Practical advice on use of biosimilars

Declaration of sponsorship Biogen

Read time: 15 mins

Last updated:13th Dec 2022

Published:7th Aug 2020

Practical advice and considerations for the use of Biosimilars

Appraise clinical advice on the optimal use of biosimilars in conditions such as Crohn’s disease or ulcerative colitis.

Learn why therapeutic drug monitoring (TDM) can optimise the effect of biologics or biosimilars on patient outcomes
Review strategies to prevent the formation of anti-drug antibodies, including systematic maintenance therapy using biosimilars

Consider factors for cycling to another tumour necrosis factor alpha inhibitor (anti-TNF) therapeutic drug, or switching to a drug with a different mechanism of action, when an anti-TNF fails

In this short video, Professor Thomas Dörner (Charité University Hospitals, Berlin, Germany) summarises the current level of adoption of therapeutic drug monitoring (TDM) in rheumatology, its potential in the future, and the pragmatic argument for changing the therapeutic principle in non-responding patients.

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Therapeutic drug monitoring of anti-TNF inhibitors

One treatment strategy to optimise the effect of biologics or biosimilars is therapeutic drug monitoring (TDM), which uses drug concentration measurements to inform dose adjustments to ensure serum levels are maintained within a therapeutic range².

For patients with Crohn’s disease (CD) or ulcerative colitis (UC), infliximab biosimilar dosing is based on body weight (5 mg/kg), starting with an induction phase at weeks 0, 2 and 6, followed by a maintenance phase (5–10 mg/kg every 8 weeks)⁶. This is also true for infliximab (reference drug)⁷. However, there is substantial variability regarding drug exposure and treatment responses among patients who receive standard infliximab biosimilar doses². By using TDM, dosing levels can be adjusted so that infliximab serum levels are between 3 and 7 μg/mL, a range associated with optimal outcomes during maintenance treatment². There are, however, limitations to adjusting serum levels of infliximab due to costs constraints².

A key concern when prescribing biologics (including biosimilars) is immunogenicity. To prevent the formation of anti-drug antibodies, several treatment strategies can be implemented, including systematic maintenance therapy, which is mainly true for infliximab, concomitant immunosuppression and prophylactic systemic steroids^8-10.

One study of a cohort of 121 patients with rheumatoid arthritis (RA) found that anti-drug antibodies were present in 17% of patients treated for 28 weeks with adalimumab¹¹. At 28 weeks, patients with RA who were responding to treatment were less likely to have anti-drug antibodies than those not responding (5% vs 34%; P=0.032)¹¹. Concomitant use of an immunosuppressive agent (methotrexate) was lower in the group with anti-drug antibodies (52% vs 84%; P=0.003)¹¹. With episodic infliximab therapy, immunosuppressive agents should be considered to decrease immunogenicity and secondary loss of response¹².

The incidence of anti-drug antibodies reported in the literature for patients with psoriasis treated with adalimumab ranged from 6.5% to 45%¹³.It has been shown that the development of anti-drug antibodies is associated with lower adalimumab serum concentrations and, as a result, impaired treatment outcomes¹³.

Following dose optimisation, if the efficacy of an anti-TNF agent fades in a patient with initial response, a degree of flexibility is required to counteract the loss of response¹². Possible strategies include increasing drug exposure by decreasing the dosing interval or increasing the dose or switching to another agent¹². Current guidelines advise a number of alternative systemic biologic therapies for moderate-to-severe psoriasis, as well as more conventional systemic therapies and ultraviolet treatment¹⁴. When selecting the systemic treatment for patients with psoriasis, healthcare professionals (HCP) should consider the clinical criteria as well as the patient and product characteristics¹⁴.

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Cycling to another anti-TNF, or swapping to an agent with a different mechanism of action

Dr Nick Kennedy (Consultant Gastroenterologist, Royal Devon and Exeter NHS Foundation Trust; Honorary Clinical Senior Lecturer, University of Exeter Medical School, UK) examines cycling (switching) to another tumour necrosis factor alpha inhibitor (anti-TNF), compared with swapping to an agent with a different mechanism of action (MoA).

Options for patients who have an inadequate response to an anti-TNF agent include cycling (switching) to a different anti-TNF or swapping to a drug with a different MoA^22,23. But which option is optimal?

A percentage of patients with Crohn’s disease (CD) or ulcerative colitis (UC) do not respond to induction therapy with anti-TNFs ^7,24,25, and some patients may experience a loss of response over time or develop intolerance^7,25,26. Studies have shown that, overall, between one-third and one-half of patients do not respond to anti-TNFs, with a second agent often prescribed when the first fails²⁷. Similarly, 30-40% of patients with rheumatoid arthritis discontinue treatment with anti-TNFs because of an inadequate primary response, loss of response or intolerance²³. For these patients, anti-TNF cycling can be an important and cost-effective treatment strategy with substantial benefit^22,23,25.

If an anti-TNF fails to produce a response, cycling or switching to an alternative anti-TNF might also be expected to fail, given that it has the same mechanism of action. However, studies have shown that cycling can be effective. For example, one study found that after failure of an anti-TNF, 40% of patients with inflammatory bowel disease (IBD) achieved remission with an alternative anti-TNF²⁸. Another study showed that 21% of patients with CD who experienced intolerance or a loss of response to infliximab were able to achieve remission with adalimumab²⁹. There is no evidence that a single switch from an originator product to a biosimilar is associated with any significant risk or reduction in patient safety³⁰.

Among patients with rheumatological disease, anti-TNF cycling is often considered first as a treatment strategy because it represents a lower cost option, compared with switching to a drug with a different mechanism of action (MoA), and can provide successful therapeutic outcomes, given the availability of anti-TNF biosimilars^23,31. A study evaluating the utility of measuring infliximab and anti-infliximab antibodies found that cycling to a different anti-TNF was associated with a partial or complete response in 92% of patients who were positive for infliximab antibodies^32,33.

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