Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients in Sustained Remission

Abstract

Objective. Patients with rheumatoid arthritis (RA) in whom remission is achieved following combination therapy with methotrexate plus etanercept face an ongoing medication burden. This study was undertaken to investigate whether sustained remission achieved on combination therapy can be maintained with either methotrexate or etan ercept monotherapy, as assessed following discontinuation of one or the other medication from the combination.Methods. Of the 371 adult patients with RA who received combination therapy with methotrexate plus etanercept, remission (defined as a Simplified Disease Activity Index [SDAI] score of ≤3.3) was sustained in 253 patients through a 24 week open label period. These 253 patients then entered a 48 week, double blind period and were randomized to receive either 1) methotrexate monotherapy (n = 101), 2) etanercept monotherapy (n = 101), or 3) methotrexate plus etanercept combination therapy (n = 51). Patients who subsequently experienced disease worsening received rescue therapy with the combination regimen at the same dosages as used in the initial run in period. The primary end point was the proportion of patients in whom SDAI defined remission was maintained without disease worsening at week 48 in the etanercept monotherapy group as compared to the methotrexate monotherapy group. Secondary end points included time to disease worsening, and the proportion of patients in whom SDAI defined remission was recaptured after initiation of rescue therapy.Results. Baseline demographic and clinical characteristics of the RA patients were similar across the treatment groups. At week 48, SDAI defined remission was maintained in significantly more patients in the etanercept monotherapy group than in the methotrexate monotherapy group (49.5% versus 28.7%; P = 0.004). Moreover, as a secondary end point, sustained SDAI defined remission was achieved in significantly more patients who received combination therapy than in those who received methotrexate monotherapy (52.9% versus 28.7%; P = 0.006). Time to disease worsening was shorter in those who received methotrexate monotherapy than in those who received etanercept monotherapy or those who received combination therapy (each P < 0.001 versus methotrexate monotherapy). Among the patients who received rescue therapy, SDAI defined remission was recaptured in 70-80% in each treatment group. No new safety signals were reported.Conclusion. The efficacy of etanercept monotherapy was superior to that of methotrexate monotherapy and similar to that of combination therapy in maintaining remission in patients with RA. SDAI defined remission was recaptured in most of the patients who were given rescue therapy. These data could inform decision making when withdrawal of therapy is being considered to reduce treatment burden in patients with well controlled RA.ClinicalTrials.gov identifier: NCT02373813.

The Risk of Adverse Effects of TNF-α Inhibitors in Patients With Rheumatoid Arthritis: A Network Meta-Analysis

“…After excluding duplicates and irrelevant articles, 211 full-text articles were assessed for eligibility. By reading full-text, 72 articles met the inclusive criteria and exclusive criteria ( 11 – 82 ). The following diagram of the study selection process for this meta-analysis is shown in Figure 1 .…”

“…40 articles ( 12 , 15 , 17 , 22 , 25 – 28 , 30 , 31 , 33 , 34 , 36 , 38 , 40 – 42 , 45 , 49 , 54 – 56 , 58 – 60 , 62 – 66 , 72 – 77 , 79 – 82 ) reported the occurrence of AEs and 15285 RA patients was included. The network of eligible comparisons was shown in the Supplementary Figure 1 .…”

“…55 articles ( 11 – 20 , 22 , 23 , 26 – 38 , 40 , 42 , 45 , 47 – 49 , 51 , 52 , 54 , 56 – 60 , 62 – 66 , 68 , 69 , 72 – 77 , 80 – 82 ) reported the occurrence of serious infections, involving a total of 24740 RA patients. The network of eligible comparisons was shown in the Supplementary Figure 4 .…”

Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients Receiving Combination Therapy: Comment on the Article by Curtis et al

“…However, a few matters need to be addressed.First, the eligibility criteria state that patients should have an SDAI score of ≤3.3 at screening and at the end of the run-in period. However, Curtis and colleagues report that disease in 95%, 92.1%, and 96.1% of the patients in the methotrexate monotherapy arm, the etanercept monotherapy arm, and the combination arm, respectively, was in SDAI-defined remission at baseline (see Table 1 in Curtis et al [1]). Considering the eligibility criteria, these values should be 100% in each arm.Second, we noticed the discrepancy between the percentage of patients at baseline whose disease was in SDAI-defined remission (>90%) as compared to Boolean-defined remission (33-45%).…”

Sustained Remission in Rheumatoid Arthritis: Time to Withdraw Treatment?

“…Reducing medication exposure will help reduce the development of side effects and complications, especially with an aging population with polypharmacy concerns and complications. The authors of a recent article published in Arthritis & Rheumatology titled “Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients in Sustained Remission.” help explore this idea of medication withdrawal through the Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Rheumatoid Arthritis (SEAM‐RA) clinic trial and database ( 1 ).…”