Making decisions about anti-TNF biosimilars

Shared decision-making between health care professionals and patients

Shared decision-making (SDM) between health care professionals (HCP) and patients, as opposed to HCPs making decisions on behalf of patients without proper information and consent, is supported by a growing base of evidence, across a range of therapy areas from rheumatologic disease to cancer¹.  How can SDM boost treatment adherence and persistence for biologics and/or biosimilars?

Studies show that when patients have an active involvement in treatment decisions and are more educated about their treatment they will elect for more conservative treatment options². Patients who adhere to their treatments are three times more likely to achieve desired outcomes, such as improved quality of life and better functional capacity, than nonadherent patients³. 

Adherence is the extent to which a patient takes a medication as prescribed by his or her HCP, and is usually reported as medication possession ratio, or percentage of days covered⁴ 

When HCPs and patients engage in SDM there is a greater likelihood of adherence for patients, often with the added bonus of reduced health care costs³. Health care costs attributable to nonadherence annually in the US are estimated to be $100–$300 billion per year (2014 data)⁴.

In a 2021 cohort study of 1,655 Medicare beneficiaries at high risk of hospitalisation, and high-need resource use, the population-adjusted prevalence of cost-related medication nonadherence (CRN) was 53.6%; 28.4% of those who reported CRN at least once, had persistent CRN during the 15-month study period. Younger age, worse self-reported health, and depression were associated with increased chance of persistent CRN. This result indicates that CRN is prevalent, moderately persistent, and variable in the Medicare population, despite coverage by insurance⁵.

Implementation of shared decision-making in clinical practice

Treatment decisions for chronic conditions are inherently challenging as they occur over time and may need to be revisited⁶. However, SDM is only implemented in less than 50% of decisions on biologics in inflammatory bowel disease (IBD)⁶. IBD, including ulcerative colitis (UC) and Crohn’s disease (CD), develop in relatively young patients (approximately 25% of patients with IBD present before age 20 years)⁷. A recent real-world evidence (RWE) study in 5,612 patients with CD and 3,533 patients with UC demonstrated that less than half of the patients continued using their initial biologic treatment after 1 year (overall mean persistence rate of 48.48% in CD cohort; 44.78% in UC cohort)⁸. In the same study, the persistence rate for patients on different biologics ranged from 34.6% to 50.9% for CD, and 32.5% to 64.8% for UC⁸.

Benefits of shared decision-making for patients

SDM can be used to inform patients that equivalent outcomes that have been observed between originator biologics and biosimilars support the idea that, in a carefully managed environment, patients can switch between treatments^9,10. Patients are often unfamiliar with biosimilars and may express concerns about the safety and efficacy of treatment when asked to switch from a reference biologic. It is important to provide patients with evidence-based information to support a switch^11,12. 

An example of the benefits of SDM is the switching programme between reference infliximab and biosimilar infliximab that was conducted in 143 patients with IBD in one UK hospital⁹.  The programme was conducted in a carefully managed environment using SDM and found that there was no significant difference in drug persistence between the cohort who switched to biosimilar infliximab versus the cohort treated with reference infliximab in the year before the switch⁹. The IBD-specialist nurses supporting patients during the switch with care and information about their treatment may have contributed to significant improvements in patient-reported outcomes as an example of the utility of SDM (Figure 1)^9,12.

Figure 1. Survival curve showing drug persistence in relation to reference infliximab in all patients treated with reference infliximab (April 2014–March 2015), and in relation to biosimilar infliximab CT-P13 in patients switched from reference infliximab (April 2014–March 2015) at University Hospital Southampton (Adapted^9,12). IFX, infliximab.

Giving patients written information on switching to biosimilars can improve acceptance rates

There are several factors that seem to determine acceptance of biosimilars and emphasise the importance of conversation between patient and HCP. When a switch from an originator product to a biosimilar is proposed by HCPs used to offering the switch and that provide positive information on biosimilars, acceptance of the switch increases¹³. Providing patients written information on switching to biosimilars improves acceptance rates¹³. Furthermore, having the option to switch back if patients considered that tolerance or efficacy was not deemed equivalent, also contributed to increased acceptance rates¹³.

Shared decision-making for managing rheumatoid arthritis

There are both early- and late-onset forms of rheumatoid arthritis (RA) (average age of onset between 30 and 60 years) making the long-term management of treatment important with SDM increasingly taking a prominent role¹⁴. 

A systematic literature review found that, taking into account the percentage of days covered to be >80%, RA and psoriasis (PsO) adherence rates for etanercept, adalimumab, and infliximab ranged from 16%–73%, 21%–70%, and 38%–81%, respectively⁴. Communication between RA nurses and patients as part of managed switching programmes is critical to ensuring that patients are educated with the right information so that they can have confidence in biosimilars, thereby avoiding nocebo effects and enabling long-term adherence to the biosimilar¹². 

In a cross-sectional survey of 453 patients with RA, psoriatic arthritis and IBD, treatment outcomes were compared between those who participated in SDM, and those that did not¹⁵. Lower Medication Adherence Scale scores (SDM 0.17 vs. non-SDM 0.41; P<0.05) indicated greater likelihood of adherence for SDM participants, who also reported higher satisfaction with medication (SDM vs. non-SDM: 66.9 vs. 61.6; P<0.001) and longer persistence (111.2 days vs. 102.2 days for non-SDM; P=0.029) (Figure 2)¹⁵.

Figure 2. Satisfaction with biologic treatment. Results are from a cross-sectional survey of adults initiating treatment for inflammatory bowel disease, rheumatoid arthritis or psoriatic arthritis (Adapted¹⁵). SDM, shared decision-making.

SDM may represent an approach to support treatment decisions in a culturally sensitive manner. For example, SDM should reflect Indigenous-specific content areas, such as benefits and risks of RA therapy informed by data from Indigenous patient populations, or traditional modes of healing¹⁶. In a Canadian study of Indigenous women aged 37–61 years living with RA (N=7), all women were interested in having a “decision coach”, and preferred that decision aids be in paper and electronic formats for accessibility¹⁶.

Shared decision-making for managing psoriasis

Psoriasis develops in relatively young patients (approximately one third of patients develop psoriasis before 18 years of age) and quality of life (QoL) is particularly important outcome, as psoriasis is a visible disease, with worse patient-reported outcomes associated with more severe psoriasis^17,18. Patients with psoriasis require long-term treatment strategies to manage what is often a life-long disease¹⁹. In a nationwide population based cohort of almost 900,000 patients with psoriasis, reported persistence rates of 61.9% for the first, 33.3% for the third, and 22.6% for the fifth year, were reported for biologic medicine²⁰. 

Using SDM in conversations about treatment options that reduce levels of immunosuppression, or that treat a patient’s other comorbidities may improve levels of adherence and persistence²¹ 

In a survey of patients with psoriasis in Italy; 231 that had standard of care and 171 that were exposed to a decision-board, 67.9% of patients wanted to be involved in decision-making, 28.4% wanted to leave decisions entirely to the doctor and 3.7% preferred making decisions alone²². A systematic review of SDM in psoriasis suggested that there was a need to strengthen the relationship between HCPs and patients in order to positively impact patient satisfaction, treatment compliance and ultimately health outcomes²³.

Adult patients with psoriatic arthritis (PsA) often lack agency in making treatment decisions and can feel overwhelmed by the potential harms of systemic medication. Increased knowledge and trust with collaborative medical teams, using strategies for managing risks and treatment side-effects, may improve treatment decision-making for people with PsA²⁴.

How biosimilars are changing exit strategies with anti-TNF therapy

In this short video, Professor Thomas Dörner (Charité University Hospitals, Berlin, Germany) summarises treating patients with minimal disease levels, including the benefits and drawbacks of early treatment, tapering down treatment, and treatment discontinuation in patients with minimal disease levels or remission.

Tumour necrosis factor alpha inhibitor biosimilars

More tumour necrosis factor alpha inhibitor (anti-TNF) biosimilars available on the market represent increasing treatment options for patients and potentially improved rates of remission²⁵. Healthcare professionals (HCP) are starting to re-evaluate the need of applying exit strategies for anti-TNF therapy with the reduced costs of these treatments, following the advent of biosimilars.

For each major class of treatment used alone or in combination, there is a risk of relapse following dose reduction or stopping of treatment²⁶. Generally, patients in clinical, biochemical and endoscopic remission have an increased chance of maintaining health when treatments are stopped²⁶. Whether or not to stop a treatment depends on each individual patient and SDM with the patient should take place²⁶.  

The risks, benefits, and timing of stopping anti-TNF treatment for inflammatory bowel disease (IBD) when patients are in stable remission on therapy, remain a topic of discussion²⁷. In a meta-analysis of 27 studies evaluating discontinuation of anti-TNF therapies in patients with IBD, the overall risk of relapse after discontinuation of anti-TNF therapy was 44% for Crohn’s disease (CD) [95% CI 36–51%; 912 patients] and 38% for ulcerative colitis (UC) [23–52%; 266 patients] over the course of a year²⁸. When anti-TNF treatment was stopped based exclusively on achievement of clinical remission, 42% of patients with CD relapsed during the following year. However, if patients discontinued anti-TNF therapy after achieving not only clinical but also endoscopic remission, the relapse rate at 1 year decreased to 26%²⁸.

Biosimilars and exit strategies for anti-TNF therapies

The availability of biosimilars is causing an revaluation of the current guidelines on exit strategies for anti-TNF therapies^29,30. For instance, a single-centre retrospective analysis of 30 patients with IBD, found low relapse rates in patients with CD and UC who discontinued treatment with infliximab after achieving sustained remission³¹. Patients’ mean length of infliximab treatment before discontinuation was 38.5 months³¹. At 24 months after discontinuation, 91% of the 22 patients with available data remained in clinical remission^31,32. After stopping infliximab, 50% of patients took no other medications for their IBD³¹. In total, 13.3% of patients had relapsed, and restarted biologic therapy. A cost analysis showed that discontinuing infliximab saved the hospital the equivalent of €379,351.56 over the study period³¹. The study demonstrated that discontinuing infliximab in patients with sustained remission was safe and cost-effective³¹.

A real-world study assessing the persistence of biologic therapies in UC and CD in patients independent of prior biologic experience, found that the sustainability of biologic treatment was less in UC than in CD patients, and not strongly determined by prior biologic exposure. These findings suggest the need for new non-biologic/small molecules to demonstrate their relative sustainability as IBD therapies (Figure 3)³³.

Figure 3. Median time to discontinuation between biologic naïve and biologic experienced patients with ulcerative colitis (UC) and Crohn’s disease (CD) (Adapted³³). 

In a meta-analysis of 16 clinical trials, including 1,264 patients with rheumatoid arthritis (RA), almost half of RA patients in remission relapsed after elective anti-TNF therapy discontinuation (relapse rate=0.47 [95% CI 0.41–0.54])³⁴. 

A meta-analysis of six trials reported that the continuation of anti-TNF therapy in patients with RA in sustained remission or low disease activity, increased the probability of low disease activity (relative risk [RR]=0.66; 95% CI 0.51–0.84) and remission (RR=0.57, 95% CI 0.44–0.74), and reduced radiographic progression (RR=0.91, 95% CI 0.85–0.98)³⁵. 

Biosimilars, with reduced treatment costs compared to reference biologics, could initiate a paradigm shift in starting treatment earlier^36,37

In a study of 566 patients with psoriatic arthritis (PsA) receiving either etanercept, infliximab or adalimumab, disease remission was achieved by 27, 36, and 35% of patients at 6, 12, and 18 months, respectively^38,39. 

Other data from a retrospective study, carried out in a routine clinical setting on 268 ankylosing spondylitis and PsA patients receiving a total of 353 anti-TNF treatment courses (97 adalimumab, 180 etanercept, 76 infliximab) showed at 6-month follow-up, >85% of patients who cycled to another anti-TNF product were responsive to the second anti-TNF product, and >70% of patients with a mean follow-up of 33.7 months were still receiving anti-TNF therapy⁴⁰. The mean average (±SD) persistence of anti-TNF therapy was 30.2 (±24.7) months for etanercept, 43.7 (±25.6) months for infliximab and 16.5 (±15.4) months for adalimumab, (P<0.0001)⁴⁰. 

Biosimilars can reduce the economic need to use exit strategies

The decreased cost of biosimilars means patients may initiate treatment earlier and remain on treatment for longer. In a 5-year, open-label, observational cohort study evaluating 65 patients with dermatologic disease, a sustained clinical response was reported at the end of anti-TNF biosimilar treatment, with a drug survival/persistence rate of 76% for etanercept, 57% for infliximab, and 50% for adalimumab⁴¹. All anti-TNF agents were effective, generally well-tolerated and clinical improvement was maintained through the 5 years⁴¹.

The increasing availability of biosimilars therefore represents an opportunity to reduce the economic need to employ exit strategies for patients with dermatology disease in the knowledge that the chance of relapse will be reduced⁴¹.