Successful stopping of biologic therapy for remission in children and young people with juvenile idiopathic arthritis

Abstract

Objectives Clinicians concerned about long-term safety of biologics in JIA may consider tapering or stopping treatment once remission is achieved despite uncertainty in maintaining drug-free remission. This analysis aims to (i) calculate how many patients with JIA stop biologics for remission, (ii) calculate how many later re-start therapy and after how long, and (iii) identify factors associated with re-starting biologics. Methods Patients starting biologics between 1 January 2010 and 7 September 2021 in the UK JIA Biologics Register were included. Patients stopping biologics for physician-reported remission, those re-starting biologics and factors associated with re-starting, were identified. Multiple imputation accounted for missing data. Results Of 1451 patients with median follow-up of 2.7 years (IQR 1.4, 4.0), 269 (19%) stopped biologics for remission after a median of 2.2 years (IQR 1.7, 3.0). Of those with follow-up data (N = 220), 118 (54%) later re-started therapy after a median of 4.7 months, with 84% re-starting the same biologic. Patients on any-line tocilizumab (prior to stopping) were less likely to re-start biologics (vs etanercept; odds ratio [OR] 0.3; 95% CI: 0.2, 0.7), while those with a longer disease duration prior to biologics (OR 1.1 per year increase; 95% CI: 1.0, 1.2) or prior uveitis were more likely to re-start biologics (OR 2.5; 95% CI: 1.3, 4.9). Conclusions This analysis identified factors associated with successful cessation of biologics for remission in JIA as absence of uveitis, prior treatment with tocilizumab and starting biologics earlier in the disease course. Further research is needed to guide clinical recommendations.

When to stop medication in juvenile idiopathic arthritis

“…In the prospective trial of Lovell et al [22] in children with pJIA who stopped bDMARDs, the hazard of flare was significantly lower in those who were older at diagnosis, had a shorter disease duration, shorter time from diagnosis to first CID, and shorter time from onset of CID to enrollment (all P < 0.05). Several other studies have found similar significant associations between shorter time to start bDMARDs [14] and flare [13 ▪ ]. Studies have also demonstrated a negative association between time in remission prior to medication withdrawal and flare rates in patients with pJIA.…”

“…Similarly, an observational study from the UK JIA Biologics Registry that included 1451 JIA patients, 447 of whom had oJIA (162 persistent, 285 extended), found that of patients who stopped bDMARDs for CID, those with a longer disease duration at bDMARD initiation were more likely to need to eventually re-start biologic therapy (OR 1.1 per additional year; 95% CI: 1.0, 1.2) [13 ▪ ]. Patients with prior uveitis were also more likely to re-start biologic therapy (OR 2.4, 95% CI: 1.2, 4.8) [13 ▪ ]. Additionally, longer time in remission prior to attempting medication withdrawal has also been associated with lower flare rates in oJIA [11,15].…”

“…Flare rates after discontinuing DMARDs in patients with oJIA vary considerably, ranging from 14% to 83% [9–11,12 ▪ ,13 ▪ ,14,15,16 ▪ ,17]. As referenced in Table 1, the flare definitions and the proportion of patients with persistent versus extended oJIA included in these studies vary, which likely partially explains the disparate reported flare rates.…”

“…Earlier bDMARD initiation has been associated with lower flare rates in oJIA, with a prospective study including 171 patients with oJIA (43 persistent, 128 extended) finding that patients who started bDMARDs early (≤2 years from symptom onset) were significantly more likely to be in DFID than those who began treatment later in propensity score-adjusted analyses [14]. Similarly, an observational study from the UK JIA Biologics Registry that included 1451 JIA patients, 447 of whom had oJIA (162 persistent, 285 extended), found that of patients who stopped bDMARDs for CID, those with a longer disease duration at bDMARD initiation were more likely to need to eventually re-start biologic therapy (OR 1.1 per additional year; 95% CI: 1.0, 1.2) [13 ▪ ]. Patients with prior uveitis were also more likely to re-start biologic therapy (OR 2.4, 95% CI: 1.2, 4.8) [13 ▪ ].…”

“…DMARDs are a cornerstone of therapy for polyarticular course JIA [8,20]. Flare rates within 12 months after withdrawal of medication in pJIA range from 13.5% to 69% [9–11,12 ▪ ,13 ▪ ,14,15,16 ▪ ,17,21,22], with these large discrepancies likely due to differences in study design and flare definition (Table 2). In one prospective trial of 136 polyarticular course patients with CID for at least 6 months, all stopped bDMARD therapy and 37% flared by 8 months [22].…”