A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month Findings
Objective To assess 12‐month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO‐controlled, double‐blind trial (A randomized, double‐blind, placebo‐controlled, multicenter, efficacy and safety study of methotrexate to increase response rates...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
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| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.11578 |
| _version_ | 1797743404827803648 |
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| author | John K. Botson Kenneth Saag Jeff Peterson Katie Obermeyer Yan Xin Brian LaMoreaux Lissa Padnick‐Silver Supra Verma Suneet Grewal Amar Majjhoo John R. P. Tesser Michael E. Weinblatt |
| author_facet | John K. Botson Kenneth Saag Jeff Peterson Katie Obermeyer Yan Xin Brian LaMoreaux Lissa Padnick‐Silver Supra Verma Suneet Grewal Amar Majjhoo John R. P. Tesser Michael E. Weinblatt |
| author_sort | John K. Botson |
| collection | DOAJ |
| description | Objective To assess 12‐month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO‐controlled, double‐blind trial (A randomized, double‐blind, placebo‐controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRROR RCT]). Methods Patients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8‐mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level <6 mg/dl for ≥80% of examined month) in the intent‐to‐treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU‐monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values. Results Month 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%‐44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%‐44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks. Conclusion Twelve‐month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect. |
| first_indexed | 2024-03-12T14:55:01Z |
| format | Article |
| id | doaj.art-c71bc9ec9b1f49569a56a18335199e93 |
| institution | Directory Open Access Journal |
| issn | 2578-5745 |
| language | English |
| last_indexed | 2024-03-12T14:55:01Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | ACR Open Rheumatology |
| spelling | doaj.art-c71bc9ec9b1f49569a56a18335199e932023-08-15T03:36:50ZengWileyACR Open Rheumatology2578-57452023-08-015840741810.1002/acr2.11578A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month FindingsJohn K. Botson0Kenneth Saag1Jeff Peterson2Katie Obermeyer3Yan Xin4Brian LaMoreaux5Lissa Padnick‐Silver6Supra Verma7Suneet Grewal8Amar Majjhoo9John R. P. Tesser10Michael E. Weinblatt11Orthopedic Physicians Alaska Anchorage, AlaskaUniversity of Alabama at BirminghamWestern Washington Arthritis Clinic BothellHorizon Therapeutics plc Deerfield IllinoisHorizon Therapeutics plc Deerfield IllinoisHorizon Therapeutics plc Deerfield IllinoisHorizon Therapeutics plc Deerfield IllinoisHorizon Therapeutics plc Deerfield IllinoisEast Bay Rheumatology Medical Group Inc. San Leandro CaliforniaShores Rheumatology St. Clair Shores MichiganArizona Arthritis & Rheumatology Associates PC PhoenixBrigham and Women's Hospital Boston MassachusettsObjective To assess 12‐month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO‐controlled, double‐blind trial (A randomized, double‐blind, placebo‐controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRROR RCT]). Methods Patients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8‐mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level <6 mg/dl for ≥80% of examined month) in the intent‐to‐treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU‐monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values. Results Month 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%‐44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%‐44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks. Conclusion Twelve‐month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect.https://doi.org/10.1002/acr2.11578 |
| spellingShingle | John K. Botson Kenneth Saag Jeff Peterson Katie Obermeyer Yan Xin Brian LaMoreaux Lissa Padnick‐Silver Supra Verma Suneet Grewal Amar Majjhoo John R. P. Tesser Michael E. Weinblatt A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month Findings ACR Open Rheumatology |
| title | A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month Findings |
| title_full | A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month Findings |
| title_fullStr | A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month Findings |
| title_full_unstemmed | A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month Findings |
| title_short | A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month Findings |
| title_sort | randomized double blind placebo controlled multicenter efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase 12 month findings |
| url | https://doi.org/10.1002/acr2.11578 |
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