Background/Purpose:

On January 14th 2016 EMA approved the biosimilar Etanercept (SB4, Benepali) for clinical use. A non-medical switch from originator Etanercept (ETA, Enbrel) to SB4 was conducted in all Danish outpatient clinics in 2016. Disease activity was largely unaffected in the majority of patients; however 9 patients stopped treatment during the follow-up. There is limited outcome data in switch failures.

Methods:

At King Christian X’s Hospital for Rheumatic Diseases, a non-medical switch from ETA to SB4 was carried out in June 2016. Clinical assessment was performed at baseline, after 4 and 8 month. We recorded clinical outcome measurements according to the Danish DANBIO registry for RA and AS. In case of a lack of effect (LOE) and/or adversive events (AE) during the first 4 month after switch, we altered the biologic treatment based on the following objectives:

A. The clinical situation on Enbrel was stable, but Flare (ASDAS >2.1 or DAS28CRP > 3.2) observed at least once during a 24 month period before switch.

B. The clinical situation on Enbrel was characterized by complete remission (ASDAS rate < 1.2 or DAS28CRP < 2.6) for at least 24 months.

Results: We registrated unchanged efficacy after switch in 76 out of 85 cases. In nine cases we recorded significant LOE and/or AE during the first 4 month after switch. Four of the nine cases matched scenario A. The treatment with Benepali continued in two of those cases. In the other two cases a change to a third biologic treatment was performed due to prolonged disease activity. Five cases matched scenario B (One case of AE, three cases of LOE and one case of combined AE & LOE).The patients had experienced complete remission at least for 2 (and up to 9) years. In these cases we interpreted Benepali to be potentially causative and performed the switch back to Enbrel. All five patients regained complete remission without further adversive events.

Conclusion:

No studies exist, that investigate the outcome of Etanercept switch on an individual level. In our study, 89% of the patients experienced the non-medical switch to Benepali as the uncomplicated continuation of a successful treatment. For the last 11 % the situation was different. From the patient’s perspective, it is obvious that experienced AE’s and/ or LOE’s are suspicious to be a consequence of the switch. A meticulous assessment and documentation before performing the switch is crucial. It is our experience that a prolonged SB4 treatment was adequate in those cases, where the doctor was able to illustrate that episode(s) of Flares also previously had occurred.

In contrast, complete remission before switch followed by significant LOE’s or AE’s after switch, led to considerations about the structural differences of the compounds. Furthermore, it has to be taken into account, that the patient’s willingness to continue with Benepali is limited in this situation.

Explaining the patient that “the same current comes out of the socket, even though the new factory creates the electricity” keeps true in almost 90 % of the cases, but switch failure is a challenge. We switched back to Enbrel in five cases of significant contrast of clinical outcome before and after switch. The Switch back was successful in these cases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/when-etanercept-switch-fails-clinical-considerations/