New advances in the treatment of gout: review of pegloticase

Figures & data

Table 1 Antihyperuricemic drugs in gout

Drug	Action: indication	Daily dose: standard	Characteristics
Allopurinol orally	XOi: all	100–900 mg: 300 mg	Dosage adjustment to renal function
Benzbromarone orally	Urate transporter: low excretor, subject to intolerance or allergy to allopurinol	50–200 mg: 100 mg	Poor efficacy in severe renal function impairment
Febuxostat orally	XOi: all, particularly in Allo intolerance	40–120 mg: 80 mg	No dosage adjustment in renal impairment
Probenecid orally	Urate transporter: low excretor	500–2,000 mg: 1,000 mg	Poor efficacy in moderate to severe renal function
Rasburicase iv	UrO: lytic effect on tophi	Compassionate use: eg, 0.2 mg/kg in 60 min; infusion on d 1, then 1x per wk; (+methylprednisolone 100 mg iv)	Biological
Pegloticase iv	UrO: chronic refractory gout	8 mg every 2–4 wk	Biological

Abbreviations: XOi, xanthine oxidase inhibitor; iv, intravenous; UrO, urate oxidase.

Table 2 Suggested, current experience-based strategy for initiation of antihyperuricemic therapy⁶

Confirmation of diagnosis: detect urate crystals by means of polarization microscopy Two or more gout flares per year or tophi/joint destruction due to gout attacks Therapeutic advicea: allopurinol 100–300 mg/db allopurinol intolerance: consider febuxostat Laboratory monitoring of the effectiveness at 6–8 wkc: sUr < 0.30 mmol/L, then continue allopurinol sUr > 0.30–0.36 mmol/L, but no further attacks (without colchicine/NSAID/corticosteroids), then continue allopurinol sUr > 0.30 mmol/L plus gout attacks/persistent tophi and uUr > 1.5 mmol/24 h, go to 5 sUr > 0.30 mmol/L plus gout attacks/persistent tophi with uUr < 1.5 mmol/24 h, go to 6 Therapeutic advice: increase allopurinol (eg, +100 mg/d or double the dose); then go to 4 Allopurinol inefficacy at maximum dosage (corrected for renal function): consider febuxostat Therapeutic advice: add uricosuricum, eg, benzbromarone 100 mg/d or probenecid 500 mg twice daily; then go to 4 Laboratory monitoring of the effectiveness of sUr and uUr (possibly pHd) after 6 mo: see 5 Note: when trying to clear tophi, target value is sUr < 0.30 mmol/L. Consider pegloticase when target value cannot be reached with conventional oral drugs or for more rapid debulkment in severe bulky disease

a Notes: Subject to motivation and tolerance by patient;

b Subject to calculated creatinine clearance (cCC) > 50 mL/min, if cCC < 50 mL/min, then only increase allopurinol with 100 mg/day. Serum oxipurinol concentrations might be measured in patients with renal insufficiency;

c Target value for sUr ≤ 0.36 mmol/L might be sufficient when there are no further gout attacks despite withdrawing colchicine/NSAID, otherwise lower target value of 0.30 mmol/L;

d If experiencing kidney stones or uUr > 6.0 mmol/24 hours and pH < 7.0 consider alkalizing with sodium bicarbonate.

Abbreviations: sUr, serum urate; NSAID, nonsteroidal anti-inflammatory drug; uUr, 24-hour excretion of urate in urine.

Table 3 Efficacy and tolerability of pegloticase in randomized controlled trials

Study	Treatment, dosage	No. of patients	Duration	sUr < 6 mg/dL (0.36 mmol/L)a	Gout flares	Tophus dissolution (final visit)	Withdrawal due to ADR
Phase I^Citation43	4–24 mg sc	13	single dose	–	–	–	–
Phase I^Citation44	0.5–12 mg iv	24	single dose	–	–	–	–
Phase II^Citation45,Citation46	4 mg iv q2w	41	3 mo	4/7 (57.1%)	86%	Not available	15 (37%)
	8 mg iv q2w			7/8 (87.5%)	63%	Case reports^Citation48
	8 mg iv q4w			7/13 (53.8%)	92%
	12 mg iv q4w			8/13 (61, 5%)	100%
GOUT 1 and GOUT 2^Citation49,Citation50	8 mg iv q2w	43 + 42	26 wk	20/43 (46.5%) (P < 0.001)b and 16/42 (38.1%) (P < 0.001)b	mo 1–3: 77%; mo 4–6: 41% (P = 0.007)b	21/52 (40.4%)	1 (2%)
	8 mg iv q4w	41 + 43		8/41 (19.5%) (P = 0.044)b and 21/43 (48.8%) (P < 0.001)b	mo 1–3: 81%; mo 4–6: 57%	11/52 (21.2%)	16 (19%)
	Placebo	20 + 23		0/20 (0%) and 0/23 (0%)	mo 1–3: 54%; mo 4–6: 67%	2/29 (6.9%)	17 (20%)

a Notes: Proportion of subjects maintaining a PUA concentration <6 mg/dL for at least 80% of the time during the treatment period (Phase II) or during the months 3 and 6 (Phase II);

b Pegloticase vs placebo.

Abbreviations: ADR, adverse drug reactions; PAU, plasma uric acid.

Table 4 Summary of treatment-emergent AEs including IRs and gout flares reported¹¹

Safety characteristics (No.)	GOUT 1 and 2			GOUT 3
	Placebo (N = 43)	Pegloticase q2 wk (N = 85)	Pegloticase q4 wk (N = 84)	Pegloticase q2 wk (N = 85)	Pegloticase q4 wk (N = 84)
Adverse events (AEs)	370	693	870	1,044	1,411
Subjects with AEs	41 (95%)	80 (94%)	84 (100%)	83 (98%)	84 (100%)
Subjects with serious AEs (SAE)	5 (12%)	20 (24%)	19 (23%)	24 (28%)	27 (32%)
Subjects with infections	22 (51%)	30 (35%)	40 (48%)	41 (48%)	54 (64%)
Subjects with serious infections	4 (9%)	3 (4%)	5 (6%)	3 (4%)	7 (8%)
Subjects with malignancy	1 (2%)	0 (0%)	1 (1%)	0 (0%)	1 (1%)
Subjects with infusion reactions (IR)	2 (5%)	22 (26%)	34 (41%)	26 (31%)	38 (45%)
Subjects who discontinued due to AEs	1 (2%)	16 (19%)	17 (20%)	18 (21%)	21 (25%)
Deaths	1 (2%)	3 (4%)	1 (1%)	0 (0%)	2 (2%)

Note: Except for the “number of AEs”, subjects are counted only once in each row.

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