Biosimilars in Saudi Arabia: a single-centre, open-label case series examining infliximab switching

Author byline as per print journal:
Mansour Somaily¹, MD; Hana Alahmari¹, MD; Wejdan Abbag²; Shahenda Yousif⁴, MD; Nawar Tayfour⁴, MD; Nouf Almushayt²; Saleh Alhusayni³, MD; Saeed Almajadiah⁴, MD

Submitted: 16 September 2020; Revised: 30 January 2021; Accepted: 8 February 2021; Published online first: 22 February 2021

Introduction

Tumour necrosis factor (TNF) is an inflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA) [11]. It is produced by a number of cell types in the human body, including those in the synovial membrane and fluid of RA patients [2, 3]. Blocking TNF has been shown to have anti-inflammatory and protective effects in RA [4]. TNF is also important in the pathogenesis of ankylosing spondylitis (AS) [5] and previous studies have identified high levels of TNF mRNA expression near the site of new bone formation and increased TNF protein levels in serum in patients with AS [6, 7].

Infliximab was one of the first TNF inhibitors (TNFI) to be used clinically for the treatment of RA, AS and other inflammatory diseases [8]. In 2013, the first infliximab biosimilar, CT-P13, was approved by the European Medicines Agency (EMA) based on randomized controlled trials in RA and AS, demonstrating no statistically significant differences in safety profile compared with the originator [9-11].

CT-P13 was launched on the market in Saudi Arabia at the end of 2016. Clinical data support its use in the treatment of a ­number of rheumatological diseases, however, there is a lack of local data regarding its safety profile and efficacy among patients in Saudi Arabia. Therefore, the present study was carried out to explore the pharmacological, therapeutic and clinical effects of CT-P13 in patients with RA, AS and BD, encountered during clinical practice in the Department of Rheumatology in Khamis Mushayt General Hospital, Saudi Arabia.

Methodology

This study included 13 patients seen at the Department of Rheumatology in Khamis Mushayt General Hospital. All patients were being treated with originator infliximab and were required to switch to the biosimilar version due to the originator becoming unavailable. Patients were recruited between January 2018 and June 2019. Biosimilar infliximab was given as a standard (3–7.5 mg/kg) IV infusion every 8 weeks. Patients were followed up once every three months, for 12 months.

The RA disease activity score 28 (DAS28) was used for clinical assessment of RA patients. The DAS28, which is a validated tool to define remission in established cases of RA, includes measurement of the number of swollen and tender joints, levels of inflammatory markers in blood (Erythrocyte Sedimentation Rate (ESR)), and assessment of patient general health.

Assessment of AS patients was dependent on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score. This clinically validated index takes into account fatigue, neck, back and hip pain, and other joint symptoms, in addition to assessment of overall discomfort, e.g. areas tender to touch.

The assessment of BD patients depended on clinical assessment of the major manifestations of BD, such as orogenital ulceration, and ocular, musculoskeletal and cutaneous manifestations.

Information about infliximab and its possible adverse effects were described in detail and consents were given in all cases. The study proposal was also approved by the Research Ethics Local Committee, College of Medicine, University of Bisha.

The Shapiro-Wilk test revealed that the data were abnormally distributed. As such, a Wilcoxon signed ranks test was used to compare clinical scores before and after starting treatment with the biosimilar (CT-P13). A p-value < 0.05 was considered significant in all cases.

Results

In total, 13 patients (six with RA, five with AS and two with BD) were switched to biosimilar infliximab (CT-P13) between January 2018 and June 2019. Table 1 summarizes the demographic and clinical characteristics of the patients. Patients were aged between 25 and 55 years (mean age = 39.7±11.7) and 61.5% were women. The majority (n = 11/13) maintained treatment with CT-P13 throughout the follow-up period with no reported major adverse events, excluding two patients with RA who had upper respiratory infection.

Table 2 shows significant improvement in RA disease activity, as measured by the DAS28. The mean DAS28 score was 3.61±1.24 prior to infliximab biosimilar therapy, which reduced to 2.63±1.54 at one year of follow-up (p = 0.046).

Discussion

Several studies have assessed the safety, efficacy and immunogenicity of switching from the infliximab originator to the CT-P13 biosimilar version. However, the majority of these studies have not included control arms and have been observational in nature, in addition to investigating a single switch only. Importantly for Saudi Arabia, none of these studies were carried out in the locality. Therefore, this study was carried out to investigate the therapeutic and clinical effects of CT-P13 in patients with RA, SA and BD, and demonstrates local experience with the biosimilar.

A number of previous studies have investigated the effects of switching between the infliximab originator and the biosimilar, CT-P13. For example, in the second-year extension to the PLANETAS study [12], adverse events associated with biosimilar treatment were observed in 71.4% of patients who switched compared with 48.9% of those who continued receiving treatment with the originator. In addition, in the DANBIO register [13], approximately 6% of patients stopped treatment within three months of switching from originator infliximab to CT-P13 due to adverse events or lack of efficacy. In a study carried out on AS patients who switched from originator infliximab to its biosimilar, 11% of patients from the biosimilar group and 7% of the reference group discontinued the study during the 18-month follow-up period. Of those who discontinued biosimilar treatment, 80% did so due to adverse effects and 20% because of loss of efficacy [14].

The present case study did not identify any statistically significant differences in efficacy or tolerability between CT-P13 and originator infliximab in this small group of subjects in Saudi Arabia. This is in line with previous studies, such as the work of Jørgensen KK et al. [15], who reported that, according to a prespecified non-inferiority margin of 15%, the frequency of serious adverse events was not statistically different between patients treated with originator infliximab and those treated with CT-P13.

Additional observational studies and data from the extensions of the PLANETRA and PLANETAS studies identified few concerns regarding the efficacy and/or safety of CT-P13 [12, 16-19]. A recent systematic literature review including 70 full articles or abstracts evaluated the safety and efficacy of switching between originator and biosimilar infliximab in patients with inflammatory disorders. This review reported that most studies were observational, not containing a control group, and included only six randomized controlled trials (RCTs). It also concluded that no clinically relevant efficacy or safety concerns were associated with switching [20].

An additional survey carried out among adult patients in the United States (US) with RA, AS, and psoriatic arthritis who switched from infliximab to infliximab-dyyb biosimilar therapy evaluated the safety and efficacy of the biosimilar treatment, as well as patient awareness of biosimilar therapy. This paper concluded that patients were generally satisfied with their current therapy, whether this was originator infliximab or infliximab-dyyb. However, patients had concerns about switching, in particular, relating to price, safety, and efficacy [21].

The present study reported improvement in RA disease activity following biosimilar treatment (mean DAS28 of 3.61±1.24 prior to switching, compared to 2.63±1.54 one-year post-switching). However, another RCT identified no significant change in DAS28 between RA patients treated with the originator and those treated with the biosimilar [22].

In addition, in the present study, the five patients with AS who were switched from the originator to its biosimilar exhibited an improvement in their disease activity index (the BASDAI mean score reduced from 3.3±0.7 before biosimilar therapy to 0.28±0.52 after one year of biosimilar therapy, however, the result was not significant), see Table 3. This can be compared to the results of another study, where the BASDAI score was 3.7±0.4 in a group of AS patients treated with biosimilar infliximab, compared to 3.8±0.2 among those treated with the originator [23].

In terms of limitations, this study includes data from a limited number of patients (n = 13) and was not randomized nor ­double-blinded. However, the aim of the study is to report experiences with switching to biosimilar infliximab in Saudi Arabia, which has not previously been examined. The findings from this study suggest that CT-P13 has comparable tolerability and efficacy to originator infliximab and may reduce disease activity in RA patients. However, a larger, double-blind RCT is recommended to ensure the safety and efficacy of the biosimilar. These findings provide important preliminary data and are considered the first evidence (after a literature search in the PubMed and Google Scholar) on switching between originator infliximab to a biosimilar infliximab product in Saudi Arabia.

Conclusion

The findings from this study suggest that CT-P13 has comparable tolerability and efficacy to originator infliximab and may reduce disease activity in RA patients. However, a larger double-blind randomised controlled trial (RCT) is recommended to ensure the safety and efficacy of the biosimilar. These important preliminary data are considered the first evidence (based on a literature search of PubMed and Google Scholar conducted up to ­November 2020) on switching from originator infliximab to a biosimilar infliximab product in Saudi Arabia.

Ethics approval

This study received approval of the ethical clearance from the Research Ethics Local Committee of the College of Medicine, University of Bisha (UBCOM-RELOC) (registration no. H-06-BH-087) based on the recommendation of the committee issued on 15 August 2020.

Competing interests: There was no support of any kinds (including for presentation of data, travel or publication) provided to any of the authors by the manufacturer prior to or after the study was conducted.

Provenance and peer review: Not commissioned; externally peer reviewed.

Authors

Mansour Somaily¹, MD
Hana Alahmari¹, MD
Wejdan Abbag²
Shahenda Yousif⁴, MD
Nawar Tayfour⁴, MD
Nouf Almushayt²
Saleh Alhusayni³, MD
Saeed Almajadiah⁴, MD

¹Department of Medicine, Rheumatology Division, King Khalid University Medical City, 3294 Al Muruj District, Unit number 300, Building No. 8294, 62527-3989 Abha, Saudi Arabia
²College of Medicine, King Khalid University, Almahala Street, 62562 Aseer-Abha, Saudi Arabia
³Asser Central Hospital, Bani Malik Street, 62526 Abha, Saudi Arabia
⁴Department of Medicine, Rheumatology Division, Khamis Mushayt General Hospital, Almahala Street, 62562 Aseer-Abha, Saudi Arabia

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