Higher response rates in RECIPE randomized controlled trial for gout treatment by Krystexxa with mycophenolate mofetil.- Horizon Therapeutics

Horizon Therapeutics plc announced data from the first randomized controlled clinical trial (RCT) of Krystexxa (pegloticase injection) concomitantly used with an immunomodulator showed improved response rates as compared to Krystexxa monotherapy. "Reducing Immunogenicity of Pegloticase (RECIPE)" demonstrated that 86.4 percent of patients (19 of 22) receiving co-therapy of Krystexxa with the immunomodulator mycophenolate mofetil achieved serum uric acid (sUA) less than 6 mg/dL through Month 3, the primary study endpoint, compared to 40.0 percent of patients (4 of 10) receiving Krystexxa monotherapy. The data are being presented as part of the American College of Rheumatology (ACR) Convergence 2020, Nov. 5 – 9, 2020. While Krystexxa has been traditionally used as a biologic monotherapy with a clinically demonstrated impact on chronic gout refractory to con ventional therapies (uncontrolled gout), recent literature suggests that adding an immunomodulator has the potential to increase the durability of response to Krystexxa. The safety and efficacy of Krystexxa co-prescribed with an immunomodulator has not been established by any health authorities. Data from the double-blind, placebo-controlled RECIPE trial illustrate the effect of a co-treatment regimen of Krystexxa with mycophenolate mofetil (Cell Cept) . In the study, 35 adult patients with uncontrolled gout were randomized (3:1) to receive either mycophenolate mofetil or placebo for two weeks prior to starting Krystexxa (12 infusions of 8 mg every 2 weeks). Thirty-two patients participated in the trial, with three patients discontinuing prior to the first Krystexxa infusion. During the trial, patients continued to receive either mycophenolate mofetil (1g) twice daily or placebo with Krystexxa for 12 weeks. After Month 3, all patients received only Krystexxa 8 mg IV every two weeks for 12 weeks, providing a full course of Krystexxa therapy (through Month 6). The study evaluated the proportion of patients who reached and maintained response to therapy (defined as sUA levels less than 6 mg/dL over 12 weeks), as well as the safety of the regimen. In total, 86.4 percent (19 of 22) of patients receiving co-therapy of Krystexxa and mycophenolate mofetil achieved serum uric acid less than 6 mg/dL at Month 3 versus 40.0 percent (4 of 10) of patients in the Krystexxa and placebo arm , with a sustained response at Month 6 in 68.2 percent (15 of 22) of patients versus 30.0 percent (3 of 10) of patients, respectively. In the mycophenolate mofetil/Krystexxa arm, no (0 of 22 patients) infusion reactions were reported compared to 30.0 percent (3 of 10) of patients reporting infusion reactions in the placebo/Krystexxa arm. Additional adverse events reported for the mycophenolate mofetil/Krystexxa arm versus the placebo/Krystexxa arm include musculoskeletal (36.0 percent vs 10.0 percent), respiratory (18.0 percent vs 0 percent) and infections (9.0 percent vs 0 percent). These are consistent with the established safety of the therapies.2 (Reducing Immunogenicity of Pegloticase [RECIPE] with Concomitant Use of Mycophenolate Mofetil in Patients with Refractory Gout —A Phase 2 Double Blind Randomized Controlled Trial, Abstract 0952). Additional Data Presentations at ACR.: Topline 12-month data from the prospective, open-label MIRROR trial showed 78.6 percent (11 of 14 patients) reached the primary endpoint , responding to treatment at Month 6, and that eight of these patients continued Krystexxa therapy with methotrexate and were responders at Month 12. In the trial, 14 patients received oral methotrexate (15 mg/week) and folic acid (1 mg/day) four weeks prior to the first Krystexxa infusion and continued during the therapy period (8 mg every 2 weeks). The primary outcome was the proportion of responders during Month 6 (sUA <6 mg dl for at least 80.0 percent of the time). the proportion of patients experiencing flares markedly and progressively decreased over time (flares in 13 of 14 patients in the first 12 weeks and in 2 of 8 patients in weeks 37-52). the co-therapy was well tolerated overall. no new serious adverse events occurred beyond month 6; one serious adverse event of sepsis secondary to cholecystitis occurred in the first six months as previously reported. (a multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase (mirror): 12-month results of an open-label study abstract 0677). real-world trends of the concomitant use of krystexxa with either methotrexate or azathioprine indicate sustained growth of this treatment approach . from 2015 to 2018, the co-therapy rates of krystexxa and an immunomodulator were consistently low (1.2 percent–3.9 percent). in 2019, the frequency of use jumped to 15.0 percent and early 2020 data (jan. to june) shows continued growth of this trend with 16.8 percent of uncontrolled gout patients treated concomitantly with krystexxa and an immunomodulator. (trends in immunomodulation pegloticase co-therapy from 2015-2019: a claims database study, abstract 0665).>