Biological treatment in systemic juvenile idiopathic arthritis: achievement of inactive disease or clinical remission on a first, second or third biological agent

Abstract

Objectives: To analyse the effect of biological agents (BAs) in terms of achieving inactive disease (ID) or clinical remission (CR) in patients with systemic juvenile idiopathic arthritis (SJIA), to describe effects of switching or discontinuing a BA and to assess the proportion of patients able to maintain ID or CR off steroids and after withdrawing BA therapy.

Methods: Retrospective study in a French paediatric rheumatology reference centre using the CEMARA (CEntre des MAladies RAres) register.

Results: Seventy-seven patients were included with a cumulative follow-up of 245.5 patient-years (median 1.1, range 0.5-8.0). On a first BA, ID was achieved in 37 patients, including 1 patient out of 12 patients on etanercept, 26 patients out of 51 on anakinra and 7 out of 10 on canakinumab. One patient on abatacept and two patients on tocilizumab also achieved ID. Switching of BA was common. The switch to a second (n=34), third (n=18) or fourth (n=4) BA resulted in ID in a further 13 patients, either on canakinumab (n=6) or tocilizumab (n=7). At last follow-up, 40 patients were in CR (27 patients off steroids, 5 patients having never received steroid treatment), either on (n=29) or off (n=11) BA.

Conclusions: In this series of patients with SJIA, interleukin-1 inhibitors were associated with a higher proportion of ID than tumour necrosis factor inhibitors when used as first BA. Switching allowed some patients to achieve ID when treated with canakinumab or tocilizumab. CR was eventually achieved in more than half of the patients.

Keywords: DMARDs (biologic); Juvenile Idiopathic Arthritis; Outcomes research; TNF-alpha.

Figure 1

Flow chart (CEMARA, CEntre des MAladies RAres; SJIA, systemic juvenile idiopathic arthritis).

Figure 2

Kaplan-Meier estimate of drug continuation until discontinuation for tocilizumab, canakinumab, anakinra and etanercept, as a first biological agent for adverse events, ineffectiveness of treatment, loss of response, convenience of use and patient's choice. Censoring, defined as the time of discontinuation or, when a patient was still receiving the drug, the time of the last study visit, is shown by vertical lines.

Figure 3

Switching of biological agents (BAs), and achievement of inactive disease and clinical remission (CR). ETA, etanercept; TCZ, tocilizumab. ^§The only patient on adalimumab (ADA) as first-line treatment was switched after 9.5 months to anakinra (ANA) and steroids, then canakinumab (CAN) and steroids, but arthritis persisted. ^¶The only patient on abatacept (ABA) as first-line treatment initially achieved partial response and was in CR at last follow-up. *Six patients with ANA as a first BA and two patients with ANA as a second BA experienced secondary introduction of methotrexate (median delay of introduction 10.5 months after start of ANA, range 6–25 months). Four patients with ANA as a first BA achieved inactive disease that persisted at last follow-up.