Pegloticase response rates higher when co-treated with immunomodulating therapy in gout patients

Patients with uncontrolled/refractory gout have heavy disease burden, but few treatment options. Pegloticase lowers serum urate (SU), but anti-drug antibodies can limit treatment efficacy. Evidence supports immunomodulator-pegloticase co-administration to increase sustained urate-lowering rates, but published cases are limited. The study by Aaron Broadwell et al investigated experience with pegloticase-immunomodulation co-therapy at two community rheumatology practices.

Patients initiating pegloticase with immunomodulation were included in the study. Patient/treatment characteristics and proportion of responders (>=12 pegloticase infusions, SU < 6 mg/dl at infusion-12) were examined. Patients on therapy at data collection with <12 infusions were excluded from response analyses. eGFR before and after therapy was examined.

Key findings of the study were:

• Thirty-four patients (79% male, 62.4 ± 16.3 years) with uncontrolled gout (SU = 9.1 ± 2.0 mg/dl, 91% tophaceous) were included.

• Most-reported comorbidities were hypertension (76%), obesity (71%), osteoarthritis (68%), and CKD (47%).

• Pre-therapy eGFR was 65.4 ± 25.2 ml/min/1.73 m2 (41% eGFR <60 ml/min/1.73 m2 ).

• All patients initiated immunomodulation before (5.3 ± 3.0 weeks, n = 32) or at (n = 2) first pegloticase infusion.

• Subcutaneous methotrexate (15.4 ± 4.9 mg/week, n = 20), oral methotrexate (15.3 ± 3.6 mg/week, n = 9), mycophenolate mofetil (1000 mg/day, n = 3), and azathioprine (100 mg/day, n = 2) were administered. Patients received 14.6 ± 7.1 infusions over 28.5 ± 14.9 weeks.

• Overall response rate was 89%, ranging among immunomodulators (subcutaneous methotrexate: 93%, oral methotrexate: 89%, mycophenolate mofetil: 100%, azathioprine: 50%).

• On average, eGFR increased during therapy (+10.3 ± 16.9 ml/min/1.73 m2), with CKD stability/improvement in 85%.

• Nineteen patients (56%) experienced gout flares.

• No infusion reactions or infections were noted. No new safety concerns were identified.

The authors concluded that – "this case series highlights experiences with pegloticase plus immunomodulation co-therapy in a real-world clinical setting, further supporting the use of immunomodulators to increase pegloticase treatment response rates. Importantly, several different immunomodulation agents may be effective for increasing treatment response rates and seem well tolerated by patients with uncontrolled gout. However, further study is needed, particularly with AZA and MMF."

Further reading:

Community Practice Experiences with a Variety of Immunomodulatory Agents Co-Administered with Pegloticase for the Treatment of Uncontrolled Gout

Aaron Broadwell, John A. Albert, Lissa Padnick-Silver, Brian LaMoreaux Rheumatology Therapy (2022) 9:1549–1558 https://doi.org/10.1007/s40744-022-00492-3