MADRID – When biologic treatment is indicated after initial tumor necrosis factor (TNF) inhibitor therapy for juvenile idiopathic arthritis (JIA) has failed, the mechanism of action of the second biologic does not appear to matter, according to data presented at the European Congress of Rheumatology.
“There appears to be no difference in effectiveness outcomes or drug survival in patients starting a second TNF inhibitor versus an alternative class of biologic,” said, an epidemiologist at the Centre for Epidemiology Versus Arthritis at the University of Manchester (England).
Indeed, at 6 months, there were no significant differences among patients who had switched from a TNF inhibitor to another TNF inhibitor or to a biologic with an alternative mechanism of action in terms of:
- The change in Juvenile Arthritis Disease Activity Score (JADAS)-71 from baseline (mean score change, 7.3 with second TNF inhibitor vs. 8.5 with an alternative biologic class).
- The percentage of patients achieving an American College of Rheumatology Pediatric 90% response (22% vs. 15%).
- The proportion of patients achieving minimal disease activity (30% vs. 23%).
- The percentage reaching a minimal clinically important difference (MCID; 44% vs. 43%).
There was also no difference between switching to a TNF inhibitor or alternative biologic in terms of the duration of time patients remained treated with the second-line agent.
“After 1 year, 62% of patients remained on their biologic therapy, and when we looked at drug survival over the course of that year, there was no difference between the two cohorts,” Mrs. Kearsley-Fleet reported. There was no difference also in the reasons for stopping the second biologic.
“We now have a wide range of biologic therapies available; however, there is no evidence regarding which biologic should be prescribed [in JIA], and if patients switch, which order this should be,” Mrs. Kearsley-Fleet stated. Current NHS England guidelines recommend that most patients with JIA should start a TNF inhibitor (unless they are rheumatoid factor positive, in which case they should be treated with rituximab [Rituxan]), and if the first fails, to switch to a second TNF inhibitor rather than to change class. The evidence for this is limited, she noted, adding that adult guidelines for rheumatoid arthritis now recommended a change of class if not contraindicated.
Using data from two pediatric biologics registers – the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN) and Biologics for Children with Rheumatic Diseases (BCRD) – Mrs. Kearsley-Fleet and her associates looked at data on 241 children and adolescents with polyarticular JIA (or oligoarticular-extended JIA) starting a second biologic. The aim was to compare the effectiveness of starting a second TNF inhibitor versus switching to an alternative class of agent, such as a B-cell depleting agent such as rituximab, in routine clinical practice.
A majority (n = 188; 78%) of patients had etanercept (Enbrel) as their starting TNF inhibitor and those switching to a second TNF inhibitor (n = 196) were most likely to be given adalimumab (Humira; 58%). Patients starting a biologic with another mode of action (n = 45) were most likely to be given the interleukin-6 inhibitor tocilizumab (73%), followed by rituximab in 13%, and abatacept (Orencia) in 11%. The main reasons for switching to another biologic – TNF inhibitor or otherwise – were ineffectiveness (60% with a second TNF inhibitor vs. 62% with another biologic drug class) or adverse events or intolerance (19% vs. 13%, respectively).
The strength of these data are that they come from a very large cohort of children and adolescents starting biologics for JIA, with systematic follow-up and robust statistical methods, Mrs. Kearsley-Fleet said. However, she noted that JIA was rare and that only one-fifth of patients would start a biologic, and just 30% of those patients would then switch to a second biologic.
“We don’t see any reason that the guidelines should be changed,” Mrs. Kearsley-Fleet observed. “However, repeat analysis with a larger sample size is required to reinforce whether there is any advantage of switching or not.”
Versus Arthritis (formerly Arthritis Research UK) and The British Society for Rheumatology provided funding support. Mrs. Kearsley-Fleet had no financial conflicts of interest to disclose.
SOURCE: Kearsley-Fleet L et al. Ann Rheum Dis, Jun 2019;8(Suppl 2):74-5.