase infusion 1, remaining approximately 1 mg/dl for the remainder of therapy (Fig. 3). Of the 17 patients that had met treatment goals and discontinued pegloticase, 15/17 (88%) had tophi before beginning therapy. Of these 15, 13 (87%) no longer had visible tophi following pegloticase discontinuation. Ten of these 17 patients (59%) were administered allopurinol following pegloticase discontinuation at a mean dose of 360 mg/day (range, 100 to 600 mg/day).

Pegloticase response rate in patients co-treated with an immunomodulator. The AZA non-responder self-discontinued AZA 2 weeks prior to pegloticase infusion 5 (pegloticase discontinued after infusion 6). MMF mycophenolate mofetil, subQ subcutaneous, MTX methotrexate, AZA azathioprine

Mean serum urate (SU) prior to each pegloticase infusion. Mean SU remained below 1 mg/dl following infusion 16 (seven or fewer patients for infusions 17–38). Error bars represent standard deviation

Response rates for individual immunomodulators were 100% for MMF, 93% for subQ MTX, 89% for oral MTX, and 50% for AZA (Fig. 2). Of the three patients were considered non-responders, one met treatment goals after three pegloticase infusions and discontinued therapy, one had an SU of 11.3 mg/dl prior to infusion 12 but because of ongoing clinical improvement remained on therapy, without any reported infusion reactions, and one self-discontinued azathioprine 2 weeks prior to infusion 5 (SU rise after infusion 6 followed by pegloticase discontinuation).

Over the course of therapy, mean eGFR among pegloticase + immunomodulation co-treated patients improved from 65.4 ± 25.2 ml/min/1.73 m2 at baseline to 75.7 ± 30.8 ml/min/1.73 m2 at time of last pegloticase infusion (p = 0.001, N = 34). Mean eGFR change over pre-therapy values was + 10.3 ± 16.9 ml/min/1.73 m2 at last pegloticase infusion (N = 34 [all patients regardless of treatment duration or response]). Further, kidney disease remained stable or improved in 29 patients (85%), with CKD progression of one stage or less in the remaining five patients (15%). Of these, one patient moved from stage 1 to stage 2, two moved from stage 2 to stage 3a, and two moved from stage 3a to 3b. Patients with pre-therapy CKD (eGFR < 60 ml/min/1.73 m2, n = 14) were older (72.6 ± 10.1 vs. 55.2 ± 16.2 years, p < 0.001) and more often female (43 vs. 5%) than those without CKD (n = 20). Despite these differences, all findings were similar between patients with and without pre-therapy CKD, including the number of pegloticase infusions administered (CKD: 14.6 ± 8.3 vs. non-CKD: 14.7 ± 6.4 infusions), urate-lowering efficacy (91% [10/11] vs. 88% [15/17]), MTX usage (93% vs. 80%; mean dose: 14.2 ± 5.4 vs. 16.3 ± 3.4 mg/week), and mean change in eGFR (12.3 ± 21.5 vs. 8.9 ± 13.2 ml/min/1.73 m2).

No new safety concerns were identified. Twenty patients (59%) experienced one or more adverse events during pegloticase plus immunomodulation co-therapy. The most common adverse event was acute gout flare, which was observed in 19 patients (56%). In these 19 patients, a mean of 1.8 ± 1.5 flares per patient were noted. Other adverse events included unrelated stroke in one patient (3%) after 15 pegloticase infusions (treatment discontinued) and new lower extremity pain (described as “other AE”) in three patients (9%). No infusion reactions or infections were noted. Clinical laboratory values were monitored in all patients as a precaution, including liver function tests (LFTs), with no new laboratory abnormalities emerging.