Persistence After Switching From Adalimumab Biosimilar MSB11022 to Adalimumab Biosimilar GP2017 in Patients With Chronic Inflammatory Rheumatic Diseases

Abstract

Objective: Provide real-world data on switching from adalimumab biosimilar MSB11022 to GP2017 related to persistence, adherence, and safety in adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). Methods: Retrospective cohort study that used registries and medical records from a single hospital (June 2022 to April 2024). Adult patients with RA, PsA, and axSpA treated with adalimumab biosimilar MSB11022 who switched to biosimilar GP2017 were identified and followed up until April 2024, or disenrollment. Baseline demographic and clinical characteristics studied included sex, age, diagnosis, and previous treatment. Adherence was measured using medication possession ratio (MPR); patients with MPR ≥85% were considered adherent. Persistence, cause of discontinuation, safety, and dosage regimen were collected. Results: A total of 63 patients with chronic inflammatory rheumatic diseases, of whom 36 (57.1%) were women, with an average age of 53.9 years were included. In total, 24 had axSpA, 21 had RA, and 18 had PsA. A total of 58 patients (92.1%) were biologic-naïve, and 27 (42.3%) received methotrexate. A total of 63 patients switched from adalimumab biosimilar MSB11022 to GP2017. After 12 months, 53 (84.1%) continued; 9 (14.3%) discontinued due to lack of effectiveness, side effects, or change of health department. The total persistence of patients who switched from MSB11022 to GP2017 was 12.4 ± 3.1 months. Non-naïve patients had a persistence of 13.7 ± 0.5 months, and naïve patients had 9.5 ± 3.0 months, with no significant differences. The retention rate at 12 months was 84%, with an adherence rate of 88.2%. Conclusions: Switching from adalimumab biosimilar MSB11022 to biosimilar GP2017 in patients with chronic inflammatory rheumatic diseases did not lead to signs of safety or loss of efficacy over 12 months other than those already known in the literature for the class of drugs.

Introduction

Biological therapies have revolutionized the treatment of immunological diseases, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). These therapies demonstrably improve patient outcomes and quality of life. However, their high cost remains a significant barrier to access. The expiration of patents on originator biological products facilitates the development and market entry of biosimilars. Biosimilars are highly similar alternatives that demonstrate comparable quality, safety, and efficacy to the reference product. ¹ Biosimilars reduce health care costs by introducing market competition and require less extensive and costly clinical trials compared with their originators, leading to lower development and manufacturing costs. ²

The European Medicines Agency (EMA) and the European Heads of Medicines Agencies (HMA) have issued a joint position statement supporting the safety and efficacy of switching to and between biosimilar medicines in the European Union. ³

The patent expiration of adalimumab was in 2018. It led to the introduction of multiple biosimilar alternatives while evidence supports the safety and efficacy of switching from originator adalimumab (Humira) to approved biosimilars. ⁴ Data on the outcomes of multiple switching among biosimilars remain limited. As access to cost-competitive biosimilars expands, evaluating the outcomes of multiple switches becomes crucial to establish data on their interchangeability in patients with immunomediated inflammatory diseases. This information is essential for optimizing treatment strategies and ensuring long-term clinical effectiveness. The aim of our study was to provide real-world data on switching from biosimilar adalimumab to another biosimilar, including multiple switching from original biosimilar related to persistence, adherence, and safety in adult patients with RA, PsA, and axSpA.

Materials and Methods

Retrospective cohort study that used registries and medical records from a single hospital. The study period was from June 17, 2022 (first prescription of adalimumab biosimilar MSB11022) to April 1, 2024 (all patients were on adalimumab biosimilar GP2017 treatment). The following inclusion criteria were used: all adult patients with RA, PsA, and axSpA treated with adalimumab biosimilar MSB11022 who switched to biosimilar GP2017 were identified and followed up until April 2024, or disenrollment. Patients were defined as either multiple switches (adalimumab original → MSB11022 → GP2017) or one switch (MSB11022 → GP2017) and had a medication possession ratio (MPR) ≥85%. The variables collected were sex, age, diagnosis, previous biological treatments, dosing regimen and number of intensifications and deintensifications, start date and the end date of Humira, adalimumab biosimilar MSB11022 and adalimumab biosimilar GP2017, and reason for discontinuation. Major adverse events leading to discontinuation of the drug were documented.

Persistence on adalimumab was calculated based on the dates of initiation and end of treatment of adalimumab original, adalimumab biosimilar MSB11022, and adalimumab biosimilar GP2017. The end-of-treatment date was considered to be the date at which the attending physician decided to discontinue the treatment as reflected in the patient’s medical record. If the patient was still on the treatment, persistence was calculated based on the date that patients were censored at the end of the study period (April 24).

Losses to follow-up, understood as failure by patients to visit their rheumatology doctor or the pharmacist over the course of 1 year, were considered to be censored data in the persistence analysis. ⁵

Data were obtained from the Pharmacy Department’s and validation software (Oncofarm IMF) and the patients’ electronic medical record (Integrador and Abucasis). The statistical analysis was conducted using the SPSS Statistics v23 software. Persistence for biologic treatment was calculated using Kaplan-Meier estimates. The results of categorical variables were described by means of frequencies (%) and compared through Pearson’s chi-square test. The results of the quantitative variables were described using means and standard deviation (SD) in cases where they followed a normal distribution, which was previously determined by Shapiro-Wilk’s normality test, and by means and interquartile ranges (IQRs) in cases where the distribution was not normal.

Adherence was measured using MPR. It estimates the percentage of time a patient has access to their medication. Treatment adherence was obtained from the dispensing records of the Hospital Pharmacy Department. Individualized adalimumab dispensings and correlated dates during the study period were collected using Outpatient Clinic Hospital Pharmacy software DISPENSA (Oncopharm Health Information Technology, Valencia, Spain), which allows dispensing and follow-up of outpatient treatment. The MPR rate was calculated using data from the pharmacy dispensing records corresponding to the overall adalimumab treatment. ⁶

The study was approved by the hospital’s Clinical Research Ethics Committee and was conducted according to the principles of the Declaration of Helsinki.

Results

A total of 63 patients diagnosed with chronic inflammatory rheumatic diseases were included, of whom 36 (57.1%) were women. The average age at diagnosis was 53.9 years and the study included 24 patients with axSpA, 21 patients with RA, and 18 patients with PsA (Table 1). A total of 58 patients (92.1%) were biologic-naïve, and in 5 patients (7.9%) adalimumab was the second biologic treatment used. In addition, 42.3% (27 patients) received methotrexate as concomitant treatment for symptom control. All patients had an MPR ≥85%, thus were considered adherent.

Table 1.

Patient Demographics and Outcomes of Patients Included in the Study.

	Idacio—Hyrimoz
N patients	N = 63
Age	53.9 years
Sex	36 women (57.1%) 27 men (42.9%)
Naïve	Yes 58 (82.1%) No 5 (17.9%)
Diagnostic	21 axSpA 21 RA 18 PsA
Withdrawal (at 12 months)	N = 9 (14.3%)
Reason for discontinuation	5 (7.9%) Lack efficacy 2 (3.2%) Adverse effects 2 (3.2%) Loss of follow-up

Abbreviations: axSpA, axial spondyloarthritis; PsA, psoriatic arthritis; RA, rheumatoid arthritis,

All patients switched from adalimumab biosimilar MSB11022 to adalimumab biosimilar GP2017, and 28 patients (44.4%) underwent multiple switches (original adalimumab → MSB11022 → GP2017). After 12 months, 53 patients (84.1%) continued with adalimumab biosimilar GP2017. Nine (14.3%) patients discontinued adalimumab biosimilar GP2017 due to the following reasons: lack of effectiveness (5 patients, 7.9%), side effects (2 patients, 3.2%), and change of health department (2 patients, 3.2%). The retention rate at 12 months after switching was 84% and the mean adherence was 88.2% ± 3.1%.

Regarding dose modifications, there were no treatment intensifications either by increasing the dose or decreasing the interval between administrations. No deintensifications were performed after the switching.

The total persistence of all patients included in the study who switched from MSB11022 to GP2017 was 12.4 ± 3.1 months as represented in Figure 1. In a subgroup analysis based on whether patients were pretreated with adalimumab original before switching to biosimilar adalimumab, the group pretreated with original adalimumab had a persistence of 12.0 ± 0.4 months. In contrast, patients who directly received the biosimilar adalimumab had a persistence of 14.0 ± 0.7 months. No significant differences were found between the 2 subgroups (P = 0.072), as shown in Figure 2.

Figure 1.

Patient persistence in months of study population.

Figure 2.

Analysis of persistence depending on whether they were pretreated or not with adalimumab original after switching.

When performing a subgroup analysis after switching from original adalimumab, non-naïve patients obtained persistence of 13.7 ± [0.5] months (minimum 12.7 months and maximum 14.8 months) followed by 9.5 ± [3.0] months (minimum 3.7 months and maximum 15.3 months) for naïve patients, without finding statistically significant differences (P = 0.065), as represented in Figure 3.

Figure 3.

Analysis of persistence depending on whether they were naïve to biological treatment after switching.

Discussion

Adalimumab biosimilars are a valuable option for adult patients with RA, PsA, and axSpA based on clinical equivalence that are less expensive than the original drug. ⁷ There are several reasons for biosimilar-to-biosimilar transitions. These include availability, cost, and preference. These transitions offer benefits such as maintaining treatment efficacy and potentially reducing costs, compared to reverting to a more expensive reference biologic. The clinical judgments and availability of different biosimilars are the key factors determining the frequency of such switches. ⁸ Persistence is the length of time between initiation and the last dose, which immediately precedes discontinuation, that is, a definitive suspension of the treatment. After discontinuation, there may be a period of non-persistence until the end of the prescribing period. ⁹ Treatment persistence is an important factor when treating with biologicals RA, PsA, and axSpA and, in the absence of a direct measure, may serve as a surrogate composite marker of effectiveness, adherence, safety, and treatment satisfaction. ¹⁰

To our knowledge, this is the first real-world study evaluating persistence, cause of discontinuation, and treatment patterns of switching from biosimilar adalimumab to another biosimilar among patients with RA, PsA, and axSpA. No significant differences exist regarding persistence, retention, and number of intensifications and deintensifications between patients received switching. Our findings showed there were no substantial differences in treatment persistence and switching patterns across all 3 rheumatologic disease indications. The persistence of patients who switched from MSB11022 to GP2017 was generally high, with an overall persistence of 12.4 ± 3.1 months. Subgroup analysis revealed no significant differences in persistence between patients who were pretreated with original adalimumab previously compared with those who directly received the biosimilar adalimumab. In addition, non-naïve patients had slightly longer persistence than naïve patients, but this difference was not statistically significant.

These real-world data could support that the practice of biosimilar-to-biosimilar switching is as safe and effective as being treated solely with either a reference biologic or a single biosimilar, or the switch from a reference biologic to its biosimilar in chronic inflammatory rheumatic diseases. To date, there is limited literature available on patients who have undergone switching between multiple adalimumab biosimilars. One study was conducted on this modality of change with infliximab, as demonstrated in the PERFUSE study, where no safety differences were observed between both groups. ¹¹ A retrospective observational study of 104 patients evaluate persistence, safety, efficacy, and biomarker changes in patients with inflammatory bowel disease treated with adalimumab biosimilars compared with the reference drug. After 12 months, no differences were observed in mild adverse events across groups, but the switched group had a higher rate of severe events. Biomarker reductions and clinical response rates were similar across all groups. ²

Gall et al investigated patients with chronic inflammatory rheumatic diseases undergoing a switch from adalimumab bsDMARD GP2017 to MSB 11022. A total of 102 patients were enrolled; disease activity and function remained stable after switching. No significant differences in patient satisfaction, disease activity, or safety were observed based on provider type or switching frequency. ¹² In total, 41 RA, 52 PsA, and 34 axSpA patients underwent a 2-step biosimilar switch. First, they switched from the reference adalimumab to the adalimumab biosimilar ABP501. Then, 1 year later, they switched from ABP501 to another adalimumab biosimilar, SB5. Disease activity remained stable throughout the 3-year study period. The authors concluded that switching from reference adalimumab to either ABP501 or SB5 did not affect treatment efficacy. ¹³

This study presents with a series of limitations. First of all, as it was a real-world study, treatments were not assigned through a randomization process. No pharmacokinetic monitoring was carried out in the analyzed cohorts to adjust the adalimumab original or the adalimumab MSB11022 and the adalimumab GP2017; only neutralizing antibodies were quantified. Finally, given that the findings presented in this study pertain to a single hospital, it is the authors’ intention to extend the research to other centers in order to confirm the results obtained.

One of the strengths of this study is that the patients included were considered adherent to adalimumab based on the MPR data presented. MPR is a measure of medication adherence that tracks the proportion of a patient’s medication that is dispensed over a given period. A high MPR indicates that a patient is consistently refilling their prescriptions and is therefore likely to be taking their medication as prescribed. This makes the persistence findings of the study more generalizable and reliable to real-world clinical practice. ¹⁴

The results obtained advances the state of the art in the realm of switching biosimilar-based biologic/biosimilar therapy and its use in the treatment of chronic inflammatory rheumatic diseases. One limitation of this study is the relatively short follow-up period, which extends only until April 2024. This restricted time frame may limit the ability to provide a definitive assessment of long-term outcomes, potentially affecting the value of conclusions regarding sustained efficacy and safety. As of April 2024, we censored 53 patients who were still receiving adalimumab GP2017. We plan to evaluate the persistence of these patients in future studies with more long-term follow-up period. A larger number of multicenter studies is needed to confirm the findings obtained here and to gain a better understanding of the factors that may affect the persistence and the retention after switching biosimilar-based biologic/biosimilar therapy in patients with RA, PsA, and axSpA.

Conclusions

This real-world study suggests that switching (including multiple switches) from adalimumab biosimilar MSB11022 to adalimumab biosimilar GP2017 in patients with chronic inflammatory rheumatic diseases did not lead to signs of safety or loss of efficacy over 12 months other than those already known in the literature for the class of drugs. Multiple switches did not negatively affect persistence or clinical outcomes. Multicenter, large-scale studies with longer follow-up periods are needed to gather more robust data on the persistence, efficacy, and safety of this practice.