Horizon Therapeutics initiates trial for Krystexxa (pegloticase injection) plus methotrexate to increase durability of response for patients living with chronic gout

Horizon Therapeutics plc announced the initiation of a clinical trial evaluating Krystexxa (pegloticase injection) in combination with methotrexate as a strategy to increase the durability of response for patients living with chronic gout refractory to conventional therapies – also known as uncontrolled gout. Treatment with biologic medicines can, in some patients, trigger the body’s immune system to develop anti-drug antibodies. These anti-drug antibodies can reduce the effectiveness of the biologic therapy. Immunomodulators, such as methotrexate, are often co-prescribed with biologics to help reduce this reaction. The Methotrexate to Increase Response Rates in Patients With Uncontrolled GOut Receiving Krtstexxa (MIRRORrandomized controlled trial (RCT)), will evaluate the use of methotrexate as an immunomodulator to meaningfully reduce immune response to Krystexxa in adult patients living with uncontrolled gout.

The trial will assess whether the combination of Krystexxa with methotrexate can enhance the demonstrated response rate of Krystexxa, will confirm the safety and tolerability and provide information on the pharmacokinetics (PK) of the combined use. The primary endpoint will be the ability of Krystexxa with methotrexate versus Krystexxa alone to maintain a serum uric acid <6 mg/dL through Month 6.

The MIRROR RCT follows the MIRROR open-label (OL) evaluation that was initiated last fall and is now fully enrolled (NCT03635957). The trial initiation is informed by the positive results of an independent case series led by John K. Botson, M.D., R.Ph. C.C.D. and Jeff R. Peterson, M.D., presented at the 2018 American College of Rheumatology (ACR) meeting with updates presented at the 2019 European Congress of Rheumatology (EULAR), which demonstrated that the use of methotrexate with Krystexxa was well tolerated and led to an improved overall response. In the series, all of the ten sequential patien Krystexxa combined with pre-treatment and co-administration of methotrexate, 15 mg orally once-weekly.