Pegloticase plus mycophenolate mofetil yields 86% response rate in uncontrolled gout
Concomitant use of mycophenolate mofetil with pegloticase demonstrated clinically meaningful improvement in 86% of patients with uncontrolled gout, compared with pegloticase alone, according to data published in Arthritis & Rheumatology.
Puja P. Khanna, MD, MPH, of the University of Michigan, Ann Arbor, co-author of the study, initially presented the study’s findings in November at ACR Convergence 2020.
“The response [to pegloticase] is limited in some patients due the development of anti-pegloticase antibodies,” Khanna told Healio Rheumatology at that time. “In the rheumatology space, we’re familiar with this concept and have used a variety of [disease-modifying antirheumatic drugs] 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 analyze whether mycophenolate mofetil could prolong the efficacy of pegloticase (Krystexxa, Horizon Therapeutics) in patients with uncontrolled gout, Khanna and colleagues conducted a phase 2, proof-of-concept, placebo controlled randomized trial. The researchers included a total of 32 adults — enrolled from five U.S. centers — with chronic refractory gout and serum urate levels of more than 6 mg/dL, and who had never received pegloticase or other uricase therapies.
Participants were randomized 3:1 to receive either 1,000 mg mycophenolate mofetil twice daily or placebo for 14 weeks, starting 2 weeks before, and while receiving, 8 mg of intravenous pegloticase biweekly for 24 weeks. The primary endpoint was proportion of patients who sustained a serum urate level of 6 mg/dL or less at 12 weeks. Secondary endpoints included 24‐week durability of the serum urate target, as well as the rate of adverse events. For their analysis, the researchers used Fisher’s exact test and Wilcoxon two‐sample test, as well as Kaplan‐Meier estimates and log‐rank tests.
According to the researchers, 86% of participants who received mycophenolate mofetil achieved the serum urate target of 6 mg/dL or less at 12 weeks, compared with 40% in the placebo group (P = .01). At week 24, 68% of participants in the mycophenolate mofetil group demonstrated the target serum urate level, compared with 30% in the placebo arm (P = 0.06).
Adverse event rates at week 24 were similar between the groups, with 30% of participants in the placebo arm experiencing more infusion reactions, compared with 0% of those who received mycophenolate mofetil.
“We know that when gout is left untreated, it causes severe disability in patients,” Khanna told Healio Rheumatology upon publication of the study in Arthritis & Rheumatology. “That boils down to higher numbers of hospitalizations that these patients incur, significant loss of work productivity, and ultimately contributes to the societal costs. So, I think it is time now for us to focus on gout.”
“With the RECIPE trial, we have a proof-of-concept study which is the first randomized controlled trial to demonstrate that mycophenolate mofetil mitigates the immunogenic response of pegloticase and patients are able to maintain a urate level of less than 6 mg/dL at 6 months without infusion reactions,” she added. “Our data adds to the growing body of evidence on the concomitant use of pegloticase with an immunomodulatory. This approach will help shift the treatment paradigm in uncontrolled gout so more patients can receive a full course of therapy and improve outcomes.”