Baseline Characteristics and Disease History
Four male patients, aged 70–75 years, with chronic gout and a prolonged gap (more than 4 weeks) in pegloticase therapy were selected for review. A schematic overview of each patient’s treatment and gaps in therapy is presented in Fig. 1.
At baseline evaluation, three patients (patients 1, 2, and 3) had comorbid coronary artery disease and two patients each had hypertension (patients 1 and 2) and chronic kidney disease (patients 2 and 3); all other comorbidities occurred in only one patient (Table 1). Before pegloticase treatment, patients were typically managed with allopurinol 300 mg daily, with the exception of patient 3 who received allopurinol 300 mg daily and then switched to febuxostat 80 mg (Table 2). Patients had also received at least 6 months of prophylaxis with colchicine 0.6 mg once or twice daily, depending on tolerance, and/or prednisone 5 mg daily. All patients had ongoing manifestations of uncontrolled gout, despite oral ULT (Table 1). SUA levels before the initial course of pegloticase therapy ranged from 5.2 to 10.2 mg/dL (309–607 μmol/L); eGFR and sCR levels ranged from 33 to greater than 60 mL/min/1.73 m2 and 0.9 to 2.04 mg/dL (79.6–180.3 μmol/L), respectively (Table 3; Fig. 1). For patient 4, there was a gap of approximately 1 year between his initial evaluation and treatment initiation, as pegloticase was not yet available; both values are shown in Table 3.
Consistent with standard of care, patients received pegloticase therapy (8-mg infusion every 2 weeks [Q2W]) after inadequate response to conventional oral ULT. To minimize the risk of anaphylaxis and infusion reactions (IRs), patients were pretreated with an antihistamine (diphenhydramine HCl 50 mg per os) and intravenously administered (IV) hydrocortisone 200 mg before pegloticase infusion. Patients also received concomitant prednisone 5 mg daily throughout the duration of pegloticase therapy.
Initial pegloticase treatment lasted 22–124 weeks (Table 2). As patient 3 spent 6 months of the year out of state, he underwent periods of treatment by another physician; therefore, the exact number of doses he received is not available. Patient 4 had low adherence; an occasional 3-week and one 5-week lapse occurred between treatments. During pegloticase treatment, patients’ SUA levels improved to below 1.5 mg/dL (less than 89 μmol/L) (Fig. 2). eGFR and sCR levels were largely stable while on pegloticase therapy (Table 3). Two patients reported gout flares, one minor (patient 1) and one severe (patient 3, lasting 1 week). No patients experienced IRs or other AEs during the first pegloticase treatment (Table 4).
Two patients discontinued pegloticase because of physician’s assessment following resolution of symptoms (patients 2 and 3). Pegloticase was discontinued in patient 4 as a result of poor adherence with infusions and because gout-related symptoms had almost entirely resolved. Patient 1 discontinued pegloticase because of personal reasons (death of spouse) (Table 2).
First Treatment Gap and Retreatment
The length of the first treatment gap ranged broadly between patients, with 13 to 156 weeks elapsing between doses. During the treatment gap, patients 2 and 3 received febuxostat 80 mg daily and patient 4 received allopurinol 500 mg daily; therapy during the pegloticase treatment gap for patient 1 was not available (Table 2). Following the gap in therapy, patients experienced ongoing symptoms of gout. Patients 1 and 2 developed tophi, patients 2 and 4 experienced gout flares, and patient 3 had fatigue (Table 4). Elevated SUA levels were observed in all patients, ranging from 8.3 to 10.8 mg/dL (494–642 μmol/L) (Table 3; Fig. 2); for patients 1, 3, and 4, eGFR ranged from 33 to 86 mL/min/1.73 m2 and sCR ranged from 0.9 to 2.0 mg/dL (79.6–176.8 μmol/L) (Table 3).
Patients were reinitiated on pegloticase therapy at 8 mg Q2W concurrently with concomitant prednisone 5 mg daily. As during the initial pegloticase treatment, patients were pretreated with oral diphenhydramine HCl 50 mg and IV hydrocortisone 200 mg. Retreatment with pegloticase lasted from 4 to 147 weeks (Table 2).
The duration of retreatment for patient 3 lasted only 4 weeks because of an IR following the second dose of pegloticase. Before his first retreatment infusion, patient 3 had an SUA of 8.6 mg/dL (512 μmol/L). Before his second dose, his SUA was 8.9 mg/mL (529 μmol/L) (Table 3; Fig. 2). Despite preinfusion treatment with oral diphenhydramine HCl 50 mg and IV hydrocortisone 200 mg, the resulting IR caused chest discomfort and decreased blood pressure, neither of which required an emergency department visit. The patient discontinued pegloticase treatment and continues to be treated with febuxostat 80 mg daily. As of his last evaluation, the patient had an SUA of 4.6 mg/dL (274 μmol/L) (Table 3).
With the exception of patient 3, SUA levels were low during pegloticase retreatment, and patients 1, 2, and 4 did not experience IRs, gout flares, or other AEs (Table 4; Fig. 2). Patient 1 discontinued pegloticase because of resolution of gout-related symptoms. He continues to be treated with allopurinol 300 mg and lesinurad 200 mg daily. Approximately 3 months after discontinuation of pegloticase, his SUA was 6.5 mg/dL (387 μmol/L); his eGFR and sCR levels were 62 mL/min/1.73 m2 and 1.21 mg/dL (107.0 μmol/L), respectively (Table 3). Patients 2 and 4 discontinued pegloticase because of patient choice; patient 2 experienced insurance complications and patient 4 indicated that his veins were poor during the winter and chose to discontinue pegloticase treatment until the summer (Table 2).
Second Treatment Gap and Retreatment
Patients 2 and 4 reinitiated pegloticase after a second gap in therapy of 12 and 26 weeks, respectively. During the gap, patient 2 received febuxostat 80 mg daily; treatment for patient 4 during this time was not available (Table 2). After the second gap in treatment, patient 2 developed tophi and patient 4 experienced a gout flare. SUA levels before retreatment for patients 2 and 4 were 2.4 mg/dL (143 μmol/L) and 11.9 mg/dL (708 μmol/L), respectively (Table 3; Fig. 2).
Treatment with pegloticase resumed at 8 mg Q2W with concomitant prednisone 5 mg daily. As during previous pegloticase treatments, patients were pretreated with diphenhydramine HCl 50 mg per os and hydrocortisone 200 mg IV before pegloticase infusion. Retreatment lasted 46 weeks for patient 2 and 22 weeks for patient 4 (Table 2). During this time, neither patient experienced IRs, flares, or other AEs, and SUA levels for both patients were below 1.0 mg/dL (less than 59 μmol/L) (Table 4; Fig. 2).
Both patients ultimately discontinued pegloticase treatment because of symptom resolution (Table 2). One month after his last infusion with pegloticase, patient 2 had an SUA of below 1.0 mg/dL (less than 59 μmol/L); his eGFR and sCr levels were 42 mL/min/1.73 m2 and 1.70 mg/dL (150.3 μmol/L), respectively, and he reported no gout flares (Tables 3, 4; Fig. 2). He continues to be treated with allopurinol 100 mg twice daily (Table 2). Similarly, patient 4 reported no flares 4 months after his last treatment and he continues to be treated with allopurinol 300 mg daily (Table 2).