FormalPara Key Summary Points

Why carry out this study?

ABP 501 (Amgevita®) was the first European Medicines Agency (EMA)- and US Food and Drug Administration (US FDA)-approved biosimilar to the adalimumab reference product (Humira®).

Comparative clinical trials have demonstrated biosimilarity between ABP 501 and the reference product regarding efficacy, safety, and immunogenicity in patients with rheumatoid arthritis and in patients with psoriasis, while indications of Crohn’s disease and ulcerative colitis were approved for ABP 501 on the basis of the principle of extrapolation.

In the absence of comparative clinical trial data, we sought to describe the real-world use of ABP 501 in patients with inflammatory bowel disease (IBD), to provide additional useful information to healthcare providers and patients.

What was learned from the study?

This real-world study showed that patients with IBD and their treating physicians both reported high levels of satisfaction with ABP 501 treatment, regardless of their prior exposure to adalimumab reference product.

Patient self-assessment data suggested minimally impaired health-related quality of life for both ABP 501 initiators and switchers from the reference product.

Introduction

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC), which are both chronic inflammatory disorders of the gastrointestinal tract [1]. The prevalence of IBD has continued to increase globally and is estimated to be 4–6 times higher in 2030 when compared with 2003, with an average annual percent increase of 5% [2, 3]. This rapidly increasing prevalence will pose a substantial economic burden on healthcare systems.

Common symptoms of IBD may include abdominal pain, persistent diarrhea, rectal bleeding, and fatigue. Patients typically experience periods of relapse and remission [4] which can be debilitating and significantly impair health-related quality of life (HRQoL) and work productivity [5, 6]. Clinical management for mild-to-moderate disease begins usually with aminosalicylates (for UC), corticosteroids, and thiopurines; however, those conventional treatments are reported to be ineffective in 20–40% of patients with CD or UC [7,8,9]. Anti-tumor necrosis factor (TNF) biologics, such as infliximab and adalimumab, have been established as the advanced therapy (AT) for patients with moderate-to-severe CD or UC who do not respond, lose response, or are intolerant to conventional therapies [10,11,12,13]. Anti-TNF biologic therapies have significantly improved HRQoL and reduced the need for hospitalization and surgery for patients with IBD, but barriers to utilization remain and may prevent optimum patient management [9, 14].

Biosimilars are biotherapeutic products that are similar to a previously licensed reference product (RP, also known as “originator”) in terms of quality, safety, and efficacy [15], and have the potential to lower healthcare costs and expand patient access to biological medicines [16]. Approval of a biosimilar requires a rigorous assessment of analytic structure and function, toxicity in nonclinical studies, and clinical pharmacology (e.g., pharmacokinetics and pharmacodynamics studies), as well as comparative clinical trial(s) in the most sensitive patient population(s) to evaluate clinical similarity in terms of safety, efficacy, and immunogenicity [17]. Approval for an indication can be granted on the principle of extrapolation without conducting an indication-specific comparative clinical trial if sufficient scientific justification can be provided based on the available knowledge of the RP and the totality of evidence generated during development of the proposed biosimilar [17, 18].

ABP 501 (Amgevita®; Amgen Inc., Thousand Oaks, CA, USA) was the first adalimumab biosimilar approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and was first marketed in Europe in October 2018 [19]. ABP 501 was shown to be comparable to its RP (Humira®; AbbVie Inc., North Chicago, IL, USA) in patients with plaque psoriasis [20, 21] and patients with rheumatoid arthritis [22] in terms of clinical efficacy, safety, and immunogenicity. Despite the stringent approval process, acceptance of biosimilars encountered some initial resistance, particularly for indications approved on the basis of extrapolation such as CD and UC [23]. Over the past years, there has been a significant change in the confidence of biosimilar use among IBD specialists in Europe, potentially driven by the increased knowledge of the rigorous approval pathway for biosimilars and supportive post-marketing real-world evidence (mainly for infliximab biosimilars) from clinical practices [24, 25]. However, a recently published survey among US gastroenterology advanced practice providers (e.g., physician assistants, nurse practitioners) showed that only 16% of responders were completely not concerned about the effectiveness of biosimilars, and over 60% reported not being comfortable switching patients to a biosimilar [26]. Therefore, continuous provision of real-world evidence of biosimilar use among patients with IBD is still of need. Real-world evidence from European markets can provide useful information upon adalimumab biosimilars entering the US market, especially for indications approved on the basis of extrapolation. In this current study, we evaluated the real-world experience of ABP 501 use in patients with CD or UC in five major European countries from both physicians’ and patients’ perspectives with regard to patient clinical status, treatment satisfaction, and HRQoL.

Methods

Data Source

Data were derived from the Adelphi IBD Disease Specific Programme™ (DSP), a point-in-time survey of gastroenterologists and their consulting patients in France, Germany, Italy, Spain, and the UK, conducted between September 2020 and June 2021. This DSP methodology has been described in detail and validated elsewhere [27,28,29].

Participating physicians were required to be personally responsible for and actively involved in treatment decisions and management of patients with CD and UC and have a clinic workload of more than five patients with CD and more than five patients with UC in a typical month. To be eligible for inclusion, patients were required to be at least 18 years of age, had a physician-confirmed diagnosis of CD or UC, and were not participating in a clinical trial at the time of consultation. Participating physicians were asked to complete a patient record form for the next five to eight consecutive patients with CD and the next five to seven consecutive patients with UC attending a consultation regardless of treatment. In addition to these consecutively sampled patients, an additional set of patients who were receiving ABP 501 (the over-sample) were deliberately recruited to ensure sufficient number of patients treated with ABP 501 were available for analysis. Each participating physician was invited to complete patient record forms for up to five additional patients receiving ABP 501 in the over-sample. Aside from the criteria pertaining to ABP 501 treatment for the over-sample, both consecutively sampled patients and the over-sampled patients had to fulfil the same inclusion criteria.

Data were reported by physicians through abstraction of patient clinical records, supplemented by physician’s perspective regarding patient clinical status and reasons for switch of regimens, according to their expertise, knowledge of the patient, and clinical judgement, consistent with decisions made in routine clinical practice. In addition, all patients for whom record forms were completed by physicians were asked to complete patient self-assessment questionnaires in order to collect data on HRQoL and the level of satisfaction with treatment. Completion of the self-assessment questionnaires was voluntary for patients and in cases where the patient decided not to participate, physician-reported patient record forms relating to those patients were still included in the dataset.

Patients provided informed consent for use of their anonymized and aggregated data for research and publication in scientific journals, and all data used in this study were deidentified. The original data collection methodology and questionnaires were reviewed and approved by the Western Institutional Review Board (protocol number 20200423) and were performed in accordance with the principles stated in the Declaration of Helsinki.

Study Population

Two ABP 501 treatment cohorts were drawn from the DSP sample (criteria described above), comprising patients who were receiving ABP 501 as the first-line AT at the time of consultation (“ABP 501 initiators”) and patients who were receiving ABP 501 following a direct switch from first-line AT with the adalimumab RP treatment (“RP-ABP 501 switchers”). Direct switch was defined as transitioning from the RP-containing treatment regimen to treatment regimen containing ABP 501 within 90 days of the end of the RP-containing treatment regimen with no other AT in between. In addition, a separate cohort of patients who were receiving adalimumab RP as the first-line AT (“RP initiators”) was also drawn from the DSP sample as a reference cohort.

Outcome Measures

Physician-Reported Assessment

Through completion of patient record forms, physicians provided detailed patient-level data, including patient demographics (age, sex, and ethnic origin), and date of IBD diagnosis. In addition to reporting the treatment received at the time of consultation, physicians provided the full treatment history for each patient, including the start and end dates of each treatment regimen, allowing for duration of ongoing and previous treatment regimens to be calculated. Patient clinical status at time of consultation and at initiation of current adalimumab treatment was captured as physician assessment of disease severity (based on the physician’s own definition of mild, moderate, and severe) and disease progression (categorized by physicians as improving, stable, deteriorating slowly, or deteriorating rapidly). To assess remission status, physicians were asked to select one of five categories which they felt best described the patient’s status at the time of consultation. These five categories were further combined into two categories as follows: (1) “Clinical remission” combining responses “Clinical/symptomatic remission, but full mucosal healing not achieved”, “Clinical/symptomatic remission, but mucosal healing currently unknown”, and “Clinical/symptomatic remission and full mucosal healing (histologic remission)”; (2) “Not in clinical remission” combining responses “Not in remission” and “Full mucosal healing but symptoms remain”. In addition, the Harvey-Bradshaw Index (HBI) at time of consultation was reported for patients with CD [30] and the Mayo score for patients with UC [31]. The HBI is calculated based on well-being, abdominal pain, liquid/soft stools, abdominal mass, and complications, where a score < 5 indicates remission, 5–7 indicates mild activity, 8–16 indicates moderate activity, and > 16 indicates severe activity [30]. The Mayo score, which is calculated based on stool frequency, rectal bleeding, endoscopic findings, and physician global assessment, ranges 0–12, with a score of 0–2 indicating remission, 3–5 indicating mild activity, 6–10 indicating moderate activity, and 10–12 indicating severe activity [31]. Physicians also were asked to report their level of satisfaction with the treatment received at time of consultation and select one or more reasons for the treatment/regimen switch (if any) from a predefined list of 26 options (options provided relating to efficacy, safety/tolerability, mode of action, mode of administration, COVID-19, access/cost, patient compliance, and patient request).

Patient-Reported Outcomes

The patient self-assessment questionnaires collected data on patient satisfaction with the treatment received at the time of consultation. HRQoL and daily functioning were also captured using EuroQol-5 Dimension-5 Level (EQ-5D-5L) index [32], the short version of the Inflammatory Bowel Disease Questionnaire (SIBDQ) [33], and the Work Productivity and Activity Impairment (WPAI) questionnaire [34].

The EQ-5D-5L consists of two parts: the EuroQoL visual analogue scale (EQ VAS) score and the EQ-5D-5L descriptive system of five domains. The EQ VAS score, ranging from 0 to 100, is reported as the average numeric rating, with 0 corresponding to the worst imaginable health state and 100 to the best imaginable health state. The EQ-5D-5L descriptive system assessed HRQoL from five domains, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. An overall health utility score was calculated based on these domains, with scores below 0 indicating a health state worse than death, while a score of 1 indicates perfect health [32].

The SIBDQ evaluated HRQoL from four different domains: bowel symptoms, systemic symptoms, social function, and emotional function. The scores of each domain range from 1 to 7, with higher scores indicating better health status. Total scores, ranging from 10 (indicating worst health) to 70 (indicating best health), were also calculated to report overall HRQoL [33].

The WPAI questionnaire measured IBD-related time missed from work and impairment of work and regular activities, with higher scores indicating greater impairment related to the specific WPAI component [34]. WPAI component scores are reported as percentage impairment, whereby 0% is no impairment and 100% is total loss of work productivity or activity.

Statistical Analysis

This study was descriptive in nature. No a priori hypotheses were tested, and no statistical comparisons were conducted between groups. Means and standard deviations (SD) or median and interquartile range (IQR) were reported for continuous variables, and number of patients and percentages were calculated for categorical variables. Missing data were not imputed and were excluded from the analysis. Statistical analysis was performed using Stata v15.0 [35].

Results

Overall, 301 physicians provided medical information for a total of 375 patients who were receiving ABP 501 treatment (n = 195 CD and n = 180 UC) at the time of consultation, from five European countries (n = 119 France, n = 74 Germany, n = 74 Italy, n = 79 Spain, n = 29 UK; Table S1). Of those 375 patients, 239 (63.7%) were receiving ABP 501 as the first-line AT (“ABP 501 initiators”) and 136 (36.3%) were receiving ABP 501 following a direct switch from first-line AT with the adalimumab RP treatment (“RP-ABP 501 switchers”).

ABP 501 Initiators

For the ABP 501 initiators, patient mean age was 36.6 (SD 12.3) years, 59% were male, and the majority (93.3%) were White/Caucasian. Median duration from initial diagnosis of IBD to initiation of ABP 501 was 13.9 months (IQR 1.9, 34.1) and patients had been on ABP 501 treatment for a median of 7.5 months (IQR 4.1, 14.4) at the time of consultation. Approximately 40–50% of patients received conventional therapies prior to initiation of ABP 501, including 5-aminosalicylic acid (44.4%), corticosteroids (50.6%), and immunomodulators (38.9%). At the time of consultation, 61.9% of initiators were receiving ABP 501 as monotherapy, with the remaining 38.1% receiving ABP 501 with conventional therapies (5-aminosalicylic acid, 25.5%; corticosteroids, 7.9%; immunomodulators, 13.4%; Table 1). At the time of consultation, 67.4% of patients were assessed by their treating physicians to have mild disease severity, compared to 0.8% at initiation of ABP 501; and 95.8% were reported to be either improving or had stable disease status at the time of consultation, compared to 16.3% at initiation of ABP 501 (Table 1). About three-quarters of ABP 501 initiators were assessed by physicians to be in clinical remission (Table 1) at the time of consultation. Disease activity as measured by HBI for patients with CD and by Mayo score for patients with UC suggested that 84.7% of patients with CD and 57.4% of patients with UC were in remission (Table S2). Overall, physicians reported being satisfied with ABP 501 therapy for 91.6% of ABP 501 initiators (Table 1).

Table 1 Physician-reported data on demographics, treatment pathways, and clinical assessment of patients who initiated adalimumab product as the first advanced therapy
Full size table

Of the 239 ABP 501 initiators, a subgroup of 90 patients agreed to complete self-assessment questionnaires to report their satisfaction level with treatment and HRQoL. Among these 90 patients, 95.6% reported being satisfied with the ABP 501 treatment regimen (Table 2), including 98% of patients with CD and 92.5% of patients with UC (Table S3). The mean EQ VAS score was 84.0 (SD 9.9), indicating an overall good HRQoL. The five EQ-5D-5L domain utility indices (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) consistently showed minimal impairment of HRQoL based on patients’ self-assessment. Specifically, the majority of patients reported having no impaired mobility (95.5%), no difficulties with self-care (97.7%), no problem performing usual activities (89.8%), no or only slight pain/discomfort (95.4%), and no or only slight anxiety/depression (92.1%; Table 2). Patients’ mean total SIBDQ score was 56.4 (SD 9.5) with all four domains (bowel symptoms, systemic symptoms, emotional and social functions) being scored ≥ 5.5 out of 7. The WPAI showed a mean 17.8% (SD 17.4%) activity impairment. Patients who were working reported 14.4% (SD 14.7%) overall work impairment, 3.3% (SD 10.7%) work time missed, and 11.3% (SD 11.4%) impairment while working, due to their IBD (Table 2).

Table 2 Patient self-reported measures of health-related quality of life for individuals who initiated adalimumab product as the first advanced therapy
Full size table

Reference Product Initiators

Additionally, a cohort of 329 patients who initiated adalimumab RP as the first AT was included in the analysis as a reference cohort (see Table S1 for patient numbers by diagnosis and by country). RP initiators and ABP 501 initiators appeared to have similar patient demographics, treatment pathways, and physician-assessed patient clinical status (Table 1), as well as patient self-assessed HRQoL (Table 2) while on treatment with RP or ABP 501, respectively.

RP-ABP 501 Switchers

For the RP-ABP 501 switchers (n = 136), the median duration between IBD diagnosis and initiation of adalimumab RP as the first AT was 10.0 (IQR 0.7, 30.0) months. Patients had been treated with the RP for a median of 14.0 (IQR 6.2, 28.4) months before switching to ABP 501 and had been treated with ABP 501 for a median of 7.7 (IQR 5.1, 13.7) months at the time of consultation (Table 1). The main reasons for switching from the RP-containing regimen to the treatment regimen containing ABP 501 were reported by physicians as being more cost-effective for the healthcare system or patients and driven by formulary change (Fig. 1).

Fig. 1
figure 1

Physician-reported reasons for switching from RP-containing regimen to ABP 501-containing regimen (listed categories with > 5%). ABP 501 adalimumab biosimilar, RP reference product

Full size image

At the time of consultation, 68.4% of RP-ABP 501 switchers were receiving ABP 501 as monotherapy and 31.6% were receiving ABP 501 with conventional therapies (5-aminosalicylic acid, 20.6%; corticosteroids, 2.9%; immunomodulators, 8.8%). Physicians reported that 83.1% of RP-ABP 501 switchers had mild disease and 98.6% were improving or had stable disease status (Table 3). At the time of consultation, 87.5% of patients with CD and 80.6% of patients with UC were in remission according to the HBI and Mayo scores, respectively (Table S4), providing reasonable alignment with physician assessment that 89.0% of RP-ABP 501 switchers overall were in clinical remission (Table 3). Physicians reported being satisfied with the ABP 501 therapy for 98.5% of RP-ABP 501 switchers (Table 3).

Table 3 Physician-reported data on demographics, treatment pathways, and clinical assessment of patients who switched from adalimumab RP to ABP 501 (RP-ABP 501 switchers)
Full size table

Patient questionnaires were completed by a subgroup of 49 RP-ABP 501 switchers, of which 98% reported being satisfied with the ABP 501 treatment regimen (Table 4). The mean EQ VAS score was 86.4 (SD 10.3), suggesting an overall good HRQoL. The five domain utility indices were generally aligned with the overall EQ-5D-5L score, indicating minimal impairment of HRQoL based on patients’ self-assessment. Patients reported mild burden on the pain/discomfort domain, with 38.3% of switchers reporting having slight pain or discomfort, and 61.7% reporting no pain or discomfort. Other domains were scored unaffected by the majority of patients, including 91.5% who reported having no problems in mobility, 95.7% reported no problems with self-care, 80.9% had no problems doing usual activities, and 78.7% were not anxious or depressed (Table 4). Patients’ mean total SIBDQ score was 58.8 (SD 8.7) with all four domains (bowel symptoms, systemic symptoms, emotional function, and social function) being scored ≥ 5.7 out of 7. The WPAI score showed a mean 16.5% (SD 20.3%) activity impairment, and among patients who were working, 12.7% (SD 19.6%) overall work impairment, 9.3% (SD 27.0%) work time missed, and 11.0% (SD 15.4%) impairment while working, due to their IBD (Table 4).

Table 4 Patient self-reported measures of health-related quality of life for individuals who switched from adalimumab RP to ABP 501 (RP-ABP 501 switchers)
Full size table

Discussion

This study using real-world data abstracted from the Adelphi IBD DSP, a point-in-time physician survey and patient self-assessment, found that both physicians and patients reported high levels of satisfaction with ABP 501 treatment, either as initiating or continuing adalimumab therapy. The majority of patients, including ABP 501 initiators and RP-ABP 501 switchers, were reported by physicians to have achieved clinical remission at the time of consultation, had low concomitant steroid use, and self-reported minimally impaired HRQoL. In addition, there appeared to be no substantial differences between patients initiating adalimumab RP or biosimilar ABP 501 as the first AT in terms of treatment pathways, clinical status, treatment satisfaction, and HRQoL.

ABP 501 is the first EMA- and US FDA-approved adalimumab biosimilar for treating certain immune-mediated chronic inflammatory diseases [19] and has been marketed in European countries since October 2018. Despite a growing acceptance of the use of biosimilars among physicians in Europe, a US survey from 2021 indicated that advanced practice providers were hesitant in switching patients with IBD to a biosimilar [26]. This demonstrates differing experiences and attitudes towards biosimilar use between physicians in Europe and the USA. With the market entry of adalimumab biosimilars in the USA starting in January 2023, continuous communication of real-world evidence on biosimilar use from European countries will be of benefit to the US medical community and, perhaps more importantly to patients, increase confidence in biosimilar prescriptions and use. Research into patient perspectives regarding biosimilar use is limited, with one study demonstrating that patients’ lack of awareness of biosimilars, in addition to concerns about inadequate efficacy and increased safety risks, may result in nocebo effect and limit uptake [36]. In recent years, a few real-world studies, mainly from the Italian population, have assessed the clinical effectiveness and safety of ABP 501 in patients with IBD, demonstrating overall similar safety and effectiveness of ABP 501 to those of the RP, and that switching from originator to ABP 501 was safe and effective [37,38,39,40,41]. In a propensity score-weighted multicenter cohort study [37], patients receiving the RP and patients receiving ABP 501 were observed to have similar rates of clinical response after 6 months of therapy (39.6% and 31.8%, respectively), with similar rates of steroid-free clinical remission achieved (49.1% and 54.5%, respectively) [37]. In other studies, patients receiving ABP 501 were shown to have high retention rates (> 90%) [38], with good rates of clinical response (60–86%) [38, 39], clinical remission (56%) [38], and steroid-free remission (75.3%) [39] at 3 months. Moreover, no significant difference in clinical activity was observed between patients who switched to ABP 501 from the RP compared with those continuously receiving the RP [40, 41].

In our current analysis, the study population comprised a robust sample of patients with CD or UC from five major European countries, who were consulting with physicians from different centers across those countries. In line with findings from previously published studies discussed above, we observed comparable treatment pathways, patient clinical status, and treatment satisfaction assessed by physicians between adalimumab RP initiators and ABP 501 initiators in the real-world setting. Both the majority of RP initiators as well as ABP 501 initiators were reported by their treating physicians to have mild disease and have achieved clinical remission while on their respective adalimumab treatment. We also observed that, among patients switched from RP to ABP 501, both physicians and patients were satisfied with the treatment with ABP 501 post-switch, and almost 90% were assessed by their physician to be in clinical remission. Our study also explored data relating to the real-world experience of ABP 501 use from the patient’s perspective, as such data are currently limited. Although only a small subgroup of patients participated and completed the self-assessment questionnaires, those patient-reported outcome measures, including EQ VAS, EQ-5D-5L, SIBDQ, and WPAI assessment, demonstrated an overall good HRQoL and minimal impairment of usual functions and activities for both ABP 501 initiators and RP to ABP 501 switchers.

Our study has several limitations. First, the patient sample included in our study was not entirely representative of the practicing population of gastroenterologists (the participating physicians in the IBD DSP were skewed towards those with a higher workload as a result of the inclusion criteria) and infrequently consulting patients may be underrepresented as a result of the sampling approach. In addition, data collection was point-in-time via physician- and patient-completed questionnaires, meaning the quality of the data is largely dependent on the accurate reporting by participants. Participating physicians in the IBD DSP were trained before completing the patient record forms and required to provide the most accurate reporting of patient data by referring to the electronic medical records of patients to minimize potential recall bias. Since the patient-completed questionnaire was voluntary, patient-reported outcomes have a low response rate and are subject to nonresponse bias. Lastly, as this study utilizes point-in-time data, we were only able to assess patients who were on ABP 501 therapy at the time of consultation by referring to data retrospectively, and patients who discontinued therapy were not included in this analysis and not able to be evaluated regarding long-term effectiveness, safety, and treatment patterns.

Conclusion

This study of patients with IBD initiating biologic therapy with biosimilar ABP 501, switching from the RP to ABP 501, or initiating the RP found that, at the time of consultation, most patients with IBD were reported by physicians to have mild disease, be in clinical remission, have low concomitant steroid use, and self-assessed good overall HRQoL. Both physicians and their patients were highly satisfied with the treatments, with physicians opting to switch from the RP to ABP 501 owing to the potential for lower healthcare costs. Although no statistical comparisons were made, physician and patient experiences appeared similar between ABP 501 and its RP, and high levels of treatment satisfaction and minimally impaired HRQoL also observed in RP-ABP 501 switchers. This study provides real-world evidence to help reassure both patients and physicians that the patient experience associated with the use of ABP 501 appears similar to that with the RP, regardless of whether the patient is initiated on ABP 501 or has switched from the RP to ABP 501.