Persistent Urate Lowering With Pegloticase Shows Clinical Benefits in Gout

Analysis indicated that patients with chronic refractory gout, not achieving a protocol-defined biochemical response, might still have significant clinical benefits with pegloticase treatment.

Patients with chronic gout refractory, with protocol-defined urate-lowering therapy, can still derive significant clinical benefits from pegloticase treatment, according to a study published in The Journal of Rheumatology.

Gout treatment usually focuses on lowering serum urate to ≤6 mg/dL, which is typical of treatment response in randomized, controlled trials. However, this measure may not be closely related to clinical outcomes, and patients considered to be nonresponders can potentially experience improvements.

Related Articles

For the current study, researchers analyzed the results from 2 randomized, controlled trials to assess the clinical efficacy of pegloticase treatment (8 mg every 2 weeks) in both responders and nonresponders. Serum urate levels were measured before each infusion. The investigators of the study measured Patient Global Assessment (PGA), gout flare assessment, tophus reduction, tender and swollen joint counts (TJC and SJC), pain measured with a 100-mm visual analog scale (VAS), and patient-reported outcomes from several sources (Physical Component Score [PCS], 36-Item Short Form Health Survey (SF-36), and Arthritis-Specific Health Index Score [ASHIS]).

The analysis included 4 patient groups: 43 participants receiving placebo, 49 modified intent-to-treat (mITT) nonresponders who were not available for months 3 and 6 of urate assessments but received at least 1 infusion, 36 responders with serum urate <6.0 mg/dL for ≥80% of the time through months 3 and 6, and 39 per-protocol (PP) nonresponders who received all pegloticase infusions as planned. 

No significant improvements were seen in the participants taking the placebo. Complete tophus response occurred more frequently in responders (52%) and it was also seen in 26.9% of PP nonresponders and 25.0% of mITT nonresponders. Any tophus improvement, partial or complete, was seen in 70% of responders, 63.8% of PP nonresponders, 50% of mITT nonresponders, and just 30% of patients who were given the placebo. All participants taking pegloticase had reduced gout flares by month 6, but the differences were only significant for responders (P =.0009) and mITT nonresponders (P =.0002).

Significant TJC and SJC reductions were seen for all treatment groups (P <.05), and significant improvements in PGA and SF-36 Bodily Pain were likewise seen for all pegloticase groups (P <.05).

Although all groups showed decreases in pain, as measured with VAS, only responders achieved statistical significance (P <.05). The SF-36 PCS, SF-36 ASHIS, and the HAQ-DI FIS results were variable, with only the SF-36 ASHIS had statistically significant improvements for responders, mITT nonresponders, and PP nonresponders at 6 months (P =.002, P =.02, and P =.005, respectively).

Study investigators concluded, “the results from this analysis indicate that chronic refractory gout patients not achieving a protocol-defined biochemical response may still have significant clinical benefits with pegloticase treatment. This suggests that the substantial, although transient reduction in serum urate achieved in patients categorized as nonresponders in the RCTs, can result in sustained clinical benefit. In such patients, examination of a strategy of returning to oral management (e.g., allopurinol, febuxostat) after initial pegloticase treatment deserves formal examination.”

Disclosure: This study was funded by Horizon Pharma. Michael H. Pillinger, MD, is a consultant for Horizon, Ironwood, Sobi, and AstraZeneca; he is a site investigator for a Takeda-sponsored trial; and, he has received grants for investigator-initiated studies from Horizon and Hikma. Theodore Fields, MD, serves on the advisory boards for Takeda, Horizon, and Ironwood Pharmaceuticals. Anthony E. Yeo, MBBS, PhD, MPH, is a contractor for Horizon. Peter E. Lipsky, MD, is a consultant for Horizon.


Pillinger MH, Fields T, Yeo AE, Lipsky PE. Dissociation between clinical benefit and persistent urate lowering in patients with chronic refractory gout treated with pegloticase [published online June 15, 2019]. J Rheumatol. doi:10.3899/jrheum.190161