Patients with refractory gout receiving concomitant mycophenolate mofetil (MMF) with pegloticase were significantly more likely to maintain serum uric acid (SUA) levels at or below 6 mg/dL compared with those receiving pegloticase plus placebo, according to the results of a randomized control trial (RCT) published in Arthritis & Rheumatology.
Pegloticase is a biologic treatment used in patients with uncontrolled gout to reduce SUA levels. However, the efficacy of this biologic agent is limited by the formation of antidrug antibodies. There is emerging evidence that the co-administration of pegloticase with a disease-modifying antirheumatic drug reduces its immunogenicity.
In the current study (ClinicalTrials.gov Identifier: NCT03303989), the researchers evaluated the feasibility of co-administration of MMF and pegloticase to increase the percentage of patients who achieve sustained reductions in SUA levels during pegloticase therapy.
In the phase 2 proof-of-concept RCT, SUA levels were measured in patients with uncontrolled gout who were randomly assigned 3:1 to receive 1000 mg MMF plus pegloticase or placebo plus pegloticase for 14 weeks, initiated 2 weeks before the administration of 8 mg pegloticase administered every 2 weeks for 24 weeks. The primary endpoint was the percentage of patients with SUA levels at or below 6 mg/dL at week 12; secondary endpoints included SUA levels at or below 6 mg/dL at week 24 and rate of adverse events.
Of 35 participants enrolled, 3 withdrew from the study. A total of 88% of the participants were men, with a mean age of 55.2 years. Mean gout disease duration was 13.4 years and mean baseline SUA level was 9.2 mg/dL. At 12 weeks, 19 of 22 patients (86%) in the MMF plus pegloticase group achieved SUA at or below 6 mg/dL compared with 4 of 10 (40%) in the placebo plus pegloticase group (P =.01). At week 24, 68% of patients in the treatment group had SUA levels at or below 6 mg/dL compared with 30% in the control group (P =.06). Adverse events were similar between the groups; however, more infusion reactions were observed among participants in the placebo vs treatment group (30% vs 0%, respectively).
Limitations of the study included the small sample size and the inability to achieve a 3:1 ratio in the treatment vs placebo group. Researchers noted that larger studies are needed.
“To our knowledge, this is the first [RCT] to demonstrate differential prolonged efficacy of pegloticase in the setting of co-administration of an immunomodulatory agent, as well as providing safety information on the combination with MMF which was well tolerated,” the researchers concluded. “Our study serves as an innovative approach to customize pegloticase therapy in patients with severe gout and potentially ameliorate infusion reactions.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.
Khanna PP, Khanna D, Cutter G, et al. Reducing immunogenicity of Pegloticase (RECIPE) with concomitant use of mycophenolate mofetil in patients with refractory gout – a phase II double blind placebo controlled randomized trial. Arthritis Rheumatol. Published online March 22, 2021. doi:10.1002/ART.41731