Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach inactive disease state and remission. Results of a double-blind placebo-controlled trial.
Abstract Background: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior with more rapid remission achievement. Objective Evaluation of effectiveness of early Etanercept+Methotrexate (ETA+MTX) combination therapy vs step up MTX monotherapy with ETA added in refractory disease. Methods: Multi-center, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n=35) or MTX+placebo (n=33) for up to 24 weeks, followed by a 24-week open-label phase. Efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results: By ITT analysis, more patients in the ETA+MTX group had reached the pedACR30 response at week 12 (33 (94.3%)) compared to the MTX+placebo group (20 (60.6%); p=0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. Median (+/-IQR) time to achieve an inactive disease state in the ETA+MTX and MTX+placebo groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported leading to treatment discontinuation in 6 patients. Conclusion: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step up regimen. More patients treated with a combination of ETA+MTX reached pedACR30 response and inactive disease and remission more rapidly.Trial registrationThe study was registered by the European Clinical Trials Database (EudraCT) as 2015-003384-11 on 07-21-2014.Word count: 270.
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 28. Juli Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Alexeeva, Ekaterina [VerfasserIn] |
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| doi: |
10.21203/rs.3.rs-23057/v1 |
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| PPN (Katalog-ID): |
XRA033923183 |
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| 520 | |a Abstract Background: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior with more rapid remission achievement. Objective Evaluation of effectiveness of early Etanercept+Methotrexate (ETA+MTX) combination therapy vs step up MTX monotherapy with ETA added in refractory disease. Methods: Multi-center, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n=35) or MTX+placebo (n=33) for up to 24 weeks, followed by a 24-week open-label phase. Efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results: By ITT analysis, more patients in the ETA+MTX group had reached the pedACR30 response at week 12 (33 (94.3%)) compared to the MTX+placebo group (20 (60.6%); p=0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. Median (+/-IQR) time to achieve an inactive disease state in the ETA+MTX and MTX+placebo groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported leading to treatment discontinuation in 6 patients. Conclusion: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step up regimen. More patients treated with a combination of ETA+MTX reached pedACR30 response and inactive disease and remission more rapidly.Trial registrationThe study was registered by the European Clinical Trials Database (EudraCT) as 2015-003384-11 on 07-21-2014.Word count: 270 | ||
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