Increased Efficacy and Tolerability of Pegloticase in Patients With Uncontrolled Gout Co-Treated With Methotrexate: A Retrospective Study.

INTRODUCTION: Gout is a painful inflammatory condition caused by chronically elevated serum uric acid levels (sUA). When standard urate-lowering therapies fail/are not tolerated, uncontrolled gout (elevated sUA, subcutaneous tophi, chronic gouty arthritis, frequent flares) can occur. Pegloticase, a recombinant uricase, converts uric acid to allantoin, a readily excreted molecule. Responder rate in trials was 42%, limited by anti-drug antibody (ADA) development. Immunomodulators attenuate ADA formation and case reports suggest immunomodulation increases pegloticase responder rates. The current study retrospectively examined responder rate in patients undergoing methotrexate/pegloticase co-therapy. METHODS: Patients who underwent methotrexate/pegloticase co-treatment at a single rheumatology practice were included. Demographics, clinical, treatment, and safety parameters were collected. The primary outcome was the proportion of responders (≥ 12 biweekly pegloticase infusions, sUA < 6 mg/dl just prior to infusion 12). RESULTS: Ten patients (nine men, 52.3 ± 13.5 years) with uncontrolled tophaceous gout (erosive damage, ulcerative tophi, frequent flares, gout-related hospitalizations) were included. Patients had failed allopurinol (100-300 mg) or febuxostat (40 mg) therapy (doses not increased because of intolerance, kidney concerns, noncompliance, or rapid tophi resolution requirement). Baseline sUA was 9.42 ± 2.05 mg/dl. Along with standard pre-infusion prophylaxis, nine patients received subcutaneous methotrexate (25 mg/week) initiated 14-35 days before pegloticase and one patient received oral methotrexate (12.5 mg/week) initiated 14 days after pegloticase. Eight patients (80%) were responders, receiving 15.5 ± 3.8 infusions (range, 12-21) over 31.8 ± 9.5 weeks. One patient had efficacy loss with mild infusion reaction during infusion 4 and one patient was lost to follow-up after infusion 5. One patient reported one gout flare. No new safety concerns emerged. CONCLUSIONS: Methotrexate/pegloticase co-therapy resulted in a higher responder rate than the established 42% with pegloticase alone. Therefore, methotrexate/pegloticase co-therapy may safely allow more patients to benefit from a full treatment course, likely through ADA attenuation.

Uncontrolled gout is a painful inflammatory condition caused by excess uric acid in the blood. When standard oral medicines used to lower uric acid do not work or cannot be taken, pegloticase is the only remaining treatment option. Unfortunately, less than half of patients respond to pegloticase for an adequate amount of time because their immune system develops antibodies against the medicine, causing the medicine to be quickly removed from the body preventing a durable or prolonged response. Methotrexate has been shown to limit or prevent this immune response in patients treated with biologic therapies for autoimmune diseases. The current study found that eight of ten patients (80%) treated with both methotrexate and pegloticase responded to treatment (received 12 or more biweekly pegloticase doses and had low uric acid levels in their blood just before infusion 12). No new side effects or safety concerns were reported. In this retrospective study, methotrexate appeared to allow more patients to benefit from a full course of pegloticase therapy.

Retreatment with Pegloticase after a Gap in Therapy in Patients with Gout: A Report of Four Cases.

INTRODUCTION: Pegloticase, a potent uricolytic biologic enzyme, has been shown to be an effective therapeutic option in patients with uncontrolled gout. However, there are limited data on clinical response after a gap in therapy and retreatment with pegloticase. CASE SERIES: This report describes four patients with chronic gout who were successfully managed with pegloticase and were retreated following a gap in therapy. Patient charts from a practice-based rheumatology clinic were retrospectively analyzed; four male patients, aged 70-75 years, with chronic gout and a more than 4-week gap in pegloticase therapy were reviewed. Before pegloticase treatment, patients had received allopurinol or febuxostat, but they continued exhibiting symptoms, including visible tophi and serum uric acid (SUA) levels of 5.2-10.2 mg/dL (309-607 µmol/L), despite oral urate-lowering therapy. The first pegloticase treatment (8-mg infusion every 2 weeks) lasted 22-124 weeks. Pegloticase resolved tophi and improved SUA to below 1.5 mg/dL (less than 89 µmol/L); however, patients discontinued pegloticase because of symptom resolution, poor adherence, or personal reasons. Following treatment gaps (12-156 weeks), symptoms and SUA levels increased and patients were retreated with pegloticase (4-147 weeks). In three of four patients, reinitiating pegloticase lowered SUA levels to below 1.0 mg/dL (less than 59 µmol/L) and resolved symptoms. One patient experienced an infusion reaction and discontinued; no infusion reactions, gout flares, or adverse events occurred among the other three patients. CONCLUSION: Retreatment with pegloticase after a gap in therapy appears to be an effective and tolerated option in prior responders. FUNDING: Horizon Pharma.