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Kids with polyarticular-course juvenile idiopathic arthritis (JIA) who received a second tumor necrosis factor (TNF) inhibitor after failing one initially did just as well as those who changed to a different type of drug, a registry study indicated.

Among 216 JIA patients in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry who didn't respond adequately to a first TNF inhibitor, 43% achieved minimal disease activity or better at 6 months with another TNF inhibitor versus 39% among those receiving another medical class, according to Melissa Mannion, MD, MSPH, of the University of Alabama at Birmingham, and colleagues.

The more stringent response of "inactive disease" was achieved by 29% of patients treated with a second TNF blocker versus 25% of those getting a different agent, the researchers .

"Additional larger studies, ideally including biomarker analyses, are needed to evaluate if specific medications are more effective in specific patients," Mannion and colleagues wrote. "Until future studies provide additional data to guide clinical decisions, other patient factors such as patient preferences related to administration or side effect profiles, should be considered when choosing subsequent biologics."

TNF inhibitors were, of course, the first targeted agents to be approved for autoimmune inflammatory arthritic diseases such as JIA. A variety of different alternatives have emerged since, raising questions as to which to try when patients don't respond to initial treatment. call for a different medication class in second-line treatment, such as tocilizumab (Actemra) or abatacept (Orencia), following anti-TNF treatment failure. But, Mannion and colleagues pointed out, many clinicians prefer first to try another TNF blocker, and other studies have suggested that this approach is just as effective as switching to another drug type. Indeed, among patients included in the current study, 85% ended up with a second anti-TNF drug as their second-line therapy.

Study Details

The CARRA registry was established in 2015, with some 10,000 JIA patients enrolled through 2020, the cutoff date for patients included in the new study. Mannion and colleagues identified those with the polyarticular-course type of JIA who had started a TNF inhibitor and then switched to another biologic agent (either a second TNF inhibitor or another type) and who had thorough workups around the time of switching and again 6 months afterward. That left the researchers with 216 for the study.

Etanercept (Enbrel) was by far the most common initial TNF blocker, taken by 182 of the group. Other initial drugs included infliximab (Remicade), adalimumab (Humira), and golimumab (Simponi).

Among second-line TNF blockers, adalimumab proved the most popular: it was the choice for 84% of patients going this route. Tocilizumab was the most common non-TNF inhibitor, used by 19 of the 33 patients not getting a second anti-TNF agent. Nine received abatacept and five were given the Janus kinase inhibitor tofacitinib (Xeljanz).

Some 80% of all patients in the study were girls; median patient age was 13 at the time of starting a second-line agent. Median disease duration when starting the initial TNF inhibitor was 6 years. Roughly three-quarters of patients had found their first drug ineffective; for the rest, reasons for discontinuing were split about evenly between adverse effects and "other," a category that would typically include problems with insurance and cost. A few patients stopped the first drug because they had achieved remission and felt biologic therapy was no longer necessary.

To evaluate subsequent outcomes, Mannion and colleagues used the Clinical Juvenile Arthritis Disease Activity Score-10 (cJADAS10) system, with a value of 2.5 or less defined as "inactive disease" and a score of 5 or less as "minimal activity." Median score at the time of switching was 8 among those going onto a second anti-TNF drug and 11 for patients moving to another drug type. Other measures of disease activity, such as erythrocyte sedimentation rate and affected joint counts, also suggested that non-TNF inhibitors were chosen preferentially for patients with worse symptoms.

But the non-TNF inhibitors may have been more effective. Mean cJADAS10 scores at the 6-month mark were 6.03 (SD 5.99) among those getting a second anti-TNF agent and 4.94 (SD 4.15) in patients who switched classes; changes from baseline in these two groups averaged -2.94 with a second TNF inhibitor versus -6.48 with a different medication type (P not reported).

Mannion and colleagues' report also included reanalyzed in the United Kingdom, covering 240 patients who had switched from an initial anti-TNF drug to either a second such agent or another type. In this group, both drug classes in second line appeared to be similarly effective in bringing down disease activity scores. Mannion's group noted that the small number of patients switching to non-TNF inhibitors made comparisons difficult, both within the CARRA registry and with respect to the U.K. patients. The researchers also observed that "response[s] to biologic [treatment], either first or second, is dependent on yet to be identified characteristics."

Limitations to the study included its retrospective nature and the likelihood of unmeasured factors that influenced treatment choices and responses.

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