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

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 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.Trial registrationThe study was registered by the European Clinical Trials Database (EudraCT) as 2015-003384-11 on 07-21-2014.

Attainment of Inactive Disease Following Discontinuation of Adalimumab Monotherapy in Patients With Enthesitis-Related Arthritis

“…The number of patients was small, and we were unable to make a comparison between patients who received synthetic DMARDs compared with TNFi. In addition, because none of the participants received a combined biologic and synthetic DMARD treatment, we were unable to show the potential benefits of additional treatment (if any) as seen in other studies 12,16 …”

“…In addition, because none of the participants received a combined biologic and synthetic DMARD treatment, we were unable to show the potential benefits of additional treatment (if any) as seen in other studies. 12,16 Given the rarity and the various types of JIA, multicenter studies are needed in order to address the ideal duration of treatment with TNFi in each patient, with the aid of appropriate disease-associated risk-assessment markers. Our study focused on ERA, which is one of the most challenging subtypes of JIA, in terms of appropriate therapy and its duration and tends to demonstrate that ADA withdrawal may be feasible in a (substantial) proportion of patients, provided anti-TNFi is initiated promptly.…”