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Horizon Therapeutics Announces Data From The MIRROR Randomized Controlled Trial Of KRYSTEXXA Injection With Methotrexate Published In Arthritis & Rheumatology

Horizon Therapeutics plc (NASDAQ:HZNP) today announced the publication of data from the MIRROR randomized controlled clinical trial of KRYSTEXXA (pegloticase) injection with methotrexate, a commonly used immunomodulator,

Benzinga · 09/14/2022 08:12

Horizon Therapeutics plc (NASDAQ:HZNP) today announced the publication of data from the MIRROR randomized controlled clinical trial of KRYSTEXXA (pegloticase) injection with methotrexate, a commonly used immunomodulator, in Arthritis & Rheumatology [https://doi.org/10.1002/art.42335].

“The publication of this data coupled with the recently expanded labeling provides clinicians the opportunity to evolve how we care for patients with uncontrolled gout,” said Suneet Grewal, M.D., co-author and rheumatologist at East Bay Rheumatology Medical Group, Inc. “Our patients often live with the impact of uncontrolled gout for 10 to 15 years before seeing a specialist. They have significant comorbidities like hypertension and chronic kidney disease, as well as inflammation and damage from urate crystals formed because of chronically elevated uric acid levels. These insights should encourage more clinicians to focus on care that rapidly reduces the urate burden and will change the course of disease for more patients.”

The co-administration of KRYSTEXXA with an immunomodulator like methotrexate has increasingly been employed for patients with uncontrolled gout (chronic gout refractory to oral therapies) to help reduce the development of anti-drug antibodies, which can affect treatment efficacy.1,2 Following a series of case studies and an open-label study, the MIRROR randomized controlled trial (Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving KRYSTEXXA trial, NCT03994731) was conducted3-5 and evaluated differences in treatment response for KRYSTEXXA with methotrexate compared to KRYSTEXXA with placebo.

The primary endpoint was the proportion of serum uric acid (sUA) responders defined as sUA <6 mg/dL for at least 80% of the time during Month 6 (Weeks 20-24). The study’s secondary endpoints included the proportion of sUA responders during Month 12 (Weeks 48-52), defined as sUA <6 mg/dL for at least 80% of the time, and the proportion of participants with complete resolution of at least one tophus with no new tophus and no single tophus showing progression (using digital photography) at Week 52 in subjects with tophi at baseline.6

The Month 6 MIRROR randomized controlled trial results included:

  • Greater than 30 percentage-point increase in patient response rate during Month 6 (p<0.0001): 71% (71 of 100) of patients randomized to receive KRYSTEXXA with methotrexate vs 39% (20 of 52) of patients randomized to receive KRYSTEXXA with placebo achieved the primary efficacy endpoint. 6
  • Marked reduction in infusion reactions: during the treatment period, 4% (4 of 96) of patients who received KRYSTEXXA with methotrexate experienced infusion reactions vs 31% (15 of 49) of patients who received KRYSTEXXA with placebo. No new safety signals were observed. 6
  • Over a 20 percentage-point increase in the complete resolution of at least one tophus at Week 24 (p=0.043): among patients with validated tophi at baseline, 35% (18 of 52) of patients who were randomized to receive KRYSTEXXA with methotrexate had complete resolution of at least one tophus at Week 24 vs 14% (4 of 29) of patients who were randomized to receive KRYSTEXXA with placebo. 6

Concentrations of methotrexate polyglutamates were maintained during the treatment course for patients randomized to receive KRYSTEXXA with methotrexate, confirming compliance with methotrexate therapy. In addition, methotrexate polyglutamate concentrations were in the same range as those reported for oral methotrexate use in patients with rheumatoid arthritis.6

A total of 152 participants were randomized 2:1 to a four-week run-in and treatment period with oral methotrexate (15 mg/week) or placebo, followed by bi-weekly infusions of KRYSTEXXA (8 mg) with either methotrexate or placebo for 52 weeks. The mean patient age was 55 years. At screening, patients had on average a 14-year history of gout (time since first diagnosis), 76% (115 of 152) of patients had an investigator-identified tophi, and all had experienced at least 1 gout flare in the prior year (10.8±14.2 flares/patient). In addition, comorbidity prevalence was high, with hypertension (63%), gastrointestinal disorders (38%) and stage 3 chronic kidney disease (32%, eGFR <60 ml/min/1.73m2) noted most frequently. Baseline characteristics were balanced across treatment groups.6

“Since acquiring KRYSTEXXA, Horizon has made significant investments to deliver on the improved efficacy and reduced infusion reactions we see in the publication of MIRROR data,” said Brian LaMoreaux, M.D., M.S., senior medical director, Horizon. “Our unmatched focus on those living with uncontrolled gout continues to drive clinical development to improve the patient experience with KRYSTEXXA as well as our early-stage gout programs.”

More information on KRYSTEXXA with methotrexate is available in the Prescribing Information and at KRYSTEXXAhcp.com. Patients with questions can speak to a Gout Nurse Advocate at 833-469-4688.