Methotrexate (MTX) cotherapy with pegloticase continues to increase treatment-response rates among patients with uncontrolled gout through 52 weeks, according to study results published in Arthritis & Rheumatology.
Investigators performed a double-blind, placebo-controlled multicenter efficacy and safety study including adult patients with uncontrolled gout randomly assigned 2:1 to receive pegloticase with blinded MTX or pegloticase plus placebo (PBO) for 52 weeks. The investigators aimed to assess 12-month safety and efficacy of these therapies and their potential to increase urate-lowering response rates.
Study endpoints for efficacy included the percentage of patients in the in the intent-to-treat population (all patients who were randomly assigned) who had a serum-urate (SU) level of less than 6 mg/dL for at least 80% of the month, as assessed at months 6, 9, and 12. Additional endpoints included the percentage of patients who had 1 or more tophi resolved, the reduction in SU, and the length of time until SU-monitoring of pegloticase was discontinued.
Safety was evaluated through the reporting of adverse events (AEs) and laboratory values.
Among patients cotreated with MTX and pegloticase, the response rate at month 12 was significantly higher (60.0%) compared with the PBO group (30.8%), with a between-group difference of 29.1% (95% CI, 13.2%-44.9%; P =.0003).
The MTX and pegloticase group also had fewer SU discontinuations (22.9%) compared with the PBO group (63.3%).
At week 52, complete resolution of 1 or more tophi occurred in 53.8% of the MTX and pegloticase group vs 31.0% of the PBO group, with a between-group difference of 22.8% (95% CI, 1.2%-44.4%; P =.048).
Comparatively, at week 24, only 34.6% of the MTX and pegloticase group saw complete resolution of 1 or more tophi compared with 13.8% of the PBO group.
The safety profile was similar between the 2 treatment groups during the 52-week period. A total of 84.4% of patients in the MTX and pegloticase group experienced 1 or more AEs vs 95.9% of the PBO group, with the majority of these AEs being of mild to moderate severity (94.4% vs 96.4%, respectively).
Acute gout flare (66.7% vs 71.4%), musculoskeletal-related issues (25.0% vs 22.4%), infection or infestation (18.8% vs 18.4%), and gastrointestinal disorders (13.5% vs 18.4%) were the most common AEs reported among the MTX and pegloticase group vs the PBO group, respectively.
Among several limitations, this study did not answer questions of optimal pegloticase therapy duration, use of oral urate-lowering therapy following pegloticase discontinuation, or immunomodulation with agents other than MTX. Additionally, the study was not designed to assess MTX toxicities specific to patients with uncontrolled gout.
“[R]esolution of visible tophi continued to occur past week 24 of pegloticase treatment, indicating that many patients may benefit from a treatment course longer than 6 months,” the study authors noted.
Disclosure: This research was supported by Horizon Therapeutics. Please see the original reference for a full list of disclosures.
Botson JK, Saag K, Peterson J, et al. A randomized, placebo-controlled study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase: primary efficacy and safety findings. Arthritis Rheumatol. 2023;75(2):293-304. doi:10.1002/art.42335