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58 Real-life single-centre experience of Tocilizumab-associated neutropenia in children with juvenile idiopathic arthritis (JIA)
  1. Charlene Foley1,
  2. Ursula Fearon2,
  3. Muthana Al Obaidi1
  1. 1Great Ormond Street Hospital
  2. 2Bristol


Background Tocilizumab, approved for treatment of children with Systemic-onset-JIA (SoJIA) and polyarticular-JIA (pJIA) is efficacious and well-tolerated. Transient neutropenia is a side-effect of treatment.

Aim Chart-review of children treated with Tocilizumab to report on Tocilizumab-associated-neutopenic-episodes.

Methods Retrospective review of patients receiving Tocilizumab (January 2010-January 2019). Patients with extended-oligoarticular-JIA (ExO-JIA), pJIA and SoJIA reviewed in more detail to ascertain frequency of neutropenia and related-factors. For analysis, ExO-JIA and pJIA were combined to create an ExO/pJIA group. Neutropenia defined as neutrophils<1.5, severe-neutropenia<1.0. Statistical analysis was performed using the Mann-Whitney-U and Chi-Square tests.

Results Sixty-eight children (60%female) attending the rheumatology-department at GOSH are receiving Tocilizumab. Of these, 53 (78%) have a diagnosis of ExO-JIA (n=10), pJIA (n=12) or SoJIA (n=31).

Disease duration pre-commencement of Tocilizumab was 2.9years(0.1–11). Children with SoJIA were commenced on Tocilizumab significantly (p<0.001) earlier in their disease course than children with ExO/pJIA (1.5years,0.1–7.4 versus 6.5years,0.4-11).

Median time to first neutropenia was 0.5years(0.1-3.2). No significant pattern in time from commencing Tocilizumab to developing first neutropenia was observed.

Recurrent neutropenia (i.e.>2episodes) occurred in 38% (20/53) and was significantly more common in SoJIA (p<0.05). All children with ExO/pJIA experienced a total of 2-3 neutropenic-episodes, significantly less (p<0.05) than the recurrence-rate in children with SoJIA (average7-episodes, 2-17).

Severe neutropenia occurred in 65% (n=13) and was significantly (p<0.001) more frequent in SoJIA (n=11, 85%). In those with recurrent-neutropenia, no significant correlation was identified between risk of neutropenia and interval between doses, dose (mg/kg) received, concurrent Methotrexate, duration on Tocilizumab or number of alternative treatments received pre-Tocilizumab.

Seventeen-children (32%) taking Tocilizumab had a documented infection. No relationship between neutropenia and risk of infection was identified.

Conclusion Tocilizumab-associated neutropenia is more frequent, severe and recurrent in SoJIA. Neutropenia can occur at any stage in the treatment-course. Clinicians should consider long-term blood-monitoring pre-Tocilizumab, especially for those with SoJIA.

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