High Rate of Inadequate Response to Biologics In Patients Initiating Treatment for RA

More than two-thirds of patients with rheumatoid arthritis (RA) who were previously naïve to biologic disease-modifying anti-rheumatic drugs had an inadequate response to their first biologic during 1 year of follow up, according to a Taiwanese study published April 6, 2018, in PLOS One by Qiang Shi, PhD, and colleagues.

The researchers also showed that inadequate responders had higher all-cause healthcare resource utilization (HCRU) and non-medication costs during the follow-up period compared with patients with stable disease. The high level of inadequate response found suggests an unmet need in the RA treatment paradigm, the researchers conclude. The study was supported by Eli Lilly.

Although biologics include anti—tumor necrosis factor (anti-TNF) agents, T-cell inhibitors, interleukin (IL)-1 receptor antagonists, and anti-IL-6 agents, the researchers note that biologic therapy is typically initiated using anti-TNF drugs. However, previous studies have shown nearly one-third of patients have an inadequate response to these drugs. Although patients will often switch to a different anti-TNF drug rather than a different class of medication, research has shown that inadequate response to an initial anti-TNF agent is a predictor of response and tolerance to a second anti-TNF agents.

The Taiwanese study analyzed data from 2009 through 2013 from the country’s National Health Insurance Database, which covers over 99% of Taiwan’s population. The researchers followed 818 patients with RA who initiated their first biologic in 2010. All patients either initiated adalimumab (46%) or etanercept (54%) as their first biologic therapy. After 1 year of follow up, 32% were classified as stable, 66% had an inadequate response, and 2% were lost to follow up.

During the follow-up period, mean annual total direct costs (including inpatient, outpatient, and emergency department costs, as well as medication costs) were $16,136 for stable patients compared with $14,154 for patients with inadequate response. The researchers explain that the increase in direct costs was driven by medication costs, which remained high for stable patients and decreased significantly for patients with inadequate response because the primary driver of inadequate response was low adherence.

“When only non-medication costs were considered, stable patients had lower mean outpatient, inpatient, and ED costs for years 1 through 3, post initiation,” the researchers said.

Mean annual non-medication direct costs were $937 for stable patients and $1574 for patients with inadequate response. Mean annual hospitalizations were also higher for patients with inadequate response (0.46) versus stable patients (0.10) during the 1-year follow-up period.

Seventeen percent of patients initiating a biologic in 2010 switched to a second biologic during 3 years of follow up. Patients who initiated adalimumab switched to a second-line biologic 21% of the time; those who initiated etanercept switched 13% of the time.

In Taiwan, biologics accounted for nearly 57.9% of direct medical costs for patients with RA in 2011. Because of the high medication costs associated with biologics, the early identification of inadequate response can help payers to redirect these costs to treatments with better health outcomes.

“This study will provide evidence for decision makers to understand the real-world rate of response to therapy, and the differences in HCRU and costs between patients responding and not responding to therapy,” the researchers conclude.

Reference

Shi Q, Li K-J, Treuer T, et al. Estimating the response and economic burden of rheumatoid arthritis patients treated with biologic disease-modifying antirheumatic drugs in Taiwan using the National Health Insurance Research Database (NHIRD). PLoS One. 2018;13(4):e0193489. doi: 10.1371/journal.pone.0193489.