Real-World Effectiveness of Pegloticase Associated With Use of Concomitant Immunomodulatory Therapy

Abstract

Objective: The objective of this study was to ascertain pegloticase persistence and adverse events associated with concomitant immunomodulatory drug treatment in patients with gout.

Methods: We conducted a retrospective analysis of patients with gout using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness registry from January 2016 through June 2020. The first pegloticase infusion defined the index date. Based on concomitant immunomodulatory drug treatment, we identified three exposure groups: (1) immunomodulatory drug initiators (patients initiating an immunomodulatory prescription ±60 days from the index date), (2) prevalent immunomodulatory drug recipients (patients receiving their first immunomodulatory drug prescription >60 days before the index date with at least one prescription within ±60 days of the index date), and (3) immunomodulatory nonrecipients (patients receiving pegloticase without concomitant immunomodulatory drugs). We calculated the proportion of patients who achieved serum urate levels ≤6 mg/dL and who had laboratory abnormalities (white blood cell count <3.4 x 10⁹/L, platelet count <135,000, hematocrit level <30%, alanine aminotransferase or aspartate aminotransferase level ≥1.5 times the upper limit normal value) within 180 days after the index date. Cox regression analyzed time to pegloticase discontinuation, controlling for potential confounders.

Results: We identified 700 pegloticase recipients (91 immunomodulatory drug initiators, 33 prevalent immunomodulatory drug recipients, and 576 nonrecipients), with a median follow-up of 14 months. Immunomodulatory drug recipients were less likely to discontinue pegloticase. The adjusted hazard ratios of pegloticase discontinuation associated with concomitant immunomodulatory drug initiation and prevalent treatment were 0.52 (95% confidence interval [CI] 0.37-0.75) and 0.69 (95% CI 0.42-1.16), respectively. Laboratory abnormalities were uncommon (<5%) and were not higher in concomitant immunomodulatory drug treatment.

Conclusion: Consistent with clinical trials, results from this large observational registry suggest that concomitant immunomodulatory drug treatment improves pegloticase persistence.

Figure 1:

Flowchart of patients eligible for the study

Figure 2:

Time to pegloticase discontinuation* by immunomodulatory drug use

Figure 3:

Examples of pegloticase response patterns based on representative individual patient data A)Persistent treatment response without loss of efficacy; B) Pattern is suggestive of the development of anti-drug antibodies and aloss of response to pegloticase with the continuation of pegloticase infusions; C) Pattern is suggestive of the development of anti-drug antibodies within 15 days of last treatment and discontinuation of treatment.