Biosimilar therapies in inflammatory bowel disease: should we care about patient profile?

Biosimilars represent a great opportunity to treat patients with inflammatory bowel disease (IBD) at a lower cost, especially in the long term. Recent data from real-life cohort studies show that infliximab biosimilar may not differ from the originator in terms of efficacy, safety, and immunogenicity, both in adult and pediatric IBD populations. Long-term data are still needed to confirm these preliminary observations.

We briefly discuss the recent data available on infliximab biosimilars in IBD, proposing the best patient profile to be eligible for the use of biosimilars in the next future.

In the last two decades, monoclonal antibodies (mAbs), also known as biological agents, have brought a revolution in the management of IBD, such as Crohn’s disease (CD) and ulcerative colitis (UC), in terms of controlling disease symptoms, healing mucosal lesions, and reducing the IBD-related hospitalization and surgery rates [1,2]. Costs derived from the use of mAbs account for the 15% of all costs related to IBD in the first year [3], and they are expected to increase in the next future, also considering that up to 50% of patients achieving deep remission with mAbs would need to continue biological agents over time.

The recent development of mAb biosimilars represents a great opportunity for the management of IBD, theoretically offering the same clinical efficacy with significantly high health-care resource sparing effects. Recently, two biosimilars of infliximab are available in the European Union. Since their approval by the European Medicine Agency, there has been a strong debate on the lack of data in IBD deriving from clinical studies [4–6]. Actually, the approval of biosimilars in IBD was based on data coming from two randomized controlled trials conducted on subjects with rheumatoid arthritis and ankylosing spondylitis, and prolonged up to 2 years [7–10], showing no clinical differences in terms of efficacy, safety, and immunogenicity, both in subjects naïve to infliximab and in those switched from the infliximab originator to the infliximab biosimilar. Between 2013 and 2014, the European Crohn’s Colitis Organization and some national IBD societies published their position papers, focusing on the need for clinical data in IBD, the need for more solid data concerning safety and immunogenicity in the long term, and expressing their concerns about the automatic substitution by a different person from the prescribing physician, and the same International Non-proprietary Name given to all the infliximab molecules (originator and biosimilars) [4–6,11].

More recently, preliminary data are coming from real-life cohort studies across different countries that may support the bioequivalence of infliximab biosimilars in IBD, as well as in rheumatology and dermatology [12–14]. Gecse et al. conducted a prospective observational multicenter nationwide cohort study across Hungary on 90 consecutive IBD patients (57 CD and 33 UC subjects) treated by infliximab biosimilar for a median time of 108 weeks for CD and 54 weeks for UC. They found a significant decrease in the clinical activity index and C-reactive protein (CRP) in the whole study population, and only four allergic reactions in subjects previously exposed to infliximab. Similar preliminary results come from the large prospective study ongoing in Norway (the NOR-SWITCH study) [15]. Data from 46 CD and 32 UC patients showed a statistically significant reduction in disease activity, fecal calprotectin, and CRP at week 14. Twenty-two patients (8 UC and 14 CD) were previously treated with other biologics. After the induction phase, 76% (32/42) of CD subjects were in clinical remission (HBI score ≤4), as well as 56% (18/32) of UC subjects.

These preliminary data show that probably no differences may be expected from biosimilars of infliximab compared to the originator. The only contrasting data come from the Irish cohort [16] that compared two groups of patients treated with infliximab originator or biosimilars, showing an increased surgery rate, less steroid-free remission rates, and less normalization of CRP. Of note, the two compared cohorts included different subjects, in different study periods (2011–2013 for infliximab originator, since 2014 for the biosimilar), and no details are currently available on baseline characteristics. Although long-term data are still missing, no concerns about safety or immunogenicity came from the available studies. Moreover, Gecse et al. [12] reported four infusion reactions in patients previously exposed to anti-TNF, which is expected also in patients treated with infliximab originator, supporting the fact that there is even no clinically meaningful structural difference between the two molecules.

Based on these considerations, are we confident in using infliximab biosimilars for the same IBD population that we usually treat with the originator? At the moment, the preclinical data, the pharmacokinetics and pharmacodynamics of the available biosimilars, and the preliminary data in adult and pediatric IBD populations [17] support the use of biosimilars in all patients naïve to infliximab, but no contraindication seem to come out from these studies about switching from the originator to the relative biosimilar. However, more long-term data on switch in patients treated with the originator in patients with prolonged remission compared to patients experiencing any loss of response during their treatment, as well as more data on drug levels and antibodies, may be needed to support this approach in all patients. Preliminary data on IBD children also show that biosimilars seem to be effective and safe in naïve to infliximab, or switched while on therapy with the originator. No data are available on IBD pregnant women at the moment, so switching from the originator to biosimilars in pregnancy clinical setting should be supported by real life or registry data.

Indeed, the main advantage in the use of biosimilars is the expected huge cost saving on health-care resources. A 5-year budget impact analysis based on the current costs in France, Italy, and the UK on three different scenarios (10%, 20%, or 30% price less than infliximab originator) would generate a cost reduction in all patients ranging from 10 million to 335 million euros in the next 5 years [18], probably generating more spendable resources for IBD patients with the same allocated budget. Despite this clear advantage, the main concern from IBD specialists and patients remains about immunogenicity, which may impact on the interchangeability between the originator and biosimilars [19,20].

Biosimilars may hugely impact on the next future management of IBD, offering the same efficacy and safety at a significant lower price. However, the need for long-term data, the importance of a widespread post-marketing pharmacovigilance, and more clinical experience on each indication have to be warranted, as clearly requested by IBD specialists and Patients’ Associations [19,20]. More studies on the real impact on cost reduction in the following years on the current and future biosimilars are also needed, to evaluate the global impact of those therapies in terms of cost–benefit ratio in IBD patients.

Financial and competing interests disclosure

G Fiorino received consultancy fees from MSD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Notes on contributors

Gionata Fiorino

Maria Fazio

Silvio Danese