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Higher Risk of Discontinuation During Biosimilar Switching Found Among Women


Switching from reference to biosimilar adalimumab was found to be safe and effective. Researchers cautioned that female patients may be at higher risk of discontinuation compared with their male counterparts.

With the exemption of female sex in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and Crohn disease (CD), none of the candidate predictors were linked with SB5 discontinuation, according to BioDrugs.

Persistence on SB5 was high, treatment effectiveness was sustained, and no safety signals were identified.

Although transitioning from reference adalimumab (Humira) to SB5 had formerly been analyzed previously, the researchers said that long-term, real-world evidence in representative populations was required.

First, the non-interventional PROPER study produced real-world evidence on patient-reported outcome measures (PROM) after transition in routine practice from reference adalimumab to the EMA-approved SB5 biosimilar adalimumab (Hadlima) in patients with immune-mediated inflammatory disease (IMID).

Biologic disease-modifying anti-rheumatic drugs (DMARDS) as therapy options for patients with IMIDs has proven vital. However, accessibility to DMARDs can be limited. Biosimilars can be cost-effective alternatives that might mitigate some of those restrictions.

Adults with RA, axSpA, psoriatic arthritis (PsA), CD, or ulcerative colitis (UC) across Europe at 63 siteswere enrolled in the study. Eligible patients received at least 16 weeks of routine treatment with reference adalimumab before switching to SB5, and were monitored for 48 weeks after the transition. The primary objective was to analyze candidate predictors (clinically relevant baseline variables with incidence ≥ 15% by indication cohort) linked with persistence on SB5 at 48 weeks after initiation. Key primary outcome measures were persistence on SB5 (estimated by Kaplan-Meier methodology) and clinical characteristics and disease activity scores at the time of switch to SB5 treatment (baseline).

A total of 955 eligible patients were enrolled (RA, n = 207; axSpA, n = 127; PsA, n = 162; CD, n = 447; UC, n = 12), 932 of whom (97.65) finished follow-up and 722 (75.6%) were still taking SB5 at week 48. Kaplan–Meier predictions of persistence on SB5 at week 48 for RA, axSpA, PsA, and CD were 0.86 (0.80-0.90), 0.80 (0.71-0.86), 0.81 (0.74–0.86), and 0.72 (0.67-0.76), respectively. The single candidate predictor linked with probability of SB5 discontinuation before week 48 was female sex (RA: HR, 3.53; 95% CI, 1.07-11.67; axSpA: HR, 2.38; 95% CI, 1.11-5.14; CD: HR, 2.21; 96% CI, 1.54-3.18).

Disease activity scores stayed largely unchanged throughout the study, with proportions by cohort in remission at baseline versus week 48 being 58.2% vs 57.2%, 81.0% vs 78.0%, 94.7% vs 93.7%, and 84.0% vs 85.1% for patients with RA, axSpA, PsA, and CD, respectively. Comparably, the SB5 dosing regimen stayed unchanged for most patients from baseline to week 48, the most common regimen being 40 mg every 2 weeks.

Notably, only female sex was linked with increased risk for SB5 discontinuation in the RA, axSpA, and CD cohorts of the candidate estimates of persistence. These findings were comparable with previous data.

“Most patients in each cohort were in remission or had stable disease at transition, and showed no meaningful differences in disease activity measures over time post-transition (3–12 month follow-up),” said the study authors.

In terms of safety, no new safety signals were identified in this study, and AEs were generally consistent with those previously reported in patients with rheumatic or gastroenterologic IMIDs treated with SB5.

Of note, the possible impact of a “nocebo effect” should also be considered. Efforts to mitigate this, like communication and training, may help informed decision-making in patients who are considering switching from a reference drug to a biosimilar.

Additionally, the researchers said that special consideration should be given to female patients who are considering switching, since they seem to be more vulnerable to discontinuation than their male counterparts.

“There were no meaningful differences in disease activity or PROM scores between baseline and week 48 post-transition (most patients in each cohort remained in remission or had stable disease), and no new safety signals were observed. These findings suggest that in the context of treatment persistence and within the baseline categories observed, there was no evidence to mitigate against transition,” concluded the researchers.


Müller-Ladner U, Dignass A, Gaffney K, et al. The PROPER study: A 48-week, pan-european, real-world study of biosimilar SB5 following transition from reference adalimumab in patients with immune-mediated inflammatory disease. BioDrugs. Published online August 26, 2023. doi:10.1007/s40259-023-00616-3

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