Non-medical switching in dermatology: cost-conscious policy or an affront to patient safety?

Background on non-medical switching

Non-medical switching is when patients are switched from one therapy to another for reasons unrelated to their health. The new therapy is a clinically distinct, non-generic alternative, and the reasons for switching do not include poor clinical efficacy, medication intolerance, or non-adherence (1–5). Payers often initiate non-medical switching as a cost-containment strategy. Insurers might implement formulary changes, prior authorization, or step-therapy requirements – all of which can push stable patients to abandon well-tolerated treatment regimens (3,4).

Dermatologists are regularly affected by non-medical switching because they care for complex patients who might have failed initial skin therapy, necessitating access to more expensive medications such as biologic drugs (6,7). The price of these innovative medicines is predicted to outpace the health expenditure capacities of most nations: specialty drugs account for 2% of prescriptions but more than 50% of healthcare spending, making them targets for rational cost-containment strategies, including non-medical switching (8).

This article examines the literature on non-medical switching in dermatology, with a focus on psoriasis and opines on guidelines to control costs while promoting optimal patient outcomes.

Non-medical switching involves non-interchangeable drugs

Non-medical switching involves switching between non-interchangeable drugs. The U.S. Food and Drug Administration (FDA) grants interchangeability designation to products that can be freely substituted for one another without the prescriber’s approval (9,10). To earn interchangeability designation, a drug must have the same molecular structure, pharmacokinetics, and mode of administration as the originator compound. Generic medications undergo preclinical testing to prove their bioequivalence, and by extension interchangeability, with the originator product.

Payers can initiate formulary switches incentivizing patients to switch between clinically distinct drugs that may utilize different mechanisms of action or vary in their biologic targets (e.g. switching from one IL17A inhibitor to another or from an IL-17A to an IL-23 inhibitor). Non-medical switching between these medications has the potential to alter the course of patient care, as these drugs can vary in their adverse effect profile, mode of administration, and clinical efficacy (11).

Push and pull factors in non-medical switching

A common and long-standing practice that drives non-medical switching is formulary switching. Following the introduction of a lower cost alternative treatment, insurance companies may drop a medication from their formularies or move it to a higher coverage tier (12). Thus, even if the original medication might be the best treatment option, the prescriber and patient might feel forced to choose the preferred alternative because of financial costs.

Most insurance companies have an appeals process, which may allow patients to access a drug that is no longer in the formulary (13). Appeals typically require a physician to submit a statement justifying the patient’s specific medication needs. If the insurance company deems the justification convincing, patients may be granted access to non-formulary medications at a price they can reasonably afford (13). While appealing can be effective, it puts an additional burden on busy physicians (14). Clinicians may avoid appeals knowing that the process is time-intensive, and payers are not bound to approve the appeal. Payers may delay their response for 60 days, frustrating both the patient and the provider and delaying care. A simplified appeals process with a reasonable turnaround time could limit the impact of formulary switching on patient care.

Unless interchangeability designation is granted by regulatory bodies, physicians, by their control over what medication is prescribed, will retain a say on whether a patient is switched between drugs. However, creative ways to push patients toward alternative medications are already being practiced. One insurer recently offered $500 to patients who switched their psoriasis medication from secukinumab to the presumably lower cost (for the insurer) ixekizumab. This method of cash persuasion was impactful: prescriptions for secukinumab dropped 17% in the first two months of 2021, and ixekizumab became dermatologists’ most recommended psoriasis drug (15).

Given the success of the cash reward in incentivizing patients to switch between biologics, other insurers may implement such a strategy. The effect of cash incentives on patient safety and health equity requires further investigation. We hypothesize that cash incentives may have greater impact on low-income patients, potentially furthering socioeconomic disparities in healthcare and outcomes. Regulatory bodies should ensure that such incentives do not double as financial coercion while recognizing that paying people to switch might be considered less coercive than charging enormous copays (15).

Non-medical switching is cost-conscious

Non-medical switching between different biologic products may result in considerable cost savings. Both etanercept, a tumor necrosis factor-alpha blocker, and ixekizumab, an interleukin-17 antagonist, are used to treat moderate to severe plaque psoriasis. Both treatments are well-tolerated and improve the quality of life for psoriasis patients. In some settings, ixekizumab every 4 weeks may be considerably less expensive than biweekly etanercept treatment (16).

Biosimilars are also attractive candidates for non-medical switching: they have the same mechanism of action as the originator but may cost considerably less (17). This cost reduction may be modest relative to the low cost of generics, some of which cost 90% less than the brand-name product. However, the large overall market for biologics means that even modest relative cost reductions will result in appreciable absolute savings. Thus, as biosimilars gain regulatory approval, insurers may encourage non-medical switching of biosimilars for their originators; with a large cost savings, insurers might encourage use of a biosimilar even if it involved a switch in drug class.

Biologic therapies can be a financial burden for patients, payers, and healthcare systems (18). Biosimilars have the potential to reduce this economic burden. For example, switching patients from four European countries with rheumatoid arthritis from reference infliximab to a biosimilar (30% cheaper) could save over €433 million over 5 years (19). These cost savings could be used to reduce premiums or to provide care for other patients (20).

Private insurers are not the only payers initiating non-medical switching. Guidelines instituted in Denmark mandated a switch from adalimumab originator to a biosimilar by November 2018 for all patients with psoriasis. This switch was well-tolerated with appreciable cost-savings for the health system and no apparent negative effect on drug retention (21). In Canada, a similar switching policy was met with resistance. Biologics account for 72% of total drug spending in Alberta, with the cost of these drugs increasing by 14% annually. Four originators have accounted for 75% of the spending: infliximab, adalimumab, etanercept, and ustekinumab. Approximately 60% of Alberta Health patients have been switched to a biosimilar, resulting in cost-savings for the province.

While there are apparent cost saving benefits to biosimilar medications, the regulatory guidelines on how to determine their ‘similarity’ to the originator are complex (22–24). Guidelines ask developers to investigate quality factors such as end-product stability but do not define standardized tests to determine whether these quality criteria are met nor the allowable difference between the originator and biosimilar product (22–24). Vague criteria may breed confusion about biosimilar medicines and have the potential to compromise patient outcomes. Solutions have been proposed, and the International Psoriasis Council has suggested a ‘biosimilarity index’ be defined to provide both a standardized way of investigating quality factors and of judging ultimate biosimilarity (25). When evaluating the similarity of biosimilars to originator products, it is important to keep in mind that biologics are so complex that there is also batch-to-batch variation in the innovator product.

Financial and psychological costs of non-medical switching

Patient advocacy groups argue that there are hidden costs associated with non-medical switching. Insurers’ savings could be canceled out by a greater burden on the larger healthcare system if there were extra doctor visits, treatment failures, and new adverse events (2). However, there is no consistent evidence of these potential causes of increased cost.

When Medicaid formularies switched their preferred diabetes medication from sitagliptin to linagliptin, switched patients had no increase in all-cause hospitalization rates or 12-month post-switch HbA1c levels. However, total per member per month (PMPM) spending was 43% higher for unswitched patients (26).

Insurers do not have to demonstrate that their non-medical switching policies generate overall savings for the health system (27). To justify the burden of implementation on patients and providers, these switching policies should reduce overall healthcare spending rather than solely drug costs.

In addition to financial costs, advocacy groups are concerned about the psychological costs of non-medical switching. Negative expectations could affect perceived efficacy and therapeutic adherence, ultimately reducing outcomes (28). Patients who anticipate negative effects of non-medical switching might experience ‘the nocebo effect’, causing their status to deteriorate or blaming a change in status on the drug to which they were switched (29).

Non-medical switching may elicit negative perceptions in both patients and providers. Physicians cite ethical concerns to the practice, believing that non-medical switching increases side-effects, out-of-pocket costs, and healthcare utilization (30). Negative patient expectations are in part fueled by prescribers’ discomfort with non-medical switching (2,31). Evaluating each patient’s psychological characteristics and perspectives on therapeutic substitution may also be useful. Patients with a history of anxiety, depression, or a tendency to somatize may be impacted more by non-medical switching, even between clinically equivalent products that generate cost savings (28). Candid conversations could allow providers to alleviate patient concerns and screen for risk factors, thus preventing downstream nocebo effects.

Advising patients on non-medical switching

Communicating to patients the inherent variability of biologics, even among batches of the innovator products, might be one way to alleviate concerns. While payers may institute policy switches at-large, providers can advocate for individual patients whose physical or psychological status renders them unsuitable for switching. Non-medical switching might be difficult, distressing or overwhelming to some patients. Before advising these patients, providers may benefit from rigorously reviewing their medical history, noting any heightened immunogenicity or relapse concern, keeping in mind that batch-to-batch variability in the innovator product already exists (and the far larger variability of treatment adherence among patients).

No one can guarantee that non-medical switching (or switching from one batch of an innovator to another batch of that same drug) is without consequences. Patients can develop anti-drug antibodies, which might limit the efficacy of the original therapy. The immunogenicity risk of non-medical switching may be an important consideration in treatment planning (32). Patients can be switched back to the original therapy if a new treatment fails due to poor efficacy or side effects; switching back, however, may be associated with its own risk of loss of efficacy.

When non-medical switching threatens high-risk patients, providers may have to navigate the insurance appeals process, requiring time investment for both the patient and provider. If the insurance company denies an appeal, the patient may be entitled to request an external review by an independent third party or file a complaint with state regulatory authorities (3).

Regulation of non-medical switching

Regulation of non-medical switching has been a topic of discussion at the federal level. Provider advocacy groups can work with payers and policymakers to develop appropriate non-medical switching guidelines. Some common-sense recommendations could include:

1. Switching should be initiated only after consideration of adverse effect profiles, modes of administration, and clinical efficacy. Any differences in these profiles should be communicated transparently.

2. Exceptions should be allowed for previous failure of the recommended new treatment, allergies, intolerances, and poor health status.

3. A streamlined appeals process should allow for low-impact continuation of or switching back to the original medication when needed.

4. Health equity should be a priority, and the impact of non-medical switching strategies on at-risk groups should be addressed.

Conclusion

The impact of non-medical switching may vary greatly based on the patient, their presenting condition, and the medications being switched. The switch may be a minor inconvenience to some while triggering long-term consequences for others. The decision to switch should then be made after evaluation of the patient. The available evidence suggests that non-medical switching can reduce costs on an individual and system level. As cost-containment becomes an increasingly valued measure of healthcare performance, non-medical switching may become increasingly common. While non-medical switching has clear cost savings, its impact on health equity requires further research.

Disclosure statement

Steven R. Feldman has received research, speaking and/or consulting support from Sun Pharma, Amgen, BMS, Helssin, Arcutis, Dermavant, Alvotech, Galderma, Almirall, Leo Pharma, Boehringer Ingelheim, Pfizer, Ortho Dermatology, Abbvie, Samsung, Janssen, Lilly, Novartis, Regeneron, Sanofi, UpToDate and National Psoriasis Foundation. He holds stock in Sensal Health. Palak Patel, Caitlin Purvis, and Ramiz Hamid have no conflicts to disclose. Contents of the manuscript have not been previously published and are not currently submitted elsewhere.