Issue: April 2021
Disclosures: The researchers report writing support from Horizon. Keenan reports consulting fees from Horizon, Selecta Biosciences, Atom Biosciences, Dyve Biosciences and Sobi; advisory board membership with Horizon; and research support from Sobi and Selecta Biosciences. Please see the study for all other authors’ relevant financial disclosures.
March 09, 2021
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Pegloticase plus immunomodulation boosts responder rates in uncontrolled gout

Issue: April 2021
Disclosures: The researchers report writing support from Horizon. Keenan reports consulting fees from Horizon, Selecta Biosciences, Atom Biosciences, Dyve Biosciences and Sobi; advisory board membership with Horizon; and research support from Sobi and Selecta Biosciences. Please see the study for all other authors’ relevant financial disclosures.
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Combining pegloticase with immunomodulation therapy greatly improves pegloticase response rates in patients with uncontrolled gout, according to a systematic review published in Seminars in Arthritis and Rheumatism.

“Gout is not just a disease of intermittent flares, only worthy of intermittent management with non-steroidal anti-inflammatory drugs or colchicine, but rather a disease that requires consistent urate lowering therapy and should be treated to a target urate level,” Robert T. Keenan, MD, of Duke University School of Medicine, told Healio Rheumatology. “In some patients, treating to target requires aggressive therapy, similar to that of a rheumatoid arthritis or psoriatic arthritis patient requiring combination therapy with a disease modifying anti-rheumatic drug combined with a biologic.”

“These findings reinforce the real-world and research that has been accumulating and, most importantly, show that a co-treatment approach may be one valuable option to help ensure patients are able to achieve a complete response,” Robert T. Keenan, MD, told Healio Rheumatology.
Data derived from Keenan RT, et al. Semin Arthritis Rheum. 2021;doi:10.1016/j.semarthrit.2021.01.005.

“Given the systemic impact of gout, reducing the burden of urate is critical to improving overall outcomes for our patients and their quality of life,” he added. “Patients treated with pegloticase have failed other therapies, and we want to be able to provide the best chance of success for them to complete treatment.”

To examine the effect of combination therapy with pegloticase (Krystexxa, Horizon Therapeutics) and immunomodulation, Keenan and colleagues conducted a systematic review of published cases. Using PubMed and the abstract databases of the American College of Rheumatology and EULAR meetings from 2012 to 2020, the researchers searched for the following terms: “Immunomodulator and pegloticase,” “immunomodulation and pegloticase,” “pegloticase and anti-drug antibodies,” “pegloticase and DMARD,” and “methotrexate or mycophenolate or azathioprine or cyclosporin or tacrolimus or leflunomide or sulfasalazine or rapamycin and pegloticase.”

Robert T. Keenan

Review articles, studies that used off-label pegloticase, and those did not feature cases of pegloticase used with immunomodulation were not included. In all, the researchers identified 10 publications describing 82 cases for their analysis.

According to the researchers, the overall pegloticase response rate was 82.9%. Meanwhile, patients treated with combination therapy with an individual immunomodulator demonstrated the following response rates: 87.5% with methotrexate, 86.4% mycophenolate mofetil, 63.6% with azathioprine, and 66.7% with leflunomide. A single patient co-treated with cyclosporin demonstrated a response. The two patients treated with more than one immunomodulator were each counted as responders.

“These findings reinforce the real-world and research that has been accumulating and, most importantly, show that a co-treatment approach may be one valuable option to help ensure patients are able to achieve a complete response,” Keenan said. “Ultimately, we need to maximize the response to treatment in order to manage the impact and complications associated with severe gout and improve outcomes for the long-term.”