Canakinumab as first-line biological therapy in Still's disease and differences between the systemic and the chronic-articular courses: Real-life experience from the international AIDA registry

Abstract

Objective: Interleukin (IL)-1 inhibitors are largely employed in patients with Still's disease; in cases with refractory arthritis, IL-6 inhibitors have shown to be effective on articular inflammatory involvement. The aim of the present study is to assess any difference in the effectiveness of the IL-1β antagonist canakinumab prescribed as first-line biologic agent between the systemic and the chronic-articular Still's disease.

Methods: Data were drawn from the retrospective phase of the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to Still's disease. Patients with Still's disease classified according to internationally accepted criteria (Yamaguchi criteria and/or Fautrel criteria) and treated with canakinumab as first-line biologic agent were enrolled.

Results: A total of 26 patients (17 females, 9 males; 18 patients developing Still's disease after the age of 16 years) were enrolled; 16 (61.5%) patients suffered from the systemic pattern of the disease; 10 (38.5%) patients suffered from the chronic-articular type. No differences were observed between the systemic and the chronic-articular Still's disease in the frequency of complete response, of flares after the start of canakinumab (p = 0.701) and in the persistence in therapy (p = 0.62). No statistical differences were observed between the two groups after 3 months, 12 months and at the last assessment in the decrease of: the systemic activity score (p = 0.06, p = 0.17, p = 0.17, respectively); the disease activity score on 28 joints (p = 0.54, p = 0.77, p = 0.98, respectively); the glucocorticoid dosage (p = 0.15, p = 0.50, and p = 0.50, respectively); the use of concomitant disease modifying anti-rheumatic drugs (p = 0.10, p = 1.00, and p = 1.00, respectively). No statistically significant differences were observed in the decrease of erythrocyte sedimentation rate (p = 0.34), C reactive protein (p = 0.48), and serum ferritin levels (p = 0.34) after the start of canakinumab.

Conclusion: Canakinumab used for Still's disease has been effective in controlling both clinical and laboratory manifestations disregarding the type of disease course when used as first-line biotechnological agent. These excellent results might have been further enhanced by the early start of IL-1 inhibition.

Keywords: AOSD; adult onset Still’s disease; autoinflammatory diseases; biological therapy; interleukin-1; sJIA; systemic juvenile idiopathic arthritis.

FIGURE 1

Study flow diagram illustrating the process leading to the selection of patients included in the present study among all patients recruited in the international AutoInflammatory Disease Alliance (AIDA) Registry dedicated to Still’s disease. AIDA, AutoInflammatory Disease Alliance; CAM, canakinumab.

FIGURE 2

Canakinumab retention represented as a Kaplan–Meier plot among patients with the systemic form of Still’s disease and patients with the chronic-articular type. Time 0” corresponds to the start of canakinumab and the “event” corresponds to the treatment discontinuation.

FIGURE 3

Graphical representation of (A) the number of patients reaching the different time-points during follow-up while on canakinumab treatment; (B) the frequency of complete response, partial response, and poor response in the whole group of patients enrolled at the different tume-points.

FIGURE 4

Frequency of the main clinical manifestations related to Still’s disease at the start of canakinumab and at the following time-points. MAS, macrophage activation syndrome.

FIGURE 5

The total amount of the modified Pouchot score in the whole group of patients enrolled (A) and according with the disease course (B) at the different time-points. The total amount of the systemic modified Pouchot score was higher among patients with the systemic Still’s disease in relation with the higher systemic involvement in this patients compared to the chronic-articular type.

FIGURE 6

Detailed information about the treatment outcome relating to joints involvement among the 14 patients with arthritis. In particular, the total number of tender joints (A) and swollen joints (B) in all patients enrolled, distinguished according with Still’s disease course, has been provided. The DAS28 values have also been detailed in the two types of Still’s disease (C). P-values refer to the differences between the two subgroups of patients in the number of tender joints, swollen joints and DAS28 values at each time-point. The red horizontal line in panel (C) indicates the DAS28 threshold below which arthritis may be considered in remission. DAS28, disease activity score based on 28 joints.

FIGURE 7

Median DAS28 values observed in the 14 patients with arthritis at the different time points. The red horizontal line indicates the DAS28 threshold below which arthritis may be considered in remission.

FIGURE 8

Description of (A) the median glucocorticoid (prednisone or equivalent) intake as mg/day at the start of canakinumab and at each follow-up visit, distinguishing according to the different disease pattern (systemic versus chronic-articular); (B) the total number of patients administered glucocorticoids (GC) at the different timepoints; (C) the total number of patients administered methotrexate (MTX) at the different timepoints.

FIGURE 9

Mean (A) erythrocyte sedimentation rate (ESR), (B) C-reactive protein (CRP), and (C) ferritin serum levels at the different timepoints in the group of 26 patients enrolled in the study.