New Policies Regarding Intravenous Iron Replacement Are Creating Conundrum for Providers and Payers

Dawn Holcombe, MBA, FACMPE, ACHE
Editor-in-Chief
President, DGH Consulting, South Windsor, CT

Anemia can have a significant negative impact on quality of life and overall prognosis in patients with cancer.1 Major insurers have recently announced new prior authorization and step edit policies for intravenous (IV) iron replacement therapy, which is used to treat this condition. Anthem and United Healthcare changed their policies in June 2021 and July 2021, respectively, and new policies at Cigna and Humana became effective January 1, 2022.2-5 Oncologists are expressing concern regarding the impact of these new policies on their patients, who may experience unnecessary treatment delays caused by longer periods of intentional step edits and intervening therapy failures. They are also pointing to the inconsistency of these policies, which seem to conflict with FDA-approved drug labels and the precepts of value-based care. This dissonance illustrates the need for better collaboration and more discussion among providers and payers related to complex cancer care policies.

IV Iron versus Oral Iron

Older FDA-approved IV iron therapies rely on multiple infusions or injections given over a period of weeks or months. Four of these drugs (low-molecular-weight iron dextran, iron sucrose [Venofer], ferric gluconate [Ferrlecit], and ferric derisomaltose [Monoferric]) are recommended for total treatment courses that do not exceed total dose loads of 1000 mg. Generally, these older preparations bind iron less tightly, and therefore can only be given in small doses of <250 mg at a time, over periods of weeks.6 One of these medications, iron dextran, is sometimes used at higher doses in an off-label manner by physicians to induce more rapid iron replacement in at-risk patients. This is done despite a black box warning by the FDA regarding the possibility of life-threatening anaphylaxis.

Some of the more recently approved treatments (including the 2 products that are most likely to be subject to coverage restrictions: ferric carboxymaltose [Injectafer] and ferumoxytol [Feraheme]) were developed to overcome the limitations of older iron preparations. These drugs are recommended for total treatment courses of 2 doses, with dose loads up to 1500 mg (ferric carboxymaltose) and 1020 mg (ferumoxytol). These newer formulations have carbohydrate shells that bind elemental iron more tightly, improving adverse event profiles and enabling complete iron replacement doses in 1 hour or less over a 2-dose course of treatment.

There is growing evidence within the medical community that oral iron is not as effective as IV iron for treating iron deficiency in cancer-related anemia. This would suggest that there is room for a deeper understanding of the role that oral iron replacement therapy may play in coverage policies for this type of anemia.

Auerbach and Deloughery wrote the following6:

Iron-deficiency anemia is the most common hematologic problem in the world. Although oral iron is often viewed as front-line therapy, extensive published evidence has accumulated that IV iron is superior, in both efficacy and safety, to oral iron in many clinical situations and should be introduced much sooner in the treatment paradigm of iron-deficient patients.

In addition, the National Comprehensive Cancer Network has cited the following7:

Since the majority of studies show that IV iron is superior to oral iron, the panel recommends that IV iron supplementation be used in most clinical circumstances. Low-molecular-weight iron dextran, ferric gluconate, iron sucrose, ferric carboxymaltose, and ferumoxytol are the recommended IV iron preparations.

Prior Authorizations and Step Edits Are Focused on IV Iron Therapies

Typically, prior authorizations and step edits are focused on the least costly alternatives, such as oral iron or less expensive IV iron. Under the new payer policies, IV iron therapy is considered to be reserved for use only after failure of or intolerability to, oral iron. Although there are safer FDA-approved medications that allow quicker iron replacement, these medications and doses are not deemed as being preferred in any of these payer coverage scenarios.

The focus of prior authorizations and step edits is now on the 2 newer IV iron products, which are only approved after lengthy failures on multiple other IV iron product alternatives. United Healthcare’s policy expects a history of failure for oral iron therapy, in addition to either lab work showing failure of at least 3 weeks of therapy on each of at least 2 of 3 named older IV iron drugs, or a history of failure on all 3 of the named older IV iron drugs.3 Its policy also requires that physicians attest to expected success on either of the 2 newer IV iron drugs.3 Humana’s policy requires a prior failure on oral therapy as well as failure on 2 of the older IV iron products.4 Cigna requires approval before the 2 newer IV iron products will be covered.4 Anthem places the 3 older IV iron drugs on preferred status, whereas the 3 newer IV iron products are listed as nonpreferred with step therapy review.2

Is There a Need for Value-Based Management Discussions?

Management of iron deficiencies in patients with cancer requires a delicate balance. The consequences of living with anemia are significant, and treatment with older, lower dose drugs, although fairly inexpensive, can drag on for weeks or months before patients achieve ideal iron levels. This can affect quality of life, the ability to perform activities of daily living, and overall prognosis. Physicians should be able to work with their patients to determine the most effective course of treatment. Although payers are understandably concerned about the rising costs of care, it would seem to be more productive for payers and providers to create a forum for discussion regarding the positive and negative roles that older and newer therapies play in the more comprehensive picture of the timing of iron replacement, rather than to rely on step edits that adversely affect the recovery of patients from anemia. Employers are certainly concerned with workplace productivity and presenteeism and are likely to support treatments that more rapidly improve patients’ health.

Balancing the Costs

New FDA-approved IV therapies provide safer, faster dosing to complete iron replacement levels in 1 or 2 treatments, but their use has been severely limited under new payer coverage policies. Some physicians also find success using carefully monitored higher doses of the older product iron dextran in a single administration, but that dose load (if higher than 1000 mg per dose) is considered off-label. As such, use of this option would fall under the medical judgment of the physician for a given patient and would not be appropriate for payers to require in their policy for step edit approval in a preferential position to the newer more expensive products. One of the newer products, ferric carboxymaltose, holds the only FDA approval for iron replacement dosages in 1 course of treatment up to 1500 mg.

Preventing Anemia and Costly Office Visits

With post–COVID-19 health system staffing and facility restrictions, coverage policies that require patients to fail first on older treatments via multiple lengthy treatment cycles in the office and that often may not ultimately reach full iron replacement levels, make little sense fiscally, medically, or from a quality-of-life standpoint.

Auerbach and Deloughery noted the following6:

Undoubtedly, this paradigm shift in the treatment of one of the most common maladies on earth has been driven by new formulations with improved adverse event profiles and infusion schedules, which allow complete replacement dosing in a brief single setting.

Anemia and Cancer: Quality-of-Life Issues

Policies that delay effective treatment of anemia through prior authorizations and step edits appear to ignore the bigger picture of population management and value-based care. Value-based care goals should be aimed at shorter, more intense treatments that return patients to their regular lifestyles more quickly. Often, less expensive iron replacement choices, which are based solely on the cost of a specific drug, become the more expensive and medically debilitating options when the impact of ineffective early treatment is considered. Most of the current policies require weeks and months of documented failure on older, lower dose, regimens. This is too long of a time to keep patients from their normal work and home lives, in a weakened, frail state.

Busti and colleagues noted the following1:

Cancer anemia may be associated with a broad spectrum of symptoms, depending on its severity and rapidity of development. Fatigue is the most debilitating symptom, followed by impaired mental capacity, confusion and depression, especially in elderly people. Nausea, loss of appetite, dyspnea, syncope and falls can also occur, particularly in patients with co-morbidities such as cardio-pulmonary and renal dysfunctions. Of note, the decrease in quality of life (QoL) is particularly evident when Hb drops between 11.5 and 10 g/dL, which is classically considered as mild anemia and not perceived as a problem by most doctors.

Surely, it was not the intent of these new coverage policies to sacrifice patient health with weeks of required failures on multiple lower dose products. One must wonder whether the aggregated costs of those required failures in terms of time and money are justified when physicians are required to forego recent advances in dosing loads and shorter treatment courses.

Physicians Are Pushing Back on New Policies

The physicians of the Medical Oncology Association of Southern California, representing more than 500 oncologists in California, expressed their concern regarding these policies to Anthem and United Healthcare last fall, and more recently, to Cigna and Humana. This organization expressed the following strong concerns on behalf of patients and providers8:

  • The policy does not appear to account for dynamic clinical and economic considerations in the impacted patient population. Failure to achieve full, safe, and rapid iron repletion may impact disease and comorbidity progression, as well as lead to added healthcare resource utilization over time.
  • Meaningful differences in IV iron products do not appear to have been taken into consideration, based on the most up-to-date data on efficacy and safety, healthcare resource utilization, and comparative effectiveness. These clinical and overall cost of care differences have been demonstrated in randomized controlled trials and real-world studies.
  • An effective policy should consider not only product acquisition costs, but also other clinical and economic factors when administering IV iron including, but not limited to, the number of infusions, infusion time, cost offsets/financial risk, quality metrics, and clinical profile (effectiveness and safety).
  • In 2022, effective policies should be inclusive of key quadruple aim considerations and not inadvertently create greater disparities in care, driven by variations between IV iron products that could affect patient satisfaction, clinical experience, adherence, and impacts on quality of life.

Major national medical groups such as the American Society of Clinical Oncology, American Society of Hematology, and the National Oncology State Network are reviewing their own responses to the additional prior authorization and step edit requirements that these payer policies place on the healthcare system, patients, and the precepts of value-based care.

However, as of the writing of this editorial, there has been no change in the IV iron replacement policies of any of the payers.

What Can Individual Practices Do?

If these or similar policies have recently been implemented in your region, consider their impact on the total costs of care and the patients who will be affected. The National Oncology State Network is developing talking points for individual practices to use to encourage greater discussion and collaboration with payers, and I would be happy to share these with you. I encourage you to reach out to your local state society and offer support so that each state can address improvements to these policies. Please feel free to contact me at This email address is being protected from spambots. You need JavaScript enabled to view it. if you would like to share what you are doing or if you need support.

Payer coverage policies may be driven by external advisors who look only at individual drug prices, instead of taking into account the upstream and downstream positive or negative consequences of alternative treatments. We can encourage more awareness of the effects of policy on patients’ quality of life and workplace productivity, as well as the burden of multiple visits versus single treatment visit options. Together, providers and payers should be able to engage in productive discussions that lead to better value-based treatments and coverage policies. As the ones on the front lines with patients, we can raise these issues for consideration and put them on the table for payers with the goal of balancing policies. Together, we can advance the standard of care for cancer-related anemia management with an eye toward more cost-effective care.

References

  1. Busti F, Marchi G, Ugolini S, et al. Anemia and iron deficiency in cancer patients: role of iron replacement therapy. Pharmaceuticals (Basel). 2018;11:94.
  2. Anthem. Iron infusion medical step therapy notice. April 1, 2021. https://providernews.anthem.com/california/article/iron-infusion-medical-step-therapy-notice-1. Accessed January 25, 2022.
  3. United Healthcare. Intravenous iron replacement therapy. July 1, 2021. www.uhcprovider.com/content/dam/provider/docs/public/policies/comm-medical-drug/iv-iron-replacement-therapy.pdf. Accessed January 25, 2022.
  4. Cigna. Intravenous iron replacement therapy. January 1, 2022. https://static.cigna.com/assets/chcp/pdf/coveragePolicies/pharmacy/ip_0222_coveragepositioncriteria_intravenous_iron_replacement_therapy.pdf. Accessed January 25, 2022.
  5. Humana. Pharmacy coverage policies. http://apps.humana.com/tad/tad_new/Search.aspx?searchtype=beginswith&docbegin=I&policyType=pharmacy. Accessed January 25, 2022.
  6. Auerbach M, Deloughery T. Single-dose intravenous iron for iron deficiency: a new paradigm. Hematology Am Soc Hematol Educ Program. 2016;2016:57-66.
  7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Hematopoietic Growth Factors. Version 1.2022. December 22, 2021. www.nccn.org/professionals/physician_gls/pdf/growthfactors.pdf. Accessed January 25, 2022.
  8. Medical Oncology Association of Southern California. Letter to Regional Vice President/Medical Director, Anthem – California, Nov. 18, 2021.

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