Title: Evaluating the safety of transitioning to an adalimumab biosimilar from the reference product (Humira®) in adult patients with rheumatic conditions
Authors: Riya Shah, Michelle Morales, Ava Afshar, Katina Tsagaris
Objective: To compare the difference between treatment emergent adverse events (TEAE) in patients on brand Humira® (adalimumab) compared to when switched to an adalimumab biosimilar for a non-medical reason. The goal is to provide real world, timely reference data for clinical practice regarding any safety differences.
Background: Biosimilars are highly similar to an FDA-approved biologic medication, known as the reference product, and are expected to have no clinically meaningful differences in terms of efficacy and safety. Biosimilars were introduced to increase market competition and offer efficacy that is not clinically different from the reference product but at lower cost, thus increasing access. Since 2023, ten FDA-approved adalimumab (ADA) biosimilar products have entered the US market. Insurance companies have adjusted their prescription formularies since the launch of these biosimilars, with many now mandating patients switch from the reference product, Humira®, to an adalimumab biosimilar instead.
Given the recent introduction of adalimumab (ADA) biosimilars, their real-world safety profile in a US population with rheumatic conditions remains unclear.
Methods: A single center, paired-sample, retrospective study was conducted at the two outpatient Emory Rheumatology Clinics at Emory University Hospital Midtown (EUHM) in Atlanta, GA. Eligible patients were identified via the electronic medical record. Inclusion criteria consisted of adults managed and prescribed Humira® by an EUHM rheumatologist. Patients must have been on Humira® for at least 3 months before switching to an ADA biosimilar for a non-medical reason by an EUHM rheumatologist. In addition, the switch must have occurred between 1/1/2024 and 9/1/2024 with one or more documented clinical follow-up(s) by 11/30/2024, the end of the study period, following the ADA biosimilar initiation. The primary outcome was the differences of TEAE in patients on Humira® compared to an ADA biosimilar. This was determined by comparing the number of TEAE reported on Humira® the 3 months before the ADA biosimilar switch and the number of TEAE reported while on ADA biosimilar through 11/30/2024. Secondary outcomes included ADA biosimilar discontinuation rate by the end of the study period, reason for biosimilar discontinuation (if applicable), and the type of TEAE experienced.
Results: A total of 177 patients switched from Humira® to an ADA biosimilar between 1/1/2024 and 9/1/2024 of which 94 met inclusion criteria. Of these, 9 patients (9.6%) reported TEAE with 7 reported side effects while on Humira® and 12 while on an ADA biosimilar. Two patients had TEAE on both
Humira® and 12 while on an ADA biosimilar. Two patients had TEAE on both Humira® and the ADA biosimilar, four patients had TEAE on Humira® but none with the ADA biosimilar, and three patients had no TEAE on Humira® but did on the ADA biosimilar (p = 1.000, 0.75 (95% CI 0.110- 4.433)). The following TEAE were reported with Humira®: pruritus (n=2), itchy eyes (n=1), injection site reactions (n=3), and abdominal pain (n=1). Patients reported the following on the ADA biosimilar: pruritus (n=1), scaly skin (n=1), sores on scalp (n=1), inner ear itch (n=1), spreading rash (n=1), malaise (n=1), dizziness (n=1), nausea (n=1), peeling skin (n=1), injection site reaction/redness and swelling (n=1), burning upon injection (n=1), and genital itching (n=1). In addition, 11 of 94 patients (11.7%) discontinued the ADA biosimilar for reasons like insurance preference (2/11, 1.8%), adverse events (3/11, 2.7%), decreased efficacy (3/11, 2.7%), pregnancy (1/11, 0.9%), treatment de-escalation (1/11, 0.9%), and unclear (1/11, 0.9%).
Conclusion: No statistically significant difference was found between the number of reported TEAE when patients were on Humira® versus when switched to an ADA biosimilar. The majority of patients tolerated both Humira® and the ADA biosimilars, however, there were numerical differences in the amount of TEAE on each of the medications. A larger sample is needed to determine if a difference exists in TEAE amongst patients on Humira® versus when switched to an ADA biosimilar.
