Old-Line Rheum Drugs Lose Luster in JIA

Use of conventional synthetic drugs to treat juvenile idiopathic arthritis (JIA) fell by half during 2000-2022, as targeted therapies became increasingly popular, analysis of commercial insurance claims showed.

Whereas 89.5% of new prescriptions for disease-modifying anti-rheumatic drugs (DMARDs) in 2000 were for old-line agents, by the end of the period such products accounted for only 43.2% of new starts, according to Daniel B. Horton, MD, MSCE, of Rutgers University in New Brunswick, New Jersey, and colleagues.

Biologic and other targeted drugs such as Janus kinase (JAK) inhibitors took up the slack, the group reported in Arthritis & Rheumatology. But even within this category, patterns changed considerably over time: tumor necrosis factor (TNF) inhibitors first rose in popularity and then fell, while drugs with different targets gained ground.

Even so, the blockbuster anti-TNF product adalimumab (Humira) remained the top second-line therapy: as of 2022, it accounted for 77.8% of first prescriptions for targeted therapies following conventional DMARDs.

“These real-world treatment patterns give us insight into how selection of therapies for JIA has evolved with increasing availability of effective agents and help prepare for future studies on comparative DMARD safety and effectiveness,” Horton and colleagues wrote.

“There is little research evaluating trends in DMARD use in populations with JIA over the past decade, including research on specific DMARDs and first-line b/ts [biologic/targeted synthetic] DMARDs,” they said in explaining their rationale for performing the study. “Inflection points in DMARD use were hypothesized to occur with JIA-specific approvals. We also hypothesized that bDMARD use has increased over time and that adalimumab has become the most commonly used bDMARD.”

Data for the study came from the Merative MarketScan Commercial Claims and Encounters database. Records from 2000-2022 showed 20,258 new DMARD prescriptions for 13,696 children (ages 1-18 years) with JIA diagnoses. Median patient age was 14 and two-thirds were girls. About 21% also had diagnoses of psoriasis and 7.5% had uveitis.

Up to 2018, new DMARD prescriptions were mostly for old-line agents, primarily methotrexate and hydroxychloroquine. Then the rates for these products dipped below 50%, with biologic drugs becoming the dominant class.

TNF inhibitors became the most common product within the biologic category, but overall prescription rates actually had their maximum in 2008 — the year that adalimumab gained its first JIA approval — at 40.8% of new scripts. By 2022, new TNF inhibitor prescriptions accounted for only 27.8% of the total.

Among other biologic drugs, relatively small numbers of patients were started on interleukin-6 inhibitors such as tocilizumab (Actemra) and interleukin-1 inhibitors such as canakinumab (Ilaris), and these didn’t change much over the latter third of the study period. The category that did gain substantially was “other” bDMARDs: the selective T-cell costimulation modulator abatacept (Orencia), the interleukin-17A blocker secukinumab (Cosentyx), the interleukin 12/23 inhibitor ustekinumab (Stelara), and the B-cell destroyer rituximab (Rituxan). In 2022, “other” bDMARDs accounted for 17.3% of new scripts for any DMARD. The most popular of these appeared to be ustekinumab.

JAK inhibitor use also increased in recent years, from nothing in 2012, the year tofacitinib (Xeljanz) was first approved for adult rheumatoid arthritis, to 6.8% of DMARD starts in 2022. By that time, three other JAK inhibitors had entered the market; but tofacitinib didn’t gain a formal JIA indication until 2020, and upadacitinib (Rinvoq) only got one this year, after winning approval for adult rheumatoid arthritis in 2019.

As Horton and colleagues predicted, adalimumab starts really took off after the JIA approval in 2008, going from about 7% of new DMARD scripts to nearly 15% the next year. They also expected to see a bump in adalimumab prescriptions after 2018, when a less painful formulation was introduced. There was, though not quite as dramatic as in 2008: from 18% of scripts in 2017, the rate reached 24% in 2019, though it began to slide back. As of 2022, adalimumab accounted for just over 20% of new DMARD starts — still far more than for any other individual drug.

That was even more true when the researchers looked at biologics and targeted synthetics prescribed for patients who previously had only used old-line drugs. Almost 80% of such second-line prescriptions were for adalimumab in 2022. Although etanercept (Enbrel) had once been the primary second-line drug, its use plummeted to less than 10% as of 2022. Other products had even less use at that point.

Yet having an FDA-approved JIA indication was not always necessary for a product to gain wide use. Hydroxychloroquine has never had a specific JIA approval, yet the data showed it running a close second to methotrexate in 2022 among conventional medications (15% vs 21% of all DMARD starts).

Limitations included the database’s restriction to private insurance, such that the results may not be generalizable to those on Medicaid or the uninsured, or to non-U.S. patients in general. Horton’s group also had no data on potential influences such as sociodemographic parameters and clinical details such as JIA subtype or severity. In general, reasons for drug choices could only be guessed at.

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