Methotrexate plus pegloticase improves gout evaluations, patient outcomes at 1 year
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Concomitant use of methotrexate and pegloticase resulted in “meaningful” improvements in joint assessments and patient-reported outcomes at 12 months in uncontrolled gout, according to data presented at the EULAR 2021 Virtual Congress.
The 12-month results are from the open-label MIRROR trial, which had previously suggested that methotrexate administered alongside pegloticase (Krystexxa, Horizon Therapeutics) increased the treatment responder rate at 6 months in those with uncontrolled gout, compared with pegloticase alone.
“The MIRROR open-label trial is the first clinical trial which looked at the concomitant use of immunomodulation with pegloticase to increase response rates for patients with chronic gout refractory to oral therapies — uncontrolled gout,” John Botson, MD, RPh, CCD, president of the Alaska Rheumatology Alliance, and a rheumatologist with Orthopedic Physicians Alaska, in Anchorage, told Healio Rheumatology.
“We continue to better understand the correlation between high serum uric acid levels and uric acid deposition with other comorbid conditions like chronic kidney disease, diabetes, and heart disease,” he added. “This is in addition to the permanent damage which can be seen to the bones, joints, and organs when gout is left untreated or undertreated. Unfortunately, there are patients who, despite taking oral therapies, continue to experience the signs and symptoms of gout. These patients are often treated with pegloticase, which historically has caused the development of antidrug antibodies, which prevents them from receiving a full course of therapy.”
To analyze the longer-term impacts of adding methotrexate to pegloticase among adults with uncontrolled gout, Botson and colleagues examined the 12-months exploratory endpoints of the MIRROR trial, including joint and gout global assessments, as well as serial dual-energy computed tomography (DECT) images where available.
Uncontrolled gout was defined as a serum uric acid level of greater than 6 mg/dL with at least one of the following: urate lowering therapy, intolerance to urate lowering therapy or functionally limiting tophaceous deposits. All patients with immunocompromised status, G6PD deficiency, severe renal impairment or a contraindication to methotrexate were excluded.
Patients were administered 15 mg of oral methotrexate weekly and 1 mg of daily folic acid for 4 weeks prior to and throughout pegloticase therapy, which involved a biweekly infusion of 8mg for up to 52 weeks. Exploratory outcomes included mean change from baseline in the number of impacted joints and Health Assessment Questionnaire (HAQ) scores related to Disability Index, pain and health, as well as patient and physician Gout Global Assessments. Decreases in these measures represented clinical and patient-reported improvements.
Botson and colleagues also assessed changes in urate deposition volume based on DECT imaging, where available.
The researchers performed their analysis on a modified intent-to-treat population of 14 participants who received at least one pegloticase infusion.
According to the researchers, the mean serum uric acid level prior to pegloticase treatment was 9.2 mg/dL (standard deviation = ±2.5), with 13 participants demonstrating visible tophi. A total of three patients discontinued due to two consecutive serum uric acid levels exceeding 6mg/dL, with one of these patients completing the study at week 24. In all, 10 participants completed the 52-week study.
Among these 10 participants, eight received 26 infusions, while the other two received 12 infusions before discontinuing pegloticase after meeting their treatment goal at 24 weeks and initiating allopurinol, while remaining in study under observation.
At week 52, among those who completed the study, the number of affected joints improved, as did HAQ measures, according to the researchers. Global Assessments of Gout also improved, with changes from baseline of –5.7 (SD = ±2.6) and –4.6 (SD = ±2.1) for physicians’ and patients’ assessment, respectively, at week 52. Additionally, a majority of these participants demonstrated disability index, pain and health scores of zero or one — with zero denoting “excellent health” — at the end of the study.
Just two participants had DECT imaging available. One received pegloticase-plus-methotrexate co-therapy through week 52 and demonstrated a “marked reduction” in total urate volume, from a baseline of 28.76cm3 to a week 52 reading of 1.33cm3. The other participant received only five pegloticase infusions, but nonetheless also demonstrated total urate volume reduction, from a baseline of 59.2 cm3 to a week 10 measurement of 25.07cm3. Both participants also showed improvement in bone erosion healing.
“Not only did the MIRROR open-label trial further contribute to the growing body of data on the concomitant use of pegloticase with immunomodulators, the exploratory endpoints showed methotrexate and pegloticase co-therapy improves both clinical evaluations — tophaceous, tender and swollen joint counts — and patient reported outcomes — pain and disability — in patients with uncontrolled gout,” Botson said.
“As we look to treat uncontrolled gout with the urgency and aggressiveness the condition requires, we are encouraged by the growing data around the concomitant use of pegloticase with methotrexate,” he added. “We look forward to data from the MIRROR randomized-controlled trial this fall and the continued paradigm shift in the treatment approach to help more patients achieve complete response and ultimately reach their treatment goals.”
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Botson J. Abstract AB0630: Pegloticase/methotrexate co-therapy improved joint and patient reported health assessments in patients with uncontrolled gout: 12-month exploratory outcomes of MIRROR open-label trial. Presented at: EULAR 2021 Virtual Congress; June 2-5, 2021 (virtual meeting).
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