Ekaterina Alexeeva1,2, Gerd Horneff3,4, Tatyana Dvoryakovskaya1,2, Rina Denisova1,2, Irina Nikishina5, Elena Zholobova2, Viktor Malievskiy6, Galina Santalova7, Elena Stadler7, Larisa Balykova8, Yuriy Spivakovskiy9, Ivan Kriulin2, Alina Alshevskaya10, Andrey Moskalev10. 1. Federal State Autonomous Institution, National Medical Research Center of Children's Health, Moscow, Russian Federation. 2. Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. 3. Asklepios Clinic Sankt Augustin, General Paediatrics, Arnold-Janssen-Straße 29, 53757, Sankt Augustin, Germany. g.horneff@asklepios.com. 4. Department of Pediatric and Adolescent medicine, Medical Faculty, University Hospital of Cologne, Cologne, Germany. g.horneff@asklepios.com. 5. V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation. 6. Federal State Educational Institution of Higher Education Bashkir State Medical University of the Ministry of Health of the Russian Federation, Ufa, Russian Federation. 7. State Samara Medical University, Samara, Russian Federation. 8. Medical Institute of National Research Ogarev Mordovia State University, Saransk, Russian Federation. 9. Saratov State Medical University n.a. V.I. Razumovsky, Saratov, Russian Federation. 10. Biostatistics and Clinical Trials Center, Novosibirsk, Russian Federation.
Abstract
BACKGROUND:Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. METHODS: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with eitherETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The 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 intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX 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. The median (+/-IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX 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. CONCLUSIONS: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.
RCT Entities:
BACKGROUND: Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. METHODS: A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The 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 intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX 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. The median (+/-IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX 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. CONCLUSIONS: Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.
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