4 Studies Address Successes, Failures, and Strategies in Non-Medical Biosimilar Switching

Today, 4 presentations at the 2017 American College of Rheumatology’s (ACR) Annual Meeting in San Diego, California, covered research on switching studies concerning etanercept and infliximab biosimilars.

A Closer Look at Switching Failures

Researchers investigating treatment failures that occurred when switching between reference etanercept (Enbrel) and the etanercept biosimilar SB4 (Benepali) report that from the patients’ perspective, when adverse events (AEs) or lack of effectiveness (LOE) occur after a switch, it is “obvious” to patients that the AEs and/or LOE are likely to be a result of the switch to a biosimilar.¹ Explaining to patients that the same medication is found in both the originator and biosimilar is an effective strategy in about 90% of cases, but switching failure remains a challenge, they conclude.

Oliver Hendricks, MD, and Kim Horslev-Petersen, MD, recorded their clinical experience with switching failures during a nationwide non-medical switch in Denmark from originator etanercept to SB4. They document the switching experience of 85 patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), among whom 89% experienced the switch to SB4 as an uncomplicated continuation of successful treatment. However, 11% stopped biosimilar treatment after a 4-month follow-up due to significant LOE and/or AEs.

Four of the 9 treatment failures corresponded to the following scenario:

The clinical condition on originator etanercept was stable, but flares (ankylosing spondylitis disease activity score [ASDAS] >2.1 or Disease Activity Score 28 C-reactive protein [DAS28CRP] >3.2) was observed at least once during a 24-month period before the switch to biosimilar etanercept. Treatment with SB4 continued in 2 patients, and in the other 2 a change to a third biologic treatment was undertaken due to prolonged disease activity.

Five cases corresponded with the following scenario (1 case of AE, 3 cases of LOE, 1 case of combined AE/LOE):

The clinical situation on originator etanercept was characterized by complete remission (ASDAS <1.2 or DAS28CRP <2.6) for at least 24 months. Patients had experienced complete remission at least for 2 (and up to 9) years. In these cases, the researchers believed that SB4 was potentially causative of the AEs and LOE, and performed the switch back to originator etanercerpt. All 5 patients regained complete remission without further AEs.

The researchers recommend meticulous assessment and documentation before performing the switch so the physician is able to illustrate that episode(s) of flares also had occurred previous to the switch.

Characteristics and Follow-Up of RA Patients Switching from Originators to Biosimilars

In the United Kingdom, patients with RA are actively switched from originator biologics to biosimilars largely for reasons of cost. Since 2015, the British Society for Rheumatology Biologics Registry for Rheumatoid Arthritis (BSRBR-RA) has been documenting real-world data about the efficacy and safety of switches to biosimilar infliximab (Inflectra, Remsima) and etanercept (Benepali) at 6-month intervals for 3 years (and annually thereafter).

Diederik De Cock, PhD, and colleagues report that their limited data suggest a high retention on biosimilars, but a minority of patients had a clinically significant deterioration of health, and some returned to originator drugs before 6 months of biosimilar treatment.²

Through May 2017, 1165 patients became part of the BSRBR-RA registry as they started biosimilar treatment. Over half (59%) switched directly from originator (74% to Benepali, 9% to Inflectra, 17% to Remsima). The most frequent reason cited for the switch was cost. Patients switched from originator after a median time of 5.3 years; the majority had low disease activity.

To date, follow-up data are available in 99 patients, primarily in those receiving infliximab biosimilars. After 6 months:

• 85% of these patients stayed on baseline biosimilar
• 7% switched between infliximab biosimilars
• 3% stopped treatment with a biosimilar
• 1% switched to a biologic other than the originator

Reasons for switching back to the originator were inefficacy (n = 3) and AEs (n = 2). Two reasons were missing. A deterioration in DAS28 of more than 1.2 after 6 months was experienced by 17% of patients. Only 1 serious AE was reported (in a Remsima patient). The BSRBR-RA registry will continue to collect data and issue updated reports.

Open-Label, Non-mandatory Transitioning from Originator Etanercept to Biosimilar

An open label, non-mandatory transitioning of RA patients from originator etanercept to biosimilar etanercept (SB4) showed a statistically significant but clinically nonrelevant lower retention rate compared with a historical cohort, similar to retention rates seen after mandatory infliximab transitioning, according to L. Tweehuysen and colleagues in The Netherlands.³ “Non-mandatory transitioning, when executed optimally, might therefore be an attractive alternative to mandatory transitioning,” the researchers conclude.

In 2016, 642 patients taking reference etanercept were asked to transition to SB4 using a structured implementation strategy with an opt-out option. The transition cohort of consenting patients (n = 635; 433 with RA, 238 with psoriatic arthritis [PsA], 64 with AS) was compared with a historical cohort of patients treated with reference etanercept as to 6-month retention rates.

Crude 6-month retention rates of SB4 in the transition cohort and reference etanercept in the historical cohort were 90% (95% confidence interval [CI], 88% to 93%) versus 92% (95% CI, 90% to 94%). The transition cohort had a significantly higher relative risk of discontinuation than the historical cohort. Reasons for discontinuing SB4 (10%) versus reference etanercept (8%) were LOE (43% verus 61%), AEs (47% versus 28%), malignancy (3% verus 4%), pregnancy (4% versus 4%), and other (3% versus 3%).

In the transition cohort, 17 patients restarted reference etanercept, 32 switched to another biologic, and 11 were maintained biologic-free.

Communication Strategies Around Non-Medical Switching Are Key

Introducing a non-medical switch from an originator biologic to a biosimilar product in the management of patients with rheumatic diseases may generate economic advantages, but it may also jeopardize patient engagement and empowerment, according to Tanja Schjodt Jorgensen, MSc, and colleagues, who suggest that communication strategies play an important role when introducing a biosimilar to patients.⁴

Their study involved 10 patients with RA, 5 with spondyloarthritis (SpA), and 1 with AS, as well as 2 physicians, 2 nurses, 1 medical secretary, and 4 key public stakeholders involved in disease management. A series of workshops resulted in 5 newly proposed personalized communication strategies. It was concluded that implementing a non-medical biological switch involves both dialogue and clear communication in relation to logistic and background information, and communication must be well prepared and allow sufficient time for providing all involved with an opportunity to discuss relevant educational materials.

Health economic analyses estimated that the annual savings from switching to biosimilars are approximately DKK 8900 to DKK 64,600 per patient (approximately $1384 to $8678). “The cost of implementing switching is very limited and savings incurred by the significantly lower prices of biosimilar compared to originator makes the switch instantly economically viable,” the researchers concluded.

References

1. Hendricks O, Horslev-Petersen K. When etanercept switch fails—clinical considerations. Presented at the American College of Rheumatology 2017 meeting, November 7, 2017; San Diego, California. Abstract 2484. http://acrabstracts.org/abstract/when-etanercept-switch-fails-clinical-considerations/.

2. De Cock D, Kearsley-Fleet L, Watson K. Switching from RA originator to biosimilar in routine clinical care: early data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Presented at the American College of Rheumatology 2017 meeting, November 7, 2017; San Diego, California. Abstract 2439. http://acrabstracts.org/abstract/switching-from-ra-originator-to-biosimilar-in-routine-clinical-care-early-data-from-the-british-society-for-rheumatology-biologics-register-for-rheumatoid-arthritis/.

3. Tweehuysen L, Huiskes VJB, Van den Bemt BJF, et al. Presented at the American College of Rheumatology 2017 meeting, November 7, 2017; San Diego, California. Abstract 2438. http://acrabstracts.org/abstract/open-label-transitioning-from-originator-etanercept-to-biosimilar-sb4-compared-to-continuing-treatment-with-originator-etanercept-in-a-historical-cohort-in-rheumatic-diseases-in-daily-practice/.

4. Jorgensen TS, Skougaard M, Asmussen HC, et al. Communication strategies are highly important to avoid nocebo effect when performing non-medical switch from originator product to biosimilar product: Danish results from applying the parker model—a qualitative 3-step research model. Presented at the American College of Rheumatology 2017 meeting, November 7, 2017; San Diego, California. Abstract 2260. http://acrabstracts.org/abstract/communication-strategies-are-highly-important-to-avoid-nocebo-effect-when-performing-non-medical-switch-from-originator-product-to-biosimilar-product-danish-results-from-applying-the-parker-model-a-q/.