British Columbia (BC) was the first province in Canada to implement a mandatory nonmedical switching policy from the infliximab originator (Remicade) to biosimilars. Phase 1 of the Biosimilars Initiative began on May 27, 2019, focusing on rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. Since then, only infliximab biosimilars have been approved for those conditions by the province’s drug plan, and all patients taking the reference product were required to switch during a 6-month transition period.

A recent study, published in CMAJ Open, aimed to detect any impact on health services utilization during the first year of BC’s Biosimilars Initiative to inform policy makers. The investigators wrote that patients and physicians are concerned about nonmedical switching, “despite evidence that switching is not associated with negative health impacts,” and that mandatory switching policies must be closely monitored “to provide early data on the safety of these policies.”

Using BC Ministry of Health databases, the authors constructed 3 historical cohorts between 2016 and 2018 and 1 policy cohort from 2019 of patients with inflammatory arthritis or psoriasis who were treated with infliximab. They followed each cohort for 1 year, starting on May 27, using data on drug and health services utilization outcomes as indicators of patient health. Of note, patients with inflammatory bowel disease (IBD) were not included in Phase 1 of the policy change and were not included in the study.

A total of 572 unique patients were included: 520 in the 2016 cohort, 461 in the 2017 cohort, 423 in the 2018 cohort, and 377 in the policy cohort. Many patients were in multiple cohorts, and 335 (58.6%) were included in all 4. The 2016-2018 historical cohorts reflected health care utilization before the shift in policy.

In all cohorts, about half of patients (50.4% to 53.5%) had rheumatoid arthritis. Psoriasis was the least common diagnosis (3.3% to 4.0% of patients). Patients in the policy cohort used fewer synthetic anti-inflammatory medications than those in the historical cohorts, but the investigators found no other differences in baseline characteristics between cohorts.

In the policy cohort, 233 patients (61.8%) had switched to a biosimilar infliximab product after the 6-month transition period. Within 1 year of the policy taking effect, 329 (87.3%) had switched.

Drug Utilization

Across cohorts, most patients refilled their prescriptions for infliximab at least 4 times during the 1-year follow-up. Although the first 3 refills were similar between cohorts, about 7.2% fewer patients in the policy cohort refilled their prescriptions a fourth time from January 14 to February 25 (in 2020) compared to the historical cohorts.

The authors interpreted this “small transient decrease” in infliximab refills as a delay in refilling the prescription for a fourth time by patients in the policy cohort. They speculated that the decrease might have represented attempts to discontinue treatment following remission, followed by a flare-up and reinitiation of treatment. However, they said, “in the absence of clinical data, we are unable to confirm this explanation.” Since they did not observe an increase in switching to a different biologic during this time, and the decrease was transient, the researchers said, “both are encouraging signs in terms of safety.”

Overall, in the policy cohort, there was no increase compared to the historical cohorts in the use of other anti-inflammatory medications. Compared to the historical cohorts, the policy cohort showed less use of synthetic disease-modifying antirheumatic drugs (DMARDs) and non-steroidal anti-inflammatory drugs, but similar use of oral corticosteroids. “We consider this a positive signal; that is, fewer patients from the policy cohort experienced symptoms while receiving treatment with biosimilar,” the authors wrote.

Health Services Utilization

First visits to an emergency department and first discharges from a hospital were similar between the policy cohort and historical cohorts. Whereas visits to any physician in an outpatient setting were similar between cohorts, first visits to a specialist occurred earlier in the policy cohort, and approximately 15% more patients in the policy cohort visited a specialist twice compared to the historical cohorts.

The investigators expected an increase in visits to rheumatology and dermatology specialists for patients in the policy cohort, “because patients likely discussed switching with their specialists.” They noted that similar increases had been observed in previous studies.

Monitoring “Did Not Detect Signals of Negative Impacts on Health Services Use”

Apart from a transient decrease in fourth refills of infliximab and an expected increase in visits to specialists, the investigators said they “observed no signal for a negative impact of the infliximab policy on health services utilization during the first year of follow-up.”

In summary, they said, there were no increases in switching to a different biologic or DMARDs, no increase in other anti-inflammatory medications, and no increases in emergency department visits or hospital admissions. They also noted that COVID-19 “had no detectable impact on health services utilization” for these patients during the months they analyzed in 2020.

Their findings “support the safety of the Biosimilars Initiative for infliximab users,” they said, however, “detailed, longer-term cohort studies and hypothesis-testing methods could provide additional assurance about the safety of the policy.”

Reference

Fisher A, Kim JD, Dormuth CR. Mandatory nonmedical switching from originator to biosimilar infliximab in patients with inflammatory arthritis and psoriasis in British Columbia: a cohort study. CMAJ Open. 2022;10(1):E109-E118. doi:10.9778/cmajo.20200319