Pegloticase plus mycophenolate mofetil reduces antidrug antibodies, boosts efficacy in gout
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Patients with uncontrolled gout treated with pegloticase and mycophenolate mofetil exhibited reduced probability of developing antibodies to pegloticase and improved response rates at 12 weeks, according to data presented at ACR 2020.
“The response [to pegloticase] is limited in some patients due the development of anti-pegloticase antibodies,” Puja Khanna, MD, MPH, of the Michigan Medicine Rheumatology Clinic, told Healio Rheumatology. “In the rheumatology space, we’re familiar with this concept and have used a variety of DMARDs to minimize the development of antidrug antibodies (ADAs) and increase the efficacy of therapies. Historically, we have used methotrexate to lower infliximab induced ADAs. Recently, there have been case series published on how methotrexate has successfully improved the response rate when used with pegloticase.”
“Gout patients often live with numerous comorbidities which can necessitate selecting a different immunomodulator than methotrexate, in addition with methotrexate use, side effects such as hematologic, hepatic and renal toxicities need to be carefully monitored,” she added. “With this in mind, we sought to explore other DMARDs that could be employed, and selected mycophenolate mofetil due to its known safety profile.”
To evaluate this strategy, Khanna and colleagues recruited patients from five rheumatology practices (n=35) over 18 months, and randomized them to receive either mycophenolate mofetil 1 gram twice a day or placebo with a run-in of 2 weeks prior to intravenous pegloticase at 8 mg every 2 weeks.
The primary endpoints included the proportion of patients who achieved and maintained and a serum urate (sUA) 6 mg/dL at 12 weeks, with a secondary endpoint of 6-month durability of immune modulation after discontinuation of mycophenolate mofetil at 12 weeks.
Khanna and colleagues conducted analyses using SAS (Cary, NC) Version 9.4 with Fisher’s exact test for binary outcomes and Wilcoxon two-sample test for continuous outcomes. Additionally, the researchers performed Kaplan-Meier estimates and log-rank test to compare survival curves between groups.
According to study results, 86% of patients in the mycophenolate mofetil group achieved sUA 6mg/dL at 12 weeks compared with 40% in the placebo. Additionally, 68% of patients who received mycophenolate mofetil sustained that sUA response vs. 30% among patients in the placebo group.
“Using immunomodulating therapy in patients with uncontrolled gout does in fact reduce the likelihood of developing antibodies to pegloticase,” Khanna said. “The majority of the patients had an enduring response to pegloticase at 24 weeks, even though mycophenolate mofetil was stopped after the first 12 weeks.”
Patients who received mycophenolate mofetil exhibited higher rates of adverse events vs. placebo — musculoskeletal (36% vs. 10%), respiratory (18% vs. 0%) and infections (9% vs. 0%) — yet the placebo arm demonstrated a greater percentage of infusion reactions (30% vs. 0%).
“Rheumatologists are well versed in the use of mycophenolate mofetil in a variety of rheumatic diseases such as lupus and systemic sclerosis,” Khanna said. “However, gout is far more prevalent and causes major disability, and the treatment is challenging due to the limitations of oral agents. Access to a variety of immunomodulatory options to lower the immunogenicity of pegloticase provides us with the potential to treat poorly controlled gout in a safe and effective manner.”
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Khanna P. Abstract #952. Presented at: ACR Convergence 2020; November 5-9, 2020 (virtual meeting).
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