Real-World Outcomes of a Non-Medical Switch to Adalimumab-Atto Biosimilar: Safety, Effectiveness, and Treatment Persistence in an Adult Saudi Tertiary Care Population

Abstract

Background

Adalimumab-atto, a biosimilar to adalimumab, has been widely adopted for managing autoimmune conditions due to its demonstrated safety, efficacy, and cost-effectiveness in clinical trials. However, real-world data from Saudi Arabian population remains limited.

Objective

This study aimed to evaluate the persistence, safety, and clinical outcomes of patients transitioned from originator adalimumab (Humira^®) to adalimumab-atto biosimilar (Amgevita^®) at a tertiary care center.

Methods

A retrospective self-controlled cohort study was conducted, including all patients transitioned to adalimumab-atto between January 1 and December 31, 2022, for non-medical reasons. The primary endpoint was treatment persistence at 12 months. Secondary endpoints included disease stability, adverse events, and reasons for discontinuation.

Results

The study included 265 adult patients previously treated with originator adalimumab. The mean age of the cohort was 41 ± 13 years, with 46.8% being female. The most common indications were Crohn’s disease (40.4%), rheumatoid arthritis (16.6%), and plaque psoriasis (12.1%), with a mean disease duration of 11.7 ± 6.7 years. At 12 months, 90.2% of patients persisted with adalimumab-atto, of whom 79.5% remained stable, while 20.5% were classified as unstable Twenty-six patients (9.8%) discontinued therapy, primarily due to insufficient efficacy (13 patients), with one discontinuation attributed to adverse events.

Conclusion

Adalimumab-atto demonstrated high treatment persistence and favorable safety outcomes in a diverse population of patients with autoimmune diseases. These findings support the feasibility of continued use of the biosimilar in patients with immune-mediated diseases.

Introduction

Biological therapies, particularly tumor necrosis factor (TNF) inhibitors, have transformed the management of autoimmune diseases, offering significant clinical benefits for conditions such as rheumatoid arthritis (RA), ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.^1–3 Despite their efficacy, the high cost of originator biologics, such as adalimumab, poses substantial financial challenges, particularly in resource-limited healthcare systems.^4,5

To mitigate these barriers, biosimilars have emerged as cost-effective alternatives to originator biologics, expanding patient access to biological therapies.⁵ Biosimilars are rigorously designed to be highly similar to their reference products, with no clinically meaningful differences in efficacy, safety, or immunogenicity.⁶ Adalimumab-atto, a biosimilar of Adalimumab, was approved by the U.S. Food and Drug Administration (FDA) in 2016 and the European Medicines Agency (EMA) in 2017.^7,8 These approvals were underpinned by robust evidence, including structural and functional characterization, pharmacokinetic and pharmacodynamic studies, and clinical trials.⁹

While adalimumab-atto has been widely adopted globally, real-world data from Saudi population is currently lacking. In 2022, King Faisal Specialist Hospital and Research Center (KFSH&RC) implemented a formulary-mandated transition, switching all eligible patients from originator adalimumab to biosimilar adalimumab-atto. This study aimed to evaluate the real-world outcomes of this transition, with a focus on treatment persistence, safety, and disease stability in this unique healthcare context.

Method

Study Design and Patients

This retrospective self-controlled cohort study was conducted at King Faisal Specialist Hospital and Research Center (KFSH&RC), a leading tertiary care hospital in Riyadh, Saudi Arabia, with a capacity of over 1,100 beds. The study evaluated patients who underwent a non-medical switch from adalimumab originator to adalimumab-atto biosimilar between January 1 and December 31, 2022. Data were extracted from electronic health records (EHRs), ensuring comprehensive capture of patient demographics, clinical characteristics, and treatment outcomes.

The study population included adult patients aged 18 years or older at the time of adalimumab initiation who had been on adalimumab originator for a minimum of six months prior to switching. Patients were required to be clinically stable, which is defined as maintenance on a consistence dose of the originator adalimumab without documented dose escalation or the addition of rescue therapy for six months before transitioning to the biosimilar. Exclusion criteria comprised patients who were <18 years at adalimumab initiation, naïve to adalimumab originator, individuals lacked follow-up data after switching to the biosimilar, those with less than six months of exposure to the originator, and patients who were unstable since on adalimumab originator.

Study Endpoints

The primary endpoint of the study was the proportion of patients who persisted on adalimumab-atto biosimilar for 12 months following the switch from the originator. Secondary endpoints included the proportion of patients who discontinued the biosimilar, reasons for discontinuation, and the clinical status of patients who persisted on the biosimilar, categorized as stable or unstable. Treatment persistence was evaluated as the proportion of patients who remained on adalimumab-atto during the 12-month follow-up period. It was assessed through prescription orders, medication dispensing, refills, and physicians’ documentation.

Patients who persisted on the biosimilar but were clinically unstable were also assessed. Instability was defined by the need for rescue therapy (eg, non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids), initiation of conventional therapy (eg, disease modifying anti-rheumatic drugs (DMARDs) or immunosuppressant), or dose escalation of the biosimilar. For patients who discontinued the biosimilar, reasons for discontinuation were documented, including lack of efficacy or disease flare (based on global physician assessment), adverse drug reactions (ADRs), surgical intervention, contraindications, or drug-drug interactions. Post-discontinuation management strategies were also reviewed to provide a comprehensive understanding of treatment outcomes.

Statistical Analysis

Demographic and baseline characteristics at the time of the switch were summarized using descriptive statistics. Continuous variables were reported as mean ± standard deviation (SD), while categorical variables were expressed as frequencies and percentages. Key baseline characteristics included age, sex, disease indication, disease duration, and prior use of advanced therapies. Disease indications were identified using EHRs and classified according to established diagnostic criteria. Each indication was analyzed as a separate binary variable (present/absent) for each patient, allowing patients with multiple indications to be included in more than one disease category. The median and interquartile range were used to summarize the duration.

The association between biosimilar persistence and the indication for adalimumab treatment was assessed using chi-square test. The relationship between persistence and continuous variables (eg, age, body mass index, weight) was examined using a two-sample t-test. For non-normally distributed variables, such as disease duration, the Mann–Whitney test was employed. A p-value of <0.05 was considered statistically significant. All statistical analyses were performed using STATA version 18 (StataCorp, College Station, TX, USA).

Results

Baseline Characteristics

A total of 505 patients who transitioned to the adalimumab-atto biosimilar were screened, of whom 265 met the study’s inclusion criteria (Figure 1). The mean age of the cohort was 41 ± 13 years, with 46.8% of patients being female. The most common indications for adalimumab-atto treatment were Crohn’s disease (40.4%), rheumatoid arthritis (16.6%), and plaque psoriasis (12.1%). The median disease duration was 11 (6–15) years (Table 1).

Figure 1.

Patient Screening. Flow diagram illustrating patients’ screening, exclusion, and study inclusion.

Table 1.

Baseline Demographics and Clinical Characteristics of Patients (N=265)

Variable	Value
Demographics
Age (years), mean ± SD	41 ± 13
Weight (kg), mean ± SD	75.38 ± 17.76
BMI (kg/m2), mean ± SD	27.63 ± 6.06
Female, n (%)	124 (46.8)
Disease duration (years), median (IQR)	11 (6–15)
Indications*, n (%)
Crohn’s disease	107 (40.4)
Rheumatoid arthritis	44 (16.6)
Plaque psoriasis	32 (12.1)
Ankylosing spondylitis	28 (10.6)
Ulcerative colitis	25 (9.4)
Psoriatic arthritis	17 (6.4)
Uveitis	8 (3.0)
Hidradenitis suppurativa	28 (10.6)
Concomitant Medications*, n (%)
DMARDs	60/211 (28.4)
Immunosuppressant	50/211 (23.7)
Systemic corticosteroids	29/211 (13.7)
NSAIDs	28/211 (13.3)
Mesalamine	21/211 (10)
Topical corticosteroids	19/211 (9)
Topical treatments	4/211 (1.9)

Notes: *Some patients had multiple indications and concomitant medications.

Abbreviations: SD, Standard deviation; IQR, Interquartile range; DMARDs, Disease Modifying Anti-rheumatic Drugs; NSAIDs, Non-steroidal Anti-Inflammatory drugs.

A total of 166 patients (62.6%) were receiving concomitant medications at the time of the switch, with 211 concomitant medications recorded, as some patients were receiving more than one concomitant medication. The most frequently used concomitant therapies were DMARDs (60, 28.4%), immunosuppressants (50, 23.7%), systemic corticosteroids (29, 13.7%), and NSAIDs (28, 13.3%) (Table 1).

Primary Outcome: Treatment Persistence

At 12 months post-switch, 239 patients (90.2%) persisted on adalimumab-atto biosimilar, while 26 patients (9.8%) discontinued treatment. Among the 239 patients who persisted on treatment, 190 (79.5%) demonstrated stable persistence, whereas 49 (20.5%) were classified as having unstable persistence.

Secondary Outcomes: Discontinuation

Among the 26 patients who discontinued adalimumab-atto biosimilar, the primary reason for discontinuation was insufficient efficacy or disease flare, as assessed by physician global evaluation (13 patients, 50%). Five patients (19.2%) discontinued adalimumab-atto biosimilar due to non-adherence, while two patients (7.7%) discontinued due to pregnancy. Other reasons included adverse drug reactions (1 patient developed rash and polyneuropathy), contraindications (1 patient was diagnosed with monoclonal gammopathy of undetermined significance (MGUS)), development of antibodies against adalimumab (1 patient, 3.8%), surgical intervention (1 patient, 3.8%), treatment de-escalation (1 patient, 3.8%), and undocumented reasons (1 patient, 3.8%) (Table 2).

Table 2.

Secondary Outcome: Reasons for Adalimumab-Atto Biosimilar Discontinuation (N=26)

Reasons of Discontinuation	n (%)
Insufficient effect (according to physician global assessment)*	13 (50)
Non-adherence	5 (19.2)
Pregnancy	2 (7.7)
Adverse drug reaction(s)**	1 (3.8)
Contraindication***	1 (3.8)
Developed antibodies against adalimumab	1 (3.8)
Surgical intervention	1 (3.8)
Treatment de-escalation	1 (3.8)
No documentation	1 (3.8)
Management after discontinuation	n (%)
Switched to alternative biological therapy	17 (65.3)
Ustekinumab	7/17 (41.1)
Interleukin-17 (IL-17) inhibitors	3/17 (17.6)
Guselkumab	2/17 (11.8)
Tocilizumab	2/17 (11.8)
Abatacept	2/17 (11.8)
Infliximab	1/17 (5.9)
Initiated Oral Corticosteroids	1 (3.8)
Switched to Tofacitinib	1 (3.8)
Surgical Intervention	1 (3.8)

Notes: *Defined as disease relapse or findings of active disease. **Patient developed dermatological reaction (rash) and polyneuropathy ***Diagnosed with monoclonal gammopathy of undetermined significance (MGUS).

Following discontinuation, the majority of patients (17 patients, 65.3%) were switched to alternative biologic therapies. The most commonly prescribed alternatives were ustekinumab (7 patients, 41.1%), Interleukin-17 (IL-17) inhibitors (3 patients, 17.6%), guselkumab (2 patients, 11.8%), tocilizumab (2 patients, 11.8%), abatacept (2 patient, 11.8%) and infliximab (1 patient, 5.9%). One patient was initiated on oral corticosteroid, another patient was switched to tofacitinib, and one patient underwent surgical intervention (Table 2).

Subgroup Analysis

Persistence by Demographic and Clinical Variables

Subgroup analysis of patients who persisted on treatment (239 patients) revealed no significant differences in persistence rates based on gender, and disease duration. However, significant associations with treatment persistence were observed for rheumatoid arthritis and Crohn’s disease (Table 3).

Table 3.

Association of Baseline Characteristics, Treatment Indications, and Concomitant Therapies with 12-Month Persistence of Adalimumab-Atto

Variable	Total (N)	Persisted, n (%)	Odds Ratio [95% CI]	P-value
Gender				0.730
Male*	141	128 (90.8)	1.00
Female	124	111 (89.5)	0.87 [0.39–1.95]
Treatment duration				0.9058
1–5 years*	49	44 (89.8)	1.00
6–10 years	83	74 (89.2)	0.93 [0.29–2.97]	0.908
11–14 years	55	51 (92.7)	1.45 [0.37–5.73]	0.597
≥15 years	78	70 (89.7)	0.99 [0.31–3.23]	0.992
Rheumatoid arthritis				0.047
No*	221	203 (91.9)	1.00
Yes	44	36 (81.8)	0.40 [0.16–0.99]
Ankylosing spondylarthritis				0.865
No*	237	214 (90.3)	1.00
Yes	28	25 (89.3)	0.90 [0.25–3.20]
Plaque psoriasis				0.587
No*	233	211 (90.6)	1.00
Yes	32	28 (87.5)	0.73 [0.23–2.27]
Psoriatic arthritis				0.579
No*	248	223 (89.9)	1.00
Yes	17	16 (94.1)	1.79 [0.23–14.10]
Hidradenitis suppurativa				0.865
No*	237	214 (90.3)	1.00
Yes	28	25 (89.3)	0.90 [0.25–3.20]
Crohn’s disease				0.027
No*	158	137 (86.7)	1.00
Yes	107	102 (95.3)	3.13 [1.14–8.57]
Ulcerative colitis				0.750
No*	240	216 (90.0)	1.00
Yes	25	23 (92.0)	1.28 [0.28–5.76]
Uveitis				0.796
No*	257	232 (90.3)	1.00
Yes	8	7 (87.5)	0.75 [0.09–6.38]
Other indication**				0.874
No*	262	236 (90.1)	1.00
Yes	3	3 (100.0)	0.78 [0.04–15.6] †
Juvenile rheumatoid arthritis				0.115
No*	263	238 (90.5)	1.00
Yes	2	1 (50.0)	0.11 [0.006–1.73]
Baseline Therapy
DMARDS				0.130
No*	205	188 (91.7)	1.00
Yes	60	51 (85.0)	0.51 [0.22–1.22]
Immunotherapy				0.322
No*	215	192 (89.3)	1.00
Yes	50	47 (94.0)	1.88 [0.54–6.52]
Systemic corticosteroids				0.918
No*	236	213 (90.3)	1.00
Yes	29	26 (89.7)	0.94 [0.26–3.33]
NSAIDs				0.865
No*	237	214 (90.3)	1.00
Yes	28	25 (89.3)	0.90 [0.25–3.20]
Mesalamine				0.963
No*	244	220 (90.2)	1.00
Yes	21	19 (90.5)	1.04 [0.23–4.72]
Topical corticosteroids				0.099
No*	246	224 (91.1)	1.00
Yes	19	15 (78.9)	0.37 [0.11–1.21]
Other concomitant medications				0.347†
No*	249	223 (89.6)	1.00
Yes	16	16 (100.0)	3.91 [0.23–67.11]†

Notes: *Reference category. Using male as the reference for gender, 1–5 years as the reference for treatment duration, and absence of the indication/therapy as the reference for each indication or therapy. **Other indications include: Behcet’s Disease (2), and Sacroiliitis (1) † Firth penalized logistic regression was used because of complete separation in the conventional logistic regression model. Persisted = persistence with adalimumab-atto at 12 months. ORs represent the odds of 12-month persistence relative to the reference category. The overall sample was (n = 265), with 239 (90.2%) persisting at 12 months. P-values in the table are from the corresponding logistic regression models (Firth logistic regression for Other concomitant medications and Other indication).

Secondary Outcomes: Unstable Disease Among Persisted Patients

Of the 239 patients who persisted on the biosimilar, 49 (20.5%) were classified as having unstable disease. Among these patients, management strategies included biosimilar dose-escalation (25 patients, 51%), addition of rescue therapy (14 patients, 28.6%), increase dose of conventional therapy (5 patients, 10.2%), addition of conventional therapy (2 patients, 4%), and others (10 patients, 20.4%) (Table 4).

Table 4.

Secondary Outcome: Patients with Unstable Disease Who Persisted on Adalimumab-Atto (N=49)*

Management	n (%)
Adalimumab-atto biosimilar dose escalation	25 (51)
Addition of rescue therapy	14 (28.6)
Oral Corticosteroids	10 (71.4)
Injectable Corticosteroids	3 (21.4)
Intra-articular Corticosteroids	1 (7.1)
Increase dose of conventional therapy (DMARDs or immunosuppressant)	5 (10.2)
Addition of conventional therapy (DMARDs or immunosuppressant)	2 (4)
Others Continued the same Surgical Intervention Switched back to originator	10 (20.4) 7 (27.7) 2 (11.1) 1 (5.55)

Note: *Some patients had multiple interventions.

Abbreviations: MTX, Methotrexate, DMARDs, Disease-Modifying Antirheumatic Drugs.

Discussion

This study evaluated the real-world outcomes of patients transitioning from adalimumab originator to adalimumab-atto biosimilar at a tertiary care center in Saudi Arabia. The results demonstrated a high treatment persistence rate of 90.2% at 12 months, with only 9.8% of patients discontinuing the biosimilar. The primary reason for discontinuation was insufficient efficacy, as assessed by physician global evaluation. Other reasons included adverse drug reactions, contraindications, development of antibodies against adalimumab, surgical intervention, pregnancy, treatment de-escalation, non-adherence, and undocumented factors. Our study also revealed that the majority of patients who persisted on treatment (79.5%) remained stable and did not require additional interventions, such as corticosteroids or dose escalation.

The high persistence rate observed in our study provides real-world evidence of continued use of adalimumab-atto biosimilar in patients with immune-mediated diseases and supports its sustained use in routine clinical practice. The findings of this study align with previous studies, both randomized controlled trials and real world data that have reported favorable effectiveness and safety profiles for adalimumab biosimilars in diverse patient populations.^10–12 The persistence rate in our study was slightly higher than those previously reported in similar studies,^11,12 however this difference may be attributed to variations in patient populations, healthcare systems, or follow-up protocols.

One of the key strengths of this study is its focus on real-world data from a Saudi population, addressing a significant gap in the literature on biosimilar use in this region. The inclusion of patients with a wide range of immune-mediated diseases, such as Crohn’s disease, rheumatoid arthritis, and psoriasis, enhances the generalizability of the findings. Additionally, the study design, in which patients acted as their own controls by transitioning from the originator to the biosimilar, minimizes confounding factors and strengthens the validity of the results. This approach allows for a more accurate assessment of the biosimilar’s performance in a real-world setting.

However, the study has several limitations that should be acknowledged. The retrospective, non-comparative design limits the ability to establish causal relationships and may introduce bias in data collection. As a single-center study, the findings may not be generalizable to other healthcare settings or regions. The reliance on physician assessments and electronic health records may not fully capture patient-reported outcomes such as injection-site pain or quality of life, which are important factors influencing adherence and persistence. Outcome assessment may also have been influenced by the subjective nature of physician global assessment. Furthermore, the 12-month follow-up period may not capture long-term outcomes, including delayed adverse events or secondary treatment failures. Finally, non-medical switching may be associated with nocebo effects that could influence treatment continuation or perceived disease control.

Conclusion

In conclusion, this study demonstrates that adalimumab-atto biosimilar is associated with high treatment persistence and favorable clinical outcomes in a real-world setting. The low discontinuation rate and successful transition to alternative therapies for non-responders support the feasibility of continued use of the biosimilar in patients with immune-mediated diseases. However, the presence of unstable disease in a subset of patients underscores the need for close monitoring and individualized management strategies.

Future studies should focus on long-term outcomes, patient-reported experiences, and comparative effectiveness of biosimilars versus originator biologics. Additionally, multicenter studies involving diverse populations are needed to further validate these findings and inform clinical practice. By addressing these gaps, future research can provide a more comprehensive understanding of the role of biosimilars in the management of immune-mediated diseases and optimize treatment strategies for patients worldwide.

Funding Statement

No funding was received to assist with the preparation of this manuscript.

Data Sharing Statement

The datasets generated and analyzed during this study are not publicly available due to patient confidentiality and institutional restrictions. Deidentified data may be available from the corresponding author upon request.

Ethical Considerations

The study protocol was reviewed and approved by the Research Advisory Council (RAC) ethics committee of King Faisal Specialist Hospital and Research Center with RAC number 2231191. Informed consent was waived due to the retrospective nature of the study and the absence of additional risks to patients, as all data were collected from existing medical records without direct patient contact. The study adhered to the ethical principles outlined in the Declaration of Helsinki, ensuring patient confidentiality and data security throughout the research process.

Author Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Alhanouf Almousa, Mohamed Ahmed, Meshal Aldurayhim and Rayd Almehizia. The first draft of the manuscript was written by Mohamed Ahmed, Alhanouf Almousa and all authors commented on previous versions of the manuscript. All authors read and approved the final version of the manuscript.

Disclosure

Dr Almutairdi Abdulelah reports Consulting fees from Takeda, Abbvie, J&J, Amgen, Ferring, Pfizer, BMS, Lilly; Honoraria from Takeda, Abbvie, J&J, Amgen, Ferring, Pfizer, BMS; Meeting/travel support from Takeda, Abbvie, J&J, outside the submitted work. The authors report no other conflicts of interest in this work.