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Optimising anti-TNF treatment using biosimilars

Practical Advice

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Practical advice and considerations for the use of Biosimilars

Biosimilars offer health care practices large potential cost savings and the opportunity to widen patient access to treatment, but what are the different factors that are important to consider when prescribing biosimilars in gastroenterology, rheumatology and dermatology?1

One of the main factors for consideration when optimising a biologic and/or biosimilar dose regimen is potential loss of response over time, which is often attributed to increased drug clearance linked to anti-drug antibodies.2 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 range.3 For patients with Crohn’s disease (CD) and 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 mg/kg every 8 weeks).4 However, there is substantial variability regarding drug exposure and treatment responses between patients who receive standard infliximab biosimilar doses. 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 treatment.3 There are, however, limitations to adjusting serum levels of infliximab due to approved dosing. Additionally, immunogenicity may not make dose adjustments beneficial.3

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.5–7 One study of a cohort of 121 patients with rheumatic arthritis (RA) found that anti-drug antibodies were present in 17% of patients treated for 28 weeks with adalimumab and concomitant immunosuppressive agent (methotrexate) use was lower in the group with anti-drug antibodies (52% vs. 84%, P = 0.003).8 At 28 weeks, patients with RA that were responding to treatment were less likely to have anti-drug antibodies than those not responding (5% vs. 34%).8 With episodic infliximab therapy, immunosuppressive agents should be considered to decrease immunogenicity and secondary loss of response.9

If, following dose optimisation, the efficacy of an anti-TNF fades in a patient with initial response, a degree of flexibility is required in order to counteract the loss of response. Possible strategies include increasing drug exposure by decreasing the dosing interval or increasing the dose or switching to another product.9 Current guidelines advise a number of alternative systemic biologic therapies for moderate-to-severe psoriasis, as well as more conventional systemic therapies and ultraviolet treatment.10 When selecting the systemic treatment for patients with psoriasis, HCPs should consider the clinical criteria as well as the patient and product characteristics.10

Table 1, factors associated with loss of response to anti-TNF therapy.11 ANA, antinuclear antibodies; ATI, antibodies to infliximab; BMI, body mass index; CRP, c-reactive protein; WBC, white blood cell. 

Factors associated with loss of response to anti-TNF therapy

Recent data highlights that TDM may more effectively optimise anti-TNF therapy efficacy, safety and cost compared with other treatment strategies. 

So, what is the evidence that TDM results in patients with gastroenterology, rheumatology or dermatology diseases remaining on anti-TNF therapy for longer?12

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When patients experience failure with anti-TNF therapy the clinical guidelines recommend either cycling to a new therapeutic drug or switching to a 

new drug with a different mechanism of action, but which option is the most optimal?

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References

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