Biosimilars: Patient Factors Count
By Nancy Walsh, MedPage, 11.07.2018
Outcomes were mixed among patients with inflammatory arthritis who switched to the biosimilar SB4 from etanercept (Enbrel), a nationwide real-world study in Denmark found.
Among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA), disease activity was stable during the 3 months before and after switching, according to Bente Glintborg, MD, PhD, of Gentofte and Herlev University Hospital, and colleagues.
However, treatment retention rates at 1 year were 83% among switchers and 77% among those who did not switch to the biosimilar, but 90% in a historic cohort, the researchers reported online in Annals of the Rheumatic Diseases.
When SB4 was approved in Europe in 2015, it had been tested only in patients with RA, but it is also being used for PsA and axSpA. "This is theoretically of importance since age, genetics, co-medication with conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and drug dose differ across diseases and may affect immunogenicity, pharmacokinetics, and dynamics," Glintborg and co-authors wrote.
In addition, patients in the randomized trials required to demonstrate equivalence for biosimilars tend to be more homogeneous than those treated in real-world practice.
In April 2016 a national guideline was issued in Denmark mandating that all patients with inflammatory arthritis being treated with etanercept switch to SB4, which cost almost 50% less. However, the originator etanercept remained available.
To examine outcomes in a broad population of patients who switched or did not, and to identify the reasons for withdrawal, the researchers analyzed data from DANBIO, a nationwide registry for patients with rheumatic diseases being treated with biologics. The team identified 2,061 etanercept-treated patients, and also included a historic cohort of 2,363 patients in DANBIO who received etanercept before the biosimilar was available.
Despite the guideline's stipulation that switching was mandatory, only 79% of patients agreed to the change.
Among patients with RA and PsA who switched, more were on concomitant methotrexate, the time on etanercept treatment was longer, and they had less exposure to other biologics. Switchers also typically had lower disease activity scores. Changes were minimal on disease activity scores from 3 months before the switch to 3 months after. For patients with RA, median Disease Activity Score in 28 joints (DAS28) was 1.9 at 3 months prior to the switch and 2.1 at 3 months after, while for patients with PsA, DAS28 scores were 1.8 and 2.1, respectively. For patients with axSpA, the Bath Ankylosing Spondylitis Disease Activity Index was 33 at 3 months before the switch and 31 at 3 months after.
C-reactive protein (CRP) levels at the two time points were unchanged in all patients, at 3 mg/L for those with RA and axSpA and 2 mg/L for those with PsA.
During a median follow-up of 401 days, 18% of patients who had switched and 33% of non-switchers withdrew from therapy, most commonly for a lack of efficacy (46% of switchers and 34% of non-switchers). Withdrawal was more common among patients who were not in remission at the time of the change for both switchers (HR 1.7, 95% CI 1.3-2.2) and non-switchers (HR 2.4, 95% CI 1.7-3.6, P<0.01 for both).
Among the switchers who withdrew from treatment with SB4, 104 began treatment with a different biologic agent, and 120 went back to etanercept. At the time of switching back to etanercept, only subjective patient ratings such as patient global scores showed any change; objective measures such as swollen joint counts and CRP levels remained close to zero.
During follow-up, there were more adverse events in the group who switched (26 versus 10), but the non-switchers had more cases of cancer (eight versus two) and infection (six versus one) and more deaths (10 versus three). No new safety signals were seen. The observation that withdrawal most often was seen among patients not in remission and that changes were seen primarily on subjective outcomes suggests "that patient-related factors ... rather than drug (originator or biosimilar) were important for the decision to withdraw treatment," the researchers noted. The finding that more patients had serious comorbidities such as malignancy and infection also supports the explanation that patient-related factors were important in the decision not to switch.
Awareness and understanding of biosimilars remains minimal in the general population, as well as in patients with chronic diseases, which may have contributed to individual patients' unwillingness to switch. Moreover, "the nocebo effect (i.e., negative expectations towards a given treatment), patient-related factors, and subjective health experiences may have influenced the perception of treatment outcomes and adverse events," Glintborg and colleagues wrote.
A limitation of the study, they said, was its observational design. The study was funded by Biogen.
The authors reported financial relationships with Biogen, AbbVie, Pfizer, Merck Sharp & Dohme, Orion, Bristol-Myers Squibb, Celltrion, Roche, Novartis, UCB, and Medac.