Juvenile idiopathic arthritis (JIA) is one of the most common chronic disease affecting children, with an annual prevalence of approximately 1 in 1,000.1 The tumor necrosis factor (TNF) blocker etanercept has transformed the treatment of JIA in children and young patients who do not respond to or tolerate methotrexate therapy. Since its introduction, several other biologics have become available.

When young patients often have adverse effects or insufficient response to their first biologic, there is “limited evidence to support the choice of a second or further biologic in these situations, although reports to date suggest the International League of Associations for Rheumatology (ILAR) subtype and the availability of other biologics will influence this choice,” wrote the authors of a new study published in Rheumatology.2

Noting that clarifying factors informing such choices will help future practice and research efforts, the current investigation of JIA had 3 distinct goals. First, to describe disease characteristics in patients who recently initiated different first-line biologics. Second, to describe changes in patient characteristics occurring over time in patients starting etanercept. Third, to identify patterns pertaining to the prescribing of a second biologic in patients who do not respond to or tolerate treatment with the first choice of biologic therapy.


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Researchers from several universities in the UK analyzed data from 2 ongoing prospective, observational cohorts of young patients with JIA (n= 931) initiating biologic therapy for JIA. In evaluating the second study aim–changes over time in patients starting etanercept –789 participants were divided into cohorts for comparison based on their recruitment date: before 2006 (n=231), between January 2006 and December 2009 (n=352), and after January 2010 (n=206).

Key Findings         

• Most children who were prescribed tocilizumab or anakinra had JIA compared with those starting anti-TNF therapy (86% and 100% vs <5% (P< .001)
•Anakinra and tocilizumab were more likely to be combined with corticosteroids, and anakinra was more likely to be prescribed for patients with macrophage activation syndrome (MAS) (P < .001)
•Among the 3 anti-TNF therapies, 70% of patients starting adalimumab and 73% of those starting infliximab had chronic anterior uveitis (CAU) vs 5% of patients starting etanercept (P < .001)
•ILAR subtypes differed between the 3 anti-TNF therapies, with a greater number of patients with oligoarthritis started adalimumab or infliximab (P < .001) vs. etanercept
•In 59% of patients, their biologic was started in combination with methotrexate
•Patients starting etanercept as their first biologic showed reduced disease duration and activity over time
•The number of children with either systemic JIA (sJIA) or CAU who started etanercept decreased over time [16% vs 9% vs 3% (P <.001) and 14% vs 6% vs 5% (P < .001), respectively]
•161 patients switched to a second biologic due to nonresponse, adverse effects, or both
•Most patients with sJIA who started a second biologic switched to tocilizumab (17 out of 28 patients)
•45 patients with CAU started a second biologic, with the majority switching to or between adalimumab and infliximab
•Most patients with non-systemic JIA and no history of CAU switched to a second anti-TNF therapy (63 out of 88 patients)

“Although etanercept appears to be the most common biologic prescribed for JIA, there has been a clear shift towards the use of alternative biologics….,” which is primarily driven by disease subtype and history of CAU, wrote the authors. This observed channeling of “certain children towards specific therapies will need to be considered both in terms of future comparative effectiveness studies and also as a guide to ongoing research priorities within rheumatology,” they stated.

Summary and Clinical Applicability

Etanercept remains the most-prescribed biologic for JIA, though there is an observed shift toward alternative options based on disease subtype and presence of CAU. 

Limitations and Disclosures

  • Other factors may be influencing the choice of therapy that were not measured in the current study, which did not include qualitative analysis of patients’ or physicians’ choice of therapy.

Dr Foster has received honoraria, travel bursaries and educational unrestricted grants from Pfizer, Abbvie, Roche, Novartis and Schering Plough.

Dr Hyrich has received honoraria from Pfizer and Abbvie for work unrelated to the present manuscript.

Dr Southwood. is in receipt of medical education grants from Pfizer unrelated to the present manuscript. 

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Reference

  1. American College of Rheumatology. Juvenile Arthritis. Retrieved 8/30/16 from http://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Juvenile-Arthritis
  2. Kearsley-Fleet L, Davies R, Baildam E et al. Factors associated with choice of biologic among children with Juvenile Idiopathic Arthritis: results from two UK pediatric biologic registers. Rheumatology (Oxford). 2016; 55(9):1556-65.

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