PMID- 33407590 OWN - NLM STAT- MEDLINE DCOM- 20211013 LR - 20211013 IS - 1546-0096 (Electronic) IS - 1546-0096 (Linking) VI - 19 IP - 1 DP - 2021 Jan 6 TI - Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial. PG - 5 LID - 10.1186/s12969-020-00488-9 [doi] LID - 5 AB - 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. FAU - Alexeeva, Ekaterina AU - Alexeeva E AD - Federal State Autonomous Institution, National Medical Research Center of Children's Health, Moscow, Russian Federation. AD - 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. FAU - Horneff, Gerd AU - Horneff G AUID- ORCID: 0000-0001-5491-7832 AD - Asklepios Clinic Sankt Augustin, General Paediatrics, Arnold-Janssen-Strasse 29, 53757, Sankt Augustin, Germany. g.horneff@asklepios.com. AD - Department of Pediatric and Adolescent medicine, Medical Faculty, University Hospital of Cologne, Cologne, Germany. g.horneff@asklepios.com. FAU - Dvoryakovskaya, Tatyana AU - Dvoryakovskaya T AD - Federal State Autonomous Institution, National Medical Research Center of Children's Health, Moscow, Russian Federation. AD - 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. FAU - Denisova, Rina AU - Denisova R AD - Federal State Autonomous Institution, National Medical Research Center of Children's Health, Moscow, Russian Federation. AD - 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. FAU - Nikishina, Irina AU - Nikishina I AD - V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation. FAU - Zholobova, Elena AU - Zholobova E AD - 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. FAU - Malievskiy, Viktor AU - Malievskiy V AD - Federal State Educational Institution of Higher Education Bashkir State Medical University of the Ministry of Health of the Russian Federation, Ufa, Russian Federation. FAU - Santalova, Galina AU - Santalova G AD - State Samara Medical University, Samara, Russian Federation. FAU - Stadler, Elena AU - Stadler E AD - State Samara Medical University, Samara, Russian Federation. FAU - Balykova, Larisa AU - Balykova L AD - Medical Institute of National Research Ogarev Mordovia State University, Saransk, Russian Federation. FAU - Spivakovskiy, Yuriy AU - Spivakovskiy Y AD - Saratov State Medical University n.a. V.I. Razumovsky, Saratov, Russian Federation. FAU - Kriulin, Ivan AU - Kriulin I AD - 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. FAU - Alshevskaya, Alina AU - Alshevskaya A AD - Biostatistics and Clinical Trials Center, Novosibirsk, Russian Federation. FAU - Moskalev, Andrey AU - Moskalev A AD - Biostatistics and Clinical Trials Center, Novosibirsk, Russian Federation. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20210106 PL - England TA - Pediatr Rheumatol Online J JT - Pediatric rheumatology online journal JID - 101248897 RN - 0 (Antirheumatic Agents) RN - OP401G7OJC (Etanercept) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adolescent MH - Antirheumatic Agents/*administration & dosage/therapeutic use MH - Arthritis, Juvenile/*drug therapy MH - Child MH - Child, Preschool MH - Double-Blind Method MH - Drug Therapy, Combination MH - Etanercept/*administration & dosage/therapeutic use MH - Female MH - Humans MH - Male MH - Methotrexate/*administration & dosage/therapeutic use MH - Remission Induction/methods PMC - PMC7788754 OTO - NOTNLM OT - Juvenile idiopathic arthritis OT - Remission OT - TNF inhibitor COIS- E. Alexeeva has received research funds, advisory board membership and honorary fees from Novartis, Pfizer, Sanofi, MSD, AMGEN, Eli Lilly, and Roche. G. Horneff has received research funds, advisory board membership and honorary fees from Abbvie, Pfizer and Roche. T. Dvoryakovskaya has received research funds, advisory board membership and honorary fees from Novartis, Pfizer, MSD, AMGEN, Eli Lilly, and Roche. R. Denisova has received research funds, advisory board membership and honorary fees from Novartis, Pfizer, Sanofi, MSD, and Roche. I. Nikishina has received research funds and honorary fees from Abbvie, Pfizer, Novartis, Roche, MSD. E. Zholobova has received research funds from Pfizer and Novartis, speaker honoraria, including speaker bureau and symposia, and expert witness fees from Abbvie, Pfizer, Roche, and Novartis. V. Malievskiy has received research grants from Pfizer, Janseen Research & Development LLC, speaker honoraria from Abbvie, Pfizer, Roche, and Novartis. E. Stadler has received research funds and honorary grants from Abbvie, Pfizer and Roche. L. Balykova has received research funds from Pfizer. Y. Spivakovskiy has received research grants from Pfizer and Jansen Research and received honoraria as a speaker for Novartis and Pfizer. G. Santalova, I. Kriulin, A. Alshevskaya, and A. Moskalev declare that they have no competing interests. EDAT- 2021/01/08 06:00 MHDA- 2021/10/14 06:00 PMCR- 2021/01/06 CRDT- 2021/01/07 05:48 PHST- 2020/04/22 00:00 [received] PHST- 2020/12/09 00:00 [accepted] PHST- 2021/01/07 05:48 [entrez] PHST- 2021/01/08 06:00 [pubmed] PHST- 2021/10/14 06:00 [medline] PHST- 2021/01/06 00:00 [pmc-release] AID - 10.1186/s12969-020-00488-9 [pii] AID - 488 [pii] AID - 10.1186/s12969-020-00488-9 [doi] PST - epublish SO - Pediatr Rheumatol Online J. 2021 Jan 6;19(1):5. doi: 10.1186/s12969-020-00488-9.