British Columbia (BC) was first district In Canada to implement a mandatory non-medical conversion policy from the originator of infliximab (Remicade) to biosimilars. The first phase of the Biosimilars Initiative began on May 27, 2019, focusing on rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. Since then, biosimilars to infliximab have been approved only for those cases by the county drug plan, and all patients taking the reference product were required to switch within a 6-month transition period.
recent study, Posted in Open CMAJ, intended to reveal any impact on health service use during the first year of the B.C. Biosimilarities Initiative to inform policy makers. The investigators wrote that patients and clinicians are concerned about non-medical switching, “despite evidence that the switch is not associated with negative health effects,” and that mandatory switching policies should be closely monitored “to provide early data on the safety of these policies.”
Using British Columbia Department of Health databases, the authors created 3 historical cohorts between 2016 and 2018 and 1 policy set from 2019 for patients with inflammatory arthritis or psoriasis treated with infliximab. They followed each group for one year, starting May 27, using data on drug and health services use outcomes as indicators of patient health. Of note, patients with inflammatory bowel disease (IBD) were not included in the first phase 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 groups, and 335 (58.6%) were included in all four groups. Historic 2016-2018 cohorts reflected healthcare utilization prior to the policy shift.
In all groups, about half of patients (50.4% to 53.5%) had RA. Psoriasis was the least common diagnosis (3.3% to 4.0% of patients). Patients in the policy group used fewer synthetic anti-inflammatory drugs than those in the historical groups, but the researchers found no other differences in baseline characteristics between the groups.
In the policy group, 233 patients (61.8%) switched to a biologic infliximab after a 6-month transition period. Within one year of the policy going into effect, 329 (87.3%) were changed.
Across the groups, most patients refilled their infliximab prescriptions at least 4 times during the 1-year follow-up. Although the first three refills were similar between groups, 7.2% fewer patients in the policy group refilled prescriptions a fourth time from January 14 to February 25 (in 2020) than in the historical cohorts.
The authors interpreted this “small transient decrease” in infliximab refills as a delay in the fourth prescription refill by patients in the policy group. They speculated that the decline might represent attempts to discontinue treatment after remission, followed by flare-ups and re-initiation of treatment. However, they said, “In the absence of clinical data, we cannot confirm this interpretation.” Because they did not notice 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 group, there was no increase compared to historical groups in the use of other anti-inflammatory drugs. Compared with the historical groups, the policy group showed lower use of synthetic disease-modifying antirheumatic drugs (DMARDs) and non-steroidal anti-inflammatory drugs, but similar use of oral corticosteroids. “We consider this to be a positive sign; that is, fewer patients from the policy group experienced symptoms while receiving biosimilar therapy,” the authors wrote.
Benefit from health services
First visits to the emergency department and first hospital discharge were similar between the policy group and historical cohorts. While visits to any physician in the outpatient setting were similar between cohorts, first visits to a specialist occurred earlier in the policy group, and about 15% more patients in the policy group visited specialist twice than in the historical cohorts.
The investigators expected an increase in visits to rheumatologists and dermatologists for patients in the policy group, “because patients were more likely to have discussed the switch with their specialists.” They note that similar increases have been observed in previous studies.
Monitoring “did not reveal indications of negative effects on the use of health services”
Aside from the temporary decrease in IV infliximab refills and the expected increase in visits to specialists, the investigators said they “observed no indication of an adverse effect of infliximab policy on health service use during the first year of follow-up.”
In summary, they said there were no increases in switching to different biologics or DMARDs, no increases in other anti-inflammatory drugs, and no increases in emergency department visits or hospitalizations. They also noted that COVID-19 “had no detectable effect on the use of health services” for these patients during the months they analyzed in 2020.
Their findings “support the safety of the Infliximab User Biosimilars Initiative,” they said, however, “long-term cohort studies and hypothesis-testing methods could provide additional assurance about the safety of the policy.”
Fisher A, Kim JD, Dormot CR. Mandatory non-medical switch from originator to biosimilar infliximab in patients with arthritis and psoriasis in British Columbia: a cohort study. Open CMAJ. 2022; 10 (1): E109-E118. doi: 10.9778/cmajo.2000319