Clinical remission in juvenile idiopathic arthritis after termination of etanercept

Abstract

Biologicals are very effective for inhibiting disease progression in active juvenile idiopathic arthritis (JIA). To date, there have been no recommendations on how and when to stop therapy with TNF inhibitors. Our objective was to analyze characteristics and the disease course of JIA patients who discontinued etanercept due to achievement of inactive disease. Data of 39 patients with JIA from two clinical pediatric rheumatology centers in Bydgoszcz and Lublin (Poland) were analyzed retrospectively. All patients discontinued etanercept due to a remission on treatment. Etanercept was started after a mean 33.7 ± 36 (range 3–137) months of disease. The mean duration of therapy with etanercept was 34.7 ± 16.7 (range 6–72) months, with a mean duration of remission on medication 21.3 ± 9.6 (range 4–42) months before withdrawal of etanercept. The mean duration of remission after etanercept discontinuation was 14.2 ± 12.1 (range of 1–60) months. Only 12/39 (30.8 %) patients did not develop a disease exacerbation until the end of the study. Early flares, that is less than 6 months after termination of etanercept, were observed in 15/39 (38.5 %) patients. Twelve (30.8 %) patients restarted etanercept after exacerbation—all patients responded satisfactorily. Our data show that etanercept discontinuation in a substantial proportion of JIA patients results in early disease exacerbation. In many cases, reintroduction of etanercept is needed. Patients, in whom etanercept was restarted, responded satisfactorily.

Impact of Medication Withdrawal Method on Flare‐Free Survival in Patients with Juvenile Idiopathic Arthritis on Combination Therapy

“…An important consideration when tapering medications is the difficulty in re‐achieving CID if the patient flares. In contrast to previous data, suggesting that most patients are able to quickly re‐achieve remission by restarting the same medications, only 16% of our patients were able to re‐attain CID within 6 months, 62% by 12 months, and 71% by 24 months . Additionally, 17% required increased dosing or different medications to achieve CID.…”

“…It is difficult to directly compare our data to prior medication withdrawal trials, as most protocols only studied discontinuation of TNFi without incorporating other DMARDs into their analysis. Twelve‐month flare rates in these studies ranged from 57–67% in JIA, 33–34% in early RA, and 57–75% in longstanding/severe RA . In our cohort, 83% of patients on TNFi therapy flared within 12 months of discontinuing all medications, which, as expected, is higher than flare rates reported by prior studies that discontinued TNFi while continuing DMARDS.…”

“…The few studies in JIA investigating medication withdrawal have not addressed these variables, as they predominantly consist of small retrospective and/or cohort studies that did not differentiate between JIA subtypes and focused on withdrawal of only 1 medication. One study focused on withdrawal of MTX, 2 on withdrawal of TNFi, and 3 specifically on withdrawal of etanercept (ETN) . The largest study included 171 patients who achieved CID on ETN, adalimumab (ADA), or infliximab (INF) and reported similar outcomes to the smaller studies, with flare rates of 50–67% within 12 months of TNFi withdrawal .…”

Attitudes and Approaches for Withdrawing Drugs for Children with Clinically Inactive Nonsystemic JIA: A Survey of the Childhood Arthritis and Rheumatology Research Alliance

“…(6, 8, 11) Multiple studies have failed to identify other demographic and disease-specific factors associated with flare after medication discontinuation. (8, 10, 11) Two single-center observational studies have shown improved outcomes with strategies of medication reduction (rather than discontinuation): use of low-dose etanercept (9) and continued biologic use after methotrexate withdrawal. (11)…”

Clinical utility of etanercept in the treatment of arthritides in children and adolescents

“…Postepski et al also evaluated clinical remission in JIA after termination of etanercept therapy 33. They retrospectively analyzed data of 39 children with JIA from two clinical pediatric rheumatology centers in Poland, all of whom stopped etanercept therapy as they achieved inactive disease.…”