MADRID – Biologic agents are increasingly being used in the treatment of juvenile idiopathic arthritis, earlier in the course of the disease and in less severe cases, according to longitudinal data from the Dutch National Arthritis and Biologicals in Children Register.
Etanercept was the most commonly used biologic in nonsystemic cases of JIA, while anakinra was the most commonly prescribed biologic agent for systemic disease over a 12-year evaluation period.
"Treatment strategies in JIA have changed over the past decade, especially since the introduction of biologics," said Janneke Anink, a third-year postgraduate student at Erasmus MC-Sophia Children’s Hospital in Rotterdam, the Netherlands. This has been possible due to a better understanding of the immunologic and biologic mechanisms underlying the inflammatory joint disease.
Etanercept, which blocks tumor necrosis factor (TNF), was the first biologic agent to be registered in Holland in 1999, Ms. Anink noted. Additional anti-TNF therapies, such as infliximab and adalimumab, became available in 2007-2008, followed by the interleukin (IL-1) blockers canakinumab and anakinra in 2009-2010, and, more recently, the IL-6 blocker tocilizumab in 2011.
Alongside the availability of these novel drugs, treatment goals have changed, from the prevention of long-term joint damage and disability to achieving inactive disease through more aggressive and earlier therapy, Ms. Anink said at the annual European Congress of Rheumatology (Ann. Rheum. Dis. 2013;72:154). It’s not known, however, whether the use of these drugs actually leads to better patient outcomes.
Ms. Anink and her associates therefore set out to determine how prescription trends had changed in Holland since biologic agents became available and how such trends might have influenced patient outcomes. The team used data from the Dutch National Arthritis and Biologicals in Children (ABC) Register, which is an ongoing, multicenter, prospective, observational initiative that began in 1999 with the aim of including all patients with JIA who are treated with a biologic agent for their condition.
Upon inclusion in the ABC Register, key patient characteristics are collected, including age, gender, JIA category, age at diagnosis, disease duration, and prior medication use. Patients are also assessed for current medication use, adverse events of treatment, and a host of laboratory and disease activity parameters, which are assessed again 3 and 6 months after inclusion, and then annually.
A total of 429 cases were included in the current analysis, of which 343 patients had nonsystemic and 86 had systemic disease. Patients had started treatment with at least one biologic agent between 1999 and 2010. There were 82 prescriptions for biologic agents in 2010 for both systemic and nonsystemic JIA, compared with only 12 during 1999-2000.
Biologic agents were prescribed after shorter disease durations in 2008-2010, compared with 1999-2001, dropping from 5.3 years to 3.0 years, respectively, in nonsystemic JIA and from 3.5 years to 0.4 years, respectively, for systemic disease, Ms. Anink reported.
Nonsystemic JIA patients with lower disease activity at baseline were also being treated with these drugs. Indeed, the median number of active joints at baseline fell from 18 before biologic therapy was given to 5. The median number of joints with limited motion decreased from 12 to 3, and Childhood Health Assessment Questionnaire (CHAQ) scores fell from 1.8 to 1.1 over the same time periods.
Importantly, the proportion of patients with inactive disease after 3 months of therapy increased dramatically, from 0% in 1999-2001 to 34% during 2008-2010 for nonsystemic disease and from 0% to 64% for systemic disease.
"We saw the threshold for prescription decreased, which was earlier in the disease course and in patients with lower disease activity," Ms. Anink summarized. "With these trends, we say the short-term treatment outcomes improved in all JIA categories."
Similar findings were presented separately at the meeting by a German team. Dr. Kirsten Minden of the German Rheumatism Research Centre, Berlin, and her associates reported that the use of traditional and biologic disease-modifying agents for the treatment of polyarticular JIA rose and occurred earlier over a 12-year period (Ann. Rheum. Dis. 2013;72:731). Improved patient health status, including functional capacity measured by the CHAQ score, disease activity measured by the 10-joint Juvenile Arthritis Disease Activity Score, and pain and overall well-being, coincided with treatment changes.
The ABC Register was financially supported by the Dutch Board of Health Insurances (from 2003 to 2006), Pfizer (formerly Wyeth International, since 2007), and Abbott (since 2010). Ms. Anink had no disclosures to report.